Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly. This study shows the role of cardiovascular magnetic resonance (CMR) in assessing young patients following surgical repair of ALCAPA.6 patients, aged 9-21 years, with repaired ALCAPA  underwent CMR because of clinical suspicion of myocardial ischemia. Imaging used short and long axis cine images (assess ventricular function), late-gadolinium enhancement (LGE) , adenosine stress perfusion (detect reversible ischaemia) and 3D whole-heart imaging .2, LVESV = 31.6 ± 9.4 ml/m2). In 1 patient, hypokinesia of the anterior segments was visualized. Five patients showed sub-endocardial LGE involving the basal, antero-lateral wall and the anterior papillary muscle. Three patients had areas of reversible ischemia. In these 3, 3D whole-heart MRA showed that the proximal course of the left coronary artery was occluded (confirmed with cardiac catheterisation).The left ventricular (LV) global systolic function was preserved in all patients (mean LV ejection fraction = 62.7% ± 4.23%). The LV volumes were within the normal ranges, (mean indexed LVEDV = 75.4 ± 3.5 ml/mCMR is a good, non-invasive, radiation-free investigation in the post-surgical evaluation of ALCAPA. In referred patients we show that basal, antero-lateral sub-endocardial myocardial fibrosis is a characteristic finding. Furthermore, stress adenosine CMR perfusion, can identify reversible ischemia in this group, and was indicative of left coronary artery occlusion. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital cardiovascular defect that occurs in approximately 1 in 300 000 live births . The morth-5th month of life) when pulmonary vascular resistance drops and left coronary artery flow is reduced. All blood is now supplied by the right coronary artery and if there are few coronary collateral vessels, this can lead to coronary insufficiency. Patients with better coronary collateralization may present later in life with a 'steal' phenomenon: Blood from the right coronary artery passes to the left system via collaterals, and then directly into the low pressure pulmonary artery (systemic to pulmonary shunt), thus leading to under-perfusion in the left coronary territory [Symptoms and signs usually occur in early infancy , Tackeuchi repair , left cOnce treated, the most feared complication in patients is recurrence of myocardial ischemia and potential narrowing of the surgical anastomosis. However, assessment of these patients may not be straightforward and the interpretation of image findings may be difficult. In this study, we wanted to demonstrate the CMR appearance in a small group of young patients with repaired ALCAPA.In this retrospective study, 6 patients with repaired ALCAPA underwent full CMR assessment between may 2009 and March 2010. They were all referred for assessment because of clinical suspicion of myocardial ischemia . 4 patients were originally treated with direct re-implantation of the LCA, 2 patients with Tackeuchi repair  .Retrospectively gated, balanced steady-state free-precession cine images were acquired in the vertical long-axis and 4-chamber views. They were used to plan the short-axis stack, which included the extent of both ventricles (9 to 12 slices). The cine balanced steady-state free-precession sequence parameters were as follows: TR 2.4 ms, echo time 1.2 ms, flip angle 68°, slice thickness 6-10 mm, matrix 200 × 240, and field of view, 280 to 380 mm, with 25 phases per cardiac cycle. Post-processing assessment of RV and left ventricular (LV) volumes was performed by manually defining the endocardial outline at end diastole and end systole in each of the short-axis cine images (OsiriX version 3.8). The end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated with Simpson's rule for each ventricle, and from these volumes, the stroke volume (SV) and ejection fraction (EF) were derived.Flow assessment using phase contrast MR sequences was also performed in both the ascending aorta above the aortic valve and the pulmonary trunk above the pulmonary valve. We calculated the degree of mitral valve regurgitation as the LV SV minus the total aortic flow during systole.®, gadoterate meglumine, Gd-DOTA, Guerbet, Paris, France) at 0.1 mmol/kg, injected in the ante-cubital vein at flow rate of 2-3 ml/s and followed by a saline flush of 25 ml, flow 2-3 ml/s. Short axis images were acquired with a saturation-recovery, spoiled gradient echo sequence in at least 3 slices per heart beat (slice thickness 8 mm) with the following parameters: TI 200 ms, TR 260 ms, TE 1.1 ms, flip angle 12°, matrix 192 × 144, rectangular field of view of 187 × 250 mm, number of excitations 1, acquisition every RR interval. Data from 50 cardiac cycles were acquired. Patients were asked to hold their breath for as long as possible, then revert to shallow respiration during this acquisition, or, for the child requiring general anaesthesia, data was acquired during suspended mechanical ventilation. The perfusion sequence was repeated after 15 minutes at rest with the same parameters and bolus injection of gadolinium.Myocardial perfusion was performed under pharmacological stress with intravenous adenosine in a dose of 140 μg/kg/min over 6 minutes with constant ECG and blood pressure monitoring. The target of cardiovascular stress was either a 20% increase in the heart rate or a symptomatic response . The first-pass myocardial signal increase was evaluated during a bolus injection of gadolinium (DotaremInversion-recovery late gadolinium enhanced (LGE) CMR was performed after the rest perfusion intravenous injection of gadolinium (0.1 mmol per kilogram of body weight) by using a two-dimensional T1-weighted turbo field-echo technique in the cardiac short and long-axis planes . The inversion time was adjusted for optimal suppression of signal from normal myocardium, and the images were obtained within 10-15 minutes after injection (inversion time approximately 250-350 ms). All LGE images were interpreted accordingly to the American Heart Association 17-segment model [Coronary artery imaging was achieved using a 3D whole-heart MRA sequence covering the entire heart were obtained in a sagittal orientation by using a magnetization-prepared, 3D balanced, steady-state free precession sequence . Magnetization preparation was achieved by applying a T2-weighted preparation pulse with an echo time of 50 ms and a frequency-selective fat-saturation pulse followed by a spoiler gradient. A customized shim procedure was applied to the volume of the entire heart. For real-time respiratory gating and real-time correction of the 3D volume in the craniocaudal direction, a navigator echo was acquired from a cylindrical region that was generated by a two-dimensional excitation pulse perpendicular to the right hemi-diaphragm with a gating window of ±3 mm. The navigator efficiency (%) and total scan time (minutes) was calculated for each patient.2, mean LV end-systolic volume = 33.0 ± 9.1 ml/m2). Only one patient had mild dilatation of the LV in the presence of combined moderate aortic valve regurgitation and mild mitral valve regurgitation. One patient had isolated, mild hypokinesis of the mid-ventricular anterior segment, otherwise normal LV wall motion at rest was found in all cases.The LV ejection fraction (EF) was preserved in all patients (62.7 ± 4.23%). Cardiac volumes were within the normal ranges  on 3D whole-heart MRA. Conceivably, such a pattern of ischemia may be a consequence of the collateral circulation that developed prior to repair. This may not represent the current luminal state of the coronary arteries, and may not require treatment. Alternatively, others have suggested that these areas of perfusion defect may represent areas of microvascular disease ,21.This study is limited as it is retrospective and descriptive of an inhomogeneous patient population (in terms of age and previous operative type). However, the CMR findings are consistent across this small patient group, who have all been exposed to a similar pathophysiological insult.CMR can provide a comprehensive assessment of the anatomical, functional and ischemic consequences of coronary artery disease in young patients following surgical repair of ALCAPA.The finding of a basal, antero-lateral late-gadolinium enhancement pattern, including the papillary muscles, should prompt consideration of this diagnosis in paediatric or adult patients with this finding, following a presentation with chest pain.In this small study, adenosine perfusion MR can detect occluded ALCAPA re-implantation, though ultimately, larger and longitudinal studies of this condition are required to establish the true prognostic importance of imaging findings. Due to the low prevalence of ALCAPA, this will require multicentre participation.The authors declare that they have no competing interests.AS, HN, OT, PKS, VM and MH acquired the MR data. VM optimised the MR sequences. AS, VT and AMT participated in the design and coordination of the study. AS and AMT drafted the manuscript. All authors read and approved the final manuscript.


