Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention.99mTc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement was measured using Kappa (κ). Power determined the sample sizes needed to show statistically significant changes due to intervention.Eighteen sheep were enrolled in a pilot study to evaluate [Ten sheep completed the full protocol. Data processed was performed with pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15%-35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89). Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion.This study demonstrates the suitability of large animal models for imaging with standard MPI protocols and its feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair. Advances in developmental and cell biology have created great interest in the potential of stem cell therapy to repair and regenerate the damaged heart, however, substantial challenges remain before this becomes an effective and safe therapeutic option . One of The up-scaling from basic science in rodents to clinical trials in humans often encounters a “translational gap” which can be overcome by the use of an intermediate stage using large animals. Functional and cellular consequences of myocardial infarction and response to therapy can be readily studied in sheep and pigs with techniques directly applicable to human subjects due to similarities in heart size, anatomy, coronary supply and molecular machinery. One suc111In]-labelled bone marrow-derived MSCs into the affected area of heart muscle to assess stem cell therapies have presented difficulties due to the small heart size  have attempted to trace the fate of the implanted cells using a label suitable for imaging. Studies on rodents using direct injection of 1In-labelart size . The relart size .There are no published studies using an ovine (sheep) model to study myocardial function using SPECT/CT. We therefore set out to investigate the potential to image the myocardium before and after stem cell transplantation using readily available myocardial perfusion imaging (MPI) techniques. The aim of the study was to evaluate the potential for SPECT/CT and diagnostic tools routinely used in the clinical setting to assess myocardial injury and potential recovery following stem cell transplantation in a sheep model of acute myocardial infarction. If successful, these approaches could be widely employed to more rapidly facilitate translation from the animal model into man.A pilot study approved by the local Institutional Animal Care and Ethics Committee (RNHS/UTS 0504-018A) was undertaken to study eighteen Border Leicester/Suffolk-cross female sheep using MPI SPECT/CT at (i) baseline, (ii) following myocardial infarction, and (iii) after therapeutic intervention.All studies were acquired using a hybrid SPECT/CT system consisting of a SKYLight gamma camera  and a PQ5000 CT scanner  . The she99mTc]-Sestamibi  to assess myocardial perfusion and function. The acquisition consisted of a gated MPI SPECT study using a 128×128 matrix with 16 time bins at 15 seconds per projection for 120 projections  using a high-resolution collimator (VXGP), followed by a CT scan using a fixed beam current of 100 mAs, a tube voltage of 120 kVp and a pitch of 1 giving a slice thickness of 4 mm. After two days, an MI was induced using a 60 minute balloon occlusion  of the dominant branch of the paraconal artery  using a carotid artery cut-down approach followed by reperfusion. Between 5 and 7 days after MI, a repeat MPI study was performed to confirm the presence, location, extent, size and severity of the defect. If a significant or measurable defect was identified, then the sheep were allocated to one of three arms of the study with the imaging team remaining blinded to the final treatment arm:A resting MPI study was commenced 15 minutes after injection of 1.5 GBq -Sestamibi so as to allow imaging of the heart for visual confirmation of the infarct location with the ex-vivo anatomic slices. After 5 minutes the sheep were sacrificed without recovery from anaesthesia using a lethal dose (2 g I.V.) of potassium chloride (KCl) given intravenously via the indwelling venous catheter. After the heart ceased beating, body tissues including the heart, lung, liver and kidneys were excised for further examination. The heart was fixed with formalin and then sectioned evenly through the short axis plane into 5 to 10 mm thick slices for histological sampling. The heart slices were placed on a template ordered from apex to base and imaged by placing the template directly on top of the collimator of an upturned gamma camera using a 512 × 512 matrix for 300 seconds. The heart sections were reviewed microscopic-ally to confirm the presence of an MI, to assess the extent, if any, of neovascularisation, and for correlation with MPI findings.The sheep were euthanized after the final imaging time-point 6-8 weeks after the MI. Whilst anaesthetised, the sheep were injected with 400 MBq of -Sestamibi heart slices in 5 of the 7 sheep , precluding many institutions such as our own. Our experiences suggest that this model could be reproduced in many institutions with nuclear medicine departments, and thus wide-spread experience with a realistic model of acutemyocardial infarction and response to therapy could be accelerated with many more centres participating. We used a SPECT/CT hybrid scanner to give accurate scatter and attenuation corrected SPECT images and such devices are now ubiquitous in the practice of nuclear medicine. The use of CT-based attenuation correction is now recommended, and common, in many nuclear medicine practices. Scatter correction further improves the quality and accuracy of the data.et al evaluated the anatomy and distribution of porcine coronary arteries in which they compared their findings with those reported for canines and humans  in planar and/or SPECT modes is known to produce reliable and reproducible measures of LV function in standard clinical practice in man (The size of the sheep heart is similar to a small female with an EDV of approximately 80 ml and a normal LVEF of greater than 50%, similar to that of a healthy human thus making it amenable to imaging with current SPECT gamma cameras. As a consequence of the small size, however, difficulties may arise in accurately tracking the endocardial and epicardial borders on the gated MPI studies resulting in uncertainties in the LVEF values obtained. Alternately, the measurement of LVEF using gated heart pool scanning with e in man  that is Our experienced nuclear medicine physicians found no difficulties in interpreting the MP images derived. This was confirmed by a К value of 0.89 indicating very good agreement. Total agreement gives a score of 1, with 0 indicating no agreement while negative values mean worse than by chance. A К value between 0.81-1.0 is said to represent very good agreement .A pilot study enables the investigator to test a proof of concept, with the benefit being its value in assessing the quality of the data, checking the logistics of the trial and enhancing reliability of estimates for use in sample size calculations. The logistics of testing such methodologies in human trials is complex and hard to undertake in a controlled manner hence most are performed using animal modelling. The results reported from this pilot study have demonstrated that standard clinical imaging techniques and investigations used to assess myocardial injury and response to therapy in man can be used in large animal models to test response to novel treatments such as the use of stems cells for myocardial repair. This pilot study only included small numbers of animals in each treatment group and therefore determining the most effective implantation method to improve both perfusion and function following an induced MI may not be possible. However, these initial results would suggest that both the IM and IC methods could potentially be used for this type of therapy, with the IM method in this pilot study showing an improvement in LV function and neovascularisation identified microscopically. Additionally, the experience gained with these techniques can be easily translated to human studies to assess therapeutic benefit in the clinical setting.in vivo was deliberate as this process has proven to be a reliable and reproducible method of assessing response to treatment which can be readily translated to human studies. This pilot study has shown that techniques used in the clinical setting in man, which have been highly developed and refined over many years and hundreds of thousands of investigations, can be used with large animals to follow the consequences of stem cell and other therapies. Also, this study has shown that large animal models are suitable for assessment with standard myocardial perfusion imaging, radiopharmaceu-ticals and protocols which could subsequently be applied in human clinical trials to study the efficacy of stem cell therapy. As such, the sheep model and the nuclear medicine imaging and analysis techniques used here have demonst-rated an excellent translational platform for bridging ‘mouse-bound’ pre-clinical studies and eventual clinical therapeutic use in humans. Further, both qualitative and semi-quantitative analysis can be applied to allow repeated non-invasive temporal assessment of extent, severity, defect size and LV function using standard cardiac analysis software and review packages available in the majority of nuclear medicine departments.The anatomy and coronary arterial supply of the sheep heart is similar to the human heart with very little collateral supply, and an infarct can be reliably and reproducibly induced making it an ideal model for testing therapeutic interventions post-MI. The decision to study the ‘functional consequences’ rather than directly labeling the stem cells to study the fate of the MSCs


This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure.Transverse tubules (T-tubules) are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation–contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through  In the 2+ unloading and reloading during myocyte isolation process. These factors intrinsic to the isolation of cardiomyocytes are an obstacle to identifying subtle changes in T-tubule membrane structure in disease. In addition to using living isolated cardiomyocytes, fixed myocardium tissue sections were also used for T-tubule studies  for simultaneous examination of the organization and spatial relationship between T-tubules and key E–C coupling proteins in health and diseased hearts . The heart is perfused for ~30 min with perfusate containing membrane lipophilic marker MM 4-64  at a concentration of 5 μM. For T-tubule imaging, it is not necessary for the perfusate to be at physiological temperature, and thus most studies are performed at room temperature.In order to identifying subtle and comprehensive changes in T-tubule membrane structure of cardiomyocytes in their natural habitat, our group developed methods for 2 area, which contains on average 10–20 myocytes . . Approaches to determine the integrity of the T-tubule system include measuring the density (area) structure in its native environment.Avoids artifacts associated with dissociation of cardiomyocytes.Subtle changes in T-tubule architecture can be visualized and quantitated.Ability to visualize T-tubules in multiple regions of the heart, including atrial, LV and RV epicardium.In larger species , sub-regions of the heart can be imaged, such as posterior or anterior LV.For studies of infarcted hearts, it is relatively easier to image the infarct, border and remote zones.2+ handling and mitochondrial properties .Technique can also be applied to image other features in intact hearts, such as CaIn situ T-tubule imaging is much more costly as compared to imaging in dissociated myocytes .Confocal microscope set-up must be adapted to incorporate Langendorff perfusion system.Imaging is restricted to subepicardial myocytes due to limitations in laser penetration; endocardium cannot be imaged.In situ imaging is not applicable for imaging subepicardium in large mammals .Phototoxicity issue: We do not expect greater phototoxicity in in situ imaging as compared to single cell imaging. This is because the laser power used for in situ imaging is highly comparable to that used for single cell imaging.Temporal degradation: This should not be a concern. First the experiments are performed at room temperature as used for isolated myocytes. For each heart, experiments can be done within 1–1.5 h . This length of time is even shorter than the approach of using isolated myocytes. Isolated cells are usually studied several hours  after isolation.in situ T-tubule imaging has revealed that not only is T-tubule remodeling a mediator of heart failure, but T-tubules are critical for normal cardiac development and function. In this section, we review how in situ confocal imaging has provided key insights into the timing and regional differences in T-tubule integrity following cardiac stress and in developing hearts. In addition, we describe current efforts to prevent or reverse deleterious T-tubule remodeling.Studies using electron microscopy and laser scanning confocal imaging of fixed tissue samples or isolated cardiomyocytes provided the first evidence that T-tubules are altered in failing hearts . We found that discrete local loss and global reorganization of the T-tubule system starts early in compensated hypertrophy in LV myocytes, prior to detectable LV dysfunction as assessed by echocardiography. At the onset, this process was manifested as subcellular T-tubule loss limited to discrete local regions in some LV myocytes, while the T-tubule structure in right ventricular (RV) myocytes was unaffected. However, with progression from compensated hypertrophy to early and late heart failure, T-tubule remodeling spreads from the LV to the RV. By the advanced stage of heart failure, the severity of T-tubule disruption in RV myocytes is equivalent to that seen in LV myocytes.The first application of in situ confocal T-tubule imaging also allows comparison of T-tubule integrity in different regions within the same heart, i.e., LV and RV myocytes. These data revealed that T-tubule damage is not a response to global neurohormonal changes, which would manifest as similar changes in LV and RV myocytes at each stage in heart failure progression. In addition, in situ imaging provides an opportunity to visualize and quantitate subtle changes in T-tubule architecture which may not be apparent in isolated myocytes. For example, in unpublished studies of isolated myocytes from pressure overload hypertrophied hearts, we did not observe changes in the T-tubule integrity as compared to sham control hearts , moderate remodeling in LV remote from the myocardial infarction (remote zone), and no damage to RV T-tubules. Quantitative analysis showed the TTpower is significantly different between the border and remote zones, suggesting that the damage to the border zone is more pronounced but the remote zone is also affected  is a common observation in multiple animal models of cardiac disease and is associated with adverse cardiac phenotypes in humans. (Tsutsui et al., In our studies of T-tubule remodeling in multiple models of heart failure, we consistently observed a loss in the structure protein junctophilin-2, which is implicated in the formation of T-tubule/SR junctions and thereby E–C coupling. For example, we and others have observed a significant loss in the expression of junctophilin-2 in multiple different models of heart failure. (Minamisawa et al., q (Wu et al., q activation, the transgenic mice exhibit heart failure which is reversed by cessation of Gαq activation. More importantly, we found transgenic Gαq expression causes a severe disruption of the T-tubule network and loss of junctophilin-2 expression in transgenic Gαq hearts, which could also be reversed by turning off Gαq (Figure q induction prevents T-tubule remodeling and junctophilin-2 loss. The proposed mechanism is that cardiac stress results in calpain-mediated degradation of junctophilin-2, T-tubule remodeling and E–C coupling dysfunction. Strategies to prevent the loss of junctophilin-2 may therefore represent an approach to restore cardiac function after initial T-tubule damage.The most compelling evidence that T-tubule remodeling can be reversed was obtained through studies of a reversible model of heart failure via inducible transgenic expression of the G protein coupled receptor Gαq Figure . In addiin situ confocal imaging to provide novel insights into the cardiac ultrastructure and function in intact hearts is undeniable. However, this methodology has not achieved wide-spread application because of technical considerations and experience. For example, in situ T-tubule imaging requires a dedicated confocal microscope with a Langendorff perfusion system, which is not practical for laboratories that rely on core facilities for microscopy needs. In addition, a certain degree of technical skill is required to acquire high quality images. The applicability of in situ confocal imaging is not restricted to T-tubules. Indeed, it can be used to image other parameters critical for cardiac function, such as action potential (Bu et al., 2+ dynamics (Kaneko et al., The power of The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Myocardial fibrosis has been proposed to play an important pathogenetic role in left ventricular (LV) dysfunction in obesity. This study tested the hypothesis that calibrated integrated backscatter (cIB) as a marker of myocardial fibrosis is altered in obese adolescents and explored its associations with adiposity, LV myocardial deformation, and metabolic parameters.Fifty-two obese adolescents and 38 non-obese controls were studied with conventional and speckle tracking echocardiography. The average cIB of ventricular septum and LV posterior wall was measured. In obese subjects, insulin resistance as estimated by homeostasis model assessment (HOMA-IR) and glucose tolerance were determined. Compared with controls, obese subjects had significantly greater cIB of ventricular septum , LV posterior wall  and their average . For myocardial deformation, obese subjects had significantly reduced LV longitudinal systolic strain rate (SR) (p = 0.045) and early diastolic SR (p = 0.015), and LV circumferential systolic strain (p = 0.008), but greater LV longitudinal late diastolic SR (p<0.001), and radial early (p = 0.037) and late (p = 0.002) diastolic SR than controls. For the entire cohort, myocardial cIB correlated positively with body mass index  and waist circumference , but negatively with LV circumferential systolic strain  and systolic SR . Among obese subjects, cIB tended to correlate with HOMA-IR .Obese adolescents already exhibit evidence of increased myocardial fibrosis, which is associated with measures of adiposity and impaired LV circumferential myocardial deformation. Childhood obesity has become a global epidemic involving not only developed but also developing countries. Among thWhether increased myocardial fibrosis occurs in obese children is, however, unknown. Limited data suggest that this may be the case in obese adults. Myocardial biopsy to quantify the amount of fibrous tissue is invasive and impractical. On the other hand, noninvasive assessment of myocardial fibrosis by echocardiographically-derived calibrated integrated backscatter (cIB) has been used in both adults , 11 and Alteration of myocardial composition and architecture may affect myocardial mechanics. Conventional echocardiographic assessment of LV function in obese subjects has nonetheless relied on measuring LV ejection fraction, which often yielded normal results. On the oIn the present study, we aimed to test the hypothesis that cIB is altered in obese adolescents compared with non-obese subjects. Furthermore, we explored its associations with measures of adiposity, indices of LV myocardial deformation, and, in obese adolescents, metabolic parameters including homeostasis model assessment of insulin resistance (HOMA-IR) and glucose tolerance.A total of 52 obese adolescents and 38 non-obese healthy adolescents aged 14 to 20 years were studied. Obese subjects were recruited consecutively from the paediatric clinic, while non-obese controls are friends of hospital staff and volunteers recruited from the community. The obese phenotype is defined by body mass index (BMI) at or above 95 percentile for children and adolescents of the same age and sex. Exclusion criteria included documented congenital or acquired heart diseases and current use of cardiovascular medications. Weight and height were measured and BMI was calculated accordingly. Waist circumference was measured at the midpoint between the lowest part of costal margin and highest point of the iliac crest in the mid-axillary line. Blood pressure of the right arm was measured three times with an automated oscillometric device  after the subjects had taken a rest for at least 15 minutes, and the average was used for analyses.This study was approved by the Institutional Review Board of The University of Hong Kong/ Hospital Authority West Cluster, Hong Kong and informed written consent was obtained from all subjects and parents on behalf of minors.Echocardiographic examination was performed using Vivid 7 ultrasound machine . Acquired data were stored digitally and analyzed offline using the EchoPAC software . Average values of echocardiographic indices based on readings from three cardiac cycles were used for statistical analyses.M-mode echocardiography was performed from the standard parasternal short-axis view for measurement of the following indices: LV end-systolic and end-diastolic dimensions, shortening fraction, septal and LV posterior wall thickness, and LV mass.From the four-chamber view, pulsed-wave Doppler examination was performed to determine transmitral peak early (E) and late (A) diastolic velocities, E wave deceleration time, and E/A ratio. Colour tissue Doppler imaging of the LV lateral wall was performed with frame rates >100 Hz. With the sample volume positioned at the LV lateral wall-mitral annular junction, the mitral annular peak myocardial velocities at systole (s), early diastole (e), and late diastole (a) were measured and the mitral E/e ratio was also calculated. The relatively load-independent index of ventricular systolic function, myocardial acceleration during isovolumic contraction (IVA), was also measured as reported.Left ventricular myocardial deformation was assessed also using EchoPAC software . From the four-chamber view, LV global longitudinal systolic strain and systolic and diastolic strain rate (SR) were measured. Based on the mid-ventricular parasternal short-axis plane, LV global systolic circumferential and radial strain and systolic and diastolic SR were measured. Our group has previously reported on high intra- and inter-observer reproducibility of STE in measuring LV myocardial deformation.Integrated backscatter of the ventricular septum and posterior LV wall at the mid-ventricular level was determined at end-diastole from the parasternal short-axis view. The sample volume was tracked manually to maintain the same region throughout the heart cycle. Myocardial cIB was calculated as the difference between integrated backscatter at the two sites and that of the pericardium. The average cIB at the two sites was derived for correlation analysis. The intra- and interobserver variability for CIB measurement was 4.9% and 6.5%, respectively.Oral glucose tolerance test was performed in the obese group in the morning after overnight fasting after echocardiographic assessment. Normal and impaired glucose tolerance and diabetes mellitus were defined according to standard guidelines. The HOMA1.7, the latter being reported to be more sensitive for identification of obesity-related LV hypertrophy.