Diffuse myocardial fibrosis, and to a lesser extent global myocardial edema, are important processes in heart disease which are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial extracellular volume fraction (ECV) circumvents factors that confound T1-weighted images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV would be clinically useful for detecting both focal and diffuse myocardial abnormalities in a variety of common and uncommon heart diseases.A total of 156 subjects were imaged including 62 with normal findings, 33 patients with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally-elevated ECV was defined as >2SD from the mean ECV in individuals with normal findings. In HCM the size of regions of LGE was quantified as the region >2 SD from remote.Mean ECV of 62 normal individuals was 25.4 ± 2.5% (m ± SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial infarctions (without MVO) (N = 33) measured 68.5 ± 8.6% . In HCM, the extent of abnormally elevated ECV correlated to the extent of LGE  but had a systematically greater extent by ECV (mean difference 19 ± 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients with non-ischemic DCM  and LGE in the same slice appeared “normal” in 2 of these 4 patients. Mean ECV values in other disease entities ranged 32-60% for cardiac amyloidosis (N = 4), 40-41% for systemic capillary leak syndrome (N = 2), and 39-56% within abnormal regions affected by myocarditis (N = 7).ECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse disease. The ability to display ECV maps in units that are physiologically intuitive and may be interpreted on an absolute scale offers the potential for detection of diffuse disease and measurement of the extent and severity of abnormal regions. Measurement of the extracellular volume fraction (ECV) in the myocardium could provide a quantitative method for assessing cardiomyopathies which may develop diffuse fibrosis or edema. Diffuse myocardial fibrosis is difficult to distinguish using late gadolinium enhancement (LGE) since the myocardial signal intensity is deliberately nulled to enhance the heterogeneity of abnormal myocardium thus homogeneously diffuse tissue will be nearly isointense and therefore globally “nulled” becoming indistinguishable from normal tissue . ECV relPrevious studies have measured the ECV using manual regions of interest drawn on T1-maps or by performing a manual or semi-automatic image registration of T1-maps. A fully automated method has been presented for calculating pixel-wise ECV parametric maps (ref Part I). The method included correction of respiratory and patient motion, and automatic segmentation.The goal of this research was to evaluate the utility of the automated method for producing a pixel-wise map of ECV and to establish baseline quantitative values for normal subjects. We hypothesized that measurement of ECV, a physiological parameter directly related to the tissue distribution of an extracellular gadolinium-based contrast agent, would detect both focal and diffuse myocardial abnormalities in a variety of common and uncommon diseases. We established a normal range in 62 subjects. Next, we tested the hypothesis that patients with known regional abnormalities in the heart would have regional abnormalities in ECV by imaging patients with chronic myocardial infarctions and hypertrophic cardiomyopathy. Finally, we assessed the myocardial ECV in patients with diseases that might manifest with more diffuse abnormalities such as amyloidosis, non-ischemic dilated cardiomyopathy (DCM), and systemic capillary leak syndrome (SCLS).ECV imaging was performed between Sept 2009 and May 2011. This study was approved by the local Institutional Review Boards of the National Heart, Lung, and Blood Institute and Suburban Hospital, and all subjects gave written informed consent to participate. Hematocrit was measured from a venous blood sample drawn just prior to the CMR study.All patients were referred for CMR assessment of known or suspected heart disease prospectively underwent ECV imaging. For the purpose of this study, subjects were included in this analysis based on the following criteria. Normal subjects (n = 62) were used to establish baseline values of myocardial ECV. Normal subjects were defined as patients who were without known significant systemic illness, whose studies demonstrated normal biventricular systolic function, chamber size, and wall thickness, absent significant valvular dysfunction, and lack of late gadolinium enhancement. Subjects with hypertension or diabetes were excluded from this group and their clinical characteristics have been described (ref Part I). Chronic myocardial infarction (MI) was defined as a region of increased signal intensity on LGE that included the subendocardium that was within a coronary territory, and occurring in a patient with a clinical syndrome consistent with an acute coronary syndrome at least 6 months prior to the scan. Myocarditis was defined as a clinical syndrome established by the presence abnormal cardiac biomarkers (troponin I assay) in the absence of coronary artery disease, with a regional wall motion abnormality and increased signal intensity in the corresponding region on T2-weighted images. The diagnosis of hypertrophic cardiomyopathy (HCM) was supported by left ventricular hypertrophy  in the absence of a clinical condition known to cause hypertrophy. If wall thickness was 10-15 mm, one or more additional criteria were required: (1) hypertrophy in a recognizable pattern like that of apical-variant HCM; (2) systolic anterior motion of the mitral valve with mitral regurgitation; and (3) resting left ventricular outflow tract obstruction. Cardiac amyloidosis was based on biopsy evidence of amyloidosis or presence of a disease known to cause cardiac amyloidosis (e.g. multiple myeloma). Nonischemic dilated cardiomyopathy (DCM) was defined as globally reduced systolic function (ejection fraction <45%) with an enlarged left ventricular chamber in the absence of obstructive coronary artery disease. Chronic systemic capillary leak syndrome (SCLS) was diagnosed according to established criteria  [ECV maps were derived from T1-maps acquired pre- and post-contrast using the MOLLI method  calibratThe myocardium was manually segmented for ECV and LGE measurements. In subjects with regions of abnormal ECV, mean values of these regions were measured. In cases of chronic MI, ECV values were measured in the central core region of the MI.The normal range of ECV values in the myocardium was defined as mean ± 2SD of ECV values in the normal group, and pixels were assessed as abnormal in LGE images for signal intensities greater than the mean + 2SD in a normal region in the same image.Group statistics were measured for subjects with HCM (n = 33) and chronic MI (n = 33). ECV measurements were made on subjects with non-ischemic DCM (n = 15) and cardiac amyloidosis (n = 4) but group correlations to the size of LGE regions were not performed in these entities due to the small numbers and the diffuse nature of these processes.The percentage of pixels with abnormally elevated ECV (> 30.4%) was compared with the percentage of enhanced pixels in LGE images that were greater than mean + 2SD measured in a remote region that appeared “normal”.t-test, as appropriate. Statistical significance was defined as p < 0.05.Data are presented as mean and standard deviation. Differences between means were tested by the paired or unpaired Patient characteristics for each group are summarized in TablesECV measurements Figure  were madIn the 33 patients with HCM, the percentage of myocardium with elevated ECV correlated with the amount of myocardium with abnormal LGE   were equal to 68.5 ± 8.6% . There were no cases of chronic MI with microvascular obstruction.In patients with acute myocarditis (n = 7), all subjects had focally elevated ECV > 30.4%. ECV values for subjects with elevated ECV were 44 ± 6% and 26.4 ± 3%, in focally elevated and remote regions, respectively.There were 18 subjects with non-ischemic DCM, of whom 3 did not have measurable ECV due to patient movement between pre- and post-contrast acquisitions. Regions of abnormally elevated ECV were identified in 4 of 16 patients with non-ischemic DCM and LGE in the same slice appeared “normal” in 2 of these 4 patients. ECV was 38.1 ± 1.9%  in the non-ischemic DCM patients with elevated ECV.There were 4 subjects with cardiac amyloidosis. The ECV values for these subjects had mean values ranging from 32 to 60% with an overall mean of 46 ± 12%.In subjects with SCLS with abnormally elevated ECV (n = 2), the ECV had a mean ECV of 41% with global distribution throughout the heart. Furthermore, the mean pre-contrast T1 was 1145 ms, which is abnormally long.ECV maps, T1-maps pre- and post-contrast, and corresponding PSIR late gadolinium enhancement images are shown in Figure pre/T1post/ECV = 1249 ms/ 487 ms / 51%.Note that the post-contrast T1-maps have a considerably different appearance using a fixed scale due to the variation of renal clearance of gadolinium, body composition and baseline T1, further emphasizing the difficulty of directly using post-contrast T1 values alone without ECV calculation. Elevated pre-contrast T1 is pronounced in the subject with acute myocarditis .For the DCM case , there are cases in which patient movement resulted in the slices being substantially different in appearance despite the fact that the same slice position was prescribed. Co-registration is by design only capable of correcting for in-plane motion and cannot compensate for through plane motion, although it may appear to partially compensate. In other cases, it is clear that the pre- and post-contrast images are at substantially different cardiac phases due to significant change in heart rate, despite adjusting the trigger window. Both of these factors could potentially be improved at the time of acquisition by more careful inspection at the cost of a more complicated workflow.The ability to interpret lower quality ECV maps and not mistake uncorrected motion artifacts or partial volume border pixels for sub-endocardial or sub-epicardial fibrosis is a residual and important issue. Motion related errors occur both intra-series and between pre-and post-contrast series. The correction of intra-series motion due to inadequate breath-holding was referred to as MOCO, whereas the correction of subject motion between pre- and post-contrast acquisition was referred to as co-registration. The use of error maps based on residual errors in pixel-wise T1-fitting provide a means of determining the MOCO error, and may serve as a quality metric. In terms of co-registration errors, the interpretation can be improved by examining