Approximately one in one hundred children is born with congenital heart disease. Most can be managed with corrective or palliative surgery but a small group will develop severe heart failure, leaving cardiac transplantation as the ultimate treatment option. Unfortunately, due to the inadequate number of available donor organs, only a small number of patients can benefit from this therapy, and mortality remains high for pediatric patients awaiting heart transplantation, especially compared to adults. The purpose of this review is to describe the potential role of mechanical circulatory support in this context and to review current experience. For patients with congenital heart disease, ventricular assist devices are most commonly used as a bridge to cardiac transplantation, an application which has been shown to have several important advantages over medical therapy alone or support with extracorporeal membrane oxygenation, including improved survival to transplant, less exposure to blood products with less immune sensitization, and improved organ function. While these devices may improve wait list mortality, the chronic shortage of donor organs for children is likely to remain a problem into the foreseeable future. Therefore, there is great interest in the development of mechanical ventricular assist devices as potential destination therapy for congenital heart disease patients with end-stage heart failure. This review first discusses the experience with the currently available ventricular assist devices in children with congenital heart disease, and then follows to discuss what devices are under development and may reach the bedside soon.  Although survival rates for patients with repaired or palliated congenital heart disease are now quite good, there remain a minority of patients who may experience either acute heart failure in the early postoperative period or end-stage heart failure much later . MechaniAgainst this background, ventricular assist devices (VADs) have experienced increasing use as a bridge to transplantation in children with encouraging results. Unfortunately, the number of potential heart transplant recipients far exceeds the donor pool, and heart transplantation cannot adequately meet the needs of this patient population . ConsequIn adults, VADs have been used as bridge to recovery or transplant, and even as destination therapy. In adults with end-stage heart failure, VAD support has been associated with improved survival versus medical management . AlthougIn 2010, Gazit and colleagues provided a comprehensive description and analysis of the options for mechanical circulatory support in children awaiting heart transplantation , and sumApproximately one in one hundred neonates is born with congenital heart disease . It is eDespite advances in corrective and palliative surgery for congenital heart disease, some patients will develop acute or chronic end-stage heart failure and will require cardiac transplantation. These patients with congenital heart disease and end-stage heart failure fall into three broad categories. First, there are some infants without surgical options other than cardiac transplantation due to the complexity of their problem . Second, some patients reach the point of end-stage heart failure after one or more palliative operations which adversely affect outcomes . It is eAnother interesting aspect is that pre-treatment with ECLS may help to improve pulmonary hypertension in patients awaiting cardiac transplantation for congenital heart disease although it is unclear whether this improves the overall outcome -25.Given the incidence of congenital heart disease, there will be a substantial number of patients with congenital heart disease in need of alternative treatment modalities. For instance, with approximately 4.3 million births in the United States in 2007 , it can http://www.berlinheart.de/index.php/newsroom/content/press_us/press_release_us]. While survival to transplantation is good (63%-89%) .The Maquet Cardiohelp is a compact, portable extracorporeal life support system. It has been used with the Maquet Quadrox-i adult oxygenator to provide emergency life support due to cardiogenic shock during patient transport. All components of this circuit are integrated, but changing the oxygenator to a neonatal or pediatric version  is an implantable micro-pump with a maximum capability of 3 L/min. Due to its small size and compatible flow rates, CircuLite was awarded a National Institutes of Health Fast-Track Phase I-II Small Business Innovation Research grant in July 2009 to convert their adult micro-pump into a pediatric specific pump capable of complete unloading of the heart. In preliminary juvenile bovine studies, the CircuLite Synergy System provided adequate left ventricular unloading, normal end-organ function, and no device malfunctions at a two-week time point post-implantation .An improvement to the previous Medos Delastream DP2 , this new diagonal flow rotary pump is approved in Europe for up to 7 days of continuous use. In addition to the ability to generate both pulsatile and non-pulsatile flow, the DP3 pump also has a low priming volume (16 mL) and very fine control over low flow rate adjustments, making it suitable for neonatal use . Preclinhttp://www.ventracor.com]. Due to its larger size, this device is not currently feasible for use in neonates, but larger pediatric patients may benefit from the future application of this device.Currently undergoing clinical trials, the Ventrassist pump  is a third generation, implantable LVAD with a range of 1.5-10 L/min. Currently, it is being investigated for bridge to transplant in adult patients. In 98 adult patients, 85% and 82% of patients were alive on support or transplanted at 6 and 12 months post-implantation .LaunchPoint Technologies and its collaborators at the University of Pittsburgh are designing the PediaFlow Pediatric VAD. Their newest version, the PF3, is attempting to meet the design requirements of full implantability in children 3-15 kg, flow rates of 0.3-1.5 L/min, and be sustainability of 6 months of circulatory support, while minimizing hemolytic trauma, thrombosis, and infection [Jarvik Heart, in collaboration with the University of Maryland and others, is redesigning the Jarvik 2000 axial flow pump for pediatric use. In juvenile sheep experiments, it was shown that the pediatric Jarvik 2000 could pump 1.4-2.5 L/min of blood for up to 70 days without important hemolysis or end-organ damage . The infBoth the Ension pCAS system and Pedi PumpLung from the University of Maryland will be self-contained devices capable of pumping and oxygenating blood simultaneously . It remaPerfusion quality is of the utmost importance to neonatal and pediatric patients undergoing ECLS. The minimization of post-ECLS complications, including neurological and other vital organ injury, depend on adequate perfusion of vital tissues. To this end, the faculty, perfusionists, and nurses at the Penn State Hershey Pediatric Cardiovascular Research Center have designed a new neonatal and pediatric ECLS circuit, whose components have been selected based on rigorous studies conducted by our center -50. ThisPatients with congenital heart disease and end-stage heart failure currently have a limited number of options for long-term mechanical circulatory support. In recent years, significant advances have been made, and more devices are under development with some having already reached pre-clinical trials. Over the next few years, continued improvements in the field of pediatric mechanical circulatory support are expected, including the addition of new pediatric VADs, new magnetically levitated centrifugal pumps, and new low pressure drop hollow-fiber membrane oxygenators for ECLS.


