The right ventricle is a complex structure that is challenging to quantify by two-dimensional (2D) echocardiography. Unlike disk summation three-dimensional (3D) echocardiography (3DE), single-beat 3DE can acquire large volumes at high volume rates in one cardiac cycle, avoiding stitching artifacts or long breath-holds. The aim of this study was to assess the accuracy and test-retest reproducibility of single-beat 3DE for quantifying right ventricular (RV) volumes in adult populations of acquired RV pressure or volume overload, namely, pulmonary hypertension (PH) and carcinoid heart disease, respectively. Three-dimensional and 2D echocardiographic indices were also compared for identifying RV dysfunction in PH.A prospective cross-sectional study was performed in 100 individuals who underwent 2D echocardiography, 3DE, and cardiac magnetic resonance imaging: 49 patients with PH, 20 with carcinoid heart disease, 11 with metastatic carcinoid tumors without cardiac involvement, and 20 healthy volunteers. Two operators performed test-retest acquisition and postprocessing for inter- and intraobserver reproducibility in 20 subjects.P = .031). There was significant interobserver test-retest bias for RV volume underestimation .RV single-beat 3DE was attainable in 96% of cases, with mean volume rates of 32 to 45 volumes/sec. Bland-Altman analysis of all subjects (presented as mean bias ± 95% limits of agreement) revealed good agreement for end-diastolic volume (−2.3 ± 27.4 mL) and end-systolic volume (5.2 ± 19.0 mL) measured by 3DE and cardiac magnetic resonance imaging, with a tendency to underestimate stroke volume (−7.5 ± 23.6 mL) and ejection fraction (−4.6 ± 13.8%) by 3DE. Subgroup analysis demonstrated a greater bias for volumetric underestimation, particularly in healthy volunteers . Receiver operating characteristic curve analysis showed that 3DE-derived ejection fraction was significantly superior to 2D echocardiographic parameters for identifying RV dysfunction in PH (sensitivity, 94%; specificity, 88%; area under the curve, 0.95; Single-beat 3DE is feasible and clinically applicable for volumetric quantification in acquired RV pressure or volume overload. It has improved limits of agreement compared with previous disk summation 3D echocardiographic studies and has incremental value over standard 2D echocardiographic measures for identifying RV dysfunction. Despite the ability to obtain and postprocess a full-volume 3D echocardiographic RV data set, the quality of the raw data did influence the accuracy of the data obtained. The technique performs better with dilated rather than nondilated RV cavities, with a learning curve that might affect the test-retest reproducibility for serial RV studies. Quantification of right ventricular (RV) size and function is prognostic in congenital and acquired heart disease.One possibility to overcome the limitations of 2DE is three-dimensional (3D) echocardiography (3DE), compared against CMRI in a range of congenital and acquired diseases for RV volumetric quantification.More recently, ultrasound transducer technology allows the real-time acquisition of a 90° × 90° data set in a single cardiac cycle.•n = 9), connective tissue disease associated (n = 32), and chronic thromboembolic disease (n = 8). Exclusion criteria comprised clinically significant restrictive or obstructive lung disease identified by pulmonary function tests, arrhythmia, and known independent left-sided cardiac disease unrelated to PH.A group of 49 consecutive patients with PH , with a 4V1c transducer . A standard study protocol was followed in conjunction with American Society of Echocardiography guidelines for chamber quantificationSingle-beat full-volume 3D echocardiographic RV data sets were acquired using the 4Z1c matrix-array transducer . Probe position started from the apical four-chamber view with the patient in the left lateral decubitus position. Both the patient and transducer positions were subsequently modified for optimal simultaneous visualization of the tricuspid valve, cardiac apex, infundibulum, and RV outflow tract (RVOT) as assessed by the real-time 2D four-chamber, basal sagittal, and coronal views, and by inclusion of the RV chamber in the pyramidal data set. In our experience, a more lateral apical window with posterior tilt of the probe tail was beneficial to visualize the infundibulum and RVOT in the coronal window. Image depth and sector width were adjusted for maximal visualization of the right ventricle at the highest volume rate. At least three 3D echocardiographic RV data sets were acquired during a breath-hold to ensure optimal image quality, which was subjectively graded on a five-point scale ranging from zero (very poor) to four (perfect).Full-volume 3D echocardiographic RV data sets were imported into the on-cart RV Analysis application. Manual adjustment of the RV data set was initially required to ensure the correct orientation of four-chamber, sagittal, and coronal slices; maximize the RV cavity area and identify the most apical RV view on visual assessment of the four-chamber window; and allow the identification of cardiac landmarks. This process was performed in a stepwise approach by rotation and angulation of the four-chamber window, with manipulation of this plane causing the simultaneous adjustment of the other two  orthogonal planes A. Both aEndocardial RV borders were traced at end-diastole and end-systole in four-chamber, basal sagittal, and coronal views. The software algorithm obliges the operator to intersect the endocardial border tracing in sequential views with crosshair reference markers that are positioned in response to endocardial border traces from a preceding view. Therefore, correction of a previous slice tracing was undertaken when a crosshair position suggested a prior tracing error. Trabeculae were included in the blood pool volume. To assist with RVOT delineation in the basal sagittal view, the insertion point of the RV myocardium at the interventricular septum was routinely included in the endocardial tracing.At the final stage, the algorithm presents the results of semiautomated contour tracking for the four-chamber, coronal and basal, middle and apical short-axis views. Misalignment of endocardial contours prompted identification of the region of suboptimal tracking followed by manual correction of the original tracing. Automated volumetric reconstruction was accepted only once the semiautomated endocardial border tracking was visually satisfactory and represented meaningful RV shapes in all views B, as optReproducibility was studied in 20 randomly selected subjects  for both the 3D echocardiographic acquisition and postprocessing stages by two independent sonographers (D.S.K. and A.E.G.), as described previously.n = 19) cine imaging of contiguous short-axis slicesk-t sensitivity encoding imaging (n = 81) of contiguous transaxial slicesk-t sensitivity imaging allows the collection of high spatiotemporal resolution real-time images during free breathing and is part of the standard clinical CMRI work flow at our institution in the pediatric PH population.All cardiac magnetic resonance images were acquired using a 1.5-T magnetic resonance scanner  using a 12-element phased-array coil for signal reception and the body coil for signal transmission. A vector electrocardiographic system was used for cardiac gating. Ventricular volumes and great vessel flow were measured in all patients. Volumetric RV data were obtained using either retrospectively gated balanced steady-state free precession , with Pearson correlation coefficients used to assess the relationship between 3DE- and CMRI-derived RV volumes and EF. Differences between the four participant subgroups were analyzed using one-way analysis of variance, with the Tukey post hoc tests identifying which specific means differed. P values < .05 were considered statistically significant. Image scoring data were nonparametrically distributed, represented by medians with 25th and 75th percentiles. Rank sum tests were used for comparisons of image scoring data, with the Mann-Whitney U test and the Kruskal-Wallis test used for comparisons of two and three independent groups, respectively.Statistical analysis was performed using SPSS version 21.0  and Prism 6.0b for Mac . Normally distributed continuous data were expressed as mean ± SD. Systematic differences between measurements were evaluated with Student paired Intermodality, interobserver, and intraobserver agreement was studied using the Bland-Altman method,Receiver operating characteristic (ROC) curves were derived for 2D and 3D echocardiographic parameters to identify CMRI-derived RV EFs of <50% in patients with PH and healthy volunteers.P < .001), but the median image quality score was significantly higher among patients  than controls  (P < .001). The image quality among three successive, equally populated subgroups of patients significantly improved with increasing experience with 3DE (P = .031). There was a trend, albeit not statistically significant, for greater differences in SV between modalities with worse subjective image scores .Of 100 individuals who were recruited, four had unobtainable RV echocardiographic windows. The clinical characteristics and 3D echocardiographic technical data of the final cohort of 96 subjects are presented in Correlation coefficients showed good to excellent correlations between modalities for RV metrics in patient groups and moderate to good correlations for control subjects . RV voluP = .031), with sensitivity of 94%. A fractional area change of 39%  was the best conventional 2D echocardiographic measure, superior to both peak systolic strain and TAPSE (P = .0443). TAPSE was the weakest marker to predict CMRI-derived RV EF < 50%, with sensitivity of 56% at a cutoff threshold of 19 mm.Three-dimensional echocardiographic EF was the most superior echocardiographic parameter for identifying CMRI-derived RV EF < 50%  and EF (P = .033), with accompanying large interobserver COVs and relative differences. Moreover, despite no significant differences between intraobserver EDV and ESV, the differences translated into statistically significant test-retest differences for SV (P = .032) and EF (P = .005). The interobserver and intraobserver reproducibility for RV volumes and EF by CMRI showed no significant bias and superior limits of agreement compared with 3DE.Limits of agreement were acceptable for intra- and interobserver 3D echocardiographic studies, with good to excellent ICCs . HoweverThis study demonstrates