the pre-and post-contrast T1-maps for consistent appearance of position and cardiac phase as a quality control step. Furthermore, it is expected that the use of ECV maps will be in conjunction with pre-contrast T1-maps and conventional late gadolinium enhancement images, and not interpreted independently. As such, the ability to assess and quantify diffuse fibrosis in ECV images should provide increased diagnostic confidence since LGE image quality is generally excellent and will not share the same artifacts.The partial volume issue is not only important in terms of the visual readout, but may introduce biases into quantitative measurements which become particularly significant in the context of more subtle diseases. These effects are less problematic for globally diffuse processes. One approach to reducing the bias in measurements is to restrict the measurement to the mid-wall region, although one must exercise caution for subjects with thin walled myocardium or patients with thin rims of subendocardial fibrosis. Blood pool contamination of the myocardium in border pixels can lead to biases if included in the measurement, and in general may contribute more significantly in subjects with thin myocardial wall thickness. This might lead to an apparent elevated ECV in subjects with thin walls such as healthy females or subjects with DCM, and thereby might lead to an underestimation of the difference in these populations with subjects that have hypertrophy since thicker myocardium should have less error due to partial volume at the borders.Quantitative ECV pixel maps may have potential for analysis of border zones around MI. However, caution must be exercised in differentiating partial volume effects from true pathophysiological mechanisms. Partial volume effects affect the measurement of ECV by contributing to larger variability in fine structures such as subendocardial MI. Similar to LGE, the partial volume “blurring” due to the slice thickness may contribute significantly to the apparent border zone.Despite these issues, ECV maps may be readily incorporated into the clinical workflow and may provide diagnostic information where other methods are limited. It is not intended to replace existing methods such as LGE which are excellent at depicting focal lesions, but rather to be used in concert with other techniques. When ECV is abnormally elevated, it may not be clear whether this is due to fibrosis or edema which may be either diffuse or focal. In such instances, pre-contrast T1 or T2 maps , in addiThe number of subjects is small for some of the subgroups in this study. In these cases, large scale studies are needed to establish the clinical utility. In this study which compared the percentage of abnormal tissue by ECV measurement and LGE using mean + 2SD threshold, it was not possible to conclude which measurement was more accurate. Estimates of both the mean and SD in normal appearing LGE regions are generally subject to being biased on the high side due to signal inhomogeneities, and in this case could explain the underestimation by LGE using this type of thresholding.ECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse myocardial disease states which affect the myocardial extracellular space. The ability to display ECV maps in quantitative and physiologically intuitive units that may be interpreted on an absolute scale offers the potential for simplified detection and measurement of the extent and severity of abnormalities affecting the myocardial ECV.CMR, Cardiovascular Magnetic Resonance; DCM, Dilated cardiomyopathy; ECV, Extracellular volume fraction; HCM, Hypertrophic cardiomyopathy; LGE, Late gadolinium enhancement; MI, Myocardial infarction; MOCO, Motion correction; MOLLI, Modified Look-Locker inversion recovery; SCLS, Systemic capillary leak syndrome; TI, Inversion time; ROI, Region-of-interest; PSIR, Phase sensitive inversion recovery.Dr. Arai is a principal investigator on a US government Cooperative Research And Development Agreement (CRADA) with Siemens Medical Solutions (HL-CR-05-004).PK participated in design of the study, developed the technical approach, algorithms and software, performed processing and analysis, and drafted the manuscript. JRW performed analysis of clinical studies and diagnoses. XH developed software used for motion correction. JRW and MU participated in design of the study. WPB and SMS contributed to clinical diagnosis, and KMD contributed his expertise in subjects with SCLS. AEA conceived of the study and participated in analysis. All authors contributed to editing of the manuscript and read and approved the final manuscript.


The population of children and young adults requiring a cardiac pacing device has been consistently increasing. The current generation of devices are small with a longer battery life, programming capabilities that can cater to the demands of the young patients and ability to treat brady and tachyarrhythmias as well as heart failure. This has increased the scope and clinical indications of using these devices. As patients with congenital heart disease (CHD) comprise majority of these patients requiring devices, the knowledge of indications, pacing leads and devices, anatomical variations and the technical skills required are different than that required in the adult population. In this review we attempt to discuss these specific points in detail to improve the understanding of cardiac pacing in children and young adults. Pediatric pacing has progressed substantially since the first implant in a 14 yr old with myocarditis in 1962 .[The most common indications for permanent pacemaker implantation in children, adolescents, and patients with congenital heart disease are:1) Symptomatic sinus bradycardia related to sinus node dysfunction, associated with poor cardiac output or to prevent episodes of recurrent atrial tachycardias.2) Advanced second- or third-degree AV block, either congenital or postsurgical, when associated with low cardiac output, ventricular dysfunction, complex ventricular ectopy, syncope or potential of recovery is minimal, especially after cardiac surgery.Important considerations in children and young adults are 1) an increasing number of young patients are long-term survivors of complex surgical procedures for congenital heart defects that result in palliation rather than correction of circulatory physiology. The residua of impaired ventricular function and abnormal physiology may result in symptoms due to sinus bradycardia or loss of AV synchrony at heart rates that do not produce symptoms in individuals with normal cardiovascular physiology. Hence, the indications for pacemaker implantation in these patients need to be based on the correlation of symptoms with relative bradycardia rather than absolute heart rate criteria. 2) The clinical significance of bradycardia is age dependent; e.g. a heart rate of 45 bpm may be a normal finding in an adolescent, the same rate in a newborn or infant indicates profound bradycardia. 3) Significant technical challenges may complicate device and transvenous lead implantation in very small patients or those with abnormalities of venous or intracardiac anatomy. 4) As there are no randomized clinical trials of cardiac pacing in pediatric or congenital heart disease patients, the level of evidence for most recommendations is consensus based.ICDs are recommended for patients who have survived an episode of cardiac arrest, patients with poor cardiac function with evidence of moderate to severe heart failure, patients with inducible ventricular dysrhythmia in a setting of symptomatic CHD and in patients with genetic cardiomyopathy.Sudden cardiac death (SCD) in childhood and adolescence is associated with congenital heart disease, cardiomyopathies, and genetic arrhythmia syndromes. There is paucity of clinical experience and data regarding ICD implantation for primary prevention of SCD in young patients and therefore recommendations are based on extrapolation of data from adult studies. Unexpected sudden death is reported in 1.2% to 3.0% of patients per decade after surgical treatment of tetralogy of Fallot, with risk factors including ventricular dysfunction, QRS duration, and atrial and ventricular arrhythmias. A signifThere are no randomized multicenter studies regarding use of CRT in pediatrics and young adults. The limited worldwide pediatric experiences has shown that CRT is useful in select younger patients with clinical improvements comparable to adult patients and, in some instances, can delay or remove the need for heart transplant.. The curThe implantation of devices in children and young adults can be challenging especially in view of anatomical variations due to congenital defects and surgical procedures to repair the heart defects.It is important to understand the anatomy and have a thorough knowledge of any underlying heart defects, presence of intracardiac shunts and type(s) of surgical procedure(s) if any performed in the past. Venography may help define presence or absence of left superior vena cava, any obstruction, or anomalies as well as patency of the vasculature if previous leads are present. Patients with d-transposition of the great arteries (d-TGA) with atrial switch operation have surgical baffles connecting the superior vena cava (SVC) and inferior vena cava to the pulmonary (left) ventricle. If placement of a lead is anticipated and there is presence of narrowing across the superior baffle, it is useful to consider stent angioplasty of the SVC baffle prior to lead implantation. Patients with previous cardiac surgery may have their right atrial appendage amputated at the time of canulation. In patients with Fontan palliation for single ventricular physiology, an atrial lead may be implanted transvenously in patients with atrio-pulmonary connection or lateral tunnel palliation (but not the extracardiac conduit), keeping in mind that they have a passive venous flow circulation. The presence of left SVC without a bridging vein can make the implantation technically challenging albeit possible . Future The pacing and defibrillator leads can be implanted via the transvenous  or surgical  route. The choice of route is dependent upon the size of the patient, anatomy and surgical procedures performed. The primary risk factor for obstruction after pacemaker lead implantation in children was found to be related to the size of the lead as compared to the body surface area at implantation. A ratio > 6.6 mm2/m2 was found to best predict venous obstruction, with a sensitivity of 90% and specificity of 84%. This data can be used to aid the physician in selection of a single or dual chamber lead system appropriate for the patient's size, thus decreasing the risk of venous obstruction, and hence preserving venous access. For patiChildren have faster resting heart rates than adults and higher peak heart rates - it is not unusual for infants to have resting heart rates between 120 and 150 beats/min, and it is easy for children of all ages to attain sinus rates in excess of 200 beats/min during active play. Many pacemakers cannot pace at or track sinus rates beyond 180 beats/min and rates with defibrillators are even lower. These limits to the maximum tracking rate can result in a substantial decrease in exercise performance, peak oxygen consumption and anaerobic threshold.