[Data are presented as mean±SD unless otherwise stated. Absolute values of strain and strain rates are presented to facilitate interpretation and analyses. Demographic and echocardiographic parameters between obese and non-obese cohorts were compared using unpaired Student's t test. The LV mass was indexed by both body surface area and heightertrophy. Pearson The 52  obese adolescents were studied at 17.8±1.7 years, while the 38  non-obese controls were studied at 18.1±2.1 years (p = 0.39). For Doppler parameters, obese subjects had significantly greater transmitral A velocity (p = 0.008), mitral annular a velocity (p = 0.026), and E/e ratio (p = 0.034), but lower mitral annular s velocity (p = 0.016) and e/a ratio (p = 0.013).Myocardial cIB of the ventricular septum , LV posterior wall  and average cIB of the two sites  were significantly greater in obese compared with non-obese subjects . Even wiWhen stratified by the presence (n = 14) or absence (n = 38) of glucose intolerance in obese subjects, no differences in myocardial deformation parameters were found .On the other hand, there were greater correlations between waist circumference and myocardial deformation parameters than those between BMI and the latter . Even afFor the entire cohort, the average myocardial cIB correlated positively with BMI , waist circumference  and negatively with LV circumferential systolic strain  and systolic SR  , but notThe present study demonstrates increased myocardial cIB suggestive of myocardial fibrosis and impaired LV myocardial deformation along the longitudinal and circumferential dimensions in obese adolescents. Additionally, myocardial cIB was found to associate positively with waist circumference and BMI and negatively with LV circumferential deformation.In rodent models of obesity, cardiac remodeling with ventricular hypertrophy and increased interstitial fibrosis have been described., 23, 24 Changes in extracellular matrix composition may have functional implications on LV mechanics. Previous studies on LV systolic function in obese subjects by quantification of ejection fraction usually yielded normal results. On the oFibrous tissue deposition may increase myocardial stiffness and lead to ventricular diastolic dysfunction. This is the first study to explore diastolic myocardial deformation using STE in obese children. While we did not find statistically significant correlations between cIB and indices of diastolic function, reduced LV longitudinal early diastolic SR and higher E/e ratio in our obese cohort may reflect respectively ventricular relaxation abnormality and greater LV filling pressure. The latter concurs with findings of previous studies in obese children., 31 FurtAssociations of measures of body adiposity, in particular waist circumference, with myocardial cIB and deformation indices even after adjustment of systemic blood pressure are of clinical importance. Body mass index and waist circumference, with the latter having a greater sensitivity, can predict clustering of traditional cardiovascular risk factors in children., 33 Our Within our relatively small obese paediatric cohort, the HOMA-IR tended to correlate with myocardial cIB. As aforementioned, in normotensive, non-diabetic obese adults, circulating procollagen type III aminopeptide has been shown to be associated with insulin resistance. Recent cSeveral limitations to this study warrants discussion. Firstly, the small number of patients with glucose intolerance and diabetes limits the statistical power to perform subgroup analysis. Further large scale studies of paediatric obese subjects are required to clarify the relationships between markers of myocardial fibrosis, insulin resistance, and glucose homeostasis. Secondly, the modality of T1 mapping, which is ideal for assessment of diffuse myocardial fibrosis, is not available to us. It is worth noting, however, that conditions other than fibrosis may also influence extracellular volume measurements by T1 mapping. Thirdly,In conclusion, our findings suggest increased myocardial fibrosis in obese adolescents, which is related to measures of adiposity and may have implications on subclinical LV systolic and diastolic function. Whether weight reduction and anti-fibrotic strategies such as aldosterone antagonism may alter myocardial acoustic properties and improve myocardial deformation in young subjects are topics for further studies.


The introduction of the implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death has led to an important reduction in mortality in patients with impaired left ventricular ejection fraction (LVEF) , 2. ConsThe study performed by De Haan et al. published in the current issue of the Netherlands Heart Journal included 152 patients who were referred for primary prevention ICD implantation [The lack of uniformity between imaging modalities to assess LVEF has been well documented. Although comparative studies have shown some discrepancies, most of the data suggest that LVEF tends to be highest when utilising 2D echocardiography and subsequently gradually declines with CMR and nuclear ventriculography, respectively . The quathe most clinically accurate and appropriate in their institution’ [So what should our practice be in the meantime? As current clinical guidelines for ICD implantation are predominantly based on studies using 2D echocardiography, it could be argued that this type of imaging should be preferred to practice evidence-based medicine. Indeed, the ACC/AHA/ESC 2006 guidelines for ICD implantation actually recommend echocardiography for the assessment of left ventricular function . It is oitution’ . The cur


The aim of the current study was to compare 180° and 360° data collection modes to measure end diastolic volume (EDV), end systolic volume (ESV) and ejection fraction (EF) values of the cardiac system by gated myocardial perfusion tomography.Thirty-three patients underwent gated myocardial perfusion tomography. Single photon emission computed tomography data of patients’ heart were acquired by 180°, 45° left posterior oblique to 45° right anterior oblique, and 360° to obtain EDV, ESV, EF and cardiac volume changes  throughout each cardiac cycle.Results of the current study indicated that there were no significant differences between 180° and 360° angular sampling in terms of measuring EDV, ESV and EF in myocardial perfusion imaging. Cardiac volume change patterns during a cardiac cycle were also similar in 360° and 180° scans. We also observed that there was no difference in EDV, ESV and EF values between the group with stress induced by exercise and the group with stress imposed by dipyridamole.As there is no difference between 180°and 360° cardiac scanning in terms of EDV, ESV and EF, half-orbit scan is recommended to study these cardiac system parameters because it offers more comfort to patients and a shorter scanning time. In the late 1980s when electrocardiography (ECG) has been successfully applied in conjunction with single photon emission computed tomography (SPECT) scanner, gated myocardial perfusion SPECT or gated SPECT has been introduced as a valuable technique to study cardiac function. Study of the functional abnormalities of the myocardium by gated SPECT can be used to assess the level of associated risks and adopt appropriate therapeutic strategies ,3. GatedThe end diastolic volume (EDV), end systolic volume (ESV) and left ventricular ejection fraction (EF) data acquired in gated myocardial perfusion imaging are important parameters in determining the functional status of the myocardium ,19.Generally, two types of data sampling are used in gated SPECT; 180° acquisition and 360° acquisition. Because of the anatomical location of the heart, which is the left anterior side of the thorax, photons coming from the right posterior side is attenuated significantly, degrading the quality of image obtained by 360° tomographic acquisitions  with an average age of 51.77 (range of 33 to 75) years were included in this study. Prior to the study, all patients were informed about the procedure and informed consent forms were obtained. To perform SPECT study, all participants were injected with 740 MBq of 99mTc-sestamibi in the peak of the exercise. The stress imaging was performed about 15 to 45 minutes after injection. In the stress imaging by pharmacologic agent, which was performed on 16 cases, patients received infusion of 0.56 mg/kg of dipyridamole over 4 minutes. 99mTc-sestamibi was injected approximately three minutes after completion of this infusion.In stress imaging by exercise, which was performed on 23 individuals, patients underwent treadmill testing during which they received Gated myocardial perfusion studies were acquired for 8 frames/cardiac cycle projections over 180° and 360° using a SPECT scanner (ADAC-Pegasys). Acquisition parameters were set as a beat acceptance window at 20% of the average R-R interval, a 140-keV photopeak with a 20% window and a matrix size of 64×64.Paired Student’s t tests were applied to determine significant differences in the data. A p value less than 0.05 was defined as statistically significant.Based on the scan of 39 cases included in this study, 12 patients were detected to have ischemia and 27 cases were considered as normal. The EDV, ESV and EF values as measured by myocardial perfusion imaging in these two groups by 180° and by 360° data collection are presented in In addition, EDV, ESV and EF values measured by both 180° scan and 360° scan in stress-exercise and stress-dipyridamole stages were compared and presented in For all patients, the R-to-R interval and relevant bins were also measured. The findings indicated that there was no significant difference between normal subjects (8.00±0.024 ms) and ischemic patients (8.00±0.022 ms) (p>0.05).Changes of cardiac volume over a cycle that was measured in eight frames, for both 180° and 360° scan modes, are presented in Volume-time curves over a cardiac cycle for normal and ischemic patients was almost similar and there was no significant difference between the volumes of corresponding phases (p>0.05). In 180°data sampling, shown in The main aim of the present study was to quantitatively compare 180° and 360° angular sampling SPECT for the assessment of EDV, ESV, EF and volume changes over a cardiac cycle. Participants of this study were divided into two groups of normal subjects and ischemic patients, then their EDV, ESV and EF values were assessed by 180° and 360° data collection methods. We observed that in myocardial image perfusion study, there was no significant difference between 180° and 360° orbits in terms of EDV, ESV and EF values. This finding indicates that measurement of the main parameters in myocardial perfusion imaging by using 180° data collection orbit may lead to the same results as obtained by 360° technique. In addition to the more favorable image quality that can be achieved in 180° scan, the required data can be obtained in a relatively shorter time in comparison with 360° orbit. Therefore, based on the results of the current attempt for a specific cardiac study, it can be concluded that 360° acquisition offers no significant advantages over 180° acquisition to evaluate myocardial function during gated myocardial perfusion. This finding is in concordance with the results of a recently published similar study (Until now, various attempts have been done to compare the two scan modes of 180° and 360° in myocardium SPECT study from different aspects. Knesaurek et al.  investigOn the other hand, a study comparing 180° and 360° data collection in myocardial 99mTc-SPECT on 12 patients by Maublant et al.  indicateDuring myocardial perfusion imaging, patients with CAD are required to perform a sufficient amount of exercise to reach maximum predicted heart rate in order to overcome the low diagnostic sensitivity of the scan ,26. In cWhat’s more, the current study depicted that the R-R bin quantification between two types of data acquisitions did not differ significantly, which indicates the unchanged diastolic parameters in these two subgroups.The main limitation of the current study was the low number of patients; therefore, it is recommended that a similar study with a larger population should be performed to compare these two scanning modes more comprehensively.180° data acquisition is suggested due to the patient comfort, shorter acquisition time and better image quality in comparison to 360° scanning mode, as reported by previous studies.