the feasibility of single-beat full-volume 3DE for RV quantification in, to our knowledge, the largest homogenous acquired RV pressure- and volume-overloaded patient populations. Single-beat 3DE is an agreeable technique compared with CMRI, albeit with significant differences especially in subjects with nondilated right ventricles. Furthermore, 3D echocardiographic parameters are of incremental benefit for RV functional quantification compared with traditional 2DE measures.Accurate quantitation of RV size and function is important in many congenital and acquired cardiac diseases and is of particular relevance in our study populations. RV size and function are of greater prognostic significance in PH than the afterload to which the right heart is exposed,The incremental benefit of 3DE over 2DE has previously been shown in congenital heart disease,RV quantification by echocardiography is advantageous through being more readily available and less expensive than CMRI. Since the first use of 3DE for RV volumetric quantification,The disadvantages of echocardiography include constraints that afford inadequate transthoracic windows, including body habitus, hyperinflated lungs, and chest deformities. Acquisition and postprocessing was feasible in 96% of subjects, consistent with previously reported studies using the technique.When comparing studies of RV quantification by 3DE, the homogeneity of the study population must be taken into account. Our populations of acquired RV disease were favorable for the 3D echocardiographic postprocessing software algorithm, because it is set up for an adult-shaped right ventricle rather than a congenital heart.The progressive increase in 3D echocardiographic image quality over the study duration reflects a significant learning curve with the technique, as also described in previous studies.Furthermore, nonsignificant differences in intraobserver EDV and ESV nevertheless resulted in significant differences in SV and EF when the errors in the raw volumes were combined. Given that small changes in endocardial border delineation are known to confer significant changes in 3DE-derived volumetric parameters in the left ventricle,This study was a single-center study based on acquisitions made by one sonographer with experience using single-beat 3DE for RV volumetric quantification. As demonstrated by our test-retest reproducibility, results cannot be applied across operators with variable experience in 3D echocardiographic RV analysis. Patients with arrhythmias were excluded because of the extra variability introduced by irregular cardiac cycles when comparing modalities. Single-beat acquisition is advantageous over traditional disk summation techniques that are limited by stitching artifacts due to irregular R-R intervals, and this patient group requires further investigation with the technique.We found a bias to underestimate cavity size, particularly in control subjects, but the study was not designed to compare the accuracy of the technique in patients with large versus small cavity sizes. This question should be addressed in a separate prospectively designed analysis of large versus small right ventricles. The sensitivity and specificity values for 3DE and 2DE to identify CMRI-derived RVEF < 50% were calculated by applying the ROC cutoff values to the same patients used to derive them as described previously,Finally, the study was not designed to provide CMRI test-retest reproducibility similar to the 3D echocardiographic study design for acquisition and postprocessing. However, CMRI does not have the same acquisition window restrictions inherent to transthoracic echocardiography, as contiguous transaxial RV slices of fixed thickness are acquired from the base of the right heart to the main pulmonary artery with the patient in the supine position. However, this difference in technique methodology is a potential source of discrepancy, with the reference standard of CMRI building volumes from multiple slices compared with the full-volume data sets of 3DE.Single-beat full-volume 3DE is a feasible technique for quantifying RV size and function in acquired right heart pressure and volume overload. The limits of agreement of 3DE are acceptable compared with CMRI but may not be sensitive enough to detect small yet clinically significant responses to treatment demonstrated by this modality.


Introduction: Atrial conduction time has important hemodynamic effects on ventricular filling and is accepted as a predictor of atrial fibrillation. In this study we assessed atrial conduction time in patients with non ischemic dilated cardiomyopathy (NIDCMP) and functional mitral regurgitation (MR) and aimed to determine factors predicting atrial conduction time prolongation.Methods: Sixty five patients with non ischemic dilated cardiomyopathy who have moderate to severe MR and 60 control subjects were included in the study. In addition to conventional echocardiographic measures used to asses left ventricle and MR, atrial electromechanical coupling , intra- and interatrial electromechanical delay (intra and inter AEMD) were measured.Results: The correlations between inter AEMD and left atrial (LA) size, MR volume, isovolumetric relaxation time (IVRT), deceleration time (DT), systolic pulmonary artery pressure (PAPs), E/A ratio and E/e’ were very poor. Similarly, intra AEMD was not correlated to LA size , MR volume, IVRT, DT, PAPs, E/A ratio and E/e’. However, both inter AEMD and intra AEMD had good correlation with left ventricular mass index, tenting area (TA), tenting distance (TD), coaptation septal distance (CSD), sphericity index (SI).Conclusion: Prolongation of inter and intra AEMDs were found to be well correlated with parameters reflecting left ventricular and mitral annular remodeling. Increased incidence of AF is attributed to elevated left atrial (LA) pressure and fibrosis secondary to pressure and/or volume overload in the LA.9 MR and reduced ejection fraction are associated with elevated LV and LA filling pressures which finally lead to AF, additionally they are related to adverse clinical conditions and reduced survival.12 Several echocardiographic parameters reflecting cardiac remodeling in functional MR such as tenting area (TA), tenting distance (TD), inter-papillary muscle distance (IPMD), coaptation septal distance (CSD) and sphericity index (SI) were examined recently to assess if they have a role in estimating adverse clinical outcome.18Functional MR is a phenomenon that occurs in the setting of adverse remodeling of the left ventricle (LV) and deformation of the mitral valve apparatus as a consequence of advanced LV systolic dysfunction.In our study, we aimed to investigate the interatrial and intraatrial conduction times and their relation with echocardiographic parameters reflecting LV global/regional remodeling in patients with NIDCMP who have functional MR compared to normal subjects.Sixty five patients with NIDCMP who have moderate and severe MR  and 60 normal subjects  were included in the study. Patient group was selected from subjects with previously confirmed etiology of heart failure by coronary angiography.Patients with a history of coronary artery disease, organic mitral valve disease, aortic valve disease, bundle branch block, atrioventricular conduction abnormalities on ECG, pericarditis, thyroid dysfunction, anemia, hypercholesterolemia, electrolyte imbalance, renal failure, pulmonary disease, echocardiographic image that was technically insufficient, patients who had electrocardiographically documented AF episode and ECG where clear-cut beginning or ending of the P wave could not be discerned were excluded from the study.A commercially available echocardiography system  was used. The pulse wave Doppler study of the mitral and tricuspidin flows was performed from the apical four-chamber view in order to obtain the following parameters: mitral peak early (E) and peak late (A) velocities, deceleration time (DT) of E and A, mitral E/A ratio and isovolumetric relaxation time (IVRT). TDI was used to measure the early diastolic myocardial velocity (e’) at the septal and lateral mitral annulus. The E/e’ ratio was obtained using the average of septal and lateral e’. Systolic pulmonary artery pressure (PAPs) was estimated from the peak velocity of the tricuspid regurgitation obtained by continuous wave Doppler.11 CSD, defined as the distance between the coaptation point of the mitral valve leaflets and the septum at the hinge point of aortic valve cusp, was measured in the parasternal long-axis view at mid-systole  was obtained at the level of the mitral leaflets in the apical four-chamber view and early diastolic tissue velocity (E’) was measured at the level of the septal mitral annulus. For determination of LV mass (LVM), the Devereux formula was used: LV mass (g): 1.04 [(LVID + PWT + IVST)3 – LVID3] – 14 . LV mass index (LVMI) was calculated by dividing LVM by body surface area.-systole  . Mitral-systole . Mitral -systole  and C. S-systole . The sev22TDI was performed by transducer frequencies of 3.5–4.0 MHz, adjusting the spectral pulsed Doppler signal filters until a Nyquist limit of 15–20 cm/s was reached, and using the minimal optimal gain. The monitor sweep speed was set at 50–100 mm/s to optimize the spectral display of myocardial velocities. In apical four-chamber view, the pulsed Doppler sample volume was subsequently placed at the level of LV lateral mitral annulus, septal mitral annulus, and right ventricular tricuspid annulus. The sampling window was positioned as parallel as possible to the myocardial segment of interest to ensure the optimal angle of imaging. The time interval (in millisecond) from the onset of P wave on surface electrocardiogram to the beginning of late diastolic wave (Am wave), which is called atrial electromechanical coupling (PA), was obtained from lateral mitral annulus, septal mitral annulus, and right ventricular tricuspid annulus and named as PA lateral, PA septum, and PA tricuspid respectively . Values 6The difference between PA lateral and PA tricuspid  was defined as inter AEMD, and the difference between PA septum and PA tricuspid (PA septum – PA tricuspid) was defined as intra AEMD.2 test was used to assess differences between categorical variables. The relationship between parameters was determined using the Pearson’s coefficient of correlation. A two- tailed P value of <0.05 was considered significant for all tests.SPSS 15.0 software  was used for statistical analysis. All values are presented as mean ± standard