[Younger patients have higher sinus rates during exertion and increased frequency of supraventricular tachycardias especially in patients with congenital heart defects. It has been reported that 30% of patients with ICDs and congenital heart disease will develop supraventricular tachyarrhythmias during follow-up.,20 Meta-The handedness of the patient is determined as the device is preferably implanted on the non-dominant side. The procedure is usually performed under general anesthesia. Antibiotic coverage is provided during and immediately after the procedure. Based onBased on variations in anatomy, the lead implantation technique may have to be revised. In patients with high DFTs at the time of ICD implantation, additional coils or subcutaneous array are implanted. The placThe patient and the device are assessed prior to discharge, in 1- 2 weeks for incision check, at 2- 3 months to assess chronic pacing thresholds and cardiac function (because of the risk of pacing-induced cardiac dysfunction), and then 6 months to yearly. Patients are advised to transmit data using the remote monitoring services on a 3 monthly basis or if any change in clinical status occurs. The remote monitoring is intensified to a monthly basis in pacemaker dependent patients and in patients nearing end of battery life. Any patient experiencing an ICD discharge is recommended to follow up in the closest emergency room to evaluate the appropriateness of the discharge, need for in-patient admission, or pharmacological intervention. Chest radiographs have been advised on a yearly basis in small children to recognize any growth related lead damage. Echocardiograms are performed on an annual basis to evaluate valvular and cardiac function. Stress test is recommended to assess exercise tolerance, maximal heart rates achievable, assess the rate response settings, and exercise related arrhythmias for fine tuning of the device for allowing maximal functionality in children and young adults.Device implantation data using the Kids' Inpatient database from 1997-2006 revealed specific complication rates for all device types were pneumothorax 2.2%, hematoma 3.3%, endocarditis/ pericarditis 1.1%, surgical infection 2.4% and death 1.7%. Biventricular pacemakers have the highest percentage of acute complications (42.3%) whereas pacemakers (17.3%) and defibrillators (16.8%) were lower. Pacemakers had higher patient-related complications (11.2%) in comparison to ICDs and biventricular pacemakers and ICDs had higher device-related complications (11.5%) in comparison to the pacemakers and biventricular pacemakers.[With the technological advances making more devices compatible for younger patients and the increasing population of adult congenital heart defect patients requiring device implantation, the need for revision or extraction will continue to increase. Considering lead implantation techniques and hardware that lend them to easier extractions would be helpful. Older lead age, a lead in the ventricular position, and polyurethane lead insulation were found to be independent predictors of the decreased likelihood of a simple extraction. Long impThe utility of cardiac devices in the pediatric population is increasing due to technological advances as well as improved survival of patients with congenital heart defects. Symptomatic bradyarrhythmias, risk of sudden death, heart failure are the broad indications for implantation of a cardiac device. The selection of device and leads as well as the technique of implantation are based on the patient size and anatomy. Careful selection of the device, leads and technique can help reduce complications associated with the implantation as well as aid in extraction of the devices in the long term.


To quantify myocardial T2 value in patients with myocarditis and correlate the distribution of abnormal T2 values with the extent of macroscopic late gadolinium enhancement (LGE).25 patients with myocarditis were retrospectively evaluated for the utility of T2 mapping in diagnosing myocarditis. Patients with elevated troponins, negative coronary angiogram, and atypical LGE were diagnosed as acute myocarditis. Patients with normal troponins and macroscopic LGE at the time of cardiac MRI were diagnosed as remote myocarditis. As per our institutional protocol, T2 mapping sequences were performed in all cases with suspected myocarditis in addition to standard LGE images on 1.5 T scanner . T2 mapping was performed on three short axis images , yielding 16 myocardial segments for analysis (AHA segments). Single 4 chamber view image was obtained in addition. Minimum, peak and mean segmental T2 values were calculated by the first reader. Average segmental T2 values were documented along with documentation of the number of segments with elevated T2 values. The presence or absence of LGE was documented by a second reader blinded to the T2 results. Average segmental T2 values were then correlated with troponin levels at the time of the MRI examination.In patients with acute myocarditis, mean T2 values were elevated in segments showing LGE . The T2 values were also elevated in myocardial segments with no macroscopic LGE (avg 60 msec). On an average, there were 6 additional segments that showed elevated T2 values and no macroscopic LGE. In patients with remote myocarditis, the T2 values were normal in areas of LGE.T2 mapping can be utilized as an objective tool for diagnosing acute myocarditis. In addition, T2 values were normal in patients with normal cardiac enzymes and a typical pattern of myocarditis associated LGE. Given the non contrast nature of this technique, normal T2 values may exclude a diagnosis of acute myocarditis in patients with renal insufficiency.None.


Duchenne muscular dystrophy (DMD) due to dystrophin deficiency leads to death by heart failure in nearly 30% of cases. An early detection of myocardial abnormalities in these patients would help in the optimization of their management. The GRMD is a canine model of DMD, that develops a severe cardiomyopathy.Post-processing of standard cine-MR images of young GRMD dogs, before any sign of cardiac global dysfunction is patent. The aim of the study was to detect minor changes in synchronism or contraction patterns of the left ventricle of golden retriever muscular dystrophy (GRMD) dog as compared to control dogs.2, NEX:3, GRAPPA:2. Each dog heart was covered by 8 slices. We used the Segment® software to define the endo- and epicardial contours and analyze radii and wall thicknesses in each slice with a 6 segment model. The radii and wall thickness curves were smoothed using a Savitzky-Golay filter. For each slice, a dyssynchrony index was calculated, as the SD of the normalized radii across the six segments throughout the cardiac cycle. Max dRadius/dt and max dWT/dt were also extracted for each segment of each slice.6-month old GRMD (n=5) and control dogs (n=4) were imaged using a Siemens Magnetom Trio TIM with a standard cine-FLASH sequence in short axis. Acquisition parameters were as follows: TE:3.06ms, TR:19.74ms, flip angle:15°, slice thickness:6mm, in plane resolution:1.8x1.8mmHR, LVEF, peak ejection rate and SV were not statistically different between GRMDs and controls. EDV was somewhat smaller in GRMDs . The GRMDs showed an higher mean dyssynchrony index of the 4 most basal slices lower than the controls . Max dRadius/dt during contraction and during relaxation was higher in GRMDs than in controls  and . The same appeared true for max dWT/dt in contraction and relaxation . Figure Pre-clinical contractile abnormalities can be detected by post-hoc analysis of standard cine MR images in GRMD dogs. This preliminary results should encourage further work on early detection of myocardial minimal dysfunction in GRMD dogs but also in DMD and Becker muscular dystrophy patients.


The major adverse consequence of obesity and metabolic syndrome is cardiovascular disease and is attributed to myocardial steatosis. CMR proton spectroscopy has the potential for quantification of amount of fat deposited in the heart.A research protocol was applied on 90 subjects, using a Siemens Verio 70 cm bore 3T-MRI scanner. All subjects were not known to have cardiac disease. MR spectroscopy was performed with water suppressed ECG gated point resolved spectroscopy (PRESS), TR/TE =1R-R/30ms. PRESS voxel was located in the septum at isovolumic phase of diastole. Short axis and 4-chamber Steady State Free Precession (SSFP) cine images were obtained to prescribe the PRESS voxel location, and saturation slabs across subcutaneous and pericardial fat were used.A breathing navigator was set on the dome of the diaphragm on a free breathing scout to reduce the breathing effects. B0 shimming parameters were optimized with a (breath-hold) rapid B0 mapping method.Fat content was quantified with Amares/MRUI and related to water in unsuppressed spectra. SSFP images were used for evaluation of global myocardial function . Variables were indexed to BSA.All subjects had same day metabolic profile evaluation, included insulin sensitivity, fasting glucose level, resting energy expenditure, maximum VO2, regional fat percentage and waist circumference. Lipid profile including serum cholesterol, HDL, LDL and serum triglycerides was obtained within one month of the scan.Seventy-seven MRS scans were analyzable, mean age 51±12 years, 46% were men, and 69% were white. BMI ranged from 19.4 to 54.8 and 36.4% had metabolic syndrome. Mean EF, EDVI, ESVI and LVMI were 62±6%, 60±15,23±7 and 54±11 respectively. Myocardial fat content ranged from 0.03 to 3.94 %, it showed mild positive correlation with BMI, waist circumference and triglycerides . There was a trend to positive correlation with free fatty acids , however, end diastolic volume and stroke volume indices showed negative correlation .Myocardial 1HMR Spectroscopy is a promising tool for quantification of ectopic fat deposition in the myocardium. High triglycerides in the body is highly associated with fat accumulation around the heart. In population with no cardiac disease, higher myocardial fat percentage is associated with lower EDVI and ESVI.


Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA).8 ± 4.3*108 mononuclear and 1.65*107 ± 1.42*107 CD34+ cells by PRCSP..From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019).PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials. An increasing number of patients with coronary artery disease remain symptomatic with disabling angina despite the optimal use of antianginal medications and percutaneous or surgical revascularization ,2. TheraPatients with Canadian Cardiovascular Society (CCS) class III-IV angina despite maximal medical or surgical therapy who were ineligible for further percutaneous or surgical revascularization (based on coronary anatomy) and who had evidence for reversible ischemia on an exercise single photon emission computed tomography (SPECT) were enrolled. A committee comprising two cardiovascular surgeons and two interventional cardiologists determined the ineligibility for percutaneous or surgical revascularization. Patients with acute myocardial infarction, percutaneous or surgical revascularization within six months of enrollment in the study, a history of malignant disease, severe renal dysfunction, or unexplained hematology or biochemical abnormalities were excluded. The local ethics committee at Clinica Maison de Sante and Centro Cardiovascular San Nicolá s approved the protocol and all patients gave informed consent. The review and analysis of the data was also approved by the IRB at the University of Utah.The baseline screening assessment of patients included clinical evaluation, electrocardiogram (ECG), laboratory evaluation . Patients kept a record of daily angina frequency for three weeks, and the severity of angina was graded according to the CCS class at baseline, 3, 12, and 24 months. Within two weeks prior to cell therapy, exercise capacity was evaluated using bicycle ergometry in conjunction with SPECT imaging to assess myocardial ischemia and left ventricular (LV) function.Patients had complete blood count, creatine kinase levels and ECG performed immediately prior to and immediate after the procedure. Complete blood count, creatine kinase, and troponin T levels were also assessed eight hours post procedure with an ECG prior to discharge. All patients were monitored in the cardiac intensive care unit for 12 hours after the procedure and were discharged the following day. A transthoracic echocardiogram was performed prior to discharge to detect the presence of pericardial effusion. The clinical follow-up evaluations including the laboratory tests described above were performed 3, 12 and 24 months after the injection procedure. At 12 and 24 months of follow-up exercise bicycle testing, and gated SPECT were performed.All patients performed a symptom-limited bicycle exercise test with a 20-W starting load and 10-W increments per minute at baseline and at 12 and 24 months after the injection procedure. Antianginal medication was continued. The test points were angina pectoris, physical exhaustion, dyspnea, significant decrease in blood pressure (10 mmHg), or achievement of maximal age-related heart rate. A 12-lead ECG was recorded before, during, and after the test. The total exercise duration, maximal workload achieved in percentages  at baseline was compared to 12 and 24 months after ABMMC delivery.99 mTechnetium Sestamibi injection using a double-head SPECT camera as previously described.  Using the bicycle exercise test, 99 mTechnetium Sestamibi was injected intravenously at peak exercise (85% of the estimated heart rate) which was continued for 2 minutes after tracer injection and images were obtained 30 minutes after the stress test. Reconstruction yielded long-and short -axis projections perpendicular to the heart axis. The short-axis slices were displayed in polar map format.For the SPECT examination, a one-day rest-stress protocol was used. On the same day, images at rest were obtained 60 minutes after the 8 ± 4.3*108 mononuclear cells and 1.65*107 ± 1.42*107 CD34+ cells.A volume of 300 ml of bone marrow was harvested from the iliac crest under local anesthesia and placed in heparinized Hanks' balanced salt solution. ABMMC were isolated by Hess 6% density gradient centrifugation with a final suspension volume of 50 ml and a mean cell concentration of 8.19*10The femoral vein was cannulated with a 7 French sheath, a 6 French catheter was placed in the coronary sinus and a 0.035 mm hydrophilic guide wire was placed in the interventricular or lateral vein followed by placement of a peripheral balloon into the mid portion of the coronary sinus to allow nonselective delivery of cells. . The balloon was inflated at very low pressure 1 to 2 atm) for 10 minutes producing stagnation of the flow as previously described with infusion of the ABMMC. 50 mls of ABMMC were injected manually through the balloon at a rate of 10 mls per minute. The average total procedure time for cell delivery was 30 minutes. Ventricular arrhythmias were not observed during cell delivery or hospitalization and no patient had post procedural pericardial effusion by two-dimensional echocardiography before discharge. One patient died four months following the procedure due to liver cirrhosis, decompensated heart failure and pulmonary hypertension.The frequency of angina episodes per day decreased from 2.9 ± 3.9 at baseline to 1.0 ± 1.4 at 3 months (p < 0.001), 0.7 ± 1.2 at 12 months (p < 0.001) and 0.6 ± 1.2 at 24 months (p < 0.001). Angina improved in 13/14 patients and the mean Canadian Cardiovascular Society class improved from 3.2 ± 0.6 baseline to 1.9 ± 0.7 at 1 year (p < 0.001) and 1.8 ± 0.4 at 2 years (p < 0.001). The individual changes for anginal episodes per day for the 14 patients are shown in Figure At baseline, 14 patients had exercise duration time of 3.1 ± 1.4 minutes. This improved to 6.8 ± 1.0 and 7.4 ± 1.7 minutes at 12 and 24 months of follow-up respectively, (p < 0.001). The individual changes for exercise time are shown in Figure The median percent of ischemic myocardium by SPECT was 38.2% at baseline and was reduced to 26.5% and 23.5% (p = 0.001) at 12 and 24 month follow-up (Table Median rest LV ejection fraction by SPECT at baseline was 31.2% and was improved to 35.4% and 35.5% at 12 and 24 month follow-up respectively (p < 0.019). (Table 9 described a reduction in anginal symptoms, improved wall motion and improved wall thickening at 3 'months follow-up in 8 patients. In addition, the area of hypoperfused myocardium was reduced on SPECT. Fuchs et al reported a reduction in anginal symptoms and improved myocardial perfusion in 27 patients with a trend toward improved LV ejection fraction [This study demonstrates that ABMMC delivered by PRCSP in patients with CRA and stress-inducible ischemia was safe, may reduce anginal symptoms and improve exercise capacity. Stem cell transplantation by PRCSP is an alternative route of delivery to the myocardium for patients with coronary artery occlusion at their initial portions, or for patients with severe multivessel disease or occluded venous and arterial grafts. In this study we have demonstrated that, in patients with chronic ischemia with or without severely impaired LV function, that ABMMC injection enhances myocardial perfusion. In addition we observed that improved systolic LV function occurred only in patients with low ejection at baseline. Improvement and maintenance of the LV ejection fraction at 24 months follow-up was most likely a result of increased myocardial perfusion and global regional wall motion. This resulted in a reduced LV end-systolic volume. Consequently, the therapeutic effect appears to be more related to enhanced myocardial contractility rather than induction of LV reverse remodeling. The findings of the present study are consistent with the hypothesis that ABMMC promote angiogenesis, resulting in increased myocardial perfusion . The prefraction . Perin efraction . In a rafraction . In thisfraction ,22 and tABMMC: autologous bone marrow mononuclear cells; CCS: Canadian Cardiovascular Society; CRA: refractory angina; ECG: electrocardiogram; LV: left ventricular; PRCSP: percutaneous retrograde coronary sinus perfusion; SPECT: single photon emission computed tomography.The authors declare that they have no competing interests.JT, RFV, AC, JC, CC, AC, JE, CY, JC enrolled and treated the patients. JT, RFV, AP conceived the study. JT, TH, AP all help to draft the manuscript and were involved in the data analysis. All authors read and approved the final manuscript.


