Myocardial ischemia causes local edema. This has traditionally been studied using unenhanced T2-weighted MR imaging and contrast agent kinetic techniques. The aim was to study the acute T1 changes in-vivo in a novel closed chest animal model of myocardial ischemia.8 rats had an inflatable balloon coronary occluder surgically inserted via thoracotomy. They were allowed to recover for 10-14 days. MRI was performed to obtain baseline measurement of ventricular function. T1 mapping was performed using the Small-Animal Look-Locker Inversion Recovery (SALLI) technique.Without removing the animals from the scanner, the left coronary artery was occluded for 30 minutes. Myocardial function and T1 were measured during ischemia.MRI was performed on a whole-body 3.0-T MR unit with a 70 mm solenoid coil for rats. After generation of survey images and of a long-axis set of cine images, a stack of LV short-axis cine images was acquired to assess global function.Short axis SALLI MR imaging was performed using the same short axis orientation in the mid ventricle, distal to the occluder. Typical SALLI parameters were as follows: 64 x 64 mm field of view, 0.60 x 0.60 mm pixel size, 3.0 mm-thick sections, 5.2/2.2, 10° flip angle, 4000 ms AD, 4000 ms RD, 12 phases , temporal undersampling factor of two, three signals acquired, and acquisition time of 8 minutes 30 seconds per slice. SALLI imaging was repeated throughout the duration of ischemia.Images were transferred to a dedicated software package and T1 values were obtained for the left ventricle at baseline, and then for both the ischemic region of interest identified by myocardial hypokinesis and a remote zone unaffected by the coronary occlusion.All Rats had myocardial ischemia initially confirmed by ECG changes and ventricular arrhythmia. Fatal arrhythmia occurred in 2 rats.T1 values increased from a baseline of 1102 +/- 76 to 1290 +/- 47 (p < 0.001) within the first 10 minutes of ischemia. T1 values remained unchanged during 30 minute period of ischemia .In rats, myocardial T1 changes occur within 10 minutes of ischemia following coronary occlusion. T1 values subsequently remain unchanged throughout a 30 minutes period of ischemia.Unenhanced T1 mapping may provide a useful way to identify myocardial edema in acute myocardial ischemia/infarction, and may prove of value in studying the myocardial area at risk.Dr O h-Ici is funded through a "Sachmittelbeihilfe" granted to Dr Messroghli by the Deutsche Forschungsgemeinschaft. Drs Kuehne and Messroghli are supported through the German Federal Ministry of Education and Research .


We hypothesize that principal component analysis (PCA) can quantify dyssynchrony in myocardial strain in a data-driven, time-independent manner that does not require any subjective user assessments of strain data.Cardiac resynchronization therapy (CRT) is effective for selected heart failure (HF) patients, but is associated with a 30-40% nonresponse rate. Identification of CRT responders may be improved with myocardial strain imaging. The circumferential uniformity ratio estimate (CURE )Dyssynchronous HF was induced in canines (N=5) with tachycardia pacing and left bundle branch ablation (LBBB-HF), while synchronous HF with narrow QRS (NQRS-HF) was induced in canines with tachycardia pacing only (N=5). Four normal canines were also studied.2: interleaves=6, TR=17 ms, TE=1.9 ms, slice thickness=8 mm, excitation flip angle=15°, in-plane resolution=2.8 x2.8 mm and displacement-encoding frequency= 0.1 cycles/mm.Spiral cine DENSE MRI was performed on a 1.5 T scanner  in all 14 canines. 2D myocardial motion was tracked in a mid-ventricular short-axis plane from DENSE images acquired using the following parameters3 to calculate left ventricular (LV) circumferential strain (Ecc), and PCA was applied to the Ecc-time curves for a 24-segment LV model. Specifically, the LV Ecc curves were decomposed spatially into principal component basis vectors. The PCA-based metric for measuring LV dyssynchrony, termed First Order Regional Conformity Estimate (FORCE), was calculated as |sum(PCL1)|/sum(|PCL1|) where PCL1 represents the loadings of the first principal component basis vector. Both FORCE and CURE range from 0 (dyssynchrony) to 1 (perfect synchrony). The Kruskal-Wallis one-way ANOVA test was used to compare FORCE and CURE among the three groups in pairwise fashion.DENSE images were analyzed1 for the Ecc of example LBBB-HF and NQRS-HF canines. The PCL1 of LV Ecc in LBBB-HF canines varied widely over LV segments, whereas PCL1 showed little variation over LV segments in NQRS-HF and normal canines. As shown in Figure Figure PCA, using the promising new FORCE parameter, effectively and automatically identifies mechanical dyssynchrony in HF in a data-driven and completely time-independent fashion. Further clinical evaluation of FORCE for prediction of CRT response is warranted.This work was funded by the American Heart Association 12GRNT12050301 and NIH Heart, Lung and Blood Institute (NHLBI) T32HL007284.


A 43-year-old man from a rural area in Brazil presented to his physician with complaints of palpitations and lightheadedness, mainly on exertion. An electrocardiogram (ECG) showed right bundle-branch block (RBBB), left anterior fascicular block (LAFB), and a premature ventricular contraction (PVC) . EchocarChagas heart disease (chronic chagasic cardiomyopathy). Chagas heart disease (CHD) is the most common etiology of cardiomyopathy in Latin America, and a major cause of cardiovascular death among middle-aged individuals in endemic areas. CHD is also the most serious and frequent manifestation of chronic Chagas disease. It develops in 20%–30% of infected persons, usually 10–30 years after Trypanosoma cruzi contamination, and manifests as three major syndromes that often coexist in the same patient: arrhythmias, heart failure, and thromboembolism Arrhythmias are very common, of different types, and may cause palpitations, dizziness, syncope, and sudden cardiac death (SCD). Frequent, complex PVCs, including couplets and runs of NSVT, are a common finding on 24-h Holter monitoring and exercise testing. They correlate with the severity of ventricular dysfunction, but can also occur in patients with quite well preserved ventricular function. Episodes of NSVT are seen in approximately 40% of patients with mild wall motion abnormalities and in virtually all patients with heart failure, an incidence that is higher than that observed in other cardiomyopathies Heart failure is often a late manifestation of CHD. It is usually biventricular with a predominance of left-sided failure at initial stages and of right-sided failure at more advanced disease. Systemic and pulmonary embolisms arising from mural thrombi in the cardiac chambers are quite frequent. Clinically, the brain is by far the most frequently recognized site of embolisms (followed by limbs and lungs), but at necropsy, embolisms are found more frequently in the lungs, kidneys, and spleen Electrocardiographic alterations are varied, but the most common are RBBB, LAFB, PVCs, primary ST-T changes, Q waves, low QRS voltage, different degrees of atrioventricular block, and manifestations of sinus node dysfunction. All these alterations may be isolated or associated. The association of RBBB with LAFB strongly suggests chronic CHD in endemic regions On the chest radiography, cardiac size is normal in the initial stages of disease and even when multiple ECG abnormalities are present. The cardiac size may be slightly, moderately, or severely increased at later stages of CHD. In nearly half of the cases with heart failure, the manifestations of pulmonary congestion are poor or even absent Holter monitoring is an excellent method for investigating patients with CHD. It may be used to identify complex ventricular arrhythmias, diagnose transitory arrhythmias, and evaluate anti-arrhythmic therapy. The exercise testing evaluates the functional capacity of the patient, qualifies and quantifies PVCs, and may verify the efficacy of anti-arrhythmic drugs.T. cruzi antigens needs to be detected by at least two different serological methods  to confirm the etiological diagnosis.In patients with high suspicion of chronic Chagas disease or in those with a compatible clinical syndrome, because parasitaemia is scarce, the presence of immunoglobulin G (IgG) antibodies against T. cruzi infection includes a complete medical history and physical examination, and a resting ECG The initial evaluation of the newly diagnosed patient with chronic Recently, some of us used a rigorous multivariate analysis to develop a risk score for mortality prediction in 424 outpatients with CHD from a regional Brazilian cohort The clinical history, the ECG abnormalities, and the findings on echo, Holter, and exercise testing in the present case are characteristic of chronic CHD. Serological tests for Chagas disease were performed and gave positive results. According to the scoring system to determine the risk of death described above, this patient would receive a score of 8 points based on his sex (2 points), the presence of apical aneurysm (3 points), and the presence of runs of NSVT (3 points). This score puts him in the intermediate-risk category (risk of death in the next 10 years of 44%).The importance of having the results of a chest radiography on board, which was not done in this case, relies on the fact that the presence of cardiomegaly would add 5 more points to the patient's risk score, moving him to a higher-risk category. Of note, the combination of NSVT and LV systolic dysfunction in patients with CHD increase the risk of subsequent death by 15 times compared to patients without these abnormalities on Holter monitoring and on echocardiography Management of patients with CHD should focus on eradication of the parasite, which may halt disease progression, alleviation of symptoms of disease, and identification of patients at high risk of death, in order to implement strategies with the potential to reduce mortality. Regarding antitrypanosomal treatment, only two agents are currently available: benznidazole and nifurtimox. On the basis of the results of some observational studies, a panel of experts convened by the US Centers for Disease Control and Prevention in 2006 recommended that antiparasitic therapy should generally be offered to adults 19–50 years of age with mild to moderate cardiomyopathy Because some evidence suggests that mild segmental LV wall motion abnormalities are predictors of deterioration of ventricular function during follow-up The ethics committee of Anis Rassi Hospital approved this report and waived the need for informed consent.Clinical manifestations of Chagas heart disease are diverse and related to three major syndromes: cardiac arrhythmias, heart failure, and thromboembolism. Improved models for risk stratification are now available, and certain guided treatments may increase survival.Segmental or global left ventricular dysfunction and episodes of nonsustained ventricular tachycardia are independent, additive risk factors for overall mortality in Chagas cardiomyopathy.Although not supported by incontestable evidence, it is possible that patients with runs of nonsustained ventricular tachycardia on Holter/exercise testing, and asymptomatic or mildly symptomatic left ventricular dysfunction on echocardiography, derive some benefit from combined therapy with an angiotensin-converting enzyme inhibitor and amiodarone.T. cruzi infections or even with mild to moderate disease.Persistence of parasites and the accompanying chronic inflammation is the basis for the pathology in Chagas heart disease. Thus, unless proved otherwise by a randomized controlled trial, benznidazole or nifurtimox should usually be offered to patients <50 years old with presumably long-standing indeterminate The potential benefits of novel therapies  need assessment in prospective randomized trials. The best therapeutic strategy for patients with apical aneurysm not containing thrombus is unknown.