Gout is a common metabolic disorder characterized by hyperuricemia and chronic inflammation. Previous studies show that hyperuricemia accelerates the occurrence and worsening of cardiovascular disease due to LV remodeling. However, it is still unclear whether hyperuricemia is the sole contributor to organic heart remodeling in patients with gout. In addition, there is a paucity of data regarding the association between LV diastolic function and gout. The objective of this study was to investigate the effects of gout on LV diastolic function.A total of 173 patients were divided into tertiles based on the following serum uric acid (UA) levels: 1) serum UA ≤ 6.5 mg/dL (n = 54), 2) serum UA >6.5 to ≤8.5 mg/dL (n = 59), and 3) serum UA > 8.5 mg/dL (n = 60).Patients underwent a comprehensive Doppler-echocardiography examination to evaluate LV volume, systolic and diastolic function, and left atrial (LA) volume.2, p < 0.001), higher E/Em , and larger maximal LAVi  than patients without gout. The prevalence of moderate to severe LV diastolic dysfunction was higher in patients with gout .LV diastolic parameters, including diastolic peak early transmitral flow velocity (E), late transmitral flow velocity (A), E/A, peak early diastolic mitral annular velocity (Em), late diastolic annular velocity (Am), Em/Am, E/Em, maximal LA volume index (LAVi) and prevalence of moderate to severe LV diastolic dysfunction were not significantly different between the three groups. Among the population being studied, 108 individuals received a gout diagnosis. Gout patients had greater LV end-systolic dimensions , higher LV mass index (107.18 ± 29.51 g/mGout, not hyperuricemia alone, is associated with LV diastolic dysfunction and LA volume enlargement. Gout is a common metabolic disorder characterized by hyperuricemia and chronic inflammation . NumerouIn previous studies it has been observed that cardiovascular events are positively associated with gout. Early evidence reported in the Framingham study found a 60 % increased risk of coronary artery disease (CAD) among gout patients . A TaiwaIt is still unclear whether hyperuricemia is the sole contributor to organic heart remodeling in patients with gout. Furthermore, there is a paucity of data on the association between LV diastolic function and gout. Therefore, the aim of the current study was to investigate the effects of gout on LV diastolic function.In this prospective study, patients without hyperuricemia, with hyperuricemia, or with gouty arthritis, who underwent echocardiographic examinations, were enrolled between October 2010 and February 2013. Initially, a total of 200 patients were enrolled in this study. Exclusion criteria were the presence of moderate or severe valvular disease, dilated or hypertrophic cardiomyopathy, LV systolic dysfunction (defined as LV ejection fraction (LVEF) <50 %), left bundle branch block, second-degree or third-degree atrioventricular conduction block, permanent cardiac pacemaker implantation, atrial arrhythmias , congenital heart disease, and a history of previous cardiac surgery. Patients were also excluded if they had poor-qualitied echocardiographic images that precluded analysis.This study was approved by Chang Gung Medical Foundation Institutional Review Board (IRB 100-3022B) and informed consent was obtained from all patients. The clinical data recorded from the enrolled patients included age, sex, height, weight, systolic blood pressure, serum creatinine levels, serum UA levels, and absence or presence of hypertension, diabetes mellitus, hypercholesterolemia, and smoking. Asymptomatic hyperuricemia was defined as UA ≥7 mg/dL. The diagnosis of gouty arthritis was made according to the American College of Rheumatology (ACR)/Wallace criteria . PatientAll subjects received transthoracic echocardiographic examinations at rest in the left lateral decubitus position using a Philips iE33 ultrasound system and S5-1 broadband phased array transducer. The LA diameter in the end-systolic phase, thickness of the interventricular septum (IVS) and posterior wall (PW) in end-diastolic phase, and LV end-diastolic and end-systolic dimensions were all determined using the M-mode in the parasternal long-axis view according to the recommendations of the American Society of Echocardiography . The left test. Categorical variables were compared using the chi square (χ2) test. Multiple regression analyses were performed to determine the associations between gout and LV diastolic functional parameters, including E/A, Em, Am, E/Em, and maximal LAV. The multivariate model was adjusted for age, sex, UA, creatinine, diabetes mellitus, hypertension, hypercholesterolemia, and smoking. Statistical significance was set at p <0.05. In 20 randomly selected subjects, the interobserver and intraobserver variability in E/Em and maximal LAV measurements were assessed by the coefficient of variation, where differences between measurements were expressed as the ratio of the SD to the mean. Interobserver variability was assessed by two independent observers and intraobserver variability by one observer twice within a two-week period. The interobserver variability of E/Em was 3.3 % and that of maximal LAV was 2.2 %. The intraobserver variability of E/Em was 1.8 % and that of maximal LAV was 1.5 %.Statistical analysis was performed using SPSS 18.0 statistical software . Continuous data are presented as mean ± standard deviation (SD), and dichotomous data as number and percentage. Comparisons of continuous variables between groups were performed using analysis of variance (ANOVA) or the unpaired two-tailed p <0.001). The clinical characteristics of the study population are listed in Table A total of 27 patients were excluded because of the presence of LV systolic dysfunction (n = 2), hypertrophic cardiomyopathy (n = 2), permanent cardiac pacemaker implantation (n = 2), atrial fibrillation (n = 2), and poor echocardiographic images that precluded analysis n = 19). Thus, the final study population consisted of 173 patients, who were divided into tertiles by serum level of UA as follows: group 1: serum UA ≤6.5 mg/dL (n = 54); group 2: serum UA >6.5 to ≤8.5 mg/dL (n = 59); and group 3: serum UA >8.5 mg/dL (n = 60).The mean UA levels of these three groups were 5.03 ± 1.07, 7.63 ± 0.52, and 10.05 ± 1.17 mg/dL, respectively . Furthermore, patients with gout had significantly worse renal function than those without gout  75.05 ± 34.2 ml/min, p = 0.059).As there were no obvious findings in relation to uric-acid-based grouping, we studied our patients according to diagnosis of gouty arthritis, asymptomatic hyperuricemia and normo-uricemia. Among the study population, 108 individuals received a diagnosis of gout: 65 patients (60 %) received uricostatic agents, 15 (14 %) received uricosuric agents and 77 (71 %) received colchicines. Table p = 0.004) and PW than those without gout . The LV mass was significantly larger in patients with gout than in those without . The LV mass index in the patients with gout was also significantly higher than in those without gout . Additionally, patients with gout had greater LV end-diastolic dimensions (LVEDd) than patients without gout . There were no significant differences in LV end-systolic dimensions (LVESd), LVEDV index, and LVESV index between the patients with and without gout. Additionally, there were no significant differences in LV systolic function between patients with and without gout. Among the LV diastolic functional parameters, the E, A, and E/A ratio were not significantly different between patients with and without gout. The patients with gout had significantly lower Em than those without gout . The Am was not significantly different between groups. The Em/Am ratio was lower in patients with gout , and the E/Em ratio was higher in the patients with gout . Furthermore, the maximal LAVi of the patients with gout was significantly larger than that of the patients without gout . Finally, the prevalence of moderate to severe LV diastolic dysfunction was higher in patients with gout than in patients without gout . There were significant differences between the normo-uricemia and hyperuricemia group, in uric acid, creatinine , IVS  and LV mass . There were no further statistically significant differences between the normo-uricemia and hyperuricemia groups (data not shown).The echocardiographic parameters of patients with and without gout are summarized in Table On multivariate analysis, the associations between gout and LV diastolic functional parameters, including Em, Am, Em/Am, E/Em and maximal LAVi, were significant when controlled for age, sex, UA, creatinine, diabetes mellitus, hypertension, hypercholesterolemia and smoking in the study groups Table .Table 2MThe major finding of this study was that gout impacts LV diastolic dysfunction and LA volume enlargement. LV diastolic remodeling may be a predictor of adverse cardiac events in gout patients. LV diastolic dysfunction refers to an abnormality of diastolic distensibility, filling, or relaxation of the LV . LV diasElevated serum UA levels are associated with diastolic dysfunction in chronic heart failure patients with LVEF <45 %, due to free radical-mediated endothelial damage resulting from increased xanthine oxidase activity . High UAGout is a metabolic disorder characterized by hyperuricemia and a type of chronic inflammatory arthritis induced by deposition of monosodium urate crystals in the synovial fluid and other tissues . Accumulr = −0.225, p = 0.018) and positively associated with E/Em  (Fig. Interestingly, lower Em and higher E/Em were detected in patients with gout than in those without gout, and the prevalence of moderate-to-severe LV diastolic dysfunction was higher in patients with gout than those without gout (23 %, vs. 8 %, p = 0.016; Table There are several limitations in the present study. First, further follow-up cohort studies are necessary to demonstrate whether LV diastolic remodeling is predictive of adverse cardiac events in patients with gout. Second, the biological link between gout and LV diastolic dysfunction remains unclear; our current hypotheses and results require further clarification through additional studies.Gout, rather than hyperuricemia, is associated with LV diastolic dysfunction and LA volume enlargement. LV diastolic remodeling may be a predictor of adverse cardiac events in patients with gout.