deviation. Normal distribution was tested with Kolmogorov-Smirnov test .Values between different groups were compared using the independent-samples student t-test. The χThe clinical characteristics and conventional echocardiographic parameters of patients included in the study are given in the Correlation analysis was performed to determine the parameters that were related to prolonged electromechanical delay in patients with functional MR. The correlations between inter AEMD and LA size , MR volume , IVRT , DT , PAPs , E/A ratio  and E/e’  were very poor. Similarly there were no correlation or a very poor one between intra AEMD and LA size , MR volume , IVRT , DT , PAPs , E/A ratio  and E/e’ . Conversely, correlations between inter AEMD and LVMI , TA , TD , CSD , SI   and corr4 Fibrosis and enlarged LA tissue prolong and divert the propagation of action potential in LA tissue, and cause multiple micro reentries resulting in AF.24AF is also one of the most commonly encountered rhythm disorders in patients with MR and is directly associated with increased mortality and morbidity. Increased incidence of AF is attributed to elevated LA pressure and fibrosis secondary to pressure overload in the left atrium.35, It was detected in our study that intra/inter AEMD were prolonged in patients with NIDCMP who have moderate to severe functional MR compared to control group. The prolongation of intra- and inter AEMD and the inhomogeneous propagation of sinus impulses are well-known electrophysiological characteristics of the atria prone to fibrillation.7 This prolongation in inter/intra AEMD corresponds to the increased AF incidence in patients with NIDCMP who have functional moderate to severe MR. In literature, our study is the first to report that both inter and intra AEMD are prolonged in this patient group.The prolongation of atrial conduction times were shown in many clinical circumstances such as amyloidosis, coronary artery disease, paroxysmal AF, mitral stenosis, rheumatoid arthritis, Behçet’s disease and NIDCMP.18 But the association between AEMD and these prognostic parameters is not well examined. So, the next aim of the study was to explore the effects of hemodynamic parameters and the parameters that reflect the left ventricular remodeling on AEMD and indirectly on the incidence of AF.Several studies have shown that LV local and global remodeling, papillary muscle dysfunction and displacement, mitral annular dilatation and intraventricular dyssynchrony contribute independently to regurgitation of the anatomically normal mitral valve. It has also been shown that global remodeling associated with chamber enlargement, increased sphericity, and several echocardiographic parameters such as TA, TD, IPMD, and CSD have been shown to reflect the geometric alterations in the mitral valve apparatus and to give accurate estimations of prognosis in patients with NIDCMP.As we examine the effects of hemodynamic and left ventricular remodeling parameters on AEMD, no association was detected between AEMD and indices reflecting left ventricular diastolic performance , PAPs and parameters reflecting the degree of MR . Good correlations were detected between AEMD and mitral annular area, LVMI, CSD, SI, TA and TD which are the determinants of left ventricular dilation and remodeling, as well as deformation of mitral annular apparatus.These results indicate that hemodynamic determinants such as the degree of diastolic dysfunction, the degree of MR, and PAPs have no important effects on AEMD in patients with NIDCMP who have mild to moderate functional MR. Because hemodynamic findings are relatively labile and may change from time to time and also in response to therapy, it is considered that they are not able to predict prolongation in AEMD which were mainly caused by chronic alterations in tissue architecture such as fibrosis and remodeling. As mitral annular area, LVMI, CSD, SI, TA and TD are the determinants of cardiac remodeling and dilatation caused by both the disease itself and functional MR, they are considered to reflect the disease severity and prolongation in AEMD more precisely.9 supports our idea that parameters reflecting global/ regional remodeling are better than hemodynamic parameters in predicting the prolongation of AEMD in patients with NIDCMP who have moderate to severe functional MR.The fact that the previous studies blamed chronic fibrotic changes and LA remodeling in the emergence of AFBoth intra/inter AEMD were prolonged in patients with NIDCMP who have functional MR compared to normal subjects. In this patient group, prolongation of AEMD times were found to be well correlated with parameters reflecting left ventricular and mitral annular remodeling. However, the correlations between AEMD times and parameters reflecting hemodynamic status such as diastolic filling parameters, PAPs, severity of MR were absent or very scant.Written informed consent was obtained from each subject and our institutional ethics committee approved the study protocol.Authors declare no conflict of interests in this study.


Therefore, both myocardial perfusion and adrenergic imaging are useful tools in the workup and management of heart failure patients. This guide is intended to reinforce the information on the use of nuclear cardiology techniques for the assessment of heart failure and associated myocardial disease.Heart failure is increasing worldwide at epidemic proportions, resulting in considerable disability, mortality, and increase in healthcare costs. Gated myocardial perfusion single photon emission computed tomography or PET imaging is the most prominent imaging modality capable of providing information on global and regional ventricular function, the presence of intraventricular synchronism, myocardial perfusion, and viability on the same test. In addition,  Heart failure (HF) is growing globally at epidemic proportions, causing considerable increases in disability and mortality as well as in healthcare costs 99mTc single photon emission computed tomography (SPECT) or PET imaging (MPI) is the most prominent imaging modality capable of providing, in a reproducible manner, information on global and regional ventricular function, the presence of intraventricular synchronism, myocardial perfusion, and viability on the same test. In addition, 123I-mIBG scintigraphy is the only imaging technique approved by various regulatory agencies able to provide information regarding the adrenergic function of the heart. Therefore, both adrenergic imaging and MPI are useful tools in the workup and management of HF patients.Gated myocardial perfusion 123I-mIBG as an adjunct to their risk stratification for treatment selection. The specific number of HF patients who would benefit from undergoing these imaging techniques for a specific country is thus dependent on accurate statistics in terms of the total number of HF patients seen in clinics, which is a difficult number to obtain, depending on the country. It is estimated that HF affects 23 million people worldwide Results from a worldwide meta-analysis of all pertinent clinical trials up to 2007 suggest that ∼1–3% of all patients discharged alive after hospitalization for HF and 15–20% of all patients seen in HF clinics meet cardiac resynchronization therapy (CRT) eligibility criteria This guidance is a consensus statement from an international panel of nuclear medicine experts assembled by the International Atomic Energy Agency (IAEA). The initial purpose was to address how to use our techniques to help manage patients with Chagas disease, but the focus quickly transitioned to the topic of addressing the potential use of nuclear medicine techniques in all patients with HF. This guidance is intended to reinforce the information on the use of available nuclear cardiology techniques for the assessment of HF and associated myocardial disease. This article is not intended as an exhaustive review of all data on the subject of HF imaging but rather as a consensus statement of experts with knowledge on the existing evidence, mainly addressed to developing countries with limited resources. Because PET radiopharmaceuticals used in HF assessment are not widely available the panel focused on scintigraphic planar and SPECT procedures.123I-mIBG imaging have an important role in the diagnostic workup and risk assessment of patients with HF.The prevalence of heart failure is increasing in both developed and developing countries. Ischemic cardiomyopathy is the most common etiology of chronic HF Recent recommendations CRT is a biventricular pacemaker with a third electrode attached to the left ventricle to assist in resynchronizing the mechanical contraction of the left ventricular (LV). CRT has been shown to benefit some patients with end-stage HF, depressed left ventricular ejection fraction (LVEF) (<35%), and a wide QRS complex on the surface ECG >120 ms , and is The specific reasons why a patient with heart failure should be referred to nuclear cardiology myocardial perfusion imaging:To assess myocardial ischemia.To assess LV global and regional viability.To assess whether LV function is preserved, including regional wall motion and thickening, LVEF, LV volumes, and myocardial LV mass.To assess LV eccentricity To assess LV intraventricular dyssynchrony To assess the last viable segment to contract in patients being considered for CRT In addition, assessing patients’ risk of cardiac death contributes to the determination of the probability of sudden death and the need for an ICD 123I-mIBG, is a powerful risk stratification tool for patients with HF 123I-mIBG imaging, which is based on a false transmitter analog of norepinephrine, we can assess cardiac sympathetic innervation.Much evidence has accumulated to show that cardiac autonomic imaging, such as with 123I-mIBG imaging procedures are well established, although more work is needed for SPECT imaging and comparative analysis with MPI.On the basis of worldwide experience, the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology have recently proposed standardized methods 123I-mIBG availability is severely limited throughout the world, being actively used only in specific regions. Although available in Japan, Europe, and Brazil for a long time, 123I-mIBG has just been recently approved in the USA by the FDA for HF evaluation.123I-mIBG imaging, especially determination of the heart-to-mediastinum (H/M) ratio, very effectively separates high-risk from low-risk patients, regardless of LVEF and NYHA clinical conditions Multiple studies have