Objective. To investigate the ability of two-dimensional longitudinal strain echocardiography (2DST), to detect the early doxorubicin cardiotoxicity. Patients and Methods. The study included 25 children with newly diagnosed acute lymphoblastic leukemia (ALL) aged 5–15 years and 30 healthy control children. They had echocardiographic examination with conventional 2-dimensional (2D), pulsed tissue Doppler (PTD), and 2DST echocardiography before and within 1 week after doxorubicin treatment. Results. There was no significant difference in left ventricle (LV) systolic and diastolic functions measured by conventional 2-D and PTD echocardiography between patients and controls. However, there was significant decrease in LV global and peak systolic strain detected by 2-DST echocardiography in study group than control. After doxorubicin treatment, there was no significant difference in LV systolic and diastolic functions measured by conventional 2-D and PTD echocardiography than before treatment except for prolonged IVCT and IVRT, but LV global and peak systolic strain was significantly lower after treatment. Conclusion. 2-D longitudinal strain echocardiography was more sensitive than conventional 2-D and PTD in detecting the early LV doxorubicin-induced cardiotoxicity in children with ALL. Doxorubicin is one of the most effective available anthracycline chemotherapeutic agents that have been widely used in the treatment of pediatric malignancies. Its introduction has led to the successful treatment of childhood cancer with improved survival rates. Nearly two-thirds of survivors have one or more related chronic medical problems and may require multidisciplinary care . BecauseChronic dose-related cardiotoxicity is the most common and dangerous and can manifest as cardiac failure, months or even years after the completion of treatment and is thought to be related to myocardial toxicity . MultiplThe increase in prevalence of doxorubicin cardiotoxicity is partly due to improved diagnosis and partially owing to longer follow-up periods . To deteB mode images. Myocardial velocity and deformation imaging, namely, strain and strain rate imaging, have been demonstrated to have potential value for the quantification of global and regional systolic and diastolic myocardial function. It seems that regional dysfunction can be detected earlier than global dysfunction [The 2-dimensional strain echocardiography (2DSE) is a relatively new echocardiographic modality based on measurement of myocardial deformation using speckle-tracking from function . This miMore studies are needed to define the best predictive parameters for those patients at risk of developing LV dysfunction who might benefit from an early start of treatment , 12. TheA group of 25 children with newly diagnosed acute lymphoblastic leukemia between 5 and 15 years of age presented to the Hematology and Oncology Unit, the Pediatric Department, Faculty of Medicine, Tanta University, Egypt, who met the inclusion criteria, were included in the study from March 2008 to March 2010. Thirty healthy children of matched age and sex were studied as a control group.Newly diagnosed children with acute lymphoblastic leukemia confirmed by complete blood picture, bone marrow examination, and immunophenotyping by flow cytometry and fluorescence in situ hybridization (FISH) technique.Previous chemotherapy or radiotherapy, presence of any cardiac disease either congenital or acquired, any cardiac lesion detected in baseline echocardiography, any associated systemic disease that can affect the cardiac function, and/or medication that can affect cardiac function, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, or beta-blockers.All children subjected to full history taking, thorough clinical examination, complete blood picture (CBC), erythrocyte sedimentation rate (ESR), serum uric acid, and liver and renal function tests. All children underwent echocardiographic Doppler examination and measurement of troponin I (cTnI), and creatine phosphokinase CPK (MB) levels before and within 1 week of starting the doxorubicin treatment. All patients were subjected to the protocol of therapy in induction of remission which showed in Echocardiographic images were obtained using a Vivid 7 ultrasound machine . To avoid intraobserver variability, 2 examinations each time were performed by the same operator for each patient in 2 different settings within 2 days. All children were examined in a semi-supine, left lateral position and according to the recommendation of the American Society of Echocardiography . M-mode Pulsed tissue doppler imaging was done using pulsed wave DTI filters, with a sample volume 5.5 mm, and frame rates of greater than 150 fps were recorded. The baseline was adjusted to low-velocity range (−20 to 20 cm/s) with minimal gain setting. The sample volume was placed within the myocardium equidistant from the endocardial and epicardial borders. Effort was done to minimize the angles as much as possible. From the apical 4-chamber planes, using pulsed-wave TDI, the myocardial velocity curves of septal and lateral mitral valve annuli were recorded. The ECG was connected and traced simultaneously to define and to time the cardiac cycle events. The beginning of QRS complex was used as a reference point .s wave reflects the systolic function of left ventricle (LV). The e′/a′  ratio of mitral valve annulus reflects the diastolic function of LV. Isometric contraction time (IVCT) was defined as the time duration between the beginnings of QRS complex in the ECG to the beginning of DTI systolic (s) wave. Isometric relaxation time (IVRT) was defined as the interval between the end of s wave and the beginning of the e′ wave. At least 10 cardiac cycles were recorded from each site on a strip-chart recorder at a speed of 100 mm/s.The G), global peak systolic strain in 3 standard apical views, and segmental peak systolic strain in; basal, mid and apical segments of anteroseptal, anterior, lateral, posterior, inferior, and septal LV walls [Q analysis software Version 4.0.3  for processing , apical 4-chamber, and apical 2-chamber views, and parameters obtained represented the average of 10 cardiac cycles, with a frame rate of 65 fps, and all segmental data (17 segments) were represented. We used automated function imaging that enables only the assessment of longitudinal strain available in Vivid 7 ultrasound machine to measure average LV global peak systolic strain  activity level was measured by immunochemiluminometric assay , which have an upper reference limit of 5 ng/mL . All part-test, with P < 0.05 considered statistically significant. Wilcoxon's signed rank test was used to assess the normality of distributions of the data. The Bonferroni correction/adjustment procedure was done to avoid “significance” due to chance only, in multiple comparison with echocardiographic parameters. Correlation between variables was evaluated using Pearson's correlation coefficient [The power level of the number of cases in the study was more than 90%. Statistical analysis was performed with Statistical Package for Social Science (SPSS version 17). Data are presented as mean (±SD) values. Comparison between the studied groups was performed with Student's fficient .P < 0.001) while hemoglobin% (HB%), systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) were significantly lower in children with ALL than those in controls (P < 0.001).The demographics and clinical characteristics of children with ALL and the control group were shown in P < 0.05); however, the E/A (which represents the LV diastolic function) showed no significant differences between the 2 groups (P > 0.05). The table also showed that there were no significant differences in the tissue Doppler parameters: s, IVCT, e′, a′, e′/a′ ratio, and IVRT (P > 0.05). The global strain (G) of the LV was significantly lower in leukemic children than that in the control group (P < 0.05), and there was less significant decrease in the peak systolic strain in apical 2-chamber view (P < 0.05), while there was no significant change in the other views apical long axis and apical 4-chamber views (P > 0.05 for both views).Echocardiographic data of children with ALL and the controls before starting the doxorubicin treatment were shown in P < 0.05). However the s wave measured by the tissue Doppler showed no significant difference before and after treatment. Meanwhile the IVCT showed significant prolongation after treatment. On the other hand, the diastolic function of the LV showed no significant differences both by conventional and tissue Doppler data except for IVRT which showed significant prolongation after the treatment with doxorubicin (P < 0.001). In 2D longitudinal strain echocardiogram, the peak systolic and global strains showed significant reduction in the apical long-axis view .The echocardiographic examination data in the patient group before and after the doxorubicin treatment are shown in G) in the long axis view and both the cTn I and CPK (MB) level.Doxorubicin-induced cardiotoxicity is suggested to be through production of oxygen free radicals and highly reactive hydroxyl radicals and peroxynitrite which induce apoptosis and cardiac myocytes damage as the heart is particularly poorly protected against oxidative stress . Other ms wave, IVCT, e′ wave, a′ wave, e′/a′ wave, and IVRT, and lastly the 2D longitudinal strain echocardiography by assessment of LV longitudinal strain.Early detection of doxorubicin cardiotoxicity is of paramount importance as it allows the use of cardioprotective agents dexrazoxane or carvedilol. In the current study, 3 echocardiographic modalities were used to early detect the doxorubicin-induced cardiotoxicity: the conventional 2D Doppler echocardiography by measuring the fraction shortening as well as the E/A ratio, the pulsed tissue Doppler by measuring the The fraction shortening showed a tendency towards becoming statistical significantly higher in the patients group when compared to the control. This difference can be explained by the presence of associated anemia and tachycardia secondary to leukemia (hyperdynamic heart). After doxorubicin treatment, the FS showed significant reduction despite still being within the normal limits. This reduction was either due to the correction of anemia prior to stating the cytotoxic therapy or as a side effect of therapy with doxorubicin. However, FS has many limitations as regard to the difficulty in accurate measurement and being affected by preload, after load, heart rate, desynchrony, as well as myocardial contractility . The traThe pulsed tissue Doppler also showed no significant changes between the controls and the patients group and in the patient group before and after treatment except for the prolonged IVCT and IVRT after doxorubicin treatment which may indicate doxorubicin-induced impairment of LV relaxation and contraction. However, our findings disagreed with the work of Kapsuta et al. who found that the pulsed tissue Doppler was a useful sensitive method to detect subclinical myocardial damage in apparently healthy children who received moderate doses of anthracyclines for treatment of childhood malignancy . This diOn the other hand, the 2D longitudinal strain echocardiography was more sensitive to detect the early cardiac effects of leukemia and that of doxorubicin treatment, where there was significant reduction in the peak systolic stain in the apical long-axis view and in the global strain both between the patients group and the controls and in the patients group before and after doxorubicin treatment. Our findings agreed with a number of studies concerned with detection of cardiotoxic effects of doxorubicin and other anthracyclines. Migrino et al. studied doxorubicin-induced cardiotoxicity in 14 male Sprague-Dawley rats. They found that the global radial strain derived from 2-dimensional strain echocardiography was useful in the early detection of doxorubicin cardiac injury and that the reduction in radial strain was associated with the degree and the onset of histologic markers of doxorubicin-induced cardiomyopathy . Tsai etWhat makes 2D strain echocardiography more sensitive than pulsed tissue Doppler is because of lack of the tethering effects from other myocardial segments which could limit the ability of tissue Doppler imaging to quantify regional function. The pulsed tissue Doppler directly measures the regional function rather than tissue velocities, which are also influenced by contractile function of other myocardial regions due to tethering. This could limit the ability of tissue Doppler velocities to provide quantitative data on regional function. However, combining both techniques can give complementary results . However, marked angle dependency is a significant limitation of strain rate imaging, so that correct echo beam orientation is critical , 25.The study was performed before the induction phase and after the end of doxorubicin treatment. So the study did not check the late and chronic effects of doxorubicin treatment on the cardiac functions. The study also concentrated on the left side of the heart and did not evaluate the right side of the heart as well as for the pulmonary pressure. The study compared the 2D longitudinal strain echocardiogram with relatively older modalities that can assess the cardiac function. It did not compare the 2D longitudinal strain echocardiogram with cardiac magnetic resonance which is considered the gold standard for assessment of LV deformation. Also, there were many chemotherapeutic drugs used during the study. So, the cardiotoxic effects may be caused by doxorubicin or other cytotoxic drugs. However, due to ethical issues, we could not deprive a group of the patients from doxorubicin treatment to be included as a control group. The study also did not revise the effect of the cumulative doses of doxorubicin on 2D longitudinal strain echocardiogram. Another limitation of the study is that echocardiograms were not blindly read, so this could have induced some bias.The 2D longitudinal strain echocardiography was more sensitive than conventional 2D and pulsed tissue Doppler echocardiography in detecting the early LV doxorubicin-induced cardiotoxicity in children with ALL. This is especially important to select the patients who need prophylactic therapy against doxorubicin-induced cardiotoxicity.