Currently, the use of multispiral cardiac X-ray and MRI tomography techniques has been accepted as the most promising approaches both in location and prediction of substrate of supraventricular arrhythmias both in coronary and non-coronary patients.Twenty persons  with recent (< 4 months) myocardial infarction of left ventricle were included. Paramagnetic contrast-enhanced T1-weighted SE  MRI of the heart has been employed for visual detection of risk as well of anatomic locations of atrial arrhythmias in twenty patients with previous myocardial infarction. Contrast enhancement was carried out using intravenous injection of widely available extracellular paramagnetics in a dose as high as 2 ml of 0,5 M solution per 10 kg of body mass (BM). Two groups were separated in accordance with the electrophysiologic and clinical data. The Group 1 included eight persons without supraventricular tachycardias (SVT) in the course of follow-up for four months, and the Group 2 comprised twelve patients with frequent SVT paroxysms, all were later suggested for maze procedure. Also eight persons were recruited to the control group, all without cardiac pathology.In the persons of the control group the index of enhancement (IE) of the T1-w. SE MRI of the atrium was essentially uniform over the atrial wall and did not exceed 1,03±0,4 anywhere.3, whereas 91,3±10,0 in the Group 2, p<0,02). The IE, calculated for the site of most prominent uptake of contrast, also differed significantly , as well as the overall volume of contrast uptake . When anatomically placing electrophysiologic data over the map of uptake of paramagnetic over the atrium, the electrophysiologic substrate of the arrhythmia was located in ten cases of twelve closely to the region of most intensive uptake of paramagnetic to the atrial wall.The MRI data delivered highly significant differences between the groups in average values of atrial volume  with concomitant increase of left atrial volume over 75 ml provide a prognostic factor for the nearest future manifestation of atrial tachyarrhythmias and endocardial destruction procedure.Therefore the contrast-enhanced MRI of the heart can be routinely employed as effective tool of selection of persons with high risk of supraventricular tachyarrhythmias among patients with ischaemic heart disease and previous myocardial infarction.N/A.


Background. Magnetic resonance imaging (MRI) strain analysis is a sensitive method to assess myocardial function. Our objective was to define the feasibility of MRI circumferential strain (εcc) analysis in assessing subtle changes in myocardial function following stem cell therapy. Methods and Results. Patients in the Amorcyte Phase I trial were randomly assigned to treatment with either autologous bone-marrow-derived stem cells infused into the infarct-related artery 5 to 11 days following primary PCI or control. MRI studies were obtained at baseline, 3, and 6 months. εcc was measured in the short axis views at the base, mid and apical slices of the left ventricle (LV) for each patient (13 treatments and 10 controls). Mid-anterior LV εcc improved between baseline −18.5 ± 8.6 and 3 months −22.6 ± 7.0, P = 0.03. There were no significant changes in εcc at 3 months and 6 months compared to baseline for other segments. There was excellent intraobserver and interobserver agreement for basal and mid circumferential strain. Conclusion. MRI segmental strain analysis is feasible in assessment of regional myocardial function following cell therapy with excellent intra- and inter-observer variability's. Using this method, a modest interval change in segmental εcc was detected in treatment group. The FT technique was previously validated for εcc assessment against harmonic phase imaging (HARP) [Circumferential strain (rtensive  or hyperrtensive  and Duchrtensive  before crtensive –8. The Artensive . Signifig (HARP)  and subsg (HARP)  and in dg (HARP) . One of Subjects with STEMI who were treated with intracoronary stent implantation within 3 days of infarction and an LVEF ≤50% by echocardiography demonstrating regional wall motion abnormality in the distribution of the infarct-related artery ≥4 days after stenting were enrolled . BrieflyAll studies were performed using 1.5 Tesla MRI scanners. Cardiac functional imaging was performed with retrospective electrocardiogram (ECG) gating, utilizing a standard SSFP technique, LV end-systolic and end-diastolic volumes, LVEF, and infarct size at baseline, 3 months, and 6 months were assessed as described previously .εcc was measured in left ventricular short axis steady-state free precession (SSFP) views at base, mid, and apex for each patient at baseline, 3 months, and 6 months by 2 independent readers who were blinded to treatment assignment. In addition, segmental εcc was measured for all individual mid-ventricular segments (segments 13 through 18), Segmental strain analysis was not undertaken in apical and basal segments due to low reproducibility  and no infarcted tissue present . Thirteen treatments and 10 controls underwent strain analysis. Using Diogenes CMR FT software , global L(t) indicates the distance between two neighboring points along the border, the strain is computed as St(t) = (L(t) − LR)/LR, where LR indicates such length at the ECG R wave. The systolic strain is therefore (LES − LR)/LR. This represents the Lagrangian strain and it is the most frequently used in cardiac imaging [Diogenes CMR FT software  is a vector-based analysis tool based on a hierarchical algorithm that operates at multiple levels using a combination of 1-dimensional and 2-dimensional tracking techniques. Based on a contour manually drawn by an expert reader along the LV endocardial border frame, the software automatically propagated the contour and followed its features throughout the remainder of the cardiac cycle. Features tracked in each voxel  by the software include brightness gradient at the tissue-cavity interface in homogeneities of the tissue , geometrical “roughness” of the tissue edges, and additional specific anatomical elements (papillary muscles and septum). Tracking is based on optical flow algorithms applied on sequentially reduced windows to ensure resolving large amplitude displacements and still discern local differences, and also implicitly accounts for spatial coherence and time-periodic motion. The tracking over all frames of a set of individual material points along the border permits to quantify their frame by frame displacement. The circumferential strain is defined as the instantaneous local border lengthening or shortening: if  imaging –16. Stra imaging   and the difference (observer 1 – observer 2) with zero or small r indicating an agreement between methods , and k is the paired sample size.Bland and Altman  analysisInfarct size as a function of dose and changes in mid anterior strain at baseline, month 3, and month 6 was analyzed using analysis of variance (ANOVA). P < 0.05. Statistical analysis was performed using SAS software version 9.2 . Statistical significance was set at Most patients (9/10 in the control group and 12/13 in the treatment group) had evidence of anterior wall myocardial infarction by late gadolinium enhancement (LGE). There was one lateral infarct in the control group and one inferior in the treatment group.εcc at any level, except for the basal slice in the treatment group, the change from baseline and 3 months was statistically significant  at 3 months and no changes were observed at 6 months . No changes were noted in any other segments in the mid-ventricular short axis between any time points.No difference was detected in the treatment or control groups in global P = 0.34 . There wεcc at basal, mid, and mid segmental with (Pearson's correlation between average and difference readings r) r = −0.03, P = 0.83, r = 0.10, P = 0.44, and r = 0.08, P = 0.14, respectively. However, there was a poor interobserver agreement on apex with r = −0.40, P = 0.0009. In addition, there was an excellent intraobserver agreement for global εcc at basal, mid, and apex with r = −0.07, P = 0.69, r = 0.19, P = 0.29, and r = 0.26, P = 0.14, respectively.Bland and Altman analyses showed an excellent interobserver agreement for global εcc at baseline, Month 3, and Month 6. As previously reported, there were no significant differences in the change in infarct size or LVEF in treatment versus control groups after 3 or 6 months.In the treatment group, ANOVA analysis showed no significant difference between the doses of stem cell, size of infarct at baseline, and changes in mid-anterior Example of patient in the treatment group is presented in εcc changes using FT technique in patients treated with intracoronary bone-marrow-derived CD34+ cell infusion after acute ST elevation MI. This is of importance as FT analysis does not require additional imaging (such as tagging) and it can be used retrospectively as cine sequences are obtained in all studies while tagging is typically not a part of the standard protocol. FT technique is specifically designed for MRI analysis and differs from recently reported velocity vector imaging (VVI) software (which was designed for echocardiographic speckle tracking) [εcc without significant changes in LVEF at 3 but not at 6 months. As most of the analyzed cohort suffered anterior wall MI, the improvement in εcc within this infarcted region was likely driven by the beneficial effects of cell therapy. Finally, both inter- and intraobserver agreement, for strain analysis were excellent for mid and basal segments. Interestingly, intraobserver (but not interobserver) variability was poor for apical segment; possible explanation is presence of apical trabeculations, which have been defined as endocardium by one reader versus compact myocardium used by other reader.The major finding of this substudy from the Amorcyte-randomized trial was feasibility of detection of segmental racking) . In addiεcc in the settings of stem cell therapy. Furthermore, the broad spectrum of data available from MRI  may obviate the need for echocardiography following cell therapy after MI. Finally a recent study by Hopp et al. [Improvement in 2D echo-derived LV strain has been reported by Herbots et al.  who demop et al.  which isεcc may be an attractive and sensitive surrogate endpoint for evaluation of benefits of stem cell therapy. A recent meta-analysis of postinfarct stem cell trials concluded that changes in LVEF were very modest and strain analysis may be amore useful and sensitive endpoint [εcc improved significantly in the absence of an appreciable change in LVEF. Although the clinical significance of improvement in segmental εcc in the absence of a more global increase in LV contractility is yet to be determined; such changes may predict a beneficial response to therapy with respect to LV remodeling and the degree of infarct zone electrical heterogeneity (which may be associated with increased risk for ventricular reentrant arrhythmias) [εcc to both global measures of LV volume or function over time and to meaningful clinical outcomes are clearly warranted.Segmental endpoint . Indeed,ythmias) . Furtherεcc in the peri-infarct zone (“gray zone”) which is more likely to provide a favorable environment for infused stem cells than the fully infarcted tissue. Additionally, only mid-myocardial strain was analyzed; it is possible that additional changes would be detected with analysis of endocardial strain. As this method relies on “perfect alignment” of analyzed SSFP images at baseline and followup, a small misalignment may miss the edge of infarct and affect the results. In addition, LGE images need to be obtained at exactly the same level as SSFP images, in order to assess changes in contractility in the infarct and peri-infarct regions. Small study population also limited the evaluation of a relationship between infarct transmurality, heterogeneity, presence of microvascular obstruction, myocardial hemorrhage, and the subsequent likelihood of response to stem cell therapy. Further improvement in FT software resolution will be needed to assess changes in εcc following intracoronary stem cell infusion after myocardial infarction. The relationship between these variable and clinical outcomes requires further study.In conclusion, FT method can detect regional changes in


Extracellular volume fraction (ECV) has been applied to the detection of diffuse myocardial interstitial fibrosis or exudative pathologic changes in various clinical settings, but there is lack of study to date concerning the significance of ECV at the early phase of left ventricular remodeling. We intended to assess myocardial ECV in essential hypertension and to study the implications of ECV to the early phase of left ventricular remodeling.t test and Pearson correlation analysis were chiefly used in statistical analysis.Thirty-six healthy volunteers and 39 essential hypertensive patients underwent cardiac magnetic resonance imaging to study left ventricular morphological and functional measures and ECV. Normalized intracellular volume (nICV) and normalized extracellular volume (nECV) were also calculated based on ECV and normalized left ventricular myocardial volume. Independent samples r = 0.645, p < 0.001) but not with nECV (p = 0.526). nICV correlated with left ventricular concentricity , E/A , and Time To Peak Filling . While nECV only correlated with left ventricular concentricity  and E/A  with smaller Peason correlation coefficients.Women's ECV was higher than men's in normotensive subjects (p < 0.001). In women, ECV of hypentensive subjects was lower than that of normotensive subjects (p = 0.028). ECV correlated with nICV  and National Nature Science Foundation of China .