shown that 123I-mIBG:The specific reasons why a patient with heart failure should be referred to nuclear cardiology 123I-mIBG cardiac uptake as given by the H/M ratio To assess To use the H/M ratio to help risk stratify the patient To use the H/M ratio in risk stratification to help decide on a change of management decision. For example, the condition of an HF patient without ICD has changed and now ICD is being considered Concerns about medical exposure to ionizing radiation in cardiac patients have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. Although several landmark epidemiological studies involving similar levels of radiation exposure show increased cancer risk, no strong data currently relate ionizing radiation specifically from cardiac imaging to increased risks of cancer In general, radiation dose is less of a concern in elderly patients with HF because the risk of dying from heart disease is far greater than any radiation concern. Patients admitted to hospital with a diagnosis of cancer often have a longer survival compared with those with a diagnosis of HF. Prognosis in HF that requires hospitalization can be considered far worse than that of many common types of cancer. For example, in the Framingham cohort, 62 and 75% of men and 38 and 42% of women, respectively, died within 5 years of being diagnosed with HF Regardless, the least amount of radiation burden for the patient should always be taken into account for each specific protocol.Because of the higher radiation exposure to the patient from thallium-201, if other tracers are available they should be considered as alternatives, although the effective dose (mSv/MBq) has been revised and lowered by one-third from 2.1E−01 to 1.4E−01 Other noninvasive imaging techniques such as echocardiography, computed tomography, and MRI can provide useful information for both diagnostic and prognostic purposes in HF patients.Transthoracic echocardiography remains the most performed myocardial imaging technique because of its widespread availability, low cost, and ability to provide information on valvular function, atrial size, right ventricular size, and contractility. Stress echocardiography, either with physical stress or with dobutamine, is extensively used to noninvasively detect the presence of CAD, the most common underlying etiology of DCM. In contrast, tissue Doppler imaging techniques However, it is important to point out the need for acceptable echocardiographic windows to precisely determine these parameters, as well as to emphasize that the technique is less reproducible than nuclear cardiology techniques, requiring a considerable level of expertise of the echocardiographer.Coronary computed tomographic angiogram (CCTA) allows the noninvasive visualization of coronary anatomy and helps to define plaque morphology. It is currently considered a well-established tool for evaluating coronary disease Coronary calcium evaluation is a useful way to noninvasively assess atherosclerotic burden and provides some guidance to the clinician for the differential diagnosis between a possible ischemic versus nonischemic etiology for LV systolic dysfunction It is important to point out that the information offered by CCTA is mainly anatomical and does not include data regarding the presence or absence of ischemia, which is of particular interest in case of patients with CAD who need a revascularization procedure. Nuclear techniques are very well standardized in this setting, offering valuable information on the presence and extension of ischemia, as well as on the status of the intraventricular synchronization, very useful in the case of patients evaluated for CRT.Cardiac magnetic resonance (CMR) is a versatile tool used to assess etiology in congestive heart failure because of its capability for tissue characterization and simultaneous assessment of LV function and wall motion and the possibility of myocardial viability detection through the late enhancement gadolinium images, which accurately delineate a scar, a powerful marker of poor prognosis in DCM. CMR has the advantage of not using ionizing radiation. The American College of Cardiology and the American College of Radiology have recommended CMR as an appropriate tool for the evaluation of LV systolic dysfunction of unknown etiology On the basis of the current available evidence, the following points represent our consensus position for guidance on the use of nuclear cardiology techniques for the assessment of HF and associated myocardial disease:18F-FDG is available for viability assessment it should be used, but in most situations an adequate SPECT MPI can provide the necessary information.To assess ischemia, a 1- or 2-day rest–stress protocol probably with pharmacologic stress and nitrates for rest should be used. Assessment of viability is important and should include assessment of scar burden. Scar burden is defined by the total amount of scar in the LV expressed as a percentage of the total LV and is an independent prognostic factor as well as a variable for treatment choice. If In HF patients, gating to help measure function is very important, although these patients have more gating problems Physicians should be aware of the differences in normal values for the functional parameters of the software being used. Specifically, the report should include assessment of LVEF, LV end-systolic volume, transient ischemic dilation, eccentricity, and LV dyssynchrony. In addition, in patients being assessed for CRT the report should also include the last viable segment to contract  and 2.LV synchrony assessment is important, particularly for patients being considered for CRT therapy It has been shown that 71% of HF patients who fulfill the CRT criteria respond to the treatment if their bandwidth is greater than 135° and/or SD is greater than 43° Segmental time of onset of contraction may be evaluated either visually from dynamic phase displays or preferably through segmental phase histogram measurements.Planar gated blood pool images have also been used for assessment of dyssynchrony Echocardiography is another option for evaluating LV dyssynchrony, particularly using the appropriate software  123I-mIBG is commonly imaged in an anterior planar view initially (15–30 min after injection) and in delayed images 4 h later, and optionally with SPECT imaging


Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32±0.09 ms, and a short mean T1 of 226±46 ms were demonstrated for the healthy volunteers at 3T. Over one million people in the United States are affected by multiple sclerosis (MS), a disease that presumably affects myelin of the central nervous system Magnetic resonance imaging (MRI) plays an important role in diagnosing as well as monitoring progression and response to therapy in demyelinating diseases because of the high contrast between normal and abnormal tissue. Researchers have been working for decades to develop non-invasive MRI techniques to accurately characterize myelin in vivo Direct imaging of myelin is likely to significantly improve specificity in evaluating myelination and demyelination However, characterizing the ultrashort T2* components, including measurement of T1, T2 and T2* requires further consideration. While T2* can be measured with techniques such as two-dimensional adiabatic inversion recovery preparation and dual echo UTE (2D IR-dUTE) acquisition at a series of TEs, techniques for robust T1 measurement are not so obvious. The purpose of the present study was to investigate a novel approach for robust T1 measurement of the ultrashort T2* components in white matter of the brain in healthy volunteers using a clinical 3T scanner.nd echo image which acquires signals mainly from the residual long T2 tissues from the 1st image would provide selective imaging of the ultrashort T2* components in white matter of the brain.The dominant signal in white matter of the brain is from the long T2 components Long T2* signal contamination is a major source of error in accurate T2* quantification of the ultrashort T2* components, which have far lower signal intensities than these of the long T2* components in white matter of the brain. We employed IR-dUTE imaging to minimize long T2* contamination. T2* of the ultrashort T2* components in white matter of the brain was measured via exponential fitting of the IR-dUTE signal acquired at a series of TE delays using the following single exponential signal decay model:Quantification of T1 of the ultrashort T2* components in white matter of the brain requires the use of UTE sequences because of their extremely short T2*s. A primary inversion recovery based approach is not feasible due to the failure to invert the ultrashort T2* components using the pulses available on clinical scanners (which have limited RF power). Saturation recovery based approaches have been used for more accurate T1 measurement xy and fz describe the behavior of the transverse magnetization and longitudinal magnetization, respectively, as a function of the half pulse b1(t) as well as the T2* and T1 of the ultrashort T2* components.Here we proposed an IR-dUTE based approach. With regular 2D UTE where the duration of the half RF pulses is of the order of T2*, the transverse magnetization for a steady-state UTE acquisition can be written as z(T2) after the adiabatic IR pulse, neglecting T1, is approximately Recent studies demonstrate that the short T2 magnetization is partially inverted or saturated by the long adiabatic inversion pulse, and recovers during TI, after which it is partly excited by the half RF pulse Here P is the attenuation factor due to long adiabatic IR pulse, and Q is the fraction of longitudinal magnetization following the adiabatic IR pulse.The steady state transverse magnetization following an adiabatic IR pulse and a half RF excitation pulse can be calculated as follows Our previous studies suggest that the ultrashort T2* components have T2*s around 0.3–0.5 ms, similar to those of cortical bone 2> is the measured signal, A is the true signal amplitude which will be used for T2* and T1 quantification and σ is the background noise.Because the ultrashort T2* components in the white matter of the brain have a very low proton density, the IR-dUTE signal is relatively low. Noise correction is important for accurate estimation of T2*, and especially T1. We used the approach proposed by Miller et al to correct the biased signal A piece of rubber  was used for validation of the T1 and T2* measurements. A piece of fresh bovine cortical bone sample with a cross