Left main stem (LMS) disease is found in approximately 5% of patients with stable angina and in approximately 7% of patients presenting with an acute myocardial infarction. Accurate assessment of the degree of left main stem stenosis has important prognostic and therapeutic implications. Clinically, angiographic LMS stenosis of 50% or more is considered significant. However, it is not known how accurately myocardial perfusion imaging detects LMS disease at this severity threshold.1).1. To measure myocardial blood flow by CMR in patients with LMS stenosis of more than 50% on quantitative angiography in the CEMARC study  and blood flow reserve between territories supplied by the LMS and remote territories.2. Following motion correction a circular ROI was selected in the left ventricle to measure the arterial input function. MBF maps were created by model-free analysis; myocardial ROIs were drawn on these maps, one in the LMS territory (ROI1: LAD+LCX) and one in a remote region (ROI2:RCA). MBF for these ROIs was calculated using the Fermi model3. Statistical calculations were performed using SPSS.Nine patients from the CEMARC study who were found to have significant LMS disease on quantitative coronary angiography underwent perfusion-CMR on a Philips 1.5 T Intera system. Myocaridal perfusion imaging was performed every heartbeat during the first pass of 0.05 mmol/kg gadolinium chelate using a T1-weighted fast (spoiled) GE sequence. Stress perfusion imaging was performed using intravenous adenosine infused for 4 minutes (140mcg/kg/min). Perfusion-CMR data were post-processed off-line using the software PMIOf the 9 datasets analysed, the results revealed significant differences p<0.001) in myocardial perfusion seen in LMS diseased territories (ROI1) compared to normal segments (ROI2), Figure  in myocaThis study demonstrates reduced myocardial blood flow reserve in patients with LMS stenosis of 50% or more, although reductions are subtle.


Current morphologic left ventricular (LV) non-compaction (LVNC) criteria seem to be still insufficient. The prevalence of borderline degree of LV hypertrabeculation is far more frequent than initially expected. LV twist and strain values are proposed as potential new functional parameters supplementing the classic morphologic LVNC criteria. The aim of this study was to assess diagnostic utility of LV twist and strain analysis in detecting regional myocardial dysfunction in patients with LVNC.Cardiovascular magnetic resonance (CMR) examinations were performed in 52 patients with LVNC and 28 healthy controls with LV hypertrabeculation. LVNC was diagnosed according to CMR diagnostic criteria published by Petersen and coworkers: a two-layered structure of the LV wall, with the end-diastolic ratio of non-compacted to compacted layer >2.3. LVNC patients with concomitant congenital heart disease, significant valvular disease or coronary artery disease were excluded from this study. Using a dedicated feature tracking software  CMR cine-images were analyzed to measure LV rotation/twist and circumferential strain. Standard 17-segment model of LV was used. Twist and strain values below or above two standard deviations of the average values in controls were considered abnormal.In 52 patients with LVNC mean number of affected LV segments was 8.7±3.0, mean maximal end-diastolic ratio of non-compacted to compacted layer was 2.9±0.9, mean trabeculated LV mass was 27.1±8.0% of the global LV mass. Patients with LVNC were divided into two groups: with LV ejection fraction (EF)≥50% (n=25) and EF<50% (n=27).LV twist values in LVNC patients with EF<50% were significantly reduced compared with LVNC patients with EF≥50% . Mean LV twist values in LVNC patients with EF≥50% and controls were not statistically different. However, in 7 (28%) patients with LVNC with EF≥50%, LV twist values were paradoxically increased. LV global circumferential strain values were significantly reduced in LVNC patients with EF<50% compared with LVNC patients with EF≥50% . However, LV global circumferential strain values were not significantly different between LVNC patients with EF≥50% and controls.LV twist is significantly reduced in LVNC patients with decreased EF. However, in some LVNC patients with preserved EF, LV twist is paradoxically increased as a possible compensatory mechanism to maintain LV output. LV circumferential strain values, although reduced in LVNC patients with decreased EF, are not useful to discriminate between LVNC patients with preserved EF and controls.Self-funded.


To characterize the range of ventricular size and function evaluated by steady-state free precession (SSFP) cine cardiac magnetic resonance (CMR) in functional single ventricle (FSV) patients late after Fontan operation and to identify factors associated with FSV dysfunction.Ventricular size and function is important in patients with FSV after Fontan and adverse remodeling has been associated with poor clinical outcomes. Due to the limitations of echocardiography and other noninvasive techniques, CMR remains the gold standard for the assessment of ventricular size and function. However, the range and distribution of FSV size and function in this population has not been characterized in a large cohort across a broad range of ages using contemporary SSFP techniques.i, ESVi, and ventricular mass index (Massi) were indexed to BSA1.3. Other clinically relevant data including demographic information, cardiac diagnoses, surgical history, and clinical symptoms and outcomes were recorded. Ventricular dysfunction was defined as ejection fraction (EF) ≤ 45% and variables associated with FSV dysfunction were analyzed.All patients at our center following a Fontan operation who had a CMR study from 4/2002 to 1/2011 were retrospectively reviewed. In patients with multiple CMR studies, the most recent study was used for analysis. If 2 ventricles were present and connected to the systemic circulation, the end-diastolic (EDV) and end-systolic (ESV) volumes were summated to describe total effective volumetric and function data. Examinations were performed on a 1.5 T scanner using a standardized, previously published imaging protocol. Combined EDVp=0.026), older at time of CMR , and had higher frequencies of ≥moderate atrioventricular valve regurgitation , non-sustained ventricular tachycardia , and stroke .Of the 261 patients who had a CMR study after the Fontan operation, 46 (18%) had incomplete data due to metallic artifacts from coils and other devices. The median age at CMR of the remaining 215 patients was 18.3 years , age at Fontan 3.6 years , and the median time since Fontan was 14.6 years . LV morphology was present in 45% of patients, RV morphology in 30%, and biventricular in 25%. The lateral tunnel Fontan operation was performed in 70% of patients, right atrium to pulmonary artery in 21%, extracardiac in 5%, and right atrium to right ventricle in 4%. The medians, interquartile range (IQR), means, standard deviations (SD), and ranges of FSV size and function are summarized in Table This study provides the range and distribution of ventricular size and function in a large cohort of patients late after the Fontan operation using contemporary CMR techniques and demonstrates important variations in those patients with significant systolic dysfunction.None.


Within the extensive range of medical imaging methods used for cardiac analysis, T2-Weighed (T2W) Cardiac Magnetic Resonance (CMR) has been one of the most promising techniques for non-invasive edema quantification and IHD severity assessment. Many authors have suggested the importance of edema quantification in the prognosis of IHD patients and in the evaluation of expected ventricular function improvement after cursory percutaneous angioplasties (PTA)The aim of the present study is to determine the prognostic value of T2W-Turbo Spin Eco (T2W-TSE) when assessing presence and persistency of myocardial edema in order to obtain concrete outcome expectancies for IHD cases after percutaneous coronary intervention (PCI).The present is a prospective observational study in which 66 patients were analyzed with axial T2W dark blood CMR sequences for myocardial edema quantification within the first 7 days after reperfusion (<7days), obtaining a follow-up study 90 ± 4 days later. Two experienced observers with extensive knowledge in CMR imaging analysis  interpreted the studies focusing on the detection of myocardial infarct with edema, confirming the quantitative data obtained by the software cmr42. A paired 2-tailed Student's t-test was done for obtaining the correlation between myocardial salvage and theLVEF% ventricular function variable between the two observations.All T2W MR studies were considered readable and suited for diagnostic purposes. The evaluated patients were: 60 men (90.9%) and 6 women (9.1%) of 52 ± 12 years. For the group, a reduction in myocardial percentage edema at the follow up study does not predicts an improvement in ventricular function (positive LVEF%); moreover, neither the individuals with complete edema clearance, nor the subjects where edema persisted had a significant tendency of improving ventricular function after PCI. Therefore, IHD prognosis is likely to be more related to variables like infarct size, microvascular obstruction presence than it is to edema persistency or clearance per se.Among IHD patients, edema quantification  does not predicts for a significant increases of the ventricular function after coronary reperfusion. Nonetheless, T2W MRI is still a valuable tool for quantifying myocardial salvage when used in parallel to LGE sequences for infarct measurements. Infarct size and microvascular obstruction quantification in these terms are of great interest for complementing the generated data related to edema persistency and overall cardiac function.