Patients with Sickle cell disease (SCD) who receive regular transfusions are at risk for developing cardiac toxicity from iron overload. The aim of this study was to assess right and left cardiac volumes and function, late gadolinium enhancement (LGE) and iron deposits in patients with SCD using CMR, correlating these values with transfusion burden, ferritin and hemoglobin levels.Thirty patients with SCD older than 20 years of age were studied in a 1.5 T scanner and compared to age- and sex-matched normal controls. Patients underwent analysis of biventricular volumes and function, LGE and T2* assessment of the liver and heart.When compared to controls, patients with SCD presented higher left ventricular (LV) volumes with decreased ejection fraction (EF) with an increase in stroke volume (SV) and LV hypertrophy. The right ventricle (RV) also presented with a decreased EF and hypertrophy, with an increased end-systolic volume. Although twenty-six patients had increased liver iron concentrations , only one patient demonstrated an abnormal heart T2* < 20 msec. Only four patients (13%) LGE, with only one patient with an ischemic pattern.Abnormal heart iron levels and myocardial scars are not a common finding in SCD despite increased liver iron overload. The significantly different ventricular function seen in SCD compared to normal suggests the changes in RV and LV function may not be due to the anemia alone. Future studies are necessary to confirm this association. Sickle cell disease (SCD) is an inherited hemoglobin synthesis disorder characterized by life-long severe hemolytic anemia, pain crises, and chronic organ damage . PatientCardiovascular magnetic resonance (CMR) is a useful noninvasive tool for evaluating the amount of iron in the heart. The technique relies on the measurement of T2 star (T2*) relaxation from gradient-echo sequences. When the storage capacity of ferritin is exceeded, iron is deposited in the myocardium as particulate hemosiderin, a form of ferrihydrite (hydrated iron oxide). This deposition disrupts local magnetic field homogeneity, reducing T2* values in an inverse relationship to iron concentration . T2* CMRThe complications of SCD are multiple. The two most common acute events are vaso-occlusive pain crisis and acute chest syndrome (ACS).The vaso-occlusive events of SCD may occur in any organ, including the heart and lungs. Additionally, patients are at risk for a progressive vasculopathy characterized by systemic and pulmonary hypertension (PH), endothelial dysfunction, and proliferative changes in the intima and smooth muscle of blood vessels. With increasing age, the incidence of chronic end-organ complications, including chronic renal failure, osteonecrosis, and PH, increases. The pulmonary complications of SCD are of particular importance, as ACS and PH have the highest associated mortality rates within this population . Thus, nGiven that CMR can provide a comprehensive and unique evaluation of the heart in a single examination, the aims of this study were to assess the right and left cardiac volumes and function, late gadolinium enhancement (LGE), and iron deposits in patients with SCD aged > 20 years, and to correlate these values with transfusion burden and ferritin and hemoglobin levels.This single-site, prospective, clinical observational study involved 30 consecutive patients  with SCD who were referred for initial myocardial T2* examination from a specialized hematology center . The patients’ mean age was 37.5 ± 14.8 years. Twenty-seven patients were receiving partial exchange transfusions (at least one per month). Transfusion burden was defined as >20 red blood cell transfusion events . Red blood cell transfusion in sickle cell was indicated only in situations of acute losses, or when the hemoglobin fell two or more grams below its baseline level. Seven percent of the patients were on transfusions for past history of cerebrovascular accidents, 2% because of osseous infarction and 1% because of perimaleolar ulcers (Table Six patients were being treated with a single iron chelation agent (deferoxamine or deferasirox) at presentation, and the other patients were receiving folic acid and hydroxyurea. Only patients on a regular transfusion regiment were included in the final analysis. The Hemorio Research Ethics Committee approved the data collection and analysis associated with this study, and all patients signed informed consent forms.–1 and slew rate of 200 T m–1 s–1. Each scan  included the measurement of hepatic (right lobe) and myocardial (mid-septum) T2*, LV and RV volumes, EF, mass, and LGE using previously published techniques . This T2* sequence generated a series of 12 images with echo times (TEs) of 1.0–16.5 ms and echo spacing of 1.4 ms.For the measurement of myocardial T2*, a single short-axis midventricular slice was acquired using a single breath-hold ECG-gated multi-echo dark blood technique . This T2* sequence generated a series of eight images with TEs of 1.9–17.3 ms and spacing of 1.7 ms.–1 gadodiamide , a single-shot breath-hold ECG-gated phase-sensitive inversion recovery sequence was acquired in the short, horizontal and vertical long axis planes  using the same position and number of slices as the cine true FISP sequence, to evaluate LGE.For LV and RV functional evaluation, the protocol included a breath-hold ECG-gated cine true fast imaging with steady-state precession (FISP) sequence in the short axis plane . In addition, 10 min after intravenous administration of 0.2 mmol kgTwo experienced radiologists analyzed the MR images at a dedicated workstation  using ARGUS and Viewer software . For hepatic T2* analysis, regions of interest (ROIs) were manually drawn in the liver using Viewing software while avoiding all major visible vessels. For myocardial T2* analysis, a full-thickness ROI was manually defined in the interventricular septum .Hepatic and myocardial T2* decay were calculated using manual analysis in an electronic spreadsheet . Signal The normal ranges for LV and RV volumes and function were taken from normal, non-anemic adult Latin American patients of the same sexes and ages , with thAll parameters are presented as means ± standard deviations. Spearman’s rank test was used to assess correlations among hepatic and myocardial T2*, blood transfusions, hemoglobin and ferritin levels, RV and LV volumes, EF, and LGE. Analysis of variance was used to assess differences across different ranges of hepatic and myocardial T2*. Two-sided statistical significance was set at p < 0.05. All statistical analyses were performed using R software .The clinical and hematological parameters of patients with SCD, and CMR parameters of control subjects and patients with SCD, are shown in Tables Compared with control subjects, patients with SCD in this study had decreased LV EF (p = 0.017) and LV dilatation in diastole and systole (both p <0.001), leading to an increased stroke volume (SV) with LV hypertrophy  patients had abnormal LICs. Although hepatic iron overload was severe, abnormal 15 ms) and borderline low (21.7 ms) myocardial T2* values were found in only one 3.3%) patient each  patients presented with LGE, with an ischemic pattern  in one case and non-ischemic patterns  in three cases Figure , Table 2.3% patieOne patient showed signs of pulmonary hypertension with right atrial and RV enlargement, moderate RV dysfunction, displacement of the interventricular septum to the left during end diastole and systole, and small areas of mesocardial LGE at the insertion points of the free RV wall in the interventricular septum. An echocardiogram confirmed that this patient’s mean pulmonary artery pressure was 42 mm Hg.The importance of the RV as an aggravating factor in heart disease and a predictor of adverse cardiac outcomes has often been overlooked in the past. Our study provides new data showing that the RV can be altered in patients with SCD, a finding not deeply studied in SCD and are worth reporting. Our main findings were a decreased RV EF, RV dilatation in systole, increased SV and RV hypertrophy, and signs of pulmonary hypertension in one patient. CMR plays an important role in the evaluation of the right chambers, especially in situations in which echocardiography is limited . CMR is SCD is an important cause of morbidity and mortality worldwide, causing damage and dysfunction in multiple organs, including the heart. Cardiac dilatation, which has been reported previously in patients with SCD, is due in part to the anemia underlying this disease but may be compounded by other factors, possibly leading to unique cardiomyopathy . Our LV In this study, we used CMR to evaluate myocardial iron loading and regional fibrosis using the LGE technique, two factors that may explain the presence of cardiomyopathy in patients with SCD. LGE is related to myocyte damage and can be observed in scar, focal or diffuse fibrosis, necrosis, inflammatory processes and tumors. The damaged myocardium retains the contrast for a longer time compared to normal myocardium and hyperintense areas, and can be seen 10–20 minutes after the administration of the contrast media (Gd). In SCD patients much of the abnormal cardiac assessment is not associated with cardiac iron deposition. However fibrosis can occur related to pulmonary hypertension, coronary disease, cardiac dilatation or hypertrophy.Myocardial iron loading increases ESV and reduces LV EF ,23, but Possible explanations for this low incidence may be that the areas of fibrosis resulting from microvascular sludge infarct may be too small to detect. More importantly, perhaps, is the reliance of LGE on the contrast between areas of normal and abnormal myocardium. A diffuse fibrotic abnormality throughout the myocardium would be difficult to assess. Sickle cell infarction may be a more diffuse process affecting the whole myocardium, and T1 mapping techniques may allow more accurate assessment.These T2* values apply only at a field strength of 1.5 T, and the relaxation parameters differ at higher field strengths, such as 3 T, which are becoming more widely available for clinical scanning. We measured myocardial T2* values in the interventricular septum and used them to assess global myocardial iron loading. Although this approach provides an indirect measurement of RV iron, direct measurement of T2* in the free RV wall is not robust because the myocardium is very thin, close to the chest wall, and susceptible to artifacts.CMR enables accurate assessment of myocardial iron levels and the detection of even very small areas of focal fibrosis using the LGE technique. However, such abnormalities are not common findings in patients with SCD. The significantly different ventricular function seen in patients with SCD compared with truly normal subjects suggests that changes in RV and LV function may not be due to anemia alone. Future studies are necessary to confirm this association.CMR: Cardiovascular magnetic resonance; ECG: Electrocardiography; EDV: End-diastolic volume; EF: Ejection fraction; ESV: End-systolic volume; FISP: Fast imaging with steady-state precession; FOV: Field of view; LIC: Liver iron concentration; LGE: Late gadolinium enhancement; LV: Left ventricle; PH: Pulmonary hypertension; ROI: Region of interest; RV: Right ventricle; SCD: Sickle cell disease; SV: Stroke volume; T: Tesla; TE: Echo time; TM: Thalassemia major; TR: Repetition time; T2*: T2 star.FPJ and JLF have received speakers’ honoraria from Novartis and performed advisory board work for Novartis.FPJ and JLF participated equally in the study design, data acquisition, and drafting of the manuscript; GMC, CMAOL, MU, DBPL, CASC, CLCL, and VLRP drafted the manuscript; SRS acquired data; TTAK performed the statistical analysis; EM conceived and co-designed the study, and is responsible for the final manuscript. All authors read and approved the final manuscript.