sectional thickness of 3 mm was harvested from tibial midshaft bought from a local slaughter house . T1 validation was further performed on this bovine bone sample. Since conventional 2D slice selective UTE imaging is subject to eddy currents which may distort the slice profile and produce inaccurate T2* measurements nd echo image In total six healthy volunteers  were recruited for this study. This study was reviewed and approved by the institutional review board (ethics committee) of the University of California, San Diego (UCSD), before the study began. And written informed consent approved by our Institutional Review Board was obtained prior to the participation of each subject. An eight-channel head coil was used for signal excitation and reception. The same rubber phantom was placed beside the brain for validation of in vivo T2* and T1 measurements. The following imaging parameters were used: FOV = 24 cm, slice thickness  = 5 mm, BW = 256 kHz, flip angle  = 70°, reconstruction matrix  = 256×256, number of projections  = 131, sampling points per projection  = 192. For T2* measurements, a TR of 1500 ms and a TI of 420 ms were used together with four sets of dual-echo UTE acquisitions . For T1 measurement the following four sets of TR/TI combinations: TR/TI = 750/260, 1000/320, 1500/420 and 2000/480 ms were used. The total scan time was 26 minutes for T2* measurement and 23 minutes for T1 measurement. The optimal TI was determined empirically by measuring the signal to noise ratio (SNR) of the white matter on the 2Quantitative evaluation of SNR, T2* and T1 were performed on each volunteer. SNRs were calculated as the ratio of the mean signal intensity inside a user drawn region of interest (ROI) to the standard deviation of the background noise (with the ROI drawn in air). T2* values were obtained using a Levenberg-Marquardt fitting algorithm based on nd echo image with a TE of 2.2 ms (SNR∼2.6), directly confirming that the long T2 components in white matter were efficiently suppressed by the adiabatic inversion pulse so that only the ultrashort T2* components were detected by the IR-dUTE first echo image with a SNR of 17.2±3.3.nd echo image, as demonstrated by the near noise level SNR of 2.4. Excellent single component exponential recovery curve fitting was achieved for the rubber. A short T1 of 195±14 ms was demonstrated. This T1 was very close to that derived from the non-selective 2D saturation recovery UTE (only 7.1% higher), and the non-selective 2D IR-UTE (only 1.5% lower), suggesting that the IR-dUTE sequence is capable of fast accurate measurement of the T1 of ultrashort T2 species. A short T1 of 234±80 ms was demonstrated for the ultrashort T2* components in white matter of the brain in this healthy volunteer.High contrast morphological imaging and quantitative evaluation of T2* and T1 were achieved for all six healthy volunteers recruited for this study. The results demonstrate that the ultrashort T2* components in brain white matter have very short T2*s ranging from 0.27 ms to 0.40 ms and short T1s ranging from 197 to 248 ms. On average, a short mean T2* of 0.32±0.09 ms, and a short mean T1 of 226±46 ms were demonstrated for the healthy volunteers at 3T.The existence of multiple water components in white matter of the brain is well recognized. Multi-component analysis of the CPMG T2 signal decay demonstrates three water components: myelin water (T2∼10–50 ms), intra/extra axonal water (T2∼80 ms) and interstitial water (T2∼2000 ms) 2O exchange does not affect the signal intensity of the ultrashort T2* components, suggesting that the ultrashort T2* signal of nerve and spinal cord samples were predominantly from myelin lipids.However, all of the water components described above are unlikely to be signal sources for the IR-dUTE signal. Conventional clinical sequences with TEs of several milliseconds or longer cannot directly detect signal from the ultrashort T2* components in white matter of the brain, which have T*s of hundreds of microseconds or less While it has been confirmed that there are ultrashort T2* components in white matter of the brain with extremely short T2* values, the T1s of these components have not been well studied. As far as the authors know, the only published T1 measurement was done by Nayak et al., who employed a 4 to 8 ms nonselective hard 90° excitation pulse together with a dephaser to suppress the long T2 magnetization, followed by UTE acquisitions  at a series of TRs  to measure T1 of the ultrashort T2* components in white matter in fixed cadaveric brain nd echo image), the characterized signal is believed to be selective for the ultrashort T2* components in white matter. As a result, a simplified T1 measurement can be achieved. This approach may also allow accurate measurement of T1 of other ultrashort T2* species such as cortical bone. We compared T1 measurement of a piece of bovine cortical bone using the two approaches described above, and found the IR-UTE approach provided a T1 of 266±9 ms which is very close to the T1 of 253±18 ms produced by the standard saturation recovery approach  may have prolonged T2 and thus become detectable with clinical UTE sequences. Some lipid protons with T2 in the range of a few hundred microseconds  are clinically detectable with UTE sequences There are several limitations of this study. Most notably the signal recovery curve shown in The relative contributions of myelin water protons (if any) and non-water protons to the IR-dUTE signal will be investigated in future studies. The IR-dUTE sequence is a 2D technique and is subject to eddy currents. 3D IR-dUTE imaging based on radial or cone trajectories provides volumetric coverage with less sensitivity to eddy currents


Measures of left ventricular cardiac mechanics such as strains and torsion are becoming increasingly important for assessing heart function. Cardiac magnetic resonance (CMR) can be used to quantify cardiac mechanics using several methods such as tagged CMR or cine Displacement Encoding with Stimulated Echoes (DENSE). These images are generally acquired during an end-expiratory breath-hold. Unfortunately, it is difficult for subjects to hold their breath at the exact same position when undergoing a series of breath-holds during a typical CMR study. For example, end-expiratory breath-hold positions have an average range of about 8 millimeters (mm). The effects of different breath-hold positions on measures of cardiac mechanics have not been investigated. We hypothesized that the normal variability in breath-hold positions would significantly affect the quantification of left ventricular strains and torsion.Eight healthy volunteers (age 27 ± 3 years) with no history of cardiovascular disease were consented. A 3T Siemens Tim Trio scanner was equipped with a navigator feedback system to enable subjects to view their diaphragm position in real time during image acquisition. We used this navigator feedback system to acquire a navigator-gated basal, mid-ventricular, and apical slice of two-dimensional cine DENSE at three different breath-hold positions spaced 4 mm apart for a total range of 8 mm. The 2D DENSE parameters were: 6 spiral interleaves, FOV = 340, matrix = 128 × 128, thickness = 8 mm, TE/TR = 1.08/17, flip angle = 20, averages = 1. A narrow navigator acceptance window of ± 2 mm was used to properly simulate the different diaphragm positions. Radial strains, circumferential strains, and torsion were calculated for each subject and compared between diaphragm locations using a repeated measures ANOVA with a Huynh Feldt correction.Diaphragm position had a minimal effect on left ventricular radial strain, circumferential strain, and torsion Figure . The onlDifferent breath-hold positions simulated with a navigator feedback system had minimal effects on the calculation of peak left ventricular cardiac strains and torsion from two-dimensional DENSE CMR. It will be important to determine whether this result holds true in a future study which includes patients with potentially heterogeneous contraction patterns in the left ventricle.NIH Early Independence Award to BKF (DP5 OD012132) University of Kentucky Cardiovascular Research Center, grant UL1RR033173 from the National Center for Research Resources (NCRR), funded by the Office of the Director, National Institutes of Health (NIH) and supported by the NIH Roadmap for Medical Research Contributions made by local businesses and individuals through a partnership between Kentucky Children's Hospital and Children's Miracle network. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources.


To investigate whether myocardial deformation imaging, assessed by a noninvasive post-processing feature tracking algorithm (FTI) on regular cardiac magnetic resonance (CMR) cine images, would allow objective quantification of regional and global left ventricular (LV) strain and provide the estimation of functional recovery in patients with first time ST-elevation myocardial infarction (STEMI).Cardiac magnetic resonance (CMR) imaging was performed in 74 consecutive patients (mean age: 57 ± 12yrs.) 2-4 days after successfully reperfused STEMI, using a 1.5T whole body MR scanner (Philips Achieva). Peak systolic circumferential and longitudinal strain were measured using the feature tracking algorithm applied to SSFP cine sequences and were compared to infarct size, determined by late gadolinium enhancement (LGE). Follow-up CMR at 6 months after STEMI was performed in order to assess follow-up ejection fraction, which deemed as the reference standard for the estimation of function.Significant correlations were observed between global circumferential and longitudinal strain with infarct size by LGE . During the follow-up period 53 of 74 (72%) patients exhibited preserved residual ejection fraction≥50%. A cut-off value of -19.3% for global circumferential strain identified patients with preserved ejection fraction ≥50% at follow-up with sensitivity of 76% and specificity of 85% , which was superior to that provided by longitudinal strain , and non-inferior to that provided by LGE . Multivariate analysis showed that global circumferential strain and LGE exhibited independent value for the prediction of preserved LV-function, surpassing that provided by age, diabetes and baseline ejection-fraction .Estimation of circumferential strain by FTI provides objective assessment of infarct size without the need for contrast agent administration and estimation of functional recovery with non-inferior accuracy compared to that provided by LGE.N/A.