Functional status/contractile behaviour of hibernating myocardium was analyzed objectively by analyzing the available quantitative parameters obtained on gated SPECT myocardial perfusion imaging (MPI) using Emory cardiac toolbox (ECTB) software.99Tc-Sestamibi MPI  who also underwent 18F-FDG Cardiac PET study for assessment of hibernating myocardium were included for analysis. Patients were divided in three categories based on summed rest score (SRS) obtained from ECTB software, depicting the extent of perfusion defects. In a study population matched for extent of perfusion defects, quantitative parameters obtained from ECTB software such as left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (EDV), left ventricular end systolic volume (ESV) and left ventricular stroke volume (SV) were compared between patients showing evidence of hibernating myocardium and patients showing no evidence of hibernating myocardium. Student ‘t’ test was applied on the given observations and a P-value <0.05 was considered as a significant difference between the means in two categories.In this retrospective study, 70 patients with perfusion defects on There was no significant difference in LVEF, EDV, ESV and SV measurements between those who demonstrate hibernating myocardium and those who show no evidence of hibernating myocardium across all the categories of patients. Few trends were evident in the present study in LVEF, EDV and ESV measurements i.e., fall in mean LVEF with increasing SRS and rise in mean EDV and ESV with increasing SRS.The findings were consistent with the nature of hibernating myocardium i.e., non-contractile and dysfunctional. The fall in the LVEF was suggestive of deteriorating myocardial function with increasing extent of perfusion defects. The increasing left ventricular EDV and ESV with increasing extent of perfusion defects was suggestive of rising incidence of gross morphological LV cavity dilatation or “Dilated ischemic cardiomyopathy” in these patients. Hibernating myocardium is a state of persistently impaired myocardial function due to reduced coronary blood flow that can be partially or completely restored to normal if the myocardial oxygen supply/demand relationship is favorably altered, either by improving blood flow and/or by reducing demand.676The concept of hibernation presupposed that a reduction in coronary blood flow was followed by a down regulation in cardiac function to a point at which the limited oxygen supply enabled the maintenance of the biochemical functions that sustained cell integrity. The hibeThe primarily clinical concept of myocardial hibernation subsequently merged with a number of experimental observations: (a) Regional myocardial function and blood flow are reduced proportionately during ischemia i.e., a state of perfusion-contraction matching (b) Metabolic parameters such as myocardial lactate consumption, creatine phosphate content and free energy change of ATP-hydrolysis recover toward their preischemic baseline values during ongoing ischemia, consistent with the idea that the reduced function is an adaptation to reduced blood flow. (c) An inotropic reserve persists in hibernating myocardium.The phenotype of hibernating myocardium, i.e., chronic, yet reversible contractile dysfunction in the setting of coronary artery disease could arise from either continued ischemia or from repetitive cycles of ischemia/reperfusion. HibernatSeveral non-invasive techniques have been developed to identify viable myocardium in the dysfunctional segments:18F-FDG cardiac PET.99mTc-Sestamibi.99mTc-Tetrofosmin.201Tl rest-redistribution technique.201Tl reinjection technique.Low dose dobutamine stress echocardiography.18F-FDG PET is the “most sensitive” marker for hibernating myocardium while Dobutamine stress echocardiography is considered to be the “most specific” marker. between individuals having evidence of hibernating myocardium and individuals with no evidence of hibernating myocardium.99mTc-Sestamibi MPI [18F-FDG cardiac PET study for the assessment of hibernating myocardium. Assessment was done visually by a single nuclear medicine physician and “Perfusion-metabolism mismatch” in any one segment on visual analysis was taken as the criterion for diagnosing hibernating myocardium.[A retrospective analysis was carried out on 70 patients with perfusion defects on mibi MPI  who alsoocardium.Patients were divided in three categories on the basis of summed rest score (SRS) depicting the extent of defects:SRS between 0 and 10.SRS between 11 and 20.SRS between 21 and 30.In this study population matched for the extent of defects, quantitative parameters such as LVEF, EDV, ESV and SV obtained from Emory Cardiac toolbox (ECTB) software were compared between patients showing evidence of hibernating myocardium and patients showing no evidence of hibernating myocardium Figures –3.99m Sestamibi (hexakis methoxy isobutyl isonitrile) MPI and 18- FDG (Fluoro deoxy glucose) cardiac PET study for assessment of hibernating myocardium (from January 2008 to March 2010 at our institute) were included in the study.All left ventricular failure patients irrespective of prior myocardial infarction, who underwent Tc-99mTc-Sestamibi. Images were obtained on Siemens dual head γ-camera (E cam) by Gated SPECT in supine position from RAO 45°to LPO 225°. The images were reconstructed into vertical long, horizontal long and short-axis slices. Quantitative parameters such as LVEF in percentage, EDV in ml, ESV in ml, SV in ml and SRS were obtained along with a polar map depicting “17 segment model” using ECTB software using a semi-automatic approach. The role of operator was limited to defining correctly the left ventricular endocardial and epicardial borders.Rest myocardial perfusion scintigraphy was performed 1 hour following intravenous administration of 18F-FDG, which was administered 1 hour after oral glucose load of 75 g, a regional cardiac PET study was acquired using a whole-body full-ring dedicated GE Advance BGO PET camera. Images acquired were processed into short axis, vertical long axis and horizontal long axis. A polar map depicting “17 segment model” was also generated.On another day (within 3 days of the MPI study), 90 minutes after intravenous injection of Assessment of hibernating myocardium was done visually by single physician. “Perfusion-metabolism mismatch” in any one segment on visual analysis was taken as the sole crieterion for hibernating myocardium.t’ test” was applied to the data in each category for each parameter and P-value <0.05 was considered as significant difference between the mean values.Mean values and standard deviations of the quantitative parameters in different categories were calculated. Unpaired “Student ‘Results are shown in Tables 5To summarize the overall results, the following observations were made:There was no significant difference in LVEF, EDV, ESV and SV measurements between those who demonstrate hibernating myocardium and those who show no evidence of hibernating myocardium across all the categories of patients.Few trends were evident in the present study in LVEF, EDV and ESV measurements:Fall in mean LVEF with increasing SRS.Mean EDV and ESV rising with increasing SRS.et al, and Rahimtoola et al, have described hibernating myocardium as non-contractile and dysfunctional.[In review of the literature, Schinkel nctional.7 Our stuLVEF was found to be inversely proportional to the SRS i.e., systolic dysfunction was found to increase with increase in extent of perfusion defect.et al,[In their study Carluccio E et al, have preFindings of our study are in agreement with the above study. Our study shows increment in left ventricular systolic and diastolic volumes or left ventricular cavity dilatation with increase in extent of perfusion defects.The quantitative parameters obtained didn’t show any significant difference in any of the categories of patients. These findings were consistent with the nature of hibernating myocardium i.e., non-contractile and dysfunctional myocardium.The trends in the LVEF, EDV and ESV were suggestive of deteriorating myocardial function with increasing extent of perfusion defects.The increase in left ventricular EDV and ESV with increasing extent of perfusion defects was suggestive of increasing incidence of gross morphological LV cavity dilatation or “Dilated ischemic cardiomyopathy” in these patients.


Altered septal curvature and left ventricular (LV) geometry secondary to right ventricular (RV) dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF) patients. The novel three-dimensional (3D) speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics.Seventy-six patients aged 23.6±8.3 years, 55 with isolated repair (group I) and 21 with subsequent pulmonary valve replacement (group II), and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. A global performance index was calculated as /SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI . All but the four apical LV segments in patients had reduced regional 3D strain compared with controls . Septal curvature correlated with LV global 3D strain , average septal strain , twist , twist gradient , and global performance index .Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement. Adverse left ventricular (LV) mechanics and its implications on long-term outcomes are increasingly recognized in patients after surgical repair of tetralogy of Fallot (TOF) The newly introduced three-dimensional speckle tracking echocardiography (3DSTE) allows simultaneous imaging of all LV segments and tracking of speckle motion vectors in three dimensions based on the full volume dataset The aim of this study was to assess comprehensively the LV mechanics in terms of true 3D systolic strain, twist, and dyssynchrony in patients after TOF repair with and without pulmonary valve replacement (PVR) with the new 3DSTE. We explored further relationships between 3D LV myocardial mechanics and ventricular septal curvature and LV geometry and the application of a new 3D global performance index.All patients and parents of minors gave written informed consent to participate in this study approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority West Cluster, Hong Kong.2 as assessed by cardiac magnetic resonance). The following patient data were collected: demographics, age at operations, and duration of follow-up since surgical repair of TOF and PVR. Healthy subjects were recruited as controls. These healthy controls were healthy volunteers, healthy siblings of patients, and subjects followed up for non-specific chest pain for which no organic causes were identifiable. The body weight and height of all subjects were measured and the body surface area was calculated accordingly.Patients who had undergone total surgical repair of TOF with and without additional PVR were recruited from the congenital heart clinic. In our centre, PVR for significant pulmonary regurgitation was performed in symptomatic patients with heart failure and/or exercise intolerance and in asymptomatic patients with progressive or moderate to severe RV dilation . All echocardiographic recordings were stored in an external hard disc for offline analyses. The average of 3 measurements was used for statistical analyses.From the apical 4-chamber view, the RV end-diastolic and RV end-systolic areas were traced. The RV fractional area change was calculated as (end-diastolic area minus end-systolic area)/end-diastolic area. Severity of pulmonary and tricuspid regurgitation was graded semi-quantitatively by colour Doppler imaging The ventricular septal configuration was quantified from the parasternal mid-short axis view at end-diastole and expressed as curvature, the reciprocal of radius Eccentricity of the left ventricle was assessed from the parasternal mid short-axis view at papillary muscle level. Distance from the endocardial surface of the mid-ventricular septum to that of the posterior-lateral LV free wall (D1) and distance of the orthogonal axis between endocardial surfaces of the anterior and inferior LV free walls (D2) were measured at end-systole and end-diastole. The systolic and diastolic LV eccentricity index (EI) was calculated as D2/D1 measured respectively at end-systole and end-diastole Real-time 3D echocardiographic imaging was performed from the apical view using a matrix array transducer interfaced to the Artida ultrasound system . Full-volume acquisition with capturing of 4 sub-volumes over 4 consecutive cardiac cycles was performed during breathhold. A wide sector width (80–90 degrees by 80–90 degrees) was chosen and care was taken to include the entire LV cavity during acquisition. The settings were optimized to ensure a volume rate of 20 to 30 volumes per second.The volume datasets were analyzed using the 3D wall motion tracking software . From the three-dimensional dataset, three planes were generated: i) apical four-chamber view (A plane), ii) an orthogonal two-chamber view (B plane), and iii) three short axis views near the apex, at mid-level, and at the base of the left ventricle (C planes) . In the Based on tracking of the endocardial surface throughout the cardiac cycle, the LV systolic and diastolic volumes and LV ejection fraction were calculated. Based on the tracking of motion vectors of speckles in three dimensions between the endocardium and epicardium, the global systolic 3D strain of the entire left ventricle and other 3DSTE