We aimed to identify the clinical utility of a simple echocardiographic approach for estimating the pulmonary capillary wedge pressure (PCWP) on the basis of the combined assessment of mitral inflow and tissue Doppler mitral annular velocities.We retrospectively enrolled 165 patients who underwent both echocardiographic examination and right heart catheterization, and determined the diagnostic accuracy of echocardiography-derived parameters for estimating PCWP >18 mmHg.E′) compared with the REF group. Eight patients in the PEF group but none in the REF group had normal LV diastolic function, represented as E′ >8 cm/s, and all of these patients had normal inflow pattern. The mean PCWP had the strongest correlation with the ratio of the peak early mitral inflow velocity (E) to the peak late diastolic mitral inflow velocity during atrial contraction (E/A) in both groups, followed by the left atrial diameter and E/E′ in both patient groups. Receiver operating characteristic (ROC) analysis demonstrated that the combination of abnormal E′ ≤8 and elevated E/A had high diagnostic accuracy compared with E/E′ in both patient groups with different cutoff values of E/A (1.81 in the PEF group and 1.16 in the REF group) for predicting mean PCWP >18 mmHg.Eighty-three patients had preserved left ventricular (LV) ejection fraction ≥50% (the PEF group) and 82 patients had reduced LVEF <50% (the REF group). The PEF group had higher peak early mitral annular velocity (E′, conventional E/A is a reliable marker for predicting high PCWP and is superior to E/E′.After excluding patients with normal diastolic function using  E) velocity to the peak early mitral annular velocity (E′) is most widely used for estimating the PCWP in the clinical setting. However, several publications have recently raised concerns about the reliability of E/E′, especially in patients with preserved LV ejection fraction (EF), mainly because E′ is affected by LV morphology, regional function, and mitral annular structure, resulting in an erroneous PCWP estimation [Invasively measured pulmonary capillary wedge pressure (PCWP) has been widely used as a surrogate for left ventricular (LV) filling pressure and is directly associated with functional capacity and prognosis in patients with heart failure –3. Severtimation , 7.E′ is influenced by multiple intrinsic factors as described above, it has a great ability to identify abnormal LV diastolic function. Therefore, a simple combination of E′ and mitral inflow pattern would provide a more precise estimation of high PCWP in patients having both reduced and preserved LVEF. Accordingly, our objective was to identify the potential reliability of a simple echocardiographic approach for predicting high LV filling pressure by the combined assessment of mitral inflow and tissue Doppler mitral annular velocities in patients with reduced and preserved LVEF with heterogeneous etiologies of heart disease.Although the mitral inflow patterns, traditional, and simple Doppler indices have U-shaped relations to LV filling pressure, they can be used for the estimation of the PCWP with reasonable accuracy after discriminating patients with diastolic dysfunction from those having normal diastolic function and, thereby, normal inflow pattern. Although mitral annular n = 69), constrictive pericarditis (n = 3), pacemaker (n = 16), prosthetic valve (n = 25), hemodialysis (n = 14), cardiac shunt (n = 16), acute coronary syndrome (n = 21), and patients who exhibited worsening or improvement in New York Heart Association (NYHA) functional class during the brief time between the right heart catheterization and the echocardiography (n = 44). This study was approved for use by the Human Studies Subcommittee of Mie University Graduate School of Medicine.We retrospectively enrolled 373 consecutive patients ≥18 years of age who underwent both right heart catheterization and transthoracic echocardiography because of concerns about hemodynamic derangements at the Mie University Hospital between June 2004 and November 2011. From this group, we selected 165 patients after excluding patients with atrial fibrillation , the ratio of E and A velocities (E/A), and the deceleration time (DT) of E velocity [E′ ≤8 was used as an indicator of LV diastolic dysfunction [E/E′ was calculated for the prediction of a high mean PCWP. All Doppler values represent an average of 3 beats. The etiology and severity of valvular heart disease, if present, was identified by comprehensive echocardiographic assessments quantified by Doppler-derived echocardiography [E′ ≤8 and high E/A can more accurately predict elevated PCWP than E/E′-derived PCWP estimation under the clinical assumption that high E/A in the setting of abnormal LV diastolic function strongly indicates the presence of high filling pressure. Care was taken to obtain all images in the traditional imaging planes by an experienced echocardiographer. All images were evaluated blindly offline by an experienced sonographer at the Mie University Hospital echo core laboratory.All patients underwent routine transthoracic echocardiography using a Vivid 7 system  or an Aplio ultrasound system  within 2 weeks (3 ± 4 days) before or after right heart catheterization. The size of the left atrium, interventricular and LV posterior wall thicknesses, LV end-diastolic and end-systolic diameter, and LVEF were assessed from the parasternal long-axis view . Pulse-wvelocity . For tisvelocity . E′ ≤8 wfunction . E/E′ waiography , 10. We t-test or the Mann–Whitney U-test. Categorical variables were presented as percentage frequencies and differences between proportions were compared using the χ2 test. Receiver operating characteristic (ROC) curves were constructed to determine the optimal sensitivity and specificity for estimating PCWP >18 mmHg using inflow and tissue Doppler mitral annular parameters, and the differences in the area under the curve (AUC) between E/E′ and the combination of E′ and E/A were assessed by using Mann–Whitney U statistics. The diagnostic performance between E/E′ and the combination of E′ and E/A was compared with McNemar’s test. Confidence intervals were calculated according to the percentile method. A p-value <0.05 was accepted as being statistically significant. Data were analyzed using standard statistical software .Continuous variables were presented as the mean ± standard deviation (SD) and compared using the Student The basic demographic and clinical characteristics of the study participants are shown in Table E velocity was similar in the two groups, the PEF group had lower E/A and longer DT compared with the REF group. The PEF group had higher E′ compared with the REF group, and 8 (10%) patients in the PEF group but none of the REF group had normal LV diastolic function, represented as E′ >8.The echocardiographic measurements are shown in Table The hemodynamic measurements are shown in Table E/A, followed by the left atrial diameter and E/E′ in both patient groups. All eight patients with normal E′ >8 cm/s in the PEF group had E/A >1.0 (1.83 ± 0.79). ROC analysis demonstrated that the combination of E′ ≤8 and high E/A had excellent diagnostic accuracy with large AUC in both patient groups with different cutoff values of E/A (1.81 in the PEF group and 1.16 in the REF group) for predicting mean PCWP >18 mmHg , indicating that patients with false-positive E/E′ results have very low E′ values, which generate disproportionally high E/E′, even in the setting of low LV filling pressure  in the REF group  for predicting mean PCWP >18 mmHg.We revealed the clinical utility of the combined use of E′ or propagation velocity (Vp) is a relatively preload-independent parameter representing LV relaxation, and, therefore, they have been shown to be useful for predicting elevated PCWP. Most of the current ultrasound systems have tissue Doppler presets for assessing mitral annular velocities [E/E′ is most widely used for estimating the PCWP in the clinical setting. However, there are several known limitations for the use of E/E′ in the estimation of LV filling pressure in various specific heart diseases or conditions, such as valvular heart disease and heart failure with preserved LVEF [E/E′ had high negative predictive value in patients with both preserved and reduced LVEF, but the positive predictive value was low, especially in patients with preserved LVEF. Although we should take into account the fact that the low prevalence of high mean PCWP might contribute to this low positive predictive value, the weak correlation between E/E′ and the mean PCWP indicates that high E/E′ is not a strong marker of high PCWP and the use of E/E′ in the estimation of LV filling pressure in patients with preserved LVEF is not recommended in the daily clinical setting. Patients with false-positive E/E′ estimation had similar E/E′ but had lower E velocity and E′ compared with those patients with true-positive results in patients with both preserved and reduced LVEF in the present study. These results indicate that patients with false-positive diagnosis on the basis of E/E′ results may have a very low E′ value, which generates disproportionally high E/E′, even in the setting of low LV filling pressure. Hay et al. investigated the effect of LV relaxation, as assessed by the exponential time constant of relaxation, on LV filling pressure in an experimental model [E/E′ in the combination of very low E′ and non-elevated E velocity may not indicate high PCWP.The elevation of LV filling pressure is a unifying feature for heart failure, regardless of the underlying cause , and PCWlocities , which aved LVEF , 7. Our al model . They deE′ ≤8 cm/s indicates impaired LV relaxation [E′ is age-dependent [E′ for identifying diastolic dysfunction might vary between age groups, a single cutoff value of 8.0 was found to successfully identify patients with normal diastolic function and, hence, normal PCWP in the present study. The main diagnostic utility of this test lies in its high specificity and positive predictive value, making it a good rule out test for the exclusion of high LV filling pressure. We propose different E/A cutoff values for different patient populations for the prediction of mean PCWP >18 mmHg: 1.81 for patients with preserved LVEF and 1.16 for those with reduced LVEF. Small and stiff LV has the characteristic of being much more sensitive to preload changes compared with dilated LV [E/A for predicting the PCWP.Because mitral inflow patterns are highly sensitive to preload and can change dramatically as LV filling pressure increases, the use of mitral valve inflow patterns for predicting high mean PCWP can be ideal after discriminating normal inflow patterns in patients with normal diastolic function. It has been well recognized that laxation . Althougependent  and, thelated LV . TherefoE/E′ estimation with wide confidence intervals. Another limitation of the present study is the heterogeneous etiologies of heart disease, especially in patients with preserved LVEF. Although we succeeded in reaching our primary point that showed statistically significant higher diagnostic accuracy and etiological varieties might bring favorable distribution in the mean PCWP, further study in larger populations is needed in order to specify the etiological differences that might contribute to the diagnostic performance of the combined assessment of mitral inflow and tissue Doppler mitral annular velocities in the prediction of high mean PCWP. We only measured septal mitral annular velocities, and neither diastolic function at the lateral mitral annulus nor the average of both annuli was assessed. However, septal E′ is considered to correlate well with LV diastolic function, and is widely used clinically [Vp, which have been shown to be robust predictors of high LV filling pressures and cardiovascular mortality [Vp.Although we succeeded in the quantitative estimation of high LV filling pressure with the optimal cutoff by the combined assessment of mitral inflow and tissue Doppler mitral annular velocities, a potential limitation of the present study is the relatively small sample size with a low rate of high mean PCWP >18 mmHg in the PEF group, which lead to low positive predictive values of inically . Right hortality –21, were