Accumulation of diffuse myocardial fibrosis / extracellular volume (ECV) in the myocardium is common to various cardiac diseases and is associated with an unfavorable prognosis. Various cardiac magnetic resonance (CMR) T1 mapping techniques have recently been proposed for the quantification of ECV, including:1. Modified Look-Locker Inversion recovery (MOLLI) T1 mapping including calculation of ECV, 2. Post-contrast multiple-breath-hold T1 mapping. 3. Native (pre-contrast) T1 mapping.T1 mapping is a promising technique, however, validation data based on myocardial biopsy are sparse.36 heart failure patients underwent CMR T1 mapping and left-ventricular biopsy within 4 weeks. CMR protocols  included non-product MOLLI and multiple-breath-hold T1 mapping.The population consisted of 22 patients with HFpEF (heart failure with preserved ejection fraction), 7 with cardiac amyloidosis, 3 with HFrEF (heart failure with reduced ejection fraction) and 4 with organic mitral regurgitation (MR).Specimens were stained using modified Trichrome. TissueFAXS and dedicated software were used to quantify ECV.ECV by TissueFAXS was 32±17% and 35±13% by CMR MOLLI. Post-contrast T1 times by the multiple-breath-hold sequence were 411±79ms, native T1 times were 1009±73ms. Patients with amyloidosis had significantly more ECV by TissueFAXS  and with CMR MOLLI  compared with the other pathologies.The amount of TissueFAXS ECV correlated significantly with native T1 times , MOLLI ECV  and with multiple-breath-hold post-contrast T1 times . When excluding patients with amyloidosis, only MOLLI ECV significantly correlated with histology , whereas multiple-breath-hold post-contrast T1 times just missed the level of significance .In our series, MOLLI ECV appears to be the most promising method for the quantification of extracellular matrix when validated against histology. Future studies need to define the prognostic value of T1 mapping in a large prospective cohort.The study received support from the Österreichischer Herzfonds and the Austrian fellowship grants KLI 245.


Three-dimensional echocardiography is a novel imaging technique based on acquisition and display of volumetric data sets in the beating heart. This permits a comprehensive evaluation of left ventricular (LV) anatomy and function from a single acquisition and expands the diagnostic possibilities of noninvasive cardiology. It provides the possibility of quantitating geometry and function of LV without preestablished assumptions regarding cardiac chamber shape and allows an echocardiographic assessment of the LV that is less operator-dependent and therefore more reproducible. Further developments and improvements for widespread routine applications include higher spatial and temporal resolution to improve image quality, faster acquisition, processing and reconstruction, and fully automated quantitative analysis. At present, three-dimensional echocardiography complements routine 2DE in clinical practice, overcoming some of its limitations and offering additional valuable information that has led to recommending its use for routine assessment of the LV of patients in whom information about LV size and function is critical for their clinical management. Quantitation of left ventricular (LV) size, geometry, and function represents the most frequent indication for an echocardiographic study and is pivotal for patient evaluation and management. Indication to cardiac surgery , to treaThe advent of three-dimensional echocardiography (3DE) represents a real breakthrough in cardiovascular ultrasound. Advancements in computer and transducer technology permit the acquisition of 3D data sets with adequate spatial and temporal resolution for assessing most of cardiac pathologies. 3DE enables the visualization of cardiac structures from virtually any perspective, providing a more anatomically sound and intuitive display, as well as an accurate quantitative evaluation of anatomy and function of heart valves –10. In aData regarding clinical applications of 3DE are burgeoning and gradually capturing an established place in the noninvasive clinical assessment of anatomy and function of cardiac structures. Recently, joint European Association of Echocardiography and American Society of Echocardiography recommendations have been published, aiming to provide clinicians with a systematic approach to 3D image acquisition and analysis . Among tThis spotlight paper is aimed at summarizing the state-of-the-art 3DE applications to assess LV geometry and function, emphasizing the advantages of 3DE over conventional 2DE and its current limitations .The milestone in the history of 3DE has been the development of fully sampled matrix array transthoracic transducers based on advanced digital processing and improved image formation algorithms which allowed the operators to obtain on-cart transthoracic (TTE) real-time volumetric imaging with shorter acquisition time, higher spatial and temporal resolution  16]. Fu. Fu16]. z axis (elevation) is fixed by the thickness of the tomographic slice, which, in turn, is related to the vertical dimension of piezoelectric elements.A conventional 2D phased array transducer is composed of multiple piezoelectric elements electrically isolated from each other and arranged in a single row. Individual ultrasound wave fronts are generated by firing individual elements in a specific sequence with a delay in phase with respect to the transmit initiation time. Each element adds and subtracts pulses to generate a single ultrasound wave with a specific direction that constitutes a radially propagating scan line . The linCurrently, 3DE matrix array transducers are composed of about 3000 independent piezoelectric elements with operating frequencies ranging from 2 to 4 MHz and 5 to 7 MHz for TTE and TOE, respectively. These piezoelectric elements are arranged in a matrix configuration within the transducer  in order2 of personal computer electronics board area). If the same beamforming approach would have been used for matrix array transducers used in 3DE, it would require around 4 kW power consumption and a huge PC board area to accommodate all the needed electronics. To reduce both the power consumption and the size of the connecting cable, several miniaturized circuit boards are incorporated into the transducer, allowing partial beamforming to be performed in the probe  are in the system and consume a lot of power  and multibeat 3D mode  18]. In. In18]. Conversely, multibeat acquisition is realized through sequential acquisitions of narrow smaller volumes obtained from several ECG-gated consecutive heart cycles (from 2 to 6) that are subsequently stitched together to create a single volumetric data set. It provides large data sets with high temporal and spatial resolution, but more prone to artifacts due to patient or respiratory motion or irregular cardiac rhythms. The most appropriate acquisition mode for the specific clinical setting will be chosen in each individual case. en face views of the tricuspid valve or cardiac defects). Two main actions are undertaken by the operator to obtain the desired view from a 3D volumetric data set: cropping and slicing. Similar to what the anatomists or the surgeons do to expose an anatomic structure within a 3DE data set, the operator should remove the surrounding chamber walls. This process of virtually removing the irrelevant neighbouring tissue is called cropping  , 2120, 23D TTE has been extensively validated against CMR  and has r = 0.79 for both), with CT outperforming both (r = 0.89). 3D TTE LV ejection fraction values were also less reproducible than those derived from CT. One might speculate that TTE's apparent disadvantage in this study is related to its operator dependence, during both acquisition and image analysis, given that the CT software automatically determined volumes while the specific 3D TTE software used in this study  requires tracings of the endocardial borders at both end-diastole and end-systole.In another recent study, 36 prospectively enrolled patients underwent 3D TTE, 2D TTE, CMR, CT with contrast, and invasive cine ventriculography . Both 3DThe systematic underestimation of LV volumes by 3D TTE stems in part from its lower spatial resolution as compared to CMR. By convention, when CMR volumes are traced according to Simpson's method of disks, the trabeculae are included in the LV cavity. With 3D TTE, it is often difficult to clearly identify the endocardial-trabecular border, and as a result, one may instead trace the blood-trabecular interface. In a systematic review of sources of error, it was shown that agreement between 3D TTE and CMR measurements improved when the trabeculae were excluded from the LV cavity . In thisA recent meta-analysis of studies evaluating 3D TTE for LV volumes demonstrated that 3D TTE was superior to older techniques requiring transducer rotation and reconstruction . Althoug3D TTE is a robust technique for quantifying LV volumes and ejection fraction in patients with abnormal LV geometry. Regional wall motion abnormalities, including those due to myocardial infarction, do not compromise the accuracy of LV volume and ejection fraction measurement –35. 3D TIn a recent meta-analysis Dorosz et al.  found siFor years, the usefulness of 3D TTE in everyday practice was limited by the absence of reference values for LV chamber volumes and ejection fraction. Recently, several publications –44 have r values generally 0.8 and higher) , 4140, 4The availability of cardiac resynchronization therapy (CRT) for refractory heart failure has generated considerable interest in LV intraventricular dyssynchrony assessment. For quantitative dyssynchrony evaluation, the LV is most commonly divided into 16 or 17 segments as per the American Heart Association standard model , and theFinally, a reliable, clinically meaningful cutoff value for the 3D dyssynchrony index has yet to be established . Larger,3D strain is a novel technology aimed at assessing LV myocardial deformation by analyzing the motion of myocardial speckles within the 3D LV data sets. This technology allows following the motion of speckles in the space without any assumption about the direction of their motion and the measurement of all LV deformation components  plus the computation of the area strain  from a single apical LV 3D data set. Theoretically, 3D speckle-tracking technology should overcome the main limitations of 2D speckle tracking: the “out-of-plane” motion of speckles due to the rotation and shortening motion of the left ventricle and the need to interpolate the whole LV myocardium from the partial information contained in a limited number of thin, tomographic slices of the LV .3D TTE strain acquired using speckle tracking has been studied in several clinical contexts. In patients surviving an acute myocardial infarction, higher baseline global longitudinal strain by 3D TTE is independently predictive of improvement in LV ejection fraction at 6-month follow-up . ImpaireTo date, the main issues that are currently limiting the applicability of 3D strain in the clinical arena are (i) lack of reference values for the regional and global strain parameters for the various deformation components; (ii) lack of multicenter outcome studies assessing its additive prognostic value over the well-established 2D strain; and (iii) significant intervendor differences of 3D strain algorithms and values among vendors, preventing its routine applicability for clinical purposes .Another application of 3DE that may open a complete new way to assess prognosis in patients with myocardial and valvular heart diseases is the quantitative analysis of LV shape. 3D TTE is well-suited to portray global and regional shape of the LV . A 3D TT3DE is a novel imaging technique based on acquisition and display of volumetric data sets in the beating heart. This permits a comprehensive evaluation of LV anatomy and function from a single acquisition and expands the diagnostic possibilities of noninvasive cardiology. It provides the possibility of quantitating geometry and function of LV without preestablished assumptions regarding cardiac chamber shape and allows an echocardiographic assessment of the LV that is less operator-dependent and therefore more reproducible.Further developments and improvements for widespread routine applications include higher spatial and temporal resolution to improve image quality, faster acquisition, processing and reconstruction, and fully automated quantitative analysis. At present, 3DE complements routine 2DE in clinical practice, overcoming some of its limitations and offering additional valuable information that has led to recommending its use for routine assessment of the LV of patients in whom information about LV size and function is critical for their clinical management.