Ebstein's anomaly of the tricuspid valve involves a congenitally displaced and dysplastic tricuspid valve (TV). The displacement of the TV towards the apex results in an enlarged right atrium (RA) with an atrialzied portion of the right ventricle (aRV) and an enlarged functional right ventricle (fRV). Brain natriuretic peptide (BNP) is a heart failure marker. Its role in Ebstein's anomaly has not been evaluated in conjunction with cardiac MRI (CMR) parameters. Hematologic parameters (hemoglobin (Hb), hematocrite (Hct)) are upregulated in states of pulmonary hypo perfusion as in congenital cyanotic heart disease. Intermittent Pulmonary hypo perfusion may be a an indicator of right heart failure in patients with Ebstein's anomaly, but has not been studied so far. The aim of the present study was to correlate CMR functional parameters and severity of disease with BNP and hematologic parameters in patients with Ebstein's anomaly.26 patients with non-corrected Ebstein's anomaly were studied prospectively. Laboratory parameters , CMR data  and left ventricular (LV) volumes and functional parameters like ejection fraction (EF), stroke volume (SV) and others) as well as exercise capacity , CO2 equivalent (VE/VCO2), maximum heart rate (max. HR) using a cycle ergometer) were all measured on the same day for an individual patient.Mean patient age was 25+-14 years (range: 10 - 60). fRV enddiastolic volume index (EDVi) was increased to 118.3+-57.0 ml/m2 . Plasma BNP-level was increased (mean: 74.3+- 123.1 ng/l), in 15% of patients markedly above the heart failure level. Hb and Hct were increased above normal levels in 20% and 23% of patients, respectively. VO2 max. was decreased to 67.1+- 22.1%, VE/VCO2 increased to 117.8+-36.1%, both of predicted normal values. Transcutaneous SaO2 was normal (98+-2.8%). Statistical analysis revealed a positive correlation of BNP and RA EDVi (p = 0.00001), fRV EDVi (p = 0.00001) and VE/VCO2 (p = 0.022), a negative correlation with LV EF (p = 0.0003) and max. HR from exercise testing (p = 0.002). Similar correlations were found for Hb and Hct. Multiple regression analysis identified BNP as an independent predictor of RA EDVi, fRV EDVi, LV EF from CMR, as well as max. HR from exercise testing. Hkt and Hb were independent predictors of fRV EF and RA SV. The higher either BNP levels, Hct or Hb were in our study population, the lower were cardiac function on CMR and physical exercise capacity during exercise testing.To the best of our knowledge, this is the first prospective study that shows a correlation of functional data from CMR and exercise testing with BNP levels and hematologic parameters -as a measure of pulmonary perfusion- in patients with Ebstein's anomaly. BNP and the studied hematologic parameters  may be useful prognostic markers in patients with Ebstein's anomaly.None to disclose.


Defibrillation and cardioversion are often used as life-saving measures in cases of cardiac arrest and arrhythmias. Previous studies in humans with cardioversion of arrhythmias, found a decrease in ejection fraction but no significant changes in preload, afterload and heart rate. However, it is not clear whether the underlying cardiac condition may have contributed to these findings. This study aimed to observe the effects of biphasic synchronized shocks on left-ventricular function parameters over a 5-hour period in a porcine model.Ten pigs received five consecutive biphasic synchronized shocks of 200J. Six pigs served as healthy controls and underwent the identical anesthesia and imaging protocol. Images were acquired with a clinical 3T MRI scanner (Siemens Magnetom Skyra). Routine functional cine imaging was completed for all pigs at baseline by acquiring a short-axis stack (7-10 slices) of the left ventricle. This imaging protocol was repeated hourly for 5 hours. All MR images were analyzed for cardiac function parameters  and in addition to assess left ventricular motion abnormalities. T2 maps were acquired at each time point to evaluate the presence of myocardial edema following the shock series.Four out of ten pigs required pharmacological vasopressor support with Phenylephrine or Noradrenaline within the first hour after the shocks to keep blood pressure stable (MAP >50 mmHg), while no vasopressors were required in the control group. A significant decrease in cardiac output (CO) from baseline 4.00 ± 0.24 L/min) was observed that was significant at 3 and 5 hours post-shock, (3.57 ± 0.19 and 3.15 ± 0.19 L/min respectively; p < 0.05, Figure 4 L/min wBiphasic synchronized shocks of cumulative 1000J in a porcine model lead to a significant decrease in EDV and CO. Shock-induced myocardial edema may be an explanation of our findings indicating diastolic dysfunction with preserved ejection fraction.Funding is provided by the Montreal Heart Institute Foundation and the Canadian Foundation for Innovation.


Mean platelet volume (MPV) and platelet distribution width (PDW) are indices that reflect platelet activity. We investigated the association between these platelet indices and left ventricular hypertrophy and cardiac function.We analyzed the data of 1241 patients who were admitted to the Cardiology Department.Both MPV and PDW were selected as independent factors associated with left ventricular systolic and diastolic dysfunction, and left ventricular hypertrophy. The highest tertile of MPV and PDW was associated with left ventricular systolic dysfunction (left ventricular ejection fraction of <50 %) with an odds ratio of 1.53 and 2.03, respectively, when the respective lowest tertile was used as reference. The highest PDW tertile was associated with left ventricular hypertrophy with an odds ratio of 1.56  and with dysfunction with an odds ratio of 3.34 .Indices of platelet activation (MPV and/or PDW) were independently associated positively with left ventricular hypertrophy and left ventricular systolic and diastolic dysfunction. Whether these platelet indices represent useful markers for identifying individuals at higher risk for thromboembolic disease and organ damage among cardiac patients awaits further investigation. Activation of platelets and their subsequent aggregation play a key role in thrombus formation at the site of vascular injury and atherothrombotic events , 2. AsseIn comparison to smaller ones, larger platelets have higher thrombotic potential  that mayMPV may be increased in other cardiovascular conditions such as pulmonary arterial hypertension , hypertrThe current retrospective study was approved by the Ethics Committee of Osaka Medical College. Between January 2012 and March 2014, 1241 patients who were admitted to the Cardiology Department and had provided written informed consent and for whom sufficient information regarding the data analysis for the current study including echocardiographic data was available were enrolled in the current study. Left ventricular diastolic dysfunction (LVDD) was assessed among the patients with both sinus rhythm and left ventricular ejection fraction (LVEF) of ≥50 %. Of 1241 overall study population, 821 patients were found to have both sinus rhythm and LVEF of ≥50 %. Among these patients, however, echocardiographic data that was necessary for the determination of the presence or absence of diastolic dysfunction was not available in 237 patients due to the poor echocardiographic imaging. Therefore, data from subgroup of 584 patients were used for the analysis of the relationship between platelet indices and LVDD.2) = 194 × (serum creatinine) −1.094 × (age) −0.287   + 0.6. LVM index (LVMI) was calculated as the ratio of LVM to the body surface area. Left ventricular hypertrophy (LVH) was defined to be present when the LVMI was greater than 118 g/m2 (men) or 108 g/m2 (women) [Echocardiographic examinations were performed as described previously . Briefly (women) . The LVELVDD was assessed as previously described . BrieflyP < 0.05 was taken to be statistically significant.Baseline characteristics were assessed with standard descriptive statistics. Data were expressed as either mean ± standard deviation or median and interquartile range. A Pearson’s correlation test was used to assess the correlation between two variables. For multivariate analysis, multivariate linear regression and multivariate logistic regression analyses were used. Data analysis was performed by SPSS statistics version 22.0 . A value of Among the 1241 patients enrolled, 910 were male (73 %) and 1008 (81 %) had sinus rhythm . When the comparison was limited to patients with sinus rhythm, the MPV values in patients with warfarin usage and that in patients without warfarin usage did not differ significantly . In addition, MPV did not differ significantly between warfarin users and non-users among patients with sinus rhythm who were taking at least one anti-platelet medication  or among patients with sinus rhythm who were not taking any anti-platelet medication .It was found that the MPV value in patients with atrial fibrillation (8.59 ± 0.91 fL) was significantly higher than that in patients with sinus rhythm .Next, we performed multivariate logistic regression analyses using LVSD or LVH as a dependent variable Tables  and 4. IIn model 2, where platelet indices were entered as tertile basis, the highest tertile of MPV and PDW was associated with LVSD with an odds ratio of 1.53 and 2.03, respectively, compared with the respective lowest tertile (Table P = 0.036). In model 2, where platelet indices were entered on a tertile basis, the highest tertile of PDW was associated with LVDD with an odds ratio of 3.34 compared with the lowest tertile  were found to have LVDD. In model 1 where platelet indices were entered on a per 1 SD basis, platelet count and PDW, respectively, were found to be significantly negatively and positively associated with LVDD  with an odds ratio of 1.53 and 2.03, respectively, as compared with the respective lowest tertile  when compared with the lowest PDW tertile after multivariate adjustment. Whether these platelet indices represent useful markers for discriminating those at higher risk for thromboembolic disease and organ damage among cardiac patients awaits further investigation.