Taurine, for example, represents 50% of total free amino acids in the heart, and Thirty-four male Wistar rats (body weight = 100 g) were weighed and randomly assigned to one of two groups: Control (C) or taurine-deficient (T (-)). Beta-alanine at a concentration of 3% was added to the animals’ water to induce taurine deficiency in the T (-) group. On day 30, the rats were individually submitted to echocardiography; morphometrical and histopathological evaluation and metalloproteinase activity, oxidative stress and inflammation evaluation were performed. Tissue samples were collected to determine the taurine concentration in the heart.Taurine deficiency led to decreases in: ventricular wall thickness, left ventricle dry weight, myocyte sectional area, left ventricle posterior wall thickness and ventricular geometry. With regard to heart function, the velocity of the A wave, the ratio between the E and A wave, the ejection fraction, fractional shortening and cardiac output values were decreased in T (-) rats, suggesting abnormal diastolic and systolic function. Increased fibrosis, inflammation and increased activation of metalloproteinases were not observed. Oxidative stress was increased in deficient animals.These data suggest that taurine deficiency promotes structural and functional cardiac alterations with unique characteristics. Patients with heart failure (HF) may have different nutritional needs than those with a normal physiological state Taurine accounts for 50% of total free amino acids in the heart Therefore, it is possible that taurine modulates morphological and functional cardiac variables. However, the physiological role of this amino acid in the heart is not fully understood. The objective of this study was to assess the role of taurine deficiency in normal rat hearts.ad libitum. In group T (-), 3% β-alanine (diluted in water), a well known antagonist of taurine transport, was administered Animals and treatment: Male Wistar rats, 21 days old and weighting 100 g, were used in the study; the animals were housed and cared for in accordance with the National Institute of Health’s Guide for the Care and Use of Laboratory Animals. The experimental protocol was approved by the Animal Ethics Committee of the Botucatu School of Medicine, UNESP, São Paulo, Brazil. The animals were randomly allocated into two groups: the control group  and the taurine-deficient group (T (-); n = 17). The animals were housed in individual cages; their feeding was monitored daily, and water was administered 3– LVSD3)/LVDD3], fractional shortening index [(LVDD – LVSD)/LVDD] x 100, cardiac output (CO) (LVDD3−LVSD3) x heart rate), flow velocity through the aorta (VAO), and cardiac index (CI) (CO divided by body weight). The velocities of transmitral diastolic flow (E and A velocities) were obtained from the apical four-chamber view. The E/A ratio, the isovolumetric relaxation time (IRT), and the isovolumetric relaxation time normalized to heart rate (IRT/RR0.5) were used as indices of LV diastolic function.Doppler-echocardiography: After the observation period, all animals were weighed and evaluated by a transthoracic echocardiographic exam Collection of biological material: Hearts were collected from the experimental animals. The right and left ventricles (including the interventricular septum) were dissected, separated and weighed. The water content and mass of the tissues was calculated by measuring the weight of the fragment after dissection, called the wet weight (WW), and the weight of the same fragment after it was dried for 48 hours in an oven at 65°C, called the dry weight (DW). Thus, the equation [(WW-DW)/WW] × 100 provides information on the water content in the tissue. The LV dry weight was determined by subtracting the water content from the original tissue weight.Picrosirius red (Sirius red F3BA in aqueous saturated picric acid). The measurements were obtained from digital images (40× magnification) that were collected with a video camera attached to a Leica microscope; the images were analyzed using Image-Pro Plus 3.0 software . The myocyte cross-sectional area (CSA) was measured with a digital pad, and the selected cells were transversely cut so that the nucleus was in the center of the myocyte Picrosirius red by analyzing digital images that were captured under polarized light (20× magnification). Perivascular collagen was excluded from this analysis Histopathologic study: A morphometric analysis of the myocardium was performed as described previously Determination of concentrations of taurine in the myocardium: Tissue concentrations of taurine were measured by high-performance liquid chromatography, using a Schimadzu ® LC10AD and a Shimadzu RF535 fluorescence detector. Phase A was a 25 mmol/L sodium phosphate solution, pH 6.9, containing 20 mL/L methanol, 20 ml/L acetonitrile, and 20 ml/L tetrahydrofuran, and phase B was a solution of 65% chromatographic-grade methanol, as described by Löser et al. (1988) e Sussman (1988) 2. The samples were then diluted in application sample buffer consisting of 0.5 M Tris, pH 6.8, 100% glycerol, and 0.05% bromophenol blue. The samples were loaded into wells of 8% SDS-polyacrylamide containing 1% gelatin. Electrophoresis was performed in a Bio-Rad apparatus at 80 V for 2 h, until the bromophenol blue reached the bottom of the gel. The gel was then incubated at 37°C overnight in activation solution consisting of 50 mM Tris, pH 8.4, 5 mM CaCl2 and ZnCl2. Staining with 0.5% Coomassie blue, 30% MeOH, and 10% acetic acid was performed for 2 h until clear bands over a dark background were observed. The gels were photographed, and the intensity of gelatinolytic action (clear bands) was analyzed in a UVP, UV, White Darkhon image analyzer.Metalloproteinase-2 and -9 activity: Metalloproteinase-2 and -9 activity was determined as previously reported by Tyagi et al Evaluation of cytokine production and adhesion molecules: The production of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and interleukin 10 (IL-10) were evaluated. Briefly, 60 mg of cardiac tissue sample was homogenized and solubilized in a solution containing 50 mM potassium phosphate buffer, pH 7.4, 0.3 M sucrose, 0.5 mM DTT, 1 mM EDTA, pH 8.0, 0.3 mM PMSF, 10 mM NaF, and 1∶100 protease inhibitor. Cytokine levels in cardiac homogenate were evaluated by ELISA, according to the manufacturer’s instructions  2+; and antioxidant enzyme activities Cardiac lipid hydroperoxide and antioxidant enzyme analysis: lipid hydroperoxide (LH) based on the hydro peroxide-mediated oxidation of Fe2), left ventricular systolic diameter adjusted by body weight (0.2 mm/kg).Statistical analysis: Comparisons between groups were made using Student’s t test for parameters with normal distribution. Otherwise, groups were compared using the Mann-Whitney U test. Data were expressed as means ± SD or medians (including the lower quartile and upper quartile). Data analysis was carried out using SigmaStat for Windows v2.03 . The significance level was 5%. This study was designed to have 80% power of detecting a difference of several parameters between the mean for the control animals and the mean for taurine-deficient animals: left ventricular end-diastolic diameter adjusted by body weight (2 mm/kg); and cross sectional area  g, T(-) = 262 (252–288) g; p = 0.558). Group T(-) animals had lower levels of taurine in the left ventricle  = 0.4±0.1 µmol/mg of tissue; p = 0.007).The morphological data assessed by echocardiogram are shown in The functional data assessed by echocardiogram are shown in Histological analysis data and metalloproteinases values are shown in The LV water content was higher  and the The data showing the cardiac lipid hydro peroxide and antioxidant enzyme activities are presented in + buffering during high-intensity exercise) The rat taurine deficiency model used in this study consisted of treatment with a solution of 3% ß-alanine. The treatment caused a 77% decrease in the concentration of taurine in the LV. This decrease in taurine concentration is higher than those observed by Parildar et al. The noteworthy finding in the present study was that taurine deficiency resulted in cardiac atrophy, as confirmed by thinning of the ventricular wall, reduced left ventricular dry weight, decreased myocyte cross sectional area, and increased oxidative stress. Regarding diastolic function, these data are consistent with decreased diastolic function in animals that are deficient in taurine. Indeed, the taurine-deficient group showed a lower velocity A and E, a higher E/A ratio, and a tendency for lower IRT/HR. With regard to systolic function, the echocardiographic data are consistent with systolic dysfunction. Decreased ejection fraction, fractional shortening and cardiac output were observed in the taurine-deficient group, compared to the control group. Moreover, in the present study, increased fibrosis and greater activation of metalloproteinases were not observed upon optical microscopy. These findings are similar to those described by Ito et al. Baskin & Taegtmeyer (2011) stated that these atrophic remodeling characteristics are cellular consequences of metabolic and hemodynamic unloading of a stressed heart Food restriction and protein-energy malnutrition induce changes in the heart such as atrophy and cardiac dysfunction Another mechanism that could explain our study findings is a decrease in protein synthesis and/or increase in protein catabolism. Protein synthesis is dependent on amino acids, and decreased protein synthesis may occur when amino acids are limiting, such as in the case of deficient diet or amino acid overuse (catabolic stress) Thus, our results suggest that the mechanisms that led to cardiac atrophy and ventricular dysfunction in taurine-deficient animals are not the same mechanisms involved in food restriction, protein-energy malnutrition or protein metabolism alteration.Another potential mechanism involved in cardiac atrophy is load alterations. Indeed, changes in the hemodynamic mechanism of myocardium "load" may result in structural remodeling. In situations in which the heart undergoes pressure overload, concentric hypertrophy is observed, whereas volume overload leads to eccentric hypertrophy Inflammation was not responsible to the cardiac dysfunction observed in our study. Since the findings atrophy with decreased cardiac myocyte area, absence of fibrosis, no differences in metalloproteinase activity and no cytokine profile differences are not compatible with changes due to inflammation.So, considering the critical role of oxidative stress in cardiac remodeling, we suggest that oxidative stress is associated with the cardiac dysfunction observed in our study. Oxidative stress has direct effects on cellular structure and function, and it can activate signaling molecules that are involved in cardiac remodeling, including apoptotic cascade In conclusion, taurine deficiency promoted structural and functional cardiac alterations, particularly with regard to the left ventricle.


Mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) correlate with the left and right ventricular  ejection fraction as well as with the prognosis of patients with heart failure. Furthermore, M/TAPSE are sensitive markers for impaired longitudinal function which can be the earliest marker of myocardial dysfunction in cardiomyopathies with preserved ejection fraction. Cardiac MRI is the reference method for ventricular function and morphology and both M/TAPSE can be easily obtained from cine images. To date, there are no age and gender specific reference values for M/TAPSE derived from a healthy collective of normal volunteers.In this study we want to provide reference values for M/TAPSE for cardiac MRI with regard to age and gender.60 male and 59 female healthy volunteers were divided into three age groups . Images were acquired on a 1.5T whole body MRI scanner (Philips Achieva) using a SSFP sequence of short axis slices covering the entire left ventricle as well as two-, three- and four-chamber views. M/TAPSE were measured on 4-chamber SSFP images. Two separate reference lines were drawn in diastole and systole from the basal lateral tricuspid (TAPSE) and the basal anterior mitral leaflet (MAPSE) to a reference point on the left chest surface. The lengths differences of the reference lines between diastole and systole were measured and represent both M/TAPSE. P<0.05 was considered significant.The normal values for MAPSE and TAPSE are shown in table In this study, we present age and gender specific reference values of longitudinal LV and RV function in a large group of normal volunteers. Interestingly, in healthy volunteers the values of M/TAPSE are only marginally influenced by age or gender. However, further investigations are needed to confirm these findings and to provide quantification of pathological values.None.


About 3.8% of patients suffering an acute pulmonary embolism will develop chronic thrombembolic pulmonary hypertension (CTEPH). As a consequence of increasing pulmonary pressure and resistance right ventricular systolic and diastolic function deteriorate while right ventricular volumes increase. Pulmonary thrombendarterectomy (PEA) offers a potential cure with excellent longterm outcome. Cardiac MRI is an ideal tool to monitor remodelling and reverse remodelling before and after PEA, because it allows complete volumetric coverage of the complex right ventricular geometry. Several non invasive parameters which characterize diastolic, systolic and ventriculo-arterial properties can be derived from theses measurements. To quantify the remodelling potential of the right ventricle we performed volumetric measurements before and after PEAMethods: 65 consecutive patients who completed retrospectively ECG gated CINE MRI were included, mean age 41 ± 124 years, 28 female. Volumetric measurements were performed 2 ± 0.5 days pre and 10 ± 2 days post surgery by SSFP Cine sequences  covering the whole right ventricle from apex to base. Ejection Fraction (EF), enddiastolic volume (EDV), endsystolic volume (ESV), stroke volume (SV), diastolic ventricular interaction (left shift of the septum) (DVI) and ventriculo-arterial coupling (Ea-pulm/Es-RV) were derived from volumetric measurements. Right heart catheter measurements in standard procedure were evaluated, if available (retrospective data).Results: Pulmonary artery mean pressure and resistance decreased from 46 ± 12 mmHg and 663.2 ± 247.8 dynes * s * cm-5 respectively preoperatively to 31 ± 9 mmHg and 368.1 ± 206.2 postoperatively. EF improved from 26 ± 12% to 44 ± 10% (p = 0.00001), EDV and ESV decreased significantly . DVI with septal left shift was recorded in 80% of patients pre PEA and only 26% of patients post PEA, p=0.00001. Ea-pulm/Es-RV was markedly increased before PEA (3.9 ± 2.8) and significantly decreased to near normal values after surgery .Conclusion: CTEPH before and after PEA is like an on/off phenomenon of pulmonary hypertension and therefore allows to study the reverse remodelling capability of the right ventricle. Cardiac MRI derived parameters reflect changes of function, loading conditions and remodelling. We were able to demonstrate improvement in diastolic properties, ejection fraction, remodelling and loading conditions of the RV in one comprehensive examination. Therefore Cardiac MRI is ideally suited to monitor hemodynamic changes non invasively.No third party funding.


This observational pilot project was performed as background to eventually create a rapid, automated and accurate assessment of RV systolic function in variable clinical subgroups. We propose new parameters that characterize the global systolic function of the right ventricle with a simple linear measurement.The tricuspid annular plane systolic excursion (TAPSE), which has been used for over a quarter century as a quick estimate of RV systolic function, was revisited using CMR. It shows good correlation with invasive hemodynamics. MRI is the current gold standard to assess the volumes and anatomy of the heart and we can measure TAPSE more precisely with cardiac MRI to accurately detect any current problems TAPSE measurements may suffer from.We studied 61 patients  with adequate, high quality, clinical CMR scans using a conventional 1.5T GE scanner were studied. In addition to simulating the echo-TAPSE parameter, additional semi-automated CMR parameters were obtained from manually identified phasic anatomic landmarks that honored the trajectory of the tricuspid annulus (TA) and right ventricle apex (RVA):1. TAPSE -Distance traveled by the TA along the direction of the fixed line joining the TA and RVA at end-diastole (simulates echo measure).2. Δ TA-RVA - Difference between lengths of line segments joining the (RVA) and TA at end-diastole and end-systole (recognizes cardiac translation).3. TA Excursion (TAE) - Euclidean distance traveled by the TA from end-diastole to end-systole (measures just the TA motion).The correlation of these parameters with conventional RVEF was obtained using linear regression analysis, and a p-value less than 0.05 was considered significant.In general, there is a weak correlation between TAPSE and RVEF and a moderate correlation using the newer parameters of Δ TA-RVA and TAE. In clinically relevant subgroups such as RV pressure overload (RVPO) and RV volume overload (RVVO), there are statistically significant differences between the traditional and conventional parameters , but this correlation can be significantly improved using the rapid, semi-automated Δ TA-RVA or TAE method. Very importantly, the choice of parameter has diametrically opposed influences on RVVO and RVPO sub-groups . These findings suggest variable alteration of longitudinal RV myocardial contraction and warrants further investigation.A portion of Dr. Sorrell's support for this project was provided by the Allan C. Hudson and Helen Lovaas Endowed Chair of Cardiac Imaging.