parameters were derived. The software automatically divided the left ventricle into 16 segments as defined by the American Society of Echocardiography The intra- and interobserver variability of 3DSTE parameters was assessed in 10 patients and 10 control subjects and reported as the coefficients of variation, calculated by dividing the SD of the differences between measurements by the mean and expressed as a percentage. The intraobserver variability for LV 3D global strain, SDI, twist, and twist gradient was 8.0%, 8.1%, 7.8%, and 8.9%, respectively; while the interobserver variability was 10.8%, 10.4%, 9.2%, and 10.7%, respectively.A 3D LV global performance plot was generated by plotting onto the x-, y-, and z-axis of respectively peak global 3D strain, LV twist gradient, and reciprocal of LV SDI. A 3D LV global performance index was calculated as /SDI.Data are expressed as mean±standard deviation. The RV area and LV volume data were normalized by body surface area. The absolute values of 3D strain were used to facilitate interpretation and analyses. Differences in demographic and echocardiographic parameters among patients without PVR, patients with PVR, and controls were compared using simple analysis of variance (ANOVA), while comparisons between two groups were performed using unpaired Student's t test. Pearson correlation analysis was used to assess for relationships between septal curvature, LV eccentricity, and parameters of LV mechanics with Bonferonni adjustment for multiple correlations. The area under the receiver operating characteristic (ROC) curve was calculated to determine capability of GPI to discriminate between patients and controls. A two-tailed p value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS 15.0 .Of the total of 114 subjects recruited, 110 (96%) subjects had optimal echocardiographic images for analysis, including 76 patients and 34 controls. The 76 patients were aged 23.6±8.3 years and had undergone TOF repair at 4.9±3.7 years. They were studied at 18.8±7.4 years after initial repair. Of the 76 patients, 55 had only isolated TOF repair (group I), while 21 had additional PVR (group II). The PVR was performed at the age of 23.1±6.9 years, and the patients were studied at 2.2±2.5 years after PVR. In group I, 5 (9%) patients were on cardiac medications, which were beta-blockers in 2, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in 2, diuretics in 1, and digoxin in 1. In group II, 7 (33%) patients were on medications, which included anti-platelet agent or anticoagulants in 6, diuretics in 2, angiotensin-converting enzyme inhibitor in 2, beta-blocker in 1, and digoxin in 1. Thirty-four controls (group III) aged 20.9±7.5 years were studied. Comparisons of demographic and echocardiographic variables among the three groups are summarized in Compared with controls, both group I and II patients had significantly larger RV end-systolic and end-diastolic areas and LV end-systolic volume and reduced RV fractional area change and LV ejection fraction  .In group I, pulmonary regurgitation was moderate-to-severe in degree in 22 patients, mild in 25, and absent in 8, while in group II, the regurgitation was moderate in 3, mild in 6, and absent in 12. All patients had absent or trivial degree of tricuspid regurgitation except for 5 group I patients who had mild to moderate degree of regurgitation. Compared with group I patients, group II patients tended to have smaller RV end-diastolic area (p = 0.05), but similar RV factional area change (p = 0.24) and LV ejection fraction (p = 0.12).The global LV 3D strain was significantly lower in group I and II (both p<0.001) patients than controls . Figure The average strain of the 5 septal segments in group I patients was 66.0±10.1% of the average values in controls, and tended to be lower than the 81.4±15.0% (p = 0.056) for the 11 non-septal segments. The average strain of the 5 septal segments in group II patients was 56.6±9.3% of the average values in controls, being significantly lower than the 78.6±14.1% (p = 0.007) for the 11 non-septal segments.As for synchronicity of the timing to peak 3D strain, the 3DSTE-derived SDI was significantly greater in both group I (p<0.001) and II (p<0.001) patients than controls. On the other hand, both the LV twist and twist gradient were significantly lower in group I and II patients than controls . Compared with group I patients, group II patients did not show significant differences in 3D strain, SDI, LV twist, and LV twist gradient despite PVR  .For the whole cohort, global 3D strain correlated negatively with SDI , RV end-systolic area , and RV end-diastolic area , but positively with LV twist , LV twist gradient , LV ejection fraction , and RV fractional area change .The 3D global performance plot, which took into account global 3D strain, SDI, and LV twist adjusted for LV length is shown in th percentile limit. Using this as the lower limit of normal, 85.5% (47/55) of group I patients and 90.0% (17/21) of group II patients had impaired 3D global LV performance. For the ROC analysis, the best GPI cutoff to discriminate between patients and controls was 5.79 (deg/cm), which had a sensitivity of 0.71 and specificity of 0.84 , while both the systolic and diastolic EIs were significantly greater in group I and II patients than controls  . The sepTo our knowledge, this is the first study to explore the usefulness of 3DSTE in the interrogation of LV mechanics in repaired TOF patients with and without PVR. Novel findings of the present study include 1) adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist adjusted for LV length in repaired TOF patients with significant pulmonary regurgitation and even in those after PVR, 2) strong associations between septal curvature and 3D indices of LV mechanics, and 3) potential usefulness of 3D global performance index in the comprehensive evaluation of LV dysfunction in patients.Characterization of LV mechanics in patients after TOF repair has been limited to the use of one-dimensional angle-dependent tissue Doppler imaging The significantly lower global 3D strain in our patients is contributed primarily by reduction of basal and mid LV segmental 3D strain , while tDispersion of the times to peak 3D strain of different LV segments further provides convenient quantification of LV systolic mechanical dyssynchrony. Exploration and quantification of LV dyssynchrony in repaired TOF patients have previously been based on tissue Doppler imaging Simultaneous acquisition of LV apical and basal motion minimizes the errors in the calculation of LV twist and twist gradient secondary to differences in heart rate when the apical and basal planes are acquired separately. The understanding of torsional mechanics in repaired TOF patients is limited. Our findings agree with the few published reports that showed a reduction of LV systolic apical rotation and twist in these patients There is a paucity of data on the relationship between alteration in septal geometry and LV dysfunction in repaired TOF patients. The ventricular septum has been regarded as a key element for ventricular systolic and diastolic ventricular interaction.To evaluate in a comprehensive manner the LV mechanics in repaired TOF patients, we used the simultaneously acquired LV indices to derive the 3D global performance plot and index. Our proposed 3D global performance plot incorporates the three important parameters of LV mechanics . This inIt is uncertain whether PVR has an impact on the altered LV mechanics and long-term outcomes. Nonetheless, our preliminary data based on a relatively small cross-sectional cohort of young adults with surgical PVR revealed similarly impaired LV 3D mechanics as those with uncorrected pulmonary regurgitation. It is intriguing that the septal curvature and RV fractional area change remained similar after PVR. The latter agrees with our previous meta-analysis that revealed the absence of significant changes in RV ejection fraction despite surgical PVR Several limitations to this study require comments. Firstly, the number of patients who had undergone PVR was relatively small in our institution. It would have been ideal to monitor the indices of 3D mechanics in a larger cohort longitudinally to track the changes before and after implantation of the pulmonary valve. Secondly, the evaluation of septal curvature remains a cross-sectional and two-dimensional one. Serial longitudinal data would provide additional information on whether alteration of septal curvature is a static, reversible, or progressive phenomenon. Nonetheless, a recent study showed decrease in maximal septal excursion, as assessed by cardiac magnetic resonance, concomitant with reduction of RV volumes after PVR in repaired TOF patients, suggesting the possibility of septal remodeling with removal of RV volume overload In conclusion, this study implicates an influence of septal curvature on LV 3D mechanics and provides the first evidence of potential usefulness of 3DSTE in the comprehensive evaluation of LV mechanics in repaired TOF patients both before and after PVR. Further longitudinal studies are warranted to evaluate the impact of PVR on septal remodeling and LV mechanics.


MIBG has also been used for monitoring treatment effects under various medications. Various positron emission tomography (PET) radioligands have been introduced for the quantitative assessment of presynaptic and postsynaptic neuronal function in vivo. 11C-hydroxyephedrine, like MIBG, has potential for assessing the severity of heart failure. Our PET study using the β-receptor antagonist 11C-CGP 12177 in patients with heart failure showed a reduction of β-receptor density, indicating downregulation, in most of the patients. More studies are needed to confirm the clinical utility of these molecular imaging modalities for the management of heart failure patients.This review focuses on molecular imaging using various radioligands for the tissue characterization of patients with heart failure.  Heart failure is a major cause of mortality and morbidity. The treatment of heart failure patients has been found to entail tremendous medical costs in many countries , 2. AlthA number of non-invasive cardiovascular imaging modalities are currently used to assess the severity of heart failure. Among them, molecular imaging has recently been a focus of interest on account of its ability to characterize tissues involved in myocardial disorders at different levels: molecular, subcellular, and cellular –12. MoleRadionuclide imaging, using either positron emission tomography (PET) or single-photon emission computed tomography (SPECT), has been the modality most commonly used for human molecular imaging, mainly due to its quite high sensitivity to radiolabeled ligands with nano- or micro-order levels compared to other methods of molecular imaging. Even though molecular imaging has low spatial and temporal resolutions and high background activity and radiation, radionuclide imaging has been safely used in a wide range of clinical applications, including evaluations of various disease processes.As a result of advances in vivo biochemical imaging using radionuclide techniques, the modulation of functional and electrophysiological properties of the heart by the autonomic nervous system has become a focus of interest in the field of cardiovascular research. Cardiac neuronal function is compromised in various cardiac diseases, including congestive heart failure, ischemia, arrhythmia, and some types of cardiomyopathy . Tracer The autonomic nervous system consists of two main parts: sympathetic and parasympathetic innervations. Their major transmitters are norepinephrine and acetylcholine, respectively, which define the stimulatory and inhibitory physiological effects of each system. Sympathetic innervation originates mainly from the right and left stellate ganglia, which provide the sympathetic nerves to form the cardiac plexus of the heart. The sympathetic nerve fibers travel parallel to the vascular structures on the epicardial surface of the heart and then penetrate the underlying myocardium in a manner similar to that seen in the coronary vessels . As regaParasympathetic innervation, by contrast, originates from the medulla and passes through the right and left vagal nerves, which further divide into the superior and inferior cardiac nerves. Parasympathetic nerve fibers primarily modulate sinoatrial nodal and atrioventricular nodal function and innervate the atria, whereas, vagal fibers to the ventricles are rather sparse . These aThere are a number of radiotracers that can be used to probe each step of autonomic neuronal functions. Table 131I MIBG as a norepinephrine analog for the selective mapping of sympathetic nerve endings in the heart . We. We11C-C123I-labeled MIBG, as a marker of adrenergic neuron function, could play an important role in the risk stratification of heart failure patients. Presynaptic and postsynaptic neuron imaging using PET can potentially allow better quantifications of autonomic function. More clinical experience is needed to confirm the clinical impact of these imaging modalities for the management of heart failure patients.Cardiovascular molecular imaging allows tissue characterization in myocardial disorders at molecular, subcellular, and cellular levels. It has potential for assessing the severity of heart failure and for monitoring treatment effects.