To determine whether the extent of myocardial fibrosis by late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), and echocardiographic ventricular dyssynchrony can independently predict response to medical therapy in patients with newly-diagnosed idiopathic dilated cardiomyopathy (DCM).established cardiomyopathy, and did not characterise patients early in the disease course and may not have included those with significant improvement in LV function soon after diagnosis. Hence, the degree of myocardial fibrosis and ventricular dyssynchrony at initial presentation, and their role in perpetuating left ventricular (LV) dysfunction in DCM remains unclear. We hypothesised that extent of myocardial fibrosis by the LGE-CMR technique and echocardiographic ventricular dyssynchrony are independent predictors of failure of improvement in LV function in new-onset DCM.Myocardial fibrosis and ventricular dyssynchrony are frequent findings in DCM. Although previous studies have reported poor prognosis with the presence of myocardial fibrosis in DCM, they focussed on patients with Patients with a new diagnosis of DCM (LV ejection fraction (EF) ≤45%) made within the preceding two weeks were recruited. Patients underwent LGE-CMR, echocardiography, 6-minute-walk testing, cardiopulmonary exercise testing, and blood sampling for measurement of serum NT-pro-BNP concentration at baseline. Baseline patient characteristics were compared with a cohort of healthy volunteers. Myocardial fibrosis by LGE-CMR was identified by experienced observers blinded to patient outcome, and was quantified by planimetry for calculation of fibrosis mass. LV systolic function was reassessed after 5 months optimal medical therapy.Sixty-eight patients with DCM and 19 healthy volunteers were studied. DCM patients were studied a median 12.5 days following diagnosis. Compared to healthy controls, DCM patients exhibited poorer functional capacity, higher serum NT-pro-BNP concentration, and greater inter- and intraventricular dyssynchrony. Twenty-four percent of DCM patients exhibited LGE at diagnosis, whereas no LGE was observed amongst controls. Within DCM patients with LGE, the mean fibrosis mass was 2.2±1.3g. On multivariate analysis, strain dyssynchrony index, and fibrosis mass were independent predictors of change in LVEF over time (p≤0.001) (Table The extent of myocardial fibrosis is a powerful predictor of a negative response to medical therapy in new-presentation DCM, and LGE-CMR may thus be an important risk-stratifying investigation in these patients. Accurate risk stratification may permit more targeted pharmacological and device therapies for patients with newly-diagnosed DCM.


This study evaluates whether integration of scar tissue into a patient specific heart model derived from Magnetic Resonance images is feasible.Treatment of coronary artery disease can only be effective if myocardial tissue can be identified, that is still viable. To localize scar tissue in relation to the coronary vessels would therefore be desirable for interventional guidance. The aim of this study was to evaluate 1) whether integration of scar tissue into a patient specific heart model derived from Magnetic Resonance (MR) images is feasible and 2) whether this patient specific heart model allows for accurate assessment of the amount of myocardial scar compared to conventional manual infarct sizing.20 patients with clinical indication for viability testing (EF 47±13%) were investigated on a 1.5 Tesla MRI . Images using a free-breathing 3D-wholeheart balanced TFE sequence triggered to end-diastole were acquired. 10 minutes after injection of a contrast agent  delayed enhancement (DE) images were acquired using a 3D inversion recovery sequence. Fully automatic segmentation of the heart and great vessels was performed using a comprehensive surface model . In addition, information of scar tissue was merged fully automatically from 3D-DE sequence into the segmented whole heart model. Finally, an automatic signal intensity threshold for scar identification was determined. Infarct size and end diastolic left ventricular (ED-LV) volume derived from this model were compared to conventional manual assessment of infarct size and LV volume.11 Patients had a chronic occlusion of the right coronary artery (RCA), 3 patients of the left circumflex (LCX) and 6 patients of the left anterior descending artery (LAD).Integration of viability information into a patient specific heart model was feasible in all cases with identical location of scar tissue compared to DE images.Infarct size averaged 19±15 g by manual tracing and 15±14 g by automatic segmentation . Location of scar tissue was identical between the two analysis methods for all cases.ED-LV volume was 151±14ml by manual assessment and 153±16ml by automatic segmentation .A cardiac model with integrated scar tissue information derived fully-automatically from a 3D whole heart MR acquisition as well as a 3D DE-data set is feasible and allows for precise localization and determination of the amount of myocardial scar.No funding.


The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction.Forty-six consecutive patients with acute myocardial infarction underwent CMR  including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic).Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035).STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique. The ability of magnetic resonance (MR) techniques to assess myocardial infarction has attracted the interest of cardiovascular researchers from the very beginning of cardiovascular MR (CMR). The behavior of acute myocardial infarction (MI) in dogs was described by Higgins as early as 1983 and both T1 and T2 were found to increase after coronary occlusion , which iA new approach for the visualization of myocardial edema in humans was introduced in 1996. In their work, Simonetti adapted the short time-from-inversion inversion recovery (STIR) black-blood technique for cardiac applications  and showSince STIR was perceived as a T2-weighted technique, several other publications subsequently investigated alternative T2 techniques to assess myocardial edema. Some authors speculated that the hyper-intense area on T2-weighted techniques represents the area at risk, and several animal studies support this concept ,8.Edema imaging has been shown to be also useful in other acute myocardial diseases, such as transplant rejection , myocardThe centers involved in these studies have translated the results from their research into their clinical practice, whereas some other centers aiming to do the same have experienced major discrepancies between their findings with T2-weighted techniques and clinical status of their patients. Specifically, a large prevalence of image artifacts and a significant variation in results depending on the choice of pulse sequence parameters has been reported , leadingWith this discussion in mind, we set to investigate if the practice to use STIR for the detection of myocardial edema in both clinical and research settings was justified. The aim of this study was therefore to review the technical principles behind STIR, and to assess the diagnostic accuracy of STIR in patients who underwent CMR in both the acute and chronic stages after MI. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction.Over a period of 14 months, 46 consecutive patients with acute first MI were prospectively enrolled to undergo CMR within the first week and at 6 months after MI at the Leeds General Infirmary, Leeds, UK. Exclusion criteria included clinical instability and the normal contraindications to CMR or the administration of gadolinium (Gd) contrast; no other exclusion criteria were applied. The local ethics committee approved the study, and written informed consent was obtained from all patients.CMR studies were performed on a 1.5 Tesla clinical MR system  with a 5-element cardiac phased-array coil. The imaging protocol included cine, STIR, and LGE imaging at standardized apical, mid-cavity, and basal short-axis levels  coveringAll images were acquired with identical geometric parameters  during end-expiration breathhold period. For cine imaging, a balanced steady-state free precession (SSFP) pulse sequence was used . For STIR, we used a triple-IR black-blood turbo-spin echo pulse sequence with inversion time (TI) 180 ms, TSE factor 32, bandwidth 504 Hz, half scan factor 0.65, TE 100 ms, TR 2 RR intervals for heart rates ≤ 80/min or 4 RR for heart rates > 80/min, coil sensitivity-based homogeneity correction (CLEAR), and 2 signal averages. Twelve minutes after intravenous application of a standard MRI contrast agent , 4 test scans were performed with increasing TI, before definitive LGE images were acquired with an IR-prepared gradient echo technique  using the TI that allowed for the best nulling of normal myocardium.Offline image analysis was performed with dedicated software  by one observer  blinded to infarct age and location. Figure All images were analyzed on a segmental and per-patient basis. If segments were considered uninterpretable, they were excluded from the analysis. LGE data of a subset of the patients have been used in previous publications ,20. InfaContinuous variables are expressed as mean ± standard deviation. Results from STIR and LGE analysis were compared using Student's t test. A p-value < 0.05 was considered significant. All analysis was performed using STATA version 10 .Forty-six consecutive patients  were prospectively studied in the acute stage (4 ± 1 days). Thirty (65%) of these were available for follow-up CMR at 6 months (196 ± 39 days). On ECG, localization of infarct was anterior in 44%, inferior in 54%, and posterolateral in 2%. Most cases (93%) presented with ST elevation. Creatine kinase (CK) levels were 1875 ± 1966 U/l (range 344 to 11719 U/l). 