The aim of the present study was to verify whether BNP might detect pre-clinical diastolic dysfunction (LVDD) in type-2 diabetic patients.One-hundred and twenty-seven consecutive outpatients with type-2 diabetes mellitus were enrolled into the study. Subjects with overt heart failure or NYHA class > 1, history of coronary artery disease, severe valvulopathy or chronic atrial fibrillation were excluded from the study. All patients underwent clinical evaluation, laboratory assessment of brain natriuretic peptide (BNP) and echocardiographic examination.No patients showed systolic impairment of left ventricular function, whereas diastolic dysfunction was detected in 53 (42%) cases . Median BNP was 27 pg/ml without any significant difference between 76 patients with normal left ventricular function and 53 with diastolic dysfunction; in 54 (43%) patients showing HBA1C≥8 (uncontrolled diabetes) normal function was found in 32 and diastolic dysfunction in 22, with a significant difference of BNP at multivariate analysis . In uncontrolled diabetic cohort, BNP was a strong predictor for LVDD  along with the duration of diabetes . BNP > 25 pg/ml was a cut-off value with high accuracy to detect a LVDD.Early screening of high-risk patients for diabetic cardiomyopathy development might be useful to better control glycemic profile in order to reduce heart disease progression or even to reverse itBNP could be a cheap, easy and useful tool to screen those ones with preclinical ventricular diastolic dysfunction in a subset of patients particularly prone to develop cardiovascular complications, like uncontrolled diabetic patients. Diabetes mellitus (DM) is not only a significant independent risk factor for developing of atherosclerotic ischemic heart disease or ventricular hypertrophy but it is also able to trigger a diabetic cardiomyopathy due to some dysmetabolic processes: inhibition of switching within the cardiomyocite from free-fatty acid (FFA) to glucose metabolism, dysregulation of FFA metabolism with increased uptake, reduced FFA oxidation, reduction of peroxisome proliferator-activated receptors (PPAR), increase of PPAR-γ and insulin-resistance, increased intracellular lipogenesis which leads to cardiomyocite lipotoxiocity .The patients with type-2 DM are at 2-5 folds higher risk for developing heart failure (HF) -5 The fiInternationally, there is an increased focus on prevention since even pre-clinical diabetic cardiomyopathy can impair significantly event-free survival , thus, iHence, the aim of the present study is to verify whether BNP might detect pre-clinical diastolic dysfunction in type-2 diabetic patients.One hundred and twenty-seven consecutive outpatients , with type-2 diabetes mellitus according to ADA/WHO criteria  were enrAll patients underwent clinical evaluation, laboratory assessment of BNP and echocardiographic examination Table . ConcernAll patients gave their written informed consent; the investigation conforms to the principles outlined in the Declaration of Helsinki and the study was approved by the local ethics committee (The University of L'Aquila).Blood samples were taken after 5 minutes of supine rest. BNP was measured using the commercially available AxSYM BNP assay, produced by Axis-Shield and Abbott Laboratories. Glycated hemoglobin (HBA1C) were measured using Menarini HA8140 assay. Microlabuminuria was defined as extemporary albuminuria value equal or greater than 20 mg/L.3 - LVDD3] + 0.6 g [2.7 in men and ≥ 47 g/m2.7 in women.M-mode, two-dimensional images and pulsed-wave and color-flow-Doppler examinations were performed on the same day of BNP assays, with a commercially available imaging system (ESAOTE MyLAB 30). Left ventricular systolic and diastolic volumes and ejection fraction (EF) were derived from the biplane apical modified Simpson's rule algorithm. Left ventricular dimensions were measured from M-mode images according to standard criteria. Diastolic dysfunction was assessed by means of transmitral pulsed-wave Doppler velocity (E/A ratio), deceleration time. In addition, pulmonary venous systolic and diastolic flow velocities were obtained as the maximal value reached during the corresponding phase of each cardiac cycle. Diastolic dysfunction was classified into 3 categories as follows: impaired relaxation, pseudonormal filling pattern and restrictive-like filling pattern, as previous reported . Left ve + 0.6 g . All ech + 0.6 g  Left venA single observer (LG) made all measurements. Using digital archiving images, intraobserver variability was tested in a blinded fashion. Intraobserver variability was 3.3%, 3.9%, 5.1%, 8.5% and 9.2% for E/A ratio, E wave deceleration time, pulmonary venous systolic and diastolic flow velocities, EF and calculated left ventricular mass index (LVMI), respectively.The aim of this study was to evaluate the diagnostic role of BNP assays in early identification of diastolic dysfunction in diabetic patients, asymptomatic for heart failure. Particularly, since that an uncontrolled diabetes is strongly related to development of left ventricular dysfunction and chronic heart failure , a furthth and 75th percentile; Categorical variables were reported as count and percentage. Distribution of continuous variables was tested for normal distribution using the Kolmogorov-Smirnov test. Paired-comparison was performed by means of Wilcoxon test whereas unpaired-comparison was performed by means of t-test or Mann-Whitney U test. Categorical data were compared by X2-test or Fisher exact test where appropriate. Logistic regression was used to identify predictive factors for LVDD. The variables initially inserted into the regression model were: age, gender, body mass index, systolic blood pressure, diastolic blood pressure, diabetes duration (years) smokers/ex-smokers, hypertension, hypercholesterolemia, obesity (BMI > 30 Kg/m2), left ventricular mass index (g/m2.7), last 2-year average HBA1C (%), creatinine (mg/dl), microalbuminuria, type of antidiabetic therapy, type of anti-hypertensive medication, BNP, hypertension plus left ventricular hypertrophy . Variables included in the final model were reported as odd ratio (OR), 95% confidence interval (CI) and p-value.Results were expressed as mean (± standard deviation) for normally distributed continuous variables, whereas non-normally distributed data were expressed as median and interquartile range (IQR): 25Receiver operating characteristic (ROC) curve analysis was used to identify predictive cut-offs. Each statistical analysis was validated in 1000 bootstrap samples. A probability value p < 0.05 was considered significant. The retrospective power calculation, using as target end-point the comparison of BNP levels between uncontrolled diabetic patients with versus without diastolic dysfunction, estimates that 18 cases were the minimum sample size per each group to achieve a power of 80% with an α-error of 0.05.All analyses were performed with the statistical software package SPSS .No patients showed systolic impairment of left ventricular function, whereas diastolic dysfunction was detected in 53 (42%) cases; all of them were classified as impaired relaxation pattern; all the remaining 74 cases showed normal diastolic function. All the population had a creatinine equal or below 1.5 mg/dl; microalbuminuria was present in 29% of cases without any difference between patients with and without ILDD  without any significant difference between 76 patients with normal left ventricular function (Group A) and those ones with diastolic dysfunction (Group B) Figure . The onlLast two-year average HBA1C value was 7.7 ± 1.8 without any difference between the two groups ; Fifty-four (43%) out of 127 patients showed HBA1C≥8 (uncontrolled diabetes) with a mean value of 9.3 ± 1.7. The remaining group of patients (73) showed a mean HBA1C of 6.5 ± 0.6 (p vs uncontrolled diabetes < 0.001). In 73 patients with well-controlled diabetes, BNP level was not predictive for diastolic dysfunction (p = 0.244), whereas BNP seems to be a good predictive in the uncontrolled-diabetes cohortThe uncontrolled diabetes group was split into 2 groups: normal function  and diastolic dysfunction . The two groups did not show any difference concerning demographic, clinical, echocardiographic data . To explain the patho-physiological basis of this left ventricular impaired relaxation, the concept that diabetes per se might cause a stand-alone cardiomyopathy should be accepted  In a verThe diagnostic role played by BNP in early detection of asymptomatic diastolic dysfunction in type-2 diabetes is still controversial -21,32-34On the contrary, Albertini and co-workers  assessedAlso Dencker et al  demonstrThe main limitation of this study is the small sample size. Another important limits is related to the echocardiographic assessment of diastolic dysfunction, that, nowadays, is more and more evaluated by means of tissue Doppler imaging (TDI).There is an important concept raising up from the present study, BNP is a good marker for detecting pre-clinical LVDD in a subset of patients particularly prone to develop cardiovascular complications, like those ones with uncontrolled diabetes. In clinical practice it is very difficult to submit all asymptomatic diabetic subjects to echocardiographic lab; so BNP could be a cheap, easy and useful tool to screen those ones with preclinical ventricular diastolic dysfunction among patients with high HBA1C. Furthermore, BNP could be use for serial assessment of this specific cohort of patients asymptomatic for heart failure.Another clinical implication concerns the possibility to better control glycemic profile in order to reduce heart disease progression or even to reverse it, especially in patients with short duration of diabetes without history of cardiovascular event ,36; In fThe authors declare that they have no competing interests.MP and LG conceived and designed the study protocol, moreover gave their final approval of the manuscript. LG performed echocardiography. SF, FG, GP provided collection of data. SR and MDM performed analyses and prepared the manuscript. All authors have read and approved the manuscript.