Heart failure secondary to cardiac siderosis is the prevalent cause of mortality in patients with primary or secondary iron overload. Myocardial iron assessment using T2* has been successfully calibrated against myocardial iron at 1.5T and the black blood (BB) technique has demonstrated high reproducibility such that it has become the clinical gold standard. T1 appears to correlate with T2* in cases of significant iron loading (T2* < 20 ms) but this relationship weakens when T2* is in the normal range. We evaluated this further.69 subjects  comprising 20 healthy volunteers (controls) and 49 patients  referred for routine iron assessment were recruited. The same mid-ventricular short axis cardiac slice was used to acquire both BB T2* images and to generate T1 MOLLI maps for each subject at 1.5T . 20 subjects underwent repeat studies on the same day to evaluate reproducibility. Regions of interest were selected in the septum using CMRtools.2 = 0.696; Figure There was a reasonable correlation between BB T2* and T1 values described by a logarithmic relationship (RIn this analysis, T1 mapping using a MOLLI sequence identified all those individuals with significant iron loading as defined by the current gold standard T2* technique and has excellent reproducibility. As expected, T1 can also identify patients with mild cardiac iron loading that is not considered clinically significant. It is possible that T1 may have a clinical role in non-cardiac conditions with very low levels of iron loading, where factors other than iron affect the T2* signal, however tissue calibration remains lacking at this time. Further work is needed to determine whether there might be clinically significant advantages of T1 over the T2* cardiac technique at 1.5T for assessment of cardiac iron, but there are none at this time.This research was supported by the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and Imperial College London.


Contrast agents are used in resting echocardiography to opacify the left ventricular (LV) cavity and to improve LV endocardial border delineation in patients with suboptimal image quality. If a wider use of contrast-enhanced echocardiography would be adopted instead of the current selective approach, diagnoses such as myocardial ischemia and LV structural abnormalities could potentially be detected earlier. The aim was therefore to retrospectively investigate if contrast-enhanced echocardiography beyond the current recommendations for contrast agent usage affects assessment of wall motion abnormalities, ejection fraction (EF) and detection of LV structural abnormalities. A secondary aim was to evaluate the user dependency during image analysis.n = 4) evaluated wall motion score index (WMSI) and measured EF on greyscale and contrast-enhanced images from 192 patients without indications for contrast-enhanced echocardiography. Additionally, screening for LV structural abnormalities was performed. Repeated measurements were performed in 20 patients by the experienced as well as by inexperienced (n = 2) readers.Experienced readers (p < 0.003). Of the 83 patients, classified as healthy by greyscale analysis, 55 % were re-classified with motion abnormalities by contrast analysis. No significant difference in EF classification  was observed. LV structural abnormalities, such as increased trabeculation (n = 21), apical aneurysm (n = 4), hypertrophy (n = 1) and thrombus (n = 1) were detected during contrast analysis. Intra- and interobserver variability for experienced readers as well as the variability between inexperienced and experienced readers decreased for WMSI and EF after contrast analysis.Contrast analysis resulted in significantly higher WMSI compared to greyscale analysis (Contrast-enhanced echocardiography beyond current recommendations for contrast agent usage increased the number of detected wall motion and LV structural abnormalities. Moreover, contrast-enhanced echocardiography increased reproducibility for assessment of WMSI and EF. Accurate assessment and high reproducibility of left ventricular (LV) volumes, ejection fraction (EF), and myocardial wall motion are important factors for diagnosis of cardiac diseases , 2. CardCurrent guidelines from both the European and American Societies (European Association of Cardiovascular imaging (EACVI) and American Society of Echocardiography (ASE)) recommend the use of contrast-enhanced echocardiography in patients with suboptimal image quality or when there is a suspicion of structural abnormalities , 8. In sat rest in the subset of patients beyond the current recommendations for contrast agent usage in standard echocardiography. Note that the greyscale images routinely are acquired with such quality that deformation analysis using speckle tracking is feasible during rest and stress. The image acquisition was performed with a GE Vivid E9 , at a transmitted frequency of 1.5–1.7 MHz. All contrast-enhanced images were acquired at a low MI index using contrast specific image sequences, such as pulse inversion. SonoVue®  (n = 187) and Optison®  (n = 5) were used as contrast agents.This retrospective study included patients who were referred to stress echocardiography from January 2013 to February 2014 at the Karolinska University Hospital in Huddinge (The heart clinic), Sweden. This patient group was selected as the image protocol at our institution routinely involves analysis of both greyscale and contrast-enhanced images both at rest and during stress, regardless of image quality. This enables a comparison of the diagnostic outcome between greyscale and contrast-enhanced images n = 4, 3–15 years of experience) of contrast-enhanced echocardiography visually evaluated whether patients should be included in the study or not. Additionally, patients were excluded if any apical 2 chamber (ch), 3ch or 4ch images in either greyscale or contrast mode were missing. The study protocol was approved by the regional ethical review board in Stockholm, Sweden.The exclusion criteria were based on the recommendations for contrast agent usage during standard echocardiography , 8. PatiThe flow chart of the image analysis is shown in Fig. From apical 2ch, 3ch and 4ch views, WMSI was obtained by dividing the LV using an 18 segment model . Each seLeft ventricular end-diastolic volume (EDV), left ventricular end-systolic volume (ESV) and EF were measured in one cardiac cycle using the biplane method of disks summation (the modified Simpson’s rule) in EchoPAC . End-diastole was visually defined as the maximal cavity area following mitral valve closing, whereas end-systole was defined as the minimal cavity area preceding mitral valve opening. In accordance with the recommendations from EACVI and ASE, papillary muscle and trabeculations were excluded from the cavity during tracing .The contrast-enhanced images (3 images/patient) were screened for LV structural abnormalities such as apical hypertrophic cardiomyopathy, ventricular non-compaction, thrombus and ventricular pseudoaneurysm. The screening for LV structural abnormalities was only conducted by the experienced readers. Note that patients, who showed structural abnormalities on the greyscale images, were already excluded from the study since they had indication for contrast-enhanced echocardiography.t test (95 % confidence level) was used to compare numerical groups. WMSI for each patient was determined by calculating the sum of all WMS divided by the number of visualized segments [t test (95 % confidence level) was used to compare WMSI before and after contrast. Patients were categorized according to reference values of EF: ≥ 55 % reference range, 45–54 % mildly abnormal, 30–44 % moderately abnormal, < 30 % severely abnormal [Data analysis was performed using the statistical software IBM SPSS Statistics 19 . Age, blood pressure, LV volumes and EF were classified as continuous data and expressed with mean and standard deviation. Paired Student segments . Paired abnormal . AdditioIn total, 321 patients referred for stress echocardiography at the Karolinska University Hospital in Huddinge, Sweden, were screened for the study. After the review process, 192 patients were included in the patient group, whereas 129 patients were excluded due to insufficient image quality (80), allergy to contrast agent (1), absence of at least one apical image view (30), suspicions of non-compaction (10), thrombus (7) or hypertrophic cardiomyopathy (1). Patient characteristics of the patient group included in the study are presented in Table Table p < 0.003). This corresponds to 99 patients having increased WMSI, 42 patients having decreased WMSI and 51 patients with no change after contrast analysis  were classified with normal wall motion after image analysis on greyscale images, i.e. WMS = 1 for every segment. Patients with NA segments were not included in these 83 patients, implying that, based on greyscale analysis, these patients were observed without wall motion abnormalities. After image analysis of contrast-enhanced images, 46 (55 %) of these patients were reclassified with abnormal wall motion  with normal wall motion (WMS = 1) and sufficient greyscale image quality (no NA segments) in every segment, where as much as 55 % of these patients, previously classified without wall motion abnormalities, were re-classified having regional wall motion abnormalities after contrast-enhanced analysis. Keeping in mind that the addition of contrast agent also allowed for detection of LV structural abnormalities in 27 patients, emphasizes that a broader use of contrast-enhanced echocardiography can contribute to earlier detection of cardiovascular diseases.The main finding from this study was that contrast-enhanced echocardiography significantly altered the assessment of cardiac function compared with greyscale echocardiography, in a patient group specifically selected due to not having an indication for contrast enhancement. This was mainly driven by an improved detection of regional wall motion abnormalities, evidenced by the fact that WMSI was significantly higher after contrast analysis compared with greyscale analysis. This was further evident when only considering patients , the number of not visualized segments were remarkably reduced from 169 segments to 14 segments when using contrast. However, it should be noted that the most common WMS shift for those NA segments was a change to normal wall motion after contrast analysis (71 % of the segments), implying that improved detection of wall motion abnormalities for contrast-enhanced images is not only restricted to segments with poor image quality, and that decreased regional wall motion indeed can be more evident using contrast even when the endocardial border is considered well visualized. This is not surprising considering