A 42-year-old woman, who presented with DCM , suffered from gallstone for years, and was scheduled for laparoscopic cholecystectomy. Echocardiography demonstrated a severely dilated left ventricle with global hypokinesia and reduction of left ventricular systolic function, ejection fraction (EF) 34% with mild mitral regurgitation and severe tricuspid regurgitation. After intubation, a transesophageal echocardiography (TEE) probe was inserted. When the IAP was gradually ascended to 14 mmHg during the laparoscopy, EF fell to 19% and the systolic pressure fell to 78 mmHg and TEE showed severely poor wall motion. But the central venous pressure (CVP) still showed about 4 mmHg throughout the whole procedure. After decreasing the IAP to 10 mmHg, we adjusted the rate of pacemaker to 70 times per minute then the systolic pressure was kept at around 100 mmHg, and the diastolic pressure was kept at 60 mmHg. EF was 30% after the reduction of IAP and the adjusting of the heart rate set. TEE is a helpful monitor in anesthesia management of patients with DCM during noncardiac surgery and CVP is useless especially for the procedure with severe hemodynamic effects. With the help of transesophageal echocardiography (TEE) we may have the real-time heart function which could be of great value in guiding the anesthesia management. With the patient’s written consent for publication, we report this case about anesthesia management for patient with DCM undergoing laparoscopic cholecystectomy.Dilated cardiomyopathy (DCM) describes a group of diseases involving the myocardium. Anesthesia management of patients with DCM is challenging. As the laparoscopic  operations are more and more popular and widespread, we must notice that the pneumoperitoneum may cause severe hemodynamic disorder.A 42-year-old woman, who presented with DCM (American Society of Anesthesia (ASA) class IV), suffered from gallstone for years, and was scheduled for laparoscopic cholecystectomy. The symptoms of DCM were well controlled by her previous medication included diuretics, small dose of digoxin. As the preoperative electrocardiogram showed complete left bundle branch block (LBBB) and the vertigo history, the patient was assigned to receive implantation of temporary pacemaker. Preoperative echocardiography demonstrated a severely dilated left ventricle with global hypokinesia and reduction of left ventricular systolic function, ejection fraction (EF) 34% with mild mitral regurgitation and severe tricuspid regurgitation. Preoperative laboratory investigations were within the normal range except a mild increase of some myocardial enzymes.Upon arrival into the operating room (OR), the patient’s blood pressure was 130/80 mmHg, heart rate was 80 beats/min and oxygen saturation (SpO2) was 97% on oxygen face mask 6L/min. Besides the routine monitors, a right radial arterial line was inserted after the Allen test negative, and central venous catheterization was performed to measure the central venous pressure (CVP) constantly. The rate of pacemaker was set at 60 times per minute. Defibrillator as well as lidocaine and amiodarone were prepared aside. Midazolam was given as anesthesia premedication. The patient was managed with a propofol and fentanyl-based anesthesia induction. Propofol was given through target-controlled infusion (TCI) with the effect site concentration (Ce) at 1 ug/ml at the beginning. Two separate dose of fentanyl (0.25mg) was given at the moment of induction and incision. Muscle relaxation was achieved with vecuronium. After intubation, a transesophageal echocardiography (TEE) probe was inserted. Anesthesia was maintained with sevoflurane and propofol TCI.The CVP was 4 mmHg and the ejection fraction (EF) showed by TEE was 32.6%  at the b2 Patients with DCM are characterized by impaired systolic function and low ejection fraction (EF<45%) with global hypokinesis of left or both ventricles. Some patients may also have right or left bundle branch block and arrhythmias such as atrial fibrillation, premature ventricular or atrial contractions and ventricular tachycardia.3 Based upon past experience, two key points during anesthesia management of these patients are to maintain the EF and to prevent malignant arrhythmias which may lead to sudden death.4The above case represents a scenario of a patient with a typical history of DCM undergoing laparoscopic cholecystectomy. The natural history of the disease onset is difficult to determine, since asymptomatic cardiomegaly could be years before the clinical symptoms.5 As for our patient, we monitored the systolic function just through the LV short-axis and four-chamber long-axis imaging, and calculated the EF under M-mode. The CVP was maintained at about 4 mmHg throughout the whole procedure, but the TEE showed a critical fall of EF and a waken wall movement of left ventricle with the increasing of IAP. Thus, instead of optimizing the preload, we should increase the CO by increasing either the stroke volume or heart rate using vasoactive or inotropic drugs.The present case had two major problems, DCM with severe cardiac dysfunction and the hemodynamic effect of laparoscopy. The principles of anesthesia for current case were maintaining her cardiac output (CO), avoiding the increase of afterload, preventing the malignant arrhythmia and alleviating the effect of pnuemoperitonieum. According to the results of TEE, we could monitor the cardiac function more directly and conveniently. In most clinical practice, the intraoperative application of TEE was limited to cardiac surgical procedures. In noncardiac surgery, the value of TEE is not determined and is limited due to its high initial cost. The familiarity in using TEE and interpretive skills of anesthesiologists does also limit the applications of perioperative TEE. However, it has been shown that TEE can influence decision making independent of the presence of CVP monitoring both in cardiac and noncardiac surgery.2 absorption from peritoneal cavity. The increased IAP can have a mechanical compression of splanchnic vascular bed, which leads to a decrease in returned blood volume and an increase in vascular resistance. At the moment of CO2 insufflation, stretch of peritoneum activates the vagus nerve, which results in heart rate decrease. The CO might not change significantly in healthy patients, but it could have a decrease in patients with cardiac disease.6 The hemodynamic response to pneumoperitoneum can be alleviated by limiting the degree of IAP and positioning change to head-up tilt. For this patient because of the mild mitral regurgitation and severe tricuspid regurgitation, we should keep the fast heart rate but the atropine was not valid. We did not try other drugs such as isoprenaline or epinephrine. By decreasing the IAP to 10 mmHg and adjusting the pacing heart rate to 70 beats/minute, the EF was recovered nearly preoperative level. There have been several cases about patient with DCM undergoing laparoscopic cholecystectomy (LC). Different kinds of anesthesia technique were used in those cases7,8, but most anesthesiologists were inclined to use epidural analgesia (EA). Aono et al compared general anesthesia (GA), epidural analgesia (EA) and GA combined with EA for LC.9 They suggested that EA cause mild hemodynamic changes in patients with limited cardiac function undergoing LC while anesthetics used in GA caused myocardium depression, heart rate reduction and blood vessels dilation. However, EA may exaggerate the hypotension in cardiomyopathic patient because of the vessel dilation likewise. In our case, we chose GA, the anesthetics we used in current case had minimal depressive effect on cardiac function. In addition, the anesthesia induction using TCI in our case was stable and induced less hemodynamic changes.Two major problems of laparoscopic approach are IAP increase and COIn conclusion, GA facilitated by TCI provides hemodynamic stability in patients with critical cardiac condition. For these people, minimally invasive surgery is a good choice. The cardiac function was depressed severely by increasing of IAP in hemodynamic unstable patients, and the CVP may be useless compared with TEE. Meanwhile it is very important to increase the IAP very slowly in patients with critical cardiac function. TEE is a helpful monitor in anesthesia management of patients with DCM during noncardiac surgery especially for the procedure with severe hemodynamic effects.