Pectus excavatum (PE) as the most common anterior chest deformity is characterized by sternal depression with corresponding leftward displacement and rotation of the heart which is troublesome for assessment by ultrasound. Therefore CMR plays a growing role in preoperative evaluation. Indication for surgical correction is based on a diameter-based assessment of the thorax  and symptoms. Imaging data describing cardiac performance after surgery are rare. The aim of the study was to assess cardiac function during follow-up (FU).37 patients with PE  underwent CMR using 1.5T MRI-scanner  prior to surgery and repeatedly postoperative . The highly experiences surgeons (more than 130 procedures/year) implanted a titan-bar (Nuss procedure) based on the usual clinical indication. CMR protocol included state of the art cine SSFP covering the left ventricle (LV) as short axis  and the right ventricle (RV) axial orientation . HI was measured on survey images  indicating a successful procedure. Pleural effusions were detectable at day 10 in almost all (24 from 25 patients) pericardial effusion in 3 and it was resolved in all completely after 1 year. There were variable findings at different FU-time-points. The most positive change in RVEF was observed at 10 days FU followed by slight reduction on 3 months and further decrease at 1 year. Despite these findings the RVEF remained significantly improved at 1 year. Interestingly, RVEF was found to change significantly from baseline to 1 year FU (p < .0001), whereas LVEF did not (p = 0.0539). RVSV and LVSV were found to change significantly from baseline to 1 year follow-up . Weak correlation was found between the delta (baseline/1 year) HI compared to RVEF.CMR is able to quantify LV and RV-morphology despite specific anatomy and/or implanted titanium bows in patients with pectus excavatum. Our results indicate that there is an improvement of stroke volumes and RVEF one year post correction.None.


Heart failure (HF) is a major and growing cause of morbidity and mortality. Despite initial successes, there have been few recent therapeutic advances. A better understanding of HF pathophysiology is needed with renewed focus on the myocardium itself. A new imaging technique is now available that holds promise. T1 mapping is a cardiovascular magnetic resonance (CMR) technique for non-invasive myocardial tissue characterization. T1 alters with disease. Pre-contrast (native) T1 changes with a number of processes such as fibrosis, edema and infiltrations. If a post contrast scan is also done, the extracellular volume fraction (ECV) can be measured, a direct measure of the interstitium and its reciprocal, the cell volume. This dichotomy is fundamental — and now measurable promising more targeted therapy and new insights into disease biology. Heart failure (HF) is a complex clinical syndrome where the ability of the heart to supply physiological perfusion to organs is impaired, either by acquired or inherited disease. The key biomarker for measuring heart failure is the left ventricular ejection fraction (LVEF) — but a low ejection fraction and HF are not synonymous. Common causes are ischemic heart disease, hypertensive heart disease, valvular heart disease, diabetes, myocarditis, cardiomyopathies, tachycardia-induced cardiomyopathy, and systemic diseases with cardiac involvement. In most HF presentations there is more than one cause. HF represents one of the most important problems for both modern medicine and society with massive impact on individuals and a major annual cost for health systems. The annual costs for HF care exceed $40 billions in the US, with the majority spent on hospitalizations for HF –3. MoreoDamage the heart and the whole organism responds — upregulated renin-angiotensin system changes, haemodynamic and skeletal muscle changes are the most well known. However, it is the myocardial response that is the most fundamental — that of the myocytes and fibroblast , and extracellular space changes. These changes may be initially adaptive but may progress to be maladaptive. Common features of this remodelling process are cardiomyocyte hypertrophy, extracellular matrix expansion and composition alteration. Calcium handling, energy metabolism, contractile function, vasculature and cell viability may also change. These processes although deeply interwoven may combine into characteristic myocardial phenotypes which, if we can measure them, may permit us to split HF up in a subtypes, opening the door for tailored therapy according to the precise myocardial phenotype .There is however a problem. There is no denying the significant advances in treatment strategies for HF, including drug and device therapy, cardiac transplantation, and mechanical circulatory support. However, despite these, the prognosis has not improved in worsening chronic HF, de novo HF and advanced or end-stage HF, which continue to have high mortality and re-admission rates –6. WhilsIn the last 10 years, CMR has provided two key technologies for HF: anatomical and functional assessment using cine imaging and tissue characterization for focal abnormalities, particularly scar imaging using the late gadolinium enhancement technique (LGE). Cine imaging provided a more accurate and reproducible quantification of LVEF, size and mass, particularly in hearts that were geometrically distorted. The LGE technique for the first time allowed visualization of focal scar. When integrated, there was a step change, but perhaps not a revolution in our understanding of HF. Scar pattern, particularly in early disease provided insights into the underlying causes of myopathy, whilst the extent of scar was prognostic — and incrementally so over LVEF. The lack of scar in particular predicted functional recovery following intervention with resynchronisation (discoordination), revascularization (hibernation) or with time (stunning). Additional techniques such as T2-weighted imaging for edema and T2* imaging for iron quantification added in selected circumstances. However, a gap still remained: the LGE technique could not detect global myocardial changes such as occur in diffuse fibrosis. In addition, all scars looked the same — whether there was 50 % or 100 % myocyte loss in a region. It is in this gap that T1 mapping provides new information.Magnetic resonance of protons varies between tissues, depending on the macromolecular environment that water finds itself in. The T1 relaxation time  is a tissue-specific magnetic property and is determined by how rapidly protons re-equilibrate their spins within their environment after been excited by radiofrequency pulse. T1 varies with measurement technique and MRI field strength. Regional difference in T1 can be visualized by T1-weighted sequences following an intravenous bolus of extracellular contrast, gadolinium, to evaluate myocardial scar or focal fibrosis.Gadolinium is an extracellular agent not able to enter through intact cell membrane and cleared from the blood pool after minutes. In tissue with damaged or dead cells, these kinetic effects are delayed and there is a higher accumulation of contrast due to ruptured cell membranes allowing gadolinium to passively diffuse into the cellular compartment. Gadolinium changes magnetic properties by shortening T1 of a tissue. If at this point, a T1-weighted inversion recovery sequence is performed, with the inversion time (TI) set manually by the operator to null “normal” remote myocardium, this will appear black and scar tissue white .The LGE technique is now the gold standard test for the detection of scar across the spectrum of cardiac disease. Its assessment is reproducible and scar visualization provides a good indicator of disease etiology whilst scar extent carries prognostic information, which in many diseases is incremental to conventional prognostic markers. In HF, the LGE technique reduces diagnostic dilemmas but raises new ones: for example, it used to be a clinical conundrum that burnt out hypertrophic cardiomyopathy (HCM) could mimic dilated cardiomyopathy. The LGE technique distinguishes these with ease. However, within the HCM spectrum, whilst in early disease, the LGE pattern may point to the underlying etiology  by end stage, all the diseases start to look the same and scarred out. LGE prognostication is incrementally useful: in a large study (n > 1000), LGE was associated with first hospitalizations for HF after CMR, death or both across the range of ejection fractions including preserved EF. Furthermore, even if LVEF was severely decreased, those without LGE appeared to have less risks of hospitalization for heart failure or death .However, the LGE technique has limits. Measuring the extent of LGE is difficult as different techniques produce different results, particularly in non-ischemic cardiomyopathy . The tecRapid technical innovations in CMR have generated a novel parametric mapping field addressing these shortcomings. These methodologies permit the routine acquisition of quantitative measure of underlying tissue-specific T1 relaxation rather than relative signal intensities.After recent technical improvements, T1 measurement (multi-breath-hold or multiple images requiring curve fitting and processing) has been replaced by T1 mapping. In a single breath-hold, using various approaches, a T1 colour relaxation map is made –13. Withincreases with pathologies where increased water is present such as edema [reduces in the presence of lipid [Myocardial native (non-contrast) T1 measures the T1 values from the extracellular and intracellular compartments. Measurement requires no exogenous contrast administration, making it feasible even in patients with severe kidney dysfunction. T1 as edema , 19 , where mutations of the α-galactosidase gene result in intracellular lipid accumulation and left ventricular hypertrophy (LVH), the native T1 falls, and falls by many standard deviations Fig. . This faIn cardiac AL amyloidosis Fig. , clinicaNative T1 is a feasible clinical tool. However, there are some specific hurdles to be overcome for clinical utility. Whilst pathology influences T1, so does magnet field strength and the precise approach used to its estimation . These dMeasuring the T1 time, following the administration of an extracellular contrast agent (gadolinium chelates), generates the possibility to dichotomize the myocardium into its cellular and extra-cellular components. In early studies, the absolute value of T1 post-contrast was used  but thisExpansion of the myocardial ECV represents a nonspecific increase in free space between cells and occurs in a variety of pathologies Table . To distFor low ECV expansion diseases, biases from blood pool partial volume errors need to be meticulously addressed. Nevertheless, even modest ECV changes appear prognostic. In 793 consecutive patients  followed over 1 year, global ECV predicted short term-mortality  represents the myocardium not accessible to the extracellular volume fraction. Accordingly, ICV represents intact myocardial cellular component proving a way to measure the cell volume. Again it is necessary to clarify that there is a bias because, even if ICV mainly represent myocytes, it also includes fibroblasts, blood cells, macrophage, etc.ICV provides incremental information. In severe AS patients ECV has been found to be elevated but interestingly LV hypertrophy regression after valvular replacement at 6 months had no change in the ECV, but the ICV fell showing non-invasively that early LVH regression was cellular rather than fibrosis regression .For HF, the above approaches are only now starting to be applied. The ability to measure diffuse fibrosis and partition the myocardium into cellular and extracellular compartments is promising. Specifically, it may allow to personalise therapeutic approaches and to develop new therapies targeted either to interstitial or intracellular pathways, but which may otherwise fail if early development applies them indiscriminately to an uncharacterised HF cohort. A number of studies are planned or on their way currently.Drug development strategies for HF have produced few positive results over the last decade and HF continues to represent an important problem in medicine with considerable impact for health system cost. To ensure success in mortality reduction a better understanding of disease pathways is needed in-vivo. CMR has established itself as the gold standard for non-invasive myocardial tissue characterization and T1 mapping takes the technology a step further, firstly, by measuring key processes in rare diseases , and secondly, by measuring diffuse fibrosis, allowing us to dichotomize the myocardium into its cellular and extra-cellular components, providing new frontiers for pathologies understanding and identifying two different therapeutic targets, cells and interstitium, with high potential impact into our understanding of HF.