the extremely strong enhancement of the endocardial border and detailed visualization of trabecula due to the maximal separation of cavity and myocardium in white and black respectively in the contrast-enhanced images.There was a significant difference in LV volumes and EF between the different imaging modes, with larger volumes and EF obtained for contrast-enhanced images. It is well known that LV volumes are underestimated when analyzing two-dimensional greyscale images, as the areas between the trabecula within the LV are excluded from the measurements, and that geometrical assumptions are made . SuboptiThe results from the study indicate improved reproducibility for WMSI and EF measurements when using contrast images instead of greyscale images, which is in line with previous findings in patients with mixed image quality –6. In ouIt has been reported in literature that approximately 10 to 15 % of all cardiac patients have indications for contrast-enhanced echocardiography . Followin = 46 patients) where a shift from normal wall motion (WMS = 1 in every segment) to abnormal wall motion was observed when comparing greyscale and contrast analysis. In total, 22 of these patients were confirmed with myocardial ischemia or infarction. When combining the results from the contrast analysis at rest in the present study with previous studies, it was concluded that the wall motion abnormalities overlapped with the diseased areas in 21 patients out of these 22 patients. This confirms that the observed shift in wall motion abnormalities in the present study after contrast analysis may indeed alter the outcome for the patients and improve the diagnostic power of resting echo, even in patients with excellent image quality. Another limitation with the present study is the over representation of patients with ischemic cardiac disease. This is not a true representation of the patient cohort normally referred to echocardiography. In fact, this is a pilot study and we are about to perform a prospective randomized study in order to study the true potential benefit of routine contrast agent use.The retrospective approach of the present study, where an objective gold standard, or alternative imaging modality to confirm the findings of regional wall motion abnormality interpretation is lacking, is a limitation. However, it should be kept in mind the contrast-enhanced imaging is known to improve diagnostic confidence and that several studies have shown that the results from the image analysis based on contrast-enhanced images correlate well with other imaging methods , 12–14. This study is a potential first step towards a broader use of contrast-enhanced echocardiography instead of the selective approach used today. From a patient safety perspective it should be kept in mind that contrast-enhanced echocardiography is probably one of the best validated techniques, because of strict protocols and completely blinded readings required for approval of contrast agents . The conThis study showed that contrast-enhanced echocardiography beyond the current recommendations for contrast agent usage indeed affects assessment of cardiovascular function, in this particular study evidenced by an increased number of detected wall motion and LV structural abnormalities during contrast analysis compared with greyscale analysis. Moreover, contrast-enhancement increased reproducibility for assessment of WMSI and EF measurements in the settings of this study. A prospective study, evaluating the full potential of a more widespread use of contrast agent instead of the current selective approach, is of considerable interest in terms of patient outcomes and increased cost-effectiveness.


According to current European classification, cardiomyopathies are defined as myocardial disorders that cannot be explained by coronary artery disease or abnormal loading conditions including valvular and congenital diseases. Six specific morphological and functional phenotypes are distinguished: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy together with two unclassified subtypes: Tako-tsubo and left ventricular noncompaction cardiomyopathies. In almost all of these phenotypes, inherited forms may be found; moreover, in some of them—for example, in hypertrophic cardiomyopathy—a genetic origin is even a rule. Therefore, genetic counseling shall be an integral part of the state-of-the-art care of patients with heart muscle disorders. The affected individuals together with their relatives have to be informed about the genetic basis of their disease and the potential risk for other family members. A detailed cardiac evaluation, including ECG and echocardiography , of first-degree relatives is necessary with their further regular follow-up. If available, genetic testing shall be discussed with the patients as it may improve their management as well as enable effective preventive genetic testing in other relatives.Because the evaluation of morphology and function of the heart, especially of the left ventricle, is a prerequisite for accurate phenotypic characterization of every myocardial disease, a multimodality imaging approach generally becomes necessary. Echocardiography is still a cornerstone of diagnostic imaging because it is accurate, widely available, safe, and without any contraindications. In recent years, advanced echo modalities gained a clinical role in the follow-up of chemotherapy-induced cardiomyopathy, and global longitudinal strain is recommended in the latest European guidelines.However, the role of cardiac magnetic resonance is increasingly important. Not only is it the current gold standard for morphological and functional assessment of heart chambers, but it has a unique opportunity of noninvasive tissue characterization. Based on evaluation of the presence of myocardial edema, hyperemia, and necrosis using dedicated sequences, cardiac magnetic resonance is capable of diagnosing acute myocarditis with high accuracy. Late gadolinium enhancement technique is widely used to assess the presence and extent of replacement myocardial fibrosis, which appears to be strongly related to the prognosis of affected individuals. Presence of myocardial fibrosis predisposes to increased risk of ventricular arrhythmias, sudden cardiac death, and progression of left ventricular dysfunction associated with heart failure worsening. One also has to mention the significant contribution of various techniques of nuclear medicine for the diagnosis of cardiac sarcoidosis and transthyretin amyloid cardiomyopathy.It is obvious that increasing knowledge on ethiopathogenesis of various myocardial disorders together with improved diagnostic possibilities shall result in novel therapeutic options. A complex immunohistochemical and PCR analysis of endomyocardial biopsy specimens allows us to characterize in more detail the presence and type of myocardial inflammation as well as the presence of possible causative infectious agents and select better more targeted treatment of acute myocarditis and inflammatory cardiomyopathy with administration of immunosuppressive or immunomodulatory drugs or antiviral agents. Many therapeutic strategies are currently investigated in the field of transthyretin amyloidosis including stabilizers of transthyretin tetramers and gene therapies aimed at suppression of transthyretin expression. Another important topic is the development of new treatment possibilities that will be able to prevent late sequelae of cytostatic therapy associated with potential cardiotoxic effect.Two original articles deal with the topic of chemotherapy-induced cardiotoxicity. P. Robinson et al. investigated in their experimental study the role of substance P in chemotherapy-associated death of cardiomyocytes and chemoresistance and nicely showed that aprepitant, a substance P receptor antagonist, is able to decrease doxorubicin induced death of cardiomyocytes as well as to increase the sensitivity of cancer cells to this drug. A. F. Yu et al. evaluated the use of 2D speckle tracking echocardiography in early diagnosis of cardiotoxicity associated with anthracyclines and radiation therapy. Their results confirm that this novel imaging modality is more sensitive in detecting left ventricular systolic dysfunction than traditional indices of ventricular function such as ejection fraction and thus can be used for long-term cardiac surveillance of adult cancer survivors.Three articles review several aspects of inflammation/infection related myocardial diseases. J. Krejci et al. largely summarize our current knowledge on pathophysiology, diagnosis, and treatment of inflammatory cardiomyopathy with emphasis on accurate evaluation of endomyocardial biopsy samples, which is prerequisite for the appropriate choice of subsequent treatment options. P. Kuchynka et al. nicely overview a difficult topic of eosinophilic myocarditis, a rare disorder necessitating quite rapid diagnosis, so early administration of immunosuppressive therapy that may improve the poor prognosis of affected individuals can be initiated. In the last article, R. H. Lumsden and G. S. Bloomfield present a brilliant review on HIV-associated cardiomyopathy which currently represents a significant cause of morbidity and mortality in this now chronic disease. The authors clearly demonstrate that there is a significant need to design clear guidelines for screening protocols and diagnostic criteria for HIV-related myocardial disease.Several issues related to hypertrophic cardiomyopathy are discussed in three articles. R. Pudil et al. aimed to investigate the significance of vascular endothelial growth factor in hypertrophic cardiomyopathy and their results show that increased levels of this substance are associated with structural and functional parameters in patients with hypertrophic cardiomyopathy suggesting the possibility of its use for a more accurate diagnosis. L. K. Williams et al. focused on left atrial function in hypertrophic cardiomyopathy. Using magnetic resonance velocity vector imaging, they convincingly demonstrate a negative impact of left ventricular outflow tract obstruction on left atrial size and function that significantly improves after septal myectomy. Finally, P. P. Dimitrow and R. Rajtar-Salwa review several aspects related to left ventricular outflow tract obstruction with emphasis on invasive as well as noninvasive treatment possibilities.If the readers will find the presented articles informative and stimulating their interest in myocardial disorders, the purpose of this special issue will be completely fulfilled.In this special issue we are pleased to introduce several interesting original as well as review articles focused on different topics in the field of myocardial diseases.Tomas PalecekJavier GanameGiovanni Di Salvo