Adverse remodeling of the left ventricle (LV) following myocardial infarction (MI) leads to heart failure. Recent studies have shown that scar anisotropy is a determinant of cardiac function post-MI, however it remains unclear how changes in extracellular matrix (ECM) organization and structure contribute to changes in LV function. The objective of this study is to develop a model to identify potential mechanisms by which collagen structure and organization affect LV function post-MI.A four-region, multi-scale, cylindrical model of the post-MI LV was developed. The mechanical properties of the infarct region are governed by a constitutive equation based on the uncrimping of collagen fibers. The parameters of this constitutive equation include collagen orientation, angular dispersion, fiber stiffness, crimp angle, and density. Parametric variation of these parameters was used to elucidate the relationship between collagen properties and LV function.The mathematical model of the LV revealed several factors that influenced cardiac function post-MI. LV function was maximized when collagen fibers were aligned longitudinally. Increased collagen density was also found to improve stroke volume for longitudinal alignments while increased fiber stiffness decreased stroke volume for circumferential alignments.The results suggest that cardiac function post-MI is best preserved through increased circumferential compliance. Further, this study identifies several collagen fiber-level mechanisms that could potentially regulate both infarct level and organ level mechanics. Improved understanding of the multi-scale relationships between the ECM and LV function will be beneficial in the design of new diagnostic and therapeutic technologies. Coronary heart disease is the leading cause of death, accounting for over 400,000 lives in the United States every year . BlockagCardiac scar tissue is composed of collagen fibers, the primary determinant of the mechanical properties of the scar, as well as cells and other extracellular matrix proteins which are considered to be a ground substance . Thus, cThe objective of this study was to illustrate how collagen alignment affects LV function post-MI using a simple, thin-walled, cylindrical LV model with a scar region governed by a collagen fiber based constitutive equation. The cylindrical model is based on a concept, previously presented by Han et al.  and OshiThe LV was modeled as a cylindrical membrane formed by folding a planar sheet consisting of three normal, healthy myocardial regions and a collagenous scar region into a cylinder Figure . The midwithc is a material constant, bff, bxx, and bfx are non-dimensional material constants and Eff, Ecc, Err,Efc, and Ecf are the components of the Green strain tensor. The subscript f denotes the fiber direction, the subscript c denotes the in-plane cross fiber direction, the subscript r denotes the radial (out-of-plane) direction and the subscript x denotes either the cross-fiber or radial direction. The Fung-type constitutive equation has been widely used in soft tissue biomechanics and is still commonly used for modeling myocardial tissue  is the identity matrix, [F] is the deformation gradient, and [C] is the right Cauchy-Green deformation tensor.where Contraction of the healthy tissue was modeled using the elastance model of active cardiac contraction proposed by Guccione et al. in the form of ,27,ls and t are the the sarcomere length and time during a cardiac cycle, respectively. ω is a function of the sarcomere length and time. σ0 is the peak contraction stress that depends on cellular calcium concentration and sarcomere length  is defined with rows ai and a matrix [ξ] is defined with rows qi then Eq. (9) can be written asMany of the basic continuum mechanics equations used below can be found in Humphrey’s Cardiovascular Solid Mechanics text . As descA] can be defined with rows NiAi representing the areas in the undeformed configuration and a matrix [Ξ] with columns Qi representing the forces in the undeformed configuration. Both [Ξ] and [A] can be related to [ξ] and [α] respectively through the deformation gradient.Similarly a matrix . Eq. (A3) can also be solved in matrix form for [α]it is seen that there are only 3 non-zero internal force components of [Substituting Eq. (A7) into Eq. (A1) and assuming negligible radial stresses yieldsξ] as given by Eq. (A6) provides a system of 4 equationsRelating the result of Eq. (A8) with the components of [From Eq. (A9.b), it is seen thatCombining this fact with Eq. (A9.c) and Eq. (A9.d) yields the following relationship between force and deformationNow that relationships between force, stress, and deformation have been established for individual regions it is necessary to examine the four region model with forces and deformations being shared as described in Figure From Eq. (A6) it is seen thatiθ and iz are unit vectors. From Eq. (A12.a) it is seen thatwhere which allows for Eq. (11.a) to be rewritten asSubstituting Eq. (A9.a) for each region into Eq. (A14) yields 2 equilibrium equationsqz can be written in polar notation asThe vector whereSubstituting Eq. (A11) into Eq. (A17) yieldsEquating Eq. (A16) with Eq. (A12.b) givesSolving Eq. (11.b) for the magnitude and equating with Eq. (A19) yieldsSubstitution of Eq. (A9.c) for each region into Eq. (A20.a) gives 2 more equilibrium equationsSubstitution of Eq. (A9.d) for each region into Eq. (A20.b) gives the last 2 equilibrium equationsCollecting Eq. A15), Eq. (A21), and Eq. (A22) and noting the shared lengths, heights, and deformations as shown in Figure 5, Eq. (AwhereThis set of 6 independent equilibrium equations can be used in conjunction with the constitutive equations to solve for the 6 independent deformation components, The authors declare that they have no competing interests.AV and HCH designed the study and developed the model. AV implemented the numerical solution techniques and analyzed the data. Both authors participated in the preparation of the manuscript and acknowledge that they have read and approved the final version of the manuscript.


Heart failure is a major public health problem and its management requires a significant amount of health care resources. Even with administration of the best available medical treatment, the mortality associated with the disease remains high. As therapeutical strategies for heart failure have been refined, the number of patients suffering from the disease has expanded dramatically. Although heart transplantation still represents the gold standard therapeutical approach, the implantation of mechanical circulatory support devices (MCSDs) evolved to a well-established management for this disease. The limited applicability of heart transplantation caused by a shortage of donor organs and the concurrent expand of the patient population with end-stage heart failure led to a considerable utilization of MCSDs. This paper outlines the current status of mechanical circulatory support. The prevalence of chronic heart failure (HF) is worldwide increasing and meanwhile averages 2.5% of the normal population , 2. In EThe prognosis of chronic HF remains poor despite a lot of recent advances in medical management, interventional therapies, and surgical techniques –8. It isHistorically, John Gibbon in 1953 was the first to introduce the idea of mechanically supporting the cardiopulmonary system, when he successfully used cardiopulmonary bypass for an atrial septal defect repair . The firThe first-generation LVADs were large pulsatile, positive displacement pumps with a lot of moving parts. The devices were limited to patients with a body surface area greater than 1.5 m² and were the first MCSDs initially introduced into clinical practice. The prototypes are the Novacor left ventricular assist system , first implanted in a human in 1984 and used successfully as BTT in that patient, the Thoratec IVAD (implantable ventricular assist device) and the HeartMate XVE , which was first tested in a clinical trial in 1986 , 19. TheRegarding the site of pump implantation commonly utilized pulsatile-flow MCSDs, in which the blood pump lies external to the patient are the Thoratec PVAD , the Berlin Heart Excor  and the Toyobo LVAS  fulfilling indications for temporary use for the BTT and BTR . The cliSimilar results regarding survival provided the nonrandomized series of Rogers et al., which evaluated the performance of the Novacor LVAS. The LVAD treatment led to improved survival compared to the medical therapy, but was associated with neurologic complications approaching a stroke risk rate of 62% .The first-generation MCSDs have been supplanted by newer devices because of their high device-related complications such as infections and mechanical failure arizing from their large size and the complexity of the pump function.The second-generation MCSDs consisted of axial pumps, which utilize continuous rather than pulsatile blood flow without valves. This continuous pulseless blood flow is physiologically entirely well-tolerated and pulseless LVADs support improves neurocognitive disturbances due to severe heart failure, just as pulsatile devices do . The preSecond-generation VADs include the Jarvik 2000 , the MicroMed DeBakey VAD  and the HeartMate II . The HeaThe outcomes of second-generation LVADs compared to those of their first-generation counterparts were evaluated in a randomized trial comparing the Heartmate II and Heartmate XVE . SurvivaThird-generation MCSDs provide like second-generation LVADs continuous blood flow, utilized from an axial or a centrifugal rotor. The impeller or rotor consists of a mechanism forced by hydrodynamic or electromagnetic energy, reducing in that way the moving parts and the areas of contact. The magnetic-levitation (maglev) system can be distinguished into three types: (i) external motor-driven system, (ii) direct-drive motor-driven system, and (iii) self-bearing or bearingless motor system. Through their technological