63% of patients had received revascularization therapy, which was successful according to clinical and ECG criteria in 47% of cases.STIR Image quality was good in 97.8% of segments (720/736) and was uninterpretable in only four segments (0.5%) in the acute stage, and good in 98.3% (472/480) and uninterpretable in four segments (0.8%) at 6 months. The uninterpretable segments were excluded on the basis of artifact. LGE image quality was good in 98.5% of segments (725/736) and interpretable in all segments at the acute stage. At 6 months LGE image quality was good in 95.8% of segments (460/480) and interpretable in all segments.Hyperintense myocardial segments were present in all subjects on STIR images acutely and corresponded to the vascular territory downstream of the occluded coronary artery at angiography Figure . At the The distribution of the segments with hyperintensity on STIR imaging and LGE can be seen in Figure Tables On a segmental basis, STIR differentiated acute from chronic infarcts with a sensitivity of 95% by both methods and a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. On the STIR images at six months, by visual assessment, three patients had STIR segments exhibiting hyper-intensity; by semi-quantitative assessment, four patients had STIR positive segments. In the three patients with persistent hyper-intensity on visual assessment, the hyperintense segments correlated with infarcted segments, and had been hyperintense at the acute stage. Potential reasons for persistent myocardial oedema could include increased wall stress and/or residual/recurring ischemia, alterations in drainage of the infarcted segments as a result of vessel damage or continuing tissue repair. In all cases the number of hyperintense segments was less than at the acute stage Figure . In the In order to compare samples from data that were not interdependent, cases were split into a chronic group (those cases where a follow-up CMR was available) and an acute group . Comparing 16 acute and 30 chronic infarcts from 46 patients, acute MI was identified with a sensitivity of 100% for both methods and a specificity of 90% and 87% for visual assessment and semi-quantitative assessment, respectively.Looking at all cases, 50 segments (7%) with hypoenhanced cores were seen on LGE images. On STIR imaging, 35 segments (5%) had hypointense cores. These segments matched in 91% of STIR images (31 cases). In the other cases, there were 4 segments on STIR imaging without matching LGE hypoenhancement, and 19 segments with hypoenhancement on LGE without corresponding STIR hypointensity. Hypoenhanced or hypointense cores were only found in acute cases.Our study shows that STIR imaging with appropriate pulse sequence parameters allows for visualization and semi-quantitative assessment of myocardial edema due to acute myocardial infarction with high diagnostic accuracy.The results of our study demonstrate the high image quality that can be achieved if a STIR sequence with appropriate pulse sequence properties is available. In our patients, we could not only assess transmurality of myocardial edema, but also clearly visualize hypointense cores within the edematous zone, a phenomenon that is related to hypoenhanced cores on LGE images ,22, probThis study confirms the high accuracy of STIR for differentiating acute from chronic cases of myocardial infarction that was first reported in the study by Abdel-Aty et al.  In contrThe increase in T2 associated with edema in acute MI is relatively small 25), and estimated to be on the order of 25-50% for T2 in range 45-50 ms for normal myocardium and 60-65 ms for acute MI [, and estThe STIR technique is based on a double-inversion recovery black-blood turbo spin echo  pulse sequence, into which a third 180° inversion pulse is integrated. The specific feature of this third inversion pulse is its relatively short TI (140-180 ms), which leads to a suppression of the signal from fatty tissue and from anything else with a T1 relaxation time of approximately 200-250 ms. As illustrated by Dwyer et al in 1988 , the secWhile these theoretical considerations clearly show that the STIR pulse sequence is favorable for the visualization of myocardial edema, at the moment the theoretical advantages are not realized in all CMR centers. A possible reason for this might be the lack of standardization of STIR pulse sequence parameters. From our experience there are numerous pulse sequence parameters in STIR that need to be set appropriately in order to optimize image quality and maximize the edema contrast. The list of these parameters includes, among others, timing and design of STIR and black-blood inversion pulses; quality of TSE read-out pulses; bandwidth; and slice thickness. Dwyer et al. also addressed the importance of allowing a sufficient repetition time (TR), when they systematically investigated signal evolution in STIR and predicted peak T1 values for additive T1 and T2 behavior at a given TR . In pracOne concern in relation to STIR imaging that is frequently raised is the fact that slow-flowing blood in the ventricular cavity can give bright signal at the endocardial border. This can be mistaken for myocardial hyperintensity. In our study, we used cine images at the same spatial and temporal location as a reference for endocardial contour detection. This method effectively helps avoid confusion with intracavity signals.A number of other methods of T2 weighted imaging have recently been described including bright ,29 and dWhile our study shows the high value of STIR for the qualitative ("yes/no") detection of focal myocardial edema, this technique is limited as any other conventional MR technique in the way that it does not allow for absolute quantification of signal intensity. In other words, the identification of myocardial edema with STIR is based on its perceptible contrast to non-edematous myocardium rather than on absolute thresholds. Therefore, applications involving diffuse processes or serial follow-up (e.g. for the assessment of inflammatory activity) should benefit from the use of alternative MR strategies enabling absolute signal quantification such as T1 mapping  or T2 maCMR using STIR enables the detection of infarct-related myocardial edema with high spatial resolution and high diagnostic accuracy. STIR imaging possesses unique properties beyond T2-weighting and fat suppression, and should be regarded as an optimized edema-weighted technique rather than a purely T2-weighted method. CMR centers and individuals interested in the use of STIR should compare their results to those of other centers in order to optimize their protocols, and should not settle for sub-optimal image quality.STIR: Short inversion time inversion recovery; CMR: Cardiovascular magnetic resonance; LGE: Late gadolinium enhancement; MI: Myocardial infarction; MR: Magnetic resonance; Gd: Gadolinium; LV: Left ventricle; SD: Standard deviations; CK: Creatine kinase; MSI: Myocardial salvage index; TSE: Turbo spin echo; TI: Inversion time.The authors declare that they have no competing interests.DOH performed all MRI data analysis and drafted the manuscript. JPR provided advice on the STIR signal behavior. TK and FB helped to design the study. MS and SP supervised patient recruitment and MRI data acquisition. DM recruited the patients, performed the MRI data acquisition, and drafted the manuscript. All authors read and approved the final manuscript.


Data are presented as mean±SD and differences compared with the two-tailed paired Student’s t-test.A saturation-recovery gated-segmented cine SSFP sequence, similar to the multi-contrast late enhancement imaging method , providesequence  calculat1-mapping (end-diastole) are shown in Fig. 1 mapping  and is significantly correlated between methods (p<0.01)  with negligible bias  and conventional T1-mapping and provides sufficient temporal and spatial resolution for end-systolic RV imaging.CLAIR yields similar LV myocardial contrast concentration and ECVF in the LV to TCIHR.Alberta HEART Team Grant.


Left ventricular ejection fraction (LVEF) is a strong predictor of subsequent cardiovascular events in patients with ischemic and non-ischemic cardiomyopathy. CMR is an excellent technique for assessment of LVEF as well as for the detection of myocardial scar. We sought to evaluate if the presence of myocardial scarring in non-ischemic cardiomyopathy could be an important predictor of cardiovascular events.Inclusion criteria were absence of coronary artery disease, a diagnosis of cardiomyopathy and an LVEF ≤ 45%. Patients with a diagnosis of infiltrative disorders, hypertrophic cardiomyopathy, or tachycardia-induced cardiomyopathy were excluded. A total of 132 patients (with greater than 12 months follow up) were analyzed. Imaging was performed on a 1.5 Tesla Avanto, or 3.0 Tesla Verio MRI scanner . Cine images were performed using a steady state free precession pulse sequence. Delayed enhancement (DE) CMR was performed 10 minutes after administration of 0.15 mmol/kg Gadopentetate Dimeglumine  with typical in-plane resolution 18 x 2.0 mm, slice thickness 6-7 mm. LV and RV volumes and EF were analyzed by manual planimetry of endocardial contours during end-diastole and end-systole. DE-CMR images were analyzed to identify hyperenhanced myocardium . The primary outcome was a combination of hospitalization for heart failure, LV assist device (LVAD) implantation, cardiac transplant, or death. Adjusted Kaplan-Meier curves were constructed for groups with and without scar by CMR with p<0.05 considered significant. Multivariate logistic regression analysis was performed.Patient's demographics are shown in table. All baseline demographic data were similar between patients with and without scar by CMR. The adjusted event-free survival rate was significantly lower for patients with scar compared to patients without scar by CMR at 2-years (p=0.03) (graph). Mean scar burden was 3 ± 8% of LV. On multivariable analysis, the presence of scar was an independent predictor of events, HR 2.5, but LVEF was not.In non-ischemic cardiomyopathy the presence of LV scar measured by DE-CMR is a stronger predictor of cardiovascular events than LVEF.Research grant from Siemens.