Weight reduction was associated with a reduction in blood pressure and heart rate. Left ventricular longitudinal global peak systolic strain was in the lower normal range (−18.7 ± 3.2%) before weight loss and was unchanged (−18.8 ± 2.4%) after 12 weeks on diet with substantial weight loss. Also, no significant change in global radial strain after weight loss was noted . Left atrial and ventricular dimensions were in normal range before fasting and remained unchanged after weight loss. In our study obesity was associated with normal systolic left ventricular function. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate. Systolic left ventricular function and morphology were not affected by rapid weight reduction.Obesity is associated with an increased risk of heart failure. Little is known about the impact of dietary changes on the cardiac sequelae in obese patients. Twenty-one obese subjects underwent a 12-week low calorie fasting phase of a formula diet. Transthoracic two-dimensional speckle-tracking echocardiography was performed to obtain systolic left ventricular strain before and after weight loss. Body mass index decreased significantly from 38.6 ± 6.2 to 31.5 ± 5.3 kg/m A BMI > 30 kg/m2 has a negative impact on health and is associated with premature atherosclerosis, increased risk of myocardial infarction, and heart failure. Severe obesity is associated with decreased survival, largely because of cardiovascular deaths [Obesity is a major public health problem, with a prevalence of 10% to 20% in Western Europe [r deaths .Most echocardiographic studies assessing left ventricular (LV) systolic function in obese patients used ejection phase indices like LV ejection fraction and LV fractional shortening. They reported normal or hyperdynamic LV systolic function and no or little differences in lean and obese subjects , 6. ImpaAlterations in cardiac function have also been shown to be reversible with weight reduction strategies , 11. WeiThe purpose of this study was to examine systolic left ventricular function and the effect of diet-induced weight loss in patients with severe obesity by transthoracic two-speckle-tracking echocardiography (STE) with LV strain imaging.The study was approved by the ethics committee of the State Medical Council of Hessen, Germany . Informed consent was obtained from each patient prior to the study participation.Initially, 33 patients were included in the study. All patients were participants in the OPTIFAST®-52 diet program , which ran for a total of 52 consecutive weeks. The specifics of the program included a fasting phase of 12 weeks with ingestion of food restricted to formula products with a high protein content. The total calorie intake in this phase is approximately 800 kcal per day. A subsequent transitional phase and a final stabilization phase aim to introduce the patients to a balanced diet. For the duration of the program, all patients received psychological, physiotherapeutic, medical, and nutritional care. Finally his study enrolled 21 patients. Twelve patients were excluded from the analysis .2, secondary and accompanying conditions requiring treatment such as hypertension, hypercholesterolemia, diabetes mellitus, and illnesses of the locomotor system. The necessity for participation in the program was documented by a medical certificate. All patients had made repeated (at least three) unsuccessful attempts to reduce weight. Exclusion criteria were cardiac arrhythmia, recent myocardial infarction, severe  general illnesses, pregnancy and nursing, or a documented eating disorder.Inclusion criteria were as follows: age ≥18 and ≤65 years, BMI > 30 kg/mClinical measurements were performed once per week. Before and after the fasting phase, weight and height were recorded in order to calculate the respective BMI. Echocardiography was performed in week 1 and in week 12. Total body composition and fat content was also measured using the dual energy X-ray absorptiometry (DXA) in week 1 and in week 12.Echocardiography was performed using a commercially available ultrasound machine  and a 3.5 MHz (3S-RS) transducer. Patients were examined in a resting, left-lateral position and, for specific parts of the examination, in end-expiration by an experienced examiner. All images were obtained from standard parasternal and apical position using 2D and M-mode echocardiographic techniques. LV ejection phase indices like LV ejection fraction and fractional shortening were calculated from parasternal M-mode measurements.Two-dimensional STE analysis was performed offline using dedicated automated software . From the apical and parasternal short-axis datasets, one cardiac cycle was selected for subsequent analysis. 2D strain was measured as previously described , 16. TheDXA is a common measurement of human body composition based on a three-compartment model. It divides the body into total body mineral, fat-free soft mass, and fat tissue mass. Body composition was evaluated by DXA with the use of a Hologic densitometer . Measurements were taken with the patient lying in the supine position on the scanning table. Scanning time was approximately 20 minutes. By means of the appropriate software, information on the body composition was obtained from the whole body scan.p values < 0.05 were considered statistically significant.The results are expressed as mean ± standard deviation (SD) for continuous variables. For the descriptive statistics, the arithmetic mean, SD, median, minimum and maximum, and first and third quartiles were calculated. For the comparison of two measurements at different times, the Wilcoxon Matched Pairs Test was applied for paired samples. Statistical analyses were performed using a statistical software package . 2. Sex and age did not have a significant impact on weight reduction.The clinical characteristics of the patients are shown in The number of patients with arterial hypertension defined as blood pressure >140 mmHg systolic and >90 mmHg diastolic decreased from 9 patients to 1 patient. Mean systolic blood pressure was significantly reduced from 148 ± 16 to 130 ± 17 mmHg and diastolic blood pressure from 95 ± 14 to 82 ± 9 mmHg. The mean heart rate also decreased significantly from 94 ± 16 to 82 ± 9 beats per minute, respectively.Body composition was evaluated by DXA in 8 patients. Total body fat mass decreased by 19% (mean) from 50.9 ± 20.9 kg to 41.1 ± 16.9 kg. Changes in fat distribution resulting from the 12 week fasting phase are reported in Complete echocardiographic data sets were acquired in 21 patients. Image quality was compromised by high body weight. Grading of the image quality before weight loss was good in 9, moderate in 7, and poor in 5 patients. After weight loss, image quality improved to good in 11, moderate in 7, and poor in 3 patients.LV ejection phase indices, LV ejection fraction and fractional shortening, were within normal range at baseline and remained unchanged after weight loss .r = −0.36, p = ns). We found a weak but not significant correlation between percentage weight loss and increase in GLPS . Also, no significant change in GRS after weight loss was noted .GLPS at baseline was −18.7 ± 3.2 in week 1 and −18.8 ± 2.4 in week 12 . The difThe left atrial diameter (anterior-posterior) measured in the parasternal long-axis view was mildly enlarged at baseline. Weight reduction after 12 weeks of diet was associated with a decrease in left atrial size, but the difference was not significant . Left atObesity is associated with structural and functional abnormalities of the heart. Previous studies have reported the presence of left ventricular diastolic dysfunction. Variable findings have been reported with respect to systolic function in obese subjects, including preserved or mildly reduced left ventricular function. Interestingly, these alterations have been shown to be reversible with weight reduction therapies , 17. EchIn the present study, LV ejection phase indices, LV ejection fraction and fractional shortening, were normal at baseline and unchanged at follow-up. Also, systolic left ventricular function quantified by GLPS and GRS was normal. We found GLPS and GRS values in a range comparable to values defined as normal in a large meta-analysis including 2,597 subjects from 24 studies –27. A reIn moderate-to-severe cases of obesity, increased cardiac output as a result of the high metabolic activity of excessive fat may lead to left atrial and ventricular dilation, increased LV wall stress, and compensatory (eccentric) LV hypertrophy , 33. In p values. We were unable to demonstrate cardiac changes due to obesity such as LV hypertrophy and enlargement or atrial dilatation as described by other authors. However, patients in our group were relatively young (mean age 43 years) in terms of the risk of other causes of structural cardiac abnormalities. GLPS measured by STE in order to determine systolic function is in part heart rate and blood pressure-dependent and is subject to change within any given patient. Finally, when studying people with obesity, echocardiographic measurements may be error-prone or imprecise.The present study did have some limitations that deserve comment. The small number of the study groups limits interpretation of the results, in particular In our study, obesity was not associated with systolic dysfunction measured by STE with strain imaging. A 12-week low calorie diet had no effect on systolic function. Dimensions of left atrial and ventricular structures were normal at baseline and not altered after weight loss. Diet with successful weight reduction goes along with reduction in blood pressure and heart rate.