Diastolic dysfunction is a key factor in the development and pathology of cardiac dysfunction in diabetes, however the exact underlying mechanism remains unknown, especially in humans. We aimed to measure contraction, relaxation, expression of calcium-handling proteins and fibrosis in myocardium of diabetic patients with preserved systolic function.2+ ATPase (SERCA2a) and phospholamban (PLB), and of β1-adrenoreceptors were determined in tissue samples by Western blot. Collagen deposition was determined by picro-sirius red staining.Right atrial appendages from patients with type 2 diabetes mellitus  and non-diabetic patients , all with preserved ejection fraction and undergoing coronary artery bypass grafting (CABG), were collected. From appendages, small cardiac muscles, trabeculae, were isolated to measure basal and β-adrenergic stimulated myocardial function. Expression levels of calcium-handling proteins, sarcoplasmic reticulum Ca1-adrenoreceptor expression levels.In trabeculae from diabetic samples, contractile function was preserved, but relaxation was prolonged . The expression of SERCA2a was increased in diabetic myocardial tissue , whereas its endogenous inhibitor PLB was reduced . Collagen deposition was increased in diabetic samples. Moreover, trabeculae from diabetic patients were unresponsive to β-adrenergic stimulation, despite no change in βHuman type 2 diabetic atrial myocardium showed increased fibrosis without systolic dysfunction but with impaired relaxation, especially during β-adrenergic challenge. Interestingly, changes in calcium-handling protein expression suggests accelerated active calcium re-uptake, thus improved relaxation, indicating a compensatory calcium-handling mechanism in diabetes in an attempt to maintain diastolic function at rest despite impaired relaxation in the diabetic fibrotic atrial myocardium. Our study addresses important aspects of the underlying mechanisms of diabetes-associated diastolic dysfunction, which is crucial to developing new therapeutic treatments. Impaired cardiac function during diastole is one of the early manifestations of cardiac dysfunction in type 2 diabetes, and it 2+ from the cytosol during the diastolic period, predominantly governed by the activity of the important sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) under direct control of its endogenous inhibitor phospholamban (PLB)[The diastolic properties of the heart are determined by factors influencing both the passive compliance and the active processes of myocardial relaxation. Thus faan (PLB), has beean (PLB). Howeveran (PLB) and leadan (PLB), it is a1-adrenoreceptors were determined via protein analysis and atrial myocardial fibrosis by measuring collagen deposition.Therefore we aimed to assess the impact of diabetes on the diastolic function of the atrial myocardium from patients with preserved EF and determine alterations in the calcium-handling proteins specifically linked to myocardial relaxation. To this end we combined active force and relaxation measurements in isolated right atrial cardiac muscles from non-diabetic and diabetic patients with preserved EF and coronary artery disease (CAD), undergoing coronary artery bypass graft (CABG) surgery. Expression levels of calcium-handling proteins and βOur study shows for the first time that in human atrial myocardium from diabetic patients with preserved EF and CAD, the force generation is preserved, whereas the relaxation is impaired, and the right atrial cardiac muscles were unresponsive to β-adrenergic stimulation. The impairment in relaxation is associated with an unexpected increase in SERCA2a/PLB protein ratio in the diabetic myocardium suggesting accelerated relaxation. This may indicate a compensatory mechanism in an attempt to maintain diastolic function at rest in the fibrotic diabetic atrial myocardium.c score ≤ 6.5% (48 mmol/mol). DM patients were selected based on their clinical diagnosis of type 2 diabetes with duration of more than 1 year. CAD was of such severity as to meet the indications for CABG, which in the majority of cases was triple vessel or high-grade double vessel disease . Patients requiring emergency CABG, patients with on-going myocardial ischemia prior to CABG and those undergoing concomitant cardiac surgical procedures in addition to CABG were excluded.The study was approved by the local Human Ethics Committee  and informed consent was obtained. Human right atrial appendages (RAAs) were acquired from patients with type 2 diabetes mellitus  and non-diabetic patients  with CAD who underwent CABG surgery. Non-diabetic patients were classified as having a fasting plasma glucose ≤ 6 mmol/L or an HbA1All patients had a clinically indicated pre-operative transthoracic echocardiogram, using a Vivid S6, 7, or E9 ultrasound system . Images were obtained by professional echosonographers, and reviewed offline by a European Association of Cardiovascular Imaging accredited cardiologist. Left ventricular (LV) and left atrial (LA) chamber volumes were derived from a biplane method of discs using the apical 4-chamber and 2-chamber views. Cardiac2+ (0.5 mM) Krebs-Henseleit buffer ((mM): 118.5 NaCl, 4.5 KCl, 1.4 CaCl2, 0.3 NaH2PO4, 1.0 MgCl26H2O, 25 NaHCO3 and 11 glucose) with 6.25 mM 2,3-butanedione monoxime (BDM) previously well oxygenated with carbogen (95%O2–5%CO2). Within 5–10 minutes after removal, the appendages were either dissected into several pieces, flash-frozen and stored at 80°C or fixed in 4% (v/v) formaldehyde solution and stored at -20°C. In a subset of the study, half of the RAA tissue was used immediately to conduct the functional force measurements.In all patients, RAAs were removed under normothermic conditions before cross clamping for cardiopulmonary bypass. Immediately after removal, all specimens were placed in a sealed vial containing a modified, low Ca2+, kept at 40°C and continuously stimulated at 60 bpm (1 Hz). After mounting, the preparations were stimulated for 1 h to allow equilibration. To impose similar stretch levels the muscles in both groups were stretched to the length (Lmax) at which isometric developed force was maximal. After determination of basal force developed (Fdev), length dependency was tested by changing muscle length from 80% to 100% Lmax with 5% incrementing steps. Hereafter the response to β-adrenoceptor stimulation on force development was tested with incrementing doses of dobutamine (10-7 to 10-5 M) given at 6 minutes interval.From myocardial samples, tiny cardiac muscles (trabeculae) were freshly dissected, transferred to an experimental bath and attached between a force transducer and a micromanipulator. The basal and length dependency of force development were measured in the isolated trabeculae, as previously described. The mus1-adrenoreceptor were detected from 75, 60, 50 or 25 μg of lysate, respectively, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or β-actin was also identified in each loading condition. Following transfer onto nitrocellulose the membranes were blocked for 1 hour with phosphate buffered saline , containing 0.5% Tween 20 and 5% (w/v) skimmed milk. For β1-adrenoceptor and β-actin proteins were transferred onto Polyvinylidene fluoride (PVDF) membranes, blocked for 1 hour with Tris buffered saline . The blots were probed with specific antibodies against RyR2, SERCA2a, PLB, GAPDH (Badrilla Ltd), β1-adrenoreceptor  or β-actin (Sapphire Bioscience Pty.Ltd) with corresponding peroxidase conjugated secondary antibodies (Sapphire Bioscience Pty.Ltd). All proteins were detected using an enhanced chemiluminescence kit. Protein band densities were normalized to GAPDH or β-actin as an internal control and are expressed as protein to GAPDH or β-actin ratio. For β1–adrenoceptor (AR) blots, β-actin was used as an internal control because GADP was to close to the β1-AR bands to be separated accurately. Although some studies suggested an impact of diabetes on the gene expression of GAPDH[protein expression of GAPDH or of β-actin (both p > 0.05) between non-DM and DM samples.Total myocardial sample lysates were prepared by manual grinding and followed by suspension in 1.5-fold (w/v) sodium dodecyl sulphate (SDS) lysis buffer (3% (w/v) SDS, 50 mM Tris–HCl (pH 7.5) and protease inhibitor mix composed of 1 mM benzamidine, 2 μg/mL leupeptin, 2 μg/mL pepstatin A, 2 μg/mL aprotinin and 0.5 mM phenylmethylsulfonyl fluoride). The homogenate was incubated on ice for 1 hour, at room temperature for 45 minutes and then centrifuged at 21,000 g for 30 minutes at 4°C where after supernatant was collected. Protein concentrations were determined using the DC protein determination kit (BioRAD) according to manufacturer’s protocol and samples volumes were adjusted for loading. Unless otherwise noted samples were further solubilized in 2× Laemmli sample buffer  glycerol, 0.01% bromophenol blue) containing 5% β-mercaptoethanol (v/v). Ryanodine receptor (RyR2), SERCA2a, PLB and βof GAPDH, othersof GAPDH and ours2O (0.5% (v/v) acetic acid in H2O) for 10 minutes. Slices were dehydrogenated in an ascending ethanol sequence  in H2O) and washed in xylene. Finally, slices were embedded in a distrene-plasticiser-xylene mounting medium. Images obtained by light microscopy were digitized and analyzed using ImageJ v1.46 software to quantify the percentage of collagen content (fibrosis), as previously described[Formalin fixed, optical cutting temperature embedded myocardial samples tissue sections of 8 μm thickness were washed with distilled water and PBS, and subsequently exposed to a picro-sirius red solution (0.001% (w/v) sirius red in saturated aqueous picric acid) for 1 hour. Tissue sections were then washed in acidified Hescribed. BrieflyDifferences among groups were compared either using a t-test, chi-square or a two-way ANOVA followed by a Bonferroni post-hoc test as indicated in the legends of the tables and Figures. A p-value of < 0.05 was considered statistically significant. Data are expressed as mean ± SEM.1c)  and fasting plasma blood glucose levels  (Table Diabetes was evident from the high fasting levels of glycated hemoglobin HbAc 58 ± 4c (58 ± 4max), the contractile parameters  were not different between muscles from non-DM and DM patients, however the relaxation parameters, minimum rate of relaxation (-dF/dtmin), 50% relaxation time (RT50%) and time constant of relaxation (Tau), were significantly prolonged in DM group (Table dev and + dF/dtmax) with incrementing length . As expected, this resulted in an increase in the amplitude of contraction .As impaired diastolic function limits cardiac performance during exercise, we alsoIn addition to impaired relaxation, changes in myocardial stiffness could also lead to diastolic dysfunction, therefore we next assessed whether increased fibrosis exists in the diabetic right atrial myocardium. Collagen deposition was determined in cardiac tissue samples using picro-sirius red, which selectively stains collagen red. A 60% increase in collagen deposition was observed in DM patients  and higher filling pressures during early filling (increased E/e’) with a tendency to slower early and late filling velocities , which in the isolated right atrial muscles were accompanied by prolongations of early and late relaxation (decreased -dF/dtmin and prolonged Tau). Together these data indicate reduced diastolic function due to impaired relaxation and increased myocardial stiffness of the heart in the diabetic population with preserved EF. This is consistent with previous echocardiography findings in type 1 and type 2 diabetic patients[et al. have reported no difference in the rate of relaxation or the contractile function of right atrial cardiac muscles from type 2 diabetic patients undergoing CABG[Our patients and withpatients and typepatients, howevering CABG. Howevering CABG,28 and oThe heart has the ability to increase its cardiac efficiency via intrinsic means, such as volume. Several1-adrenoreceptors[-5 M) concentrations, which would indicate a lack of contractile reserve even in these patients with normal resting contractile function. In addition, our new data emphasizes that caution should be taken with translating animal data directly to the human situation. It would be easy to attribute this to the use of β-adrenoceptor blocking agents, however almost all patients, both the diabetic and the non-diabetic, were on β-blocker treatment -kinase inhibitor wortmanin[2+ regulation, which promote diastolic dysfunction prior to overt systolic dysfunction, may be common to early stages of type 2 diabetes involving insulin resistance[The underlying mechanism of the impaired relaxation may be related to impaired Caobserved. In cont similar, and rec similar, which iby et al. who suggtraction. In additraction,41. Thesortmanin. This insistance,42. Moresistance.c), despite all being on hyperglycemic control medication (metformin and insulin), and therefore changes in the expression of calcium-handling proteins might still be due to altered glycemic control. These changes in Ca2+ regulation may over time increase the energy demands of the diabetic myocardium and have important ramifications for future diabetic myocardium remodeling, potentially further impairing relaxation and eventually leading to myocardial dysfunction. Therefore, the increased SERCA2A:PLB expression ratio may be compensatory and beneficial for relaxation at resting conditions, but once the myocardium is challenged, there is little reserve for an increase in Ca2+ cycling leading to the lack of response to β-adrenergic stimulation observed in our study. Alternatively, in rodent models, experimental diabetes changed the phosphorylation of the sarcomeric protein troponin I[In the present study, DM patients had an increase in hyperglycemic markers (glucose and HbA1oponin I,45 and aoponin I,47, althoponin I. HoweverA well-known underlying cause of diastolic dysfunction is increased myocardial fibrosis. The extracellular matrix remodeling plays an important role in cardiac fibrosis and the amount of extracellular collagen is caused by an imbalance between synthesis and degradation of collagen,50 and fDue to the use and access to human tissue, there are a number of limitations to our study. CAD is known to be a co-morbidity and a specific causal factor for the transition from diastolic to systolic failure. As all 2+ dynamics between the atria and ventricular myocardium exists[Another limitation is that differences in the ultrastructure and Cam exists , which m exists. On the m exists,26-28.1-adrenoreceptor expression levels, suggesting impaired downstream β-adrenergic modulation and lack of contractile reserve. Our study provides novel knowledge on the underlying pathology of diastolic dysfunction in the diabetic myocardium.In patients with CAD and preserved EF, the existence of type 2 diabetes resulted in impaired relaxation and increased fibrosis of the right atrium, with preserved myocardial contractile function. Our novel finding of increased expression of SERCA2a:PLB ratio suggests a compensatory mechanism to enhance relaxation and maintain the diastolic function at rest of the fibrotic diabetic atrial myocardium. We also demonstrate for the first time that human right atrial cardiac muscles from type 2 diabetic patients with preserved EF are unresponsive to β-adrenergic stimulation despite no change in expression of the β2+ ATPase; SV: Stroke volume; Tau: Time constant of relaxation; TBD: Tris buffered saline; TtPF: Time to peak force.A: Late ventricular filling velocity; BDM: 2,3-butanedione monoxime; BMI: Body mass index; BP: Blood pressure; CABG: Coronary artery bypass graft; CAD: Coronary artery disease; CSA: Cross sectional area; -dF/dtmin: Minimum rate of relaxation; +dF/dtmax: Maximum rate of contraction; Decel: Early ventricular deceleration time; DM: Type 2 diabetes mellitus; e’: Early ventricular myocardium relaxation velocity; E: Early ventricular filling velocity; EF: Ejection fraction; Fdev: Developed force; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; HbA1c: Glycated hemoglobin; IVSd: Interventricular septal diameter diastole; LA: Left atrial; LA-2D: Left atrial 2-dimensional diameter; Lmax: Muscle length at which isometric developed force was maximal; LV: Left ventricular; LVEDV: Left ventricular end diastolic volume; LVESV: Left ventricular end systolic volume; LVIDd: Left ventricular internal diameter diastole; LVIDs: Left ventricular internal diameter systole; LVPWd: Left ventricular posterior wall thickness end-diastole; MHC: Myosin heavy chain; non-DM: Non-diabetic; PBS: Phosphate buffered saline; PI3: Phosphoinositide 3; PLB: Phospholamban; PVDF: Polyvinylidene fluoride; RAA: Right atrial appendages; RT50: 50% relaxation time; RyR2: Ryanodine receptor 2; SDS: Sodium dodecyl sulphate; SERCA2a: Sarcoplasmic reticulum CaThe authors declare that they have no competing interests.SJL, HYW, IAEB and GH performed experimental work and primary analysis; RRL, SJL, and SC performed secondary analysis; RRL, AB, RK and PPJ managed experimental work; IFG, RWB, MJAW, PS, SC provided human tissue and patient data; RRL, SJL, and PPJ drafted the manuscript; AB, RK, JCB, PS, IFG, RWB, MJAW and SC edited manuscript; RRL and PPJ designed study. All authors read and approved the final manuscript.