The concept of “diastolic” heart failure grew out of the                    observation that many patients who have the symptoms and signs of heart failure                    had an apparently normal left ventricular (LV) ejection fraction. Thus it was                    assumed that since systolic function was “preserved” the problem                    must lie in diastole, although it is not clear by whom or when this assumption                    was made. Nevertheless, many guidelines followed on how to diagnose                    “diastolic” heart failure backed up by indicators of diastolic                    dysfunction derived from Doppler echoardiography. Diastolic heart failure is                    associated with a lower annual mortality rate of approximately 8% as compared to                    annual mortality of 19% in heart failure with systolic dysfunction, however,                    morbidity rate can be substantial. Thus, diastolic heart failure is an important                    clinical disorder mainly seen in the elderly patients with hypertensive heart                    disease. Early recognition and appropriate therapy of diastolic dysfunction is                    advisable to prevent further progression to diastolic heart failure and death.                    There is no specific therapy to improve LV diastolic function directly. Medical                    therapy of diastolic dysfunction is often empirical and lacks clear-cut                    pathophysiologic concepts. Nevertheless, there is growing evidence that calcium                    channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide                    donors can be beneficial. Treatment of the underlying disease is currently the                    most important therapeutic approach.                             Heart failure is most commonly associated with impaired LV systolic function.                However, as many as 30-40% of all patients with typical symptoms of congestive heart                failure, have a normal or slightly reduced ejection fraction. In these patients,                diastolic dysfunction is implicated as a major contributor, if not the primary cause                of congestive heart failure , 2. The             Primary diastolic dysfunction is typically seen in patients with hypertension and or                restrictive cardiomyopathy but can also occur in a variety of other clinical                disorders and has a particularly high prevalence in the elderly population , 4.                Although diastolic heart failure is common in clinical practice worldwide, its                existence has been questioned for several reasons . Firstly            Doubts regarding diastolic heart failure are cast especially because the diagnosis of                heart failure is partly clinical and prone to error. When the left ventricular                ejection fraction is low the diagnosis of heart failure is seldom                questioned-clinicians seem more willing to accept a diagnosis of systolic heart                failure. Fortunately the advent of biomarkers such as plasma B-type natriuretic                peptides should help confirm the presence of heart failure in patients with                suspected diastolic heart failure.            A second area of controversy is that while investigators may agree that some patients                with heart failure do have a normal ejection fraction, they doubt if the underlying                mechanism is truly left ventricular diastolic dysfunction, as implied by the term                diastolic heart failure. Some of these patients have subtle abnormalities of                systolic function . In some                case series the relations between left ventricular pressure and volume on cardiac                catheterization do not conform to a classical pattern of diastolic dysfunction                    . The evi                            The patho-physiology of diastolic heart failure is characterized by a low cardiac                output that results typically from a ventricle that has thick walls but a small                cavity (increased left ventricular mass/volume ratio) . When th                            The symptoms , signs , and radiographic evidence  of heart failure                (HF) occur with equal frequency in patients with diastolic heart failure when                compared with patients with systolic heart failure . Therefo                                It is now clearly recognized that all patients with HF have abnormalities in both                systolic and diastolic function. However, the coexistence of these functional                abnormalities does not necessarily mean that SHF and DHF are part of a single                continuum. There are significant differences between SHF and DHF that justify their                separation into two different groups.            There is no doubt that a normal EF does not necessarily indicate the presence of                normal myocardial or even ventricular contractility , 16. The                            The diagnosis of diastolic heart failure requires three conditions to be                simultaneously satisfied : 1), Pre            Patients with shortness of breath on exertion, pulmonary rales, or gallop sound but                with near normal systolic function are usually diagnosed with DHF .            Several non-invasive techniques have been used for assessing diastolic function                    in patients with coronary, valvular or myocardial heart disease. The most                    commonly used methods are 2D- and Doppler-echocardiography, Doppler-tissue                    imaging, radionuclide ventriculography, MR myocardial tagging and MR imaging                        .                M-mode echocardiography has been used to assess the dimensional changes and                        its first derivates during diastolic filling. The presence of LV myocardial                        fibers oriented in the longitudinal direction and located in the trabecular,                        subendocardial, and papillary muscle regions has led to an increasing                        interest in echocardiographic assessment of the LV long axis function. As                        displacement of the atrioventricular plane towards the apex is a direct                        reflection of longitudinal fiber contraction, its measurement by M mode                        echocardiography provides additional information regarding global and                        regional systolic and diastolic function. As shown by Henein and Gibson,                        delayed onset of lengthening can effectively suppress early diastolic                        trans-mitral flow, even though the minor axis increases and mitral cusps                        separate normally .                    During the last 2 decades Doppler-echocardiography has emerged as an                        important clinical tool providing reliable and useful data on diastolic                        performance. Three different approaches are routinely used in the assessment                        of diastolic dysfunction: measurement of trans-mitral and pulmonary venous                        flow as well as intra-ventricular filling patterns (Doppler flow                        propagation) .                    The trans-mitral velocity pattern remains the starting point of                        echocardiographic assessment of LV diastolic function; since it is easy to                        acquire and can rapidly categorize patients with normal or abnormal                        diastolic function by E/A ratio (early to late filling velocity) , 21. In                     Color Doppler M-mode provides a unique window into the fluid dynamics of flow                        across the mitral valve. The speed of propagation is enhanced with rapid                        relaxation and LV suction. Clinical and experimental studies have                        demonstrated that the inverse correlation to t is relatively independent of                        left atrial pressure .                           Doppler tissue imaging yields information on intra-myocardial velocity,                        providing a unique insight into LV mechanics during iso-volumic contraction                        and relaxation. In normal persons the mitral annular motion is almost a                        mirror image of the trans-mitral flow pattern, but in patients with pseudo                        normal or restrictive filling pattern, annular motion is abnormally low,                        implying that it is relatively independent of preload , 25.                    It has been shown that relaxation velocities in the myocardium are inversely                        correlated with t, so that a non-invasively calculation of the time constant                        of relaxation seems to be possible , 27. Thr                                                    This technique has been shown to be of considerable use in the morphologic                        assessment of the heart, but functional assessment can also be obtained.                        However, their clinical relevance remains to be demonstrated . Additio                                                    This technique may be used to study the rapid filling phase of diastole, the                        duration of the iso-volumic relaxation phase, the relative contribution of                        rapid filling to total diastolic filling, and the relation between regional                        non-uniformity of left ventricular function and global filling properties                            . However                                                                            Cardiac catheterization with simultaneous pressure and volume measurements is the                    ‘gold’ standard for assessing LV diastolic function.                    Prerequisites are high-fidelity pressure recordings with simultaneous angio- or                    echocardiography or the use of the conductance technique. The rate of LV                    relaxation, rate and timing of diastolic filling as well as myocardial and                    chamber stiffness can be determined .                                                        Despite the large number of individuals suffering from diastolic dysfunction, there                is a paucity of recommendations available to help guide medical therapy in these                patients. The guidelines for the European Society of Hypertension (ESH) only briefly                touch on the subject of diastolic dysfunction and offer no specific recommendations                for its management, commenting that little information is available comparing the                effects of different antihypertensive agents on diastolic dysfunction . The Joi            Diastolic dysfunction may be present for several years before any symptoms occur and                may represent the first phase of diastolic heart failure. Thus, it is important to                detect diastolic dysfunction early and to start treatment before irreversible                structural alterations and systolic dysfunction have occurred.            Four treatment goals have been advocated for the therapy of diastolic dysfunction:                1), Reduction of central blood volume (diuretics); 2), Improvement of LV relaxation                ; 3), Regression of LV hypertrophy                ;                4), Maintenance of atrial contraction and control of heart rate (beta-blockers and                antiarrhythmic).            Diuretics are effective in reducing pulmonary congestion in patients with                    diastolic dysfunction, shifting the pressure-volume relation downwards. However,                    their positive effect on LV chamber stiffness is indirect, caused particularly                    by a reduction in systemic blood volume and the lowering of right atrial blood                    volume with a decrease in pericardial constraint. However, they must be used                    judiciously because the volume sensitivity of patients with diastolic                    dysfunction bears the risk that excessive diuresis results in sudden drop of                    stroke volume . The ste                                        Beta-blockers have long been theorized to provide benefit to patients with                    diastolic dysfunction. By slowing the heart rate to allow more time for LV                    filling and lowering blood pressure to improve LV compliance, beta- blockers can                    improve diastolic function .                                               Calcium channel blockade is thought to improve diastolic function by several                    mechanisms, including attenuating calcium homeostasis, reducing blood pressure,                    promoting LV hypertrophy regression, and slowing the heart rate . Benefit                                        ACE inhibitors and ARB’s show not only an effect on blood pressure but                    elicit a direct effect on the myocardium via the local renin-angiotensin system.                    These effects are essential for the regression of LV hypertrophy, and the                    improvement in the elastic properties of the myocardium , 51. Sev                                        Digitalis should not be used in patients with diastolic dysfunction, except in                    those with atrial fibrillation. When atrial fibrillation occurs, restoration of                    sinus rhythm is mandatory and is best achieved with electric conversion. For                    prophylaxis of recurrence, beta-blockers, especially sotalol, which exerts a                    class III antiarrhythmic effect and amiodarone are the most suitable.


To determine the reproducibility of axial versus short axis methods for measurement of right ventricular volumes and ejection fraction (RVEF) in adults after Mustard palliation for complete transposition of the great arteries (TGA).The most common cause of a systemic right ventricle is atrial redirection surgery (Mustard repair) in the setting of complete TGA. Decreased RVEF is common and is a predictor of morbidity and mortality. Cardiac magnetic resonance (CMR) cine imaging is the reference standard for assessment of right heart size and function. However, the optimal method of RV planimetry using CMR in patients with Mustard palliation for complete TGA remains unclear.Consecutive adult patients with atrial redirection surgery (Mustard procedure) for complete TGA were identified from an existing database and steady state free-precession cine images acquired on 1.5 T commercially available scanners were reviewed. To obtain RVEF, both end-diastolic volumes (EDV) and end-systolic volumes (ESV) were measured in two orientations, axial and short axis, by two experienced, independent readers who were blinded to other results. One reader reanalyzed the RV volumes and function ≥ 14 days after the first set of measurements. Intra- and inter-observer variabilities were determined using Bland-Altman analysis.A total of 25 patients  were identified  between 2008 and 2010. All images had sufficient quality for analysis. From the axial stack, the medians (interquartile ranges) were RVEDV 243cc (198-297), RVESV 142cc (101-174) and RVEF 44% (38-50). From the short axis stack, medians (interquartile ranges) were RVEDV 236cc (181-281), RVESV 127cc (90-157) and RVEF 44% (41-50). Volumes derived from short axis and axial stacks were significantly different (p=0.001 for RVEDV and p<0.001 for RVESV) but there was no statistical difference in RVEF between the methods (p=0.38). Bland Altman analysis for evaluation of intra and inter-observer variabilities are summarized in table Following Mustard palliation for complete TGA, RVEF measurements derived from axial and short axis stacks are similar, although both RVEDV and RVESV values are significantly higher based on the axial acquisition. Intra-observer measurements appear to be more reliable using the axial as compared with the short axis method.