Limb girdle muscular dystrophies (LGMD) are inclusive of 7 autosomal dominant and 14 autosomal recessive disorders featuring progressive muscle weakness and atrophy. Studies of cardiac function have not yet been well-defined in deficiencies of dysferlin (LGMD2B) and fukutin related protein (LGMD2I). In this study of patients with these two forms of limb girdle muscular dystrophy, cardiovascular magnetic resonance (CMR) was used to more specifically define markers of cardiomyopathy including systolic dysfunction, myocardial fibrosis, and diastolic dysfunction.Consecutive patients with genetically-proven LGMD types 2I (n = 7) and 2B (n = 9) and 8 control subjects were enrolled. All subjects underwent cardiac magnetic resonance (CMR) on a standard 1.5 Tesla clinical scanner with cine imaging for left ventricular (LV) volume and ejection fraction (EF) measurement, vector velocity analysis of cine data to calculate myocardial strain, and late post-gadolinium enhancement imaging (LGE) to assess for myocardial fibrosis.endo was -23.8 ± 8.5vs. -23.9 ± 4.2%, εepi was -11.5 ± 1.7% vs. -10.1 ± 4.2% . Five of 7 LGE-positive patients had grade I diastolic dysfunction . that was not present in any LGE-negative patients or controls.Sixteen LGMD patients , and 8 control subjects completed CMR. All but one patient had normal LV size and systolic function; one (type 2I) had severe dilated cardiomyopathy. Of 15 LGMD patients with normal systolic function, LGE imaging revealed focal myocardial fibrosis in 7 (47%). Peak systolic circumferential strain rates were similar in patients vs. controls: εLGMD2I and LGMD2B generally result in mild structural and functional cardiac abnormalities, though severe dilated cardiomyopathy may occur. Long-term studies are warranted to evaluate the prognostic significance of subclinical fibrosis detected by CMR in these patients. This2 and end-systolic volume (ESVI) 191 ml/m2. LV EF was normal in the remaining subjects, averaging 60 ± 7%, and these patients had normal cardiac volumes . Also, all patients excluding the subject with dilated cardiomyopathy had relatively normal LV mass, which averaged 53 ± 19 g/m2. Systolic circumferential strain analysis also showed no difference between patients and controls (Table The LGMB2I patient with severe LV enlargement and systolic dysfunction (patient 6) had EF 12%, end-diastolic volume (EDVI) 217 mL/mLGE imaging showed extensive myocardial fibrosis in one LGMB2I patient with advanced cardiomyopathy (patient 6). In the remaining 15 LGMD patients, seven (47%) had focal enhancement not present in controls. Prevalence within specific genotypes was 4 of 7 (57%) patients with LGMD2I, and 3 of 9 (33%) patients with LGMD2B. Patterns of enhancement included epicardial, similar to the pattern seen in dystrophin-deficient cardiomyopathy and some myocarditis, as well as the midwall fibrosis of other nonischemic cardiomyopathies ; diastolic function was normal in the remaining patients and in all controls.The majority of patients with LGMD of 2 subtypes - 2B, and 2I - in our cohort showed normal LV size, global systolic function and peak systolic circumferential strain. However, there was evidence of subclinical myocardial fibrosis in 57% of subjects with LGMD2I and 33% of subjects with LGMD2B. This abnormality was accompanied by diastolic dysfunction in 5 patients . The combination of these findings is consistent with our previous observations and those of others demonstrating a link between myocardial fibrosis and diastolic dysfunction irrespective of etiology,39. Subjet al. studied 9 subjects, 8 of whom had reduced LVEF, increased LV mass, or increased LV end-diastolic volume[sine qua non in the CMR evaluation of cardiomyopathy[et al. characterized myocardial involvement in 11 of 13 LGMD2I patients with LGE-CMR, and found a high incidence of LV and RV myocardial fibrosis in addition to fatty replacement[There have been two prior studies evaluating myocardial abnormalities with CMR in subjects with LGMD2I. Gaul ic volume. Diastolic volume. The stuomyopathy. Wahbi eplacement. It is uet al. found significant differences in systolic circumferential strain between boys with DMD and controls, even in DMD patients with preserved ejection fraction[et al. identified abnormal circumferential strain in patients with autosomal dominant Emery-Dreifuss muscular dystrophy due to lamin A/C mutation[While previous work in muscular dystrophy-associated myocardial disease has similarly applied processing of routinely-acquired cine imaging to successfully derive strain parameters, much wo fraction. Similar mutation. Not fin mutation. Measure mutation,45.To our knowledge, our study represents the largest evaluation using CMR of LGMD2B patients. It has been proposed that dysferlin promotes cardiomyocyte repair, and that dysferlin deficiency leads to cardiomyopathy,47. DiasA study of 100 subjects with LGMD2A to 2I used echocardiographic and electrocardiographic criteria to define cardiac involvement (CI): EF <50%, intraventricular septum greater than 1.2 cm, left bundle branch block, atrial fibrillation/flutter, or atrioventricular conduction block. Using tThe prevalence of advanced cardiomyopathy in patients with LGMD2I and LGMD2B appears to be limited, but subclinical fibrosis and diastolic dysfunction do occur and may warrant institution of cardioprotective medical therapies. The combination of skeletal and cardiac muscle involvement, more common in LGMD2I, point clinicians in the direction of this genotype when faced with an unknown form of limb girdle muscular dystrophy. Longitudinal studies are warranted to define the natural history of LGMD patients with subclinical abnormalities in cardiac structure and function.The authors declare that they have no competing interests.XQR, JRM and SVR conceived of the study, and XQR directed enrollment and collection of clinical data. SVR directed implementation of the CMR studies and analysis of data. OPS supervised and SJM and ND performed strain analysis. PH contributed to literature review and manuscript preparation. TT assisted with image analysis. BMc contributed to study coordination. All authors read and approved the final manuscript.


Feature-tracking Strain (FT S) is a new technique that performs myocardial Strain evaluation on Steady State Free Precession (SSFP) cines without the need for myocardial tagging. As a pilot study to determine whether FT S may be useful in single ventricle patients, we applied this analysis to patients with hypoplastic left heart syndrome (HLHS) and tricuspid atresia (TA).We retrospectively reviewed 22 patients with a history of Fontan palliation  who had cardiac MRIs with a Siemens 1.5 Tesla Avanto  scanner, 11 with TA, 11 with HLHS. All had steady-state free precession (SSFP) sequences of 4-chamber (4ch) cine and short axis (SAx) cine stacks from cardiac base to apex. Ejection fraction (EF) was calculated from the SAx stack on a Leonardo workstation . FT S analysis of the 4ch cine was performed off-line with TomTec 2D Cardiac Performance Analysis  following two tracking protocols: endocardial trace only (Endo), epicardial to endocardial trace (Endo-Epi)  by Endo., and -16.5 (95% CI -6.9 to -26.1) by Endo-Epi tracking methods. There was fair correlation (Figure There is fair correlation between GLS and EF in single ventricle patients with feature-tracking Strain analysis tracking the ventricular endocardium. Validation in a larger sample is warranted. Comparison of FT S with tagged harmonic phase MRI in single ventricle patients may further validate this promising technique in defining regional and global strain.Dr Kevin K.Whitehead was supported in part by NIH K23 Grant HL089647 from the National Heart, Lung and Blood Institute.Dr. Mark Fogel was supported in part by NIH - R01HL098252-01, "Understanding mechanisms of Fontan failure and key predictors for patient outcome."