advancements, third-generation MCSDs are estimated to be longer mechanically stable than their second-generation counterparts. Their smaller size approaching almost that of an AA battery enables the relative noninvasive complete intrapericardial implantation, adjacent to the heart with improved patient outcomes .Third-generation MCSDS include the Levacor VAD (WorldHeart), HeartWare HVAD , VentrAssist , DuraHeart  and the Berlin Heart Incor  is evaluated in a multi-institutional trial in Europe and Australia including 23 patients. The primary end point of this bridge-to-transplant study was survival to heart transplant or survival to 180 days on the device, whichever occurred first. Actuarial survival after 6 months was 91% and 86% at the 1-year followup. The design of the HVAD pump enables a quick and less invasive implantation. The results to date demonstrate satisfactory long-term survival with excellent quality of life in this cohort . AdditioThe Berlin Heart Incor LVAD was evaluated in several studies, and it was associated with 1-year survival rate ranging from 53 to 63.4% and low adverse event rates, like thromboembolism ranging from 3.8 (0.1%/patient-year) to 23.2% (0.5%/patient-year) , 36.In a clinical trial investigating the VentrAssist, the device reached a success rate of 82% (39.4% of patients had been successfully bridged to transplant and 42.4% of patients remained transplant eligible). The serious adverse event rates regarding infection and thromboembolism at 5 months were 0.8 and 0.12%/patient-year, respectively. Implantation resulted in improved end-organ function enhanced quality of life and reduced medication use .The third-generation devices consist of smaller, potentially more reliable LVADs, which make long-term circulatory assist available to a wider range of the heart failure population, particularly those who are ineligible for transplantation or those with smaller body surface area.The increasing use and the ongoing development of mechanical circulatory support, established the need for rigorous scientific data collection and registration. Therefore, in 2001 the International Society for Heart and Lung Transplantation (ISHLT) developed and implemented the MCSD Database. In 2006, the National Heart Lung and Blood Institute (NHLBI) grounded the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), a collaborative database, which collects information on MCSD implants in the USA. Data collection started on June 23, 2006, and through June 2011, more than 4,500 patients have been registered . United The analysis of the INTERMACS collected data since its launch in 2006 revealed a dramatic change in the landscape of MCS support in the United States. From the year 2008, after the FDA approval of the HeartMate II continuous flow pump for BTT, there was a radical shift towards an extended use of continuous-flow pumps, being nowadays the most used devices with an implantation rate greater than 99% of adult primary LVAD implants. In addition, a gradual change has occurred during the past 5 years concerning the treatment strategies, reflected by the increased use of VAD as DT.INTERMACS established 7 clinical profiles  in orderFour broad indications for an MCSD are defined, with regard to the clinical intent at the time of implantation: (i) the bridge-to-transplant intent (BTT) performed on patients eligible for transplantation, while listed for a transplant; (ii) destination therapy (DT) for patients not eligible for transplantation having refractory heart failure symptoms; (iii) bridge to decision (BTD) including patients requiring MCS with the option of reevaluation of their candidacy for transplantation after improvement of clinical parameters through the MCS, (iv) bridge to myocardial recovery (BTR) applied to patients with nonischemic heart failure, with the goal to restore myocardial function targeting the explantation of the device. The decision to apply an MCSD to a patient is often difficult, thus the criteria for referral vary greatly among institutions, but nevertheless heart failure confirmed by typical signs such as pulmonary capillary wedge pressure > 20 mm Hg, cardiac index < 2.0 L/min/m², or systolic blood pressure < 80 mm Hg, despite best medical management, should be present .The REMATCH trial firstly, as mentioned before, proved the marked survival advantage of MCSDs over chronic medical therapy. As surgical techniques, postoperative care and devices improved, the mortality rates subsequently decreased to a level of approximately 9% in some centers .According to the recently published annual report of INTERMACS for the entire patient population of primary MCS for the past 5 years, overall survival has progressively improved since 2006, exceeding 80% at 1 year. There is still a dramatic improvement in survival in favour of continuous-flow compared to pulsatile LVADs. Continuous-flow pumps (CFPs) had at 2 years a significant higher survival of 74% when compared to 43% of the pulsatile-flow pumps (PFPs) cohort. With regard to the treatment-intent the survival at 1 and 2 years is, as expected, less for DT, because those patients are generally not considered for transplantation as “rescue” therapy in the event of life threatening device complications  38]..38].Apart from identifying the patient, who will benefit from MCS, similarly important is an adequate risk stratification in order to minimize the perioperative mortality of VAD implantation. In the literature, there are several series dealing with this issue, evaluating the accuracy and ability of risk stratification models in predicting early and late mortality associated with MCSD placement. In a study of Lietz et al. consisting of 280 HeartMate XVE recipients as DT, the patients were divided into high- and low-risk groups according to laboratory values and preoperative medical therapy , 43. LowAccording to the risk factor analysis in the recent INTERMACS annual report, during the early period (consisting of the first 3 months after implantation), the dominant mortality predictors are: clinical status of INTERMACS Level 1 (cardiogenic shock) and severe right ventricular failure sufficient to require BiVAD support  38]. In. In38]. Regarding the management of patients who need biventricular support, there is in some centers ongoing interest in the total artificial heart (TAH), seeing in the device an alternative to BiVAD support, but owing to the small number of TAH patients, there is not enough data to provide a useful evaluation of the potential positive effect of TAH.The main critical device-related adverse events include device malfunction or failure, neurological events, bleeding, infection, and right heart failure .Mechanical device malfunctions or failures have been, particularly in the first-generation devices one of the major limiting factors concerning their long-term use. Due to their complex mechanical function pulsatile flow pumps are prone to such malfunctions. Further technological development and advancements utilized in second- and third-generation devices resulted in increased mechanical reliability and durability . CurrentAdverse neurological events, either of ischemic or hemorrhagic origin, are a major cause of morbidity in MCSD patients. According to the INTERMACS data, primary cerebrovascular events account for 14.1% of all deaths . ContinuAnalysis of the 2nd INTERMACS annual report demonstrated that bleeding, either at the site of implantation or in the gastrointestinal (GI) tract, was the second most frequent (16.52%/patient-month) adverse event (after infection) in MCSD patients . On the The association of LVAD placement and bleeding has been described in several series. Strauch et al. compared GI bleeding rates among 20 HMII, 9 HeartMate XVE, and 4 VentrAssist recipients . Eight pA study of patients supported by the Novacor pulsatile LVAD—which necessitates anticoagulation—reported an incidence of nonsurgical bleeding as high as 32% , while aTheories that have been proposed to explain this association, assume that in continuous-flow LVADs, the impeller mechanism may cause von Willebrand's Factor (vWF) deformation, proteolysis, and an acquired deficiency of high molecular weight (HMW) vWF multimers, which predisposes to bleeding, especially in the setting of antiplatelet use . AdditioIt is likely that bleeding adverse events will decrease in frequency in light of the constantly evolvement of anticoagulation regimens with lower INR levels, the avoidance of heparin administration and the use of advanced methods of monitoring like thromboelastography.In general, the adequate level of antiplatelet and anticoagulant treatment in order to avoid both thromboembolic and hemorrhagic adverse events is unknown and seems to be device specific.The INTERMACS registry reported infection as the most common (17.46%/patient-month) adverse event accounting for 16.2% of all deaths, a finding which confirmed similar results from the REMATCH and HeartMate II BTT and DT trials . InfectiFurthermore, it appears that certain subgroups of patients  are at highest risk for infection . SeveralImprovements in device design and better patient selection strategies, particularly aiming to identify individuals with genetic susceptibility to device-related infections, may further reduce this prevalent complication and increase outcomes in patients with MCSDs .P < 0.0001, ·m², RV stroke work index ≤ 0.25 mmHg/L·m², serum creatinine ≥ 1.9 mg/dL, previous cardiac surgery and systolic blood pressure ≤ 96 mm Hg [P < 0.05), accompanied by higher survival at 1 year and long term.Although excellent survival and outcomes were documented in patients, who receive LVADs not all patients progress smoothly, due to early right heart failure (RHF) and failure to thrive (FTT), despite hemodynamic improvements. The occurrence of RHF after LVAD placement has gained attention recently, because it is associated with significantly higher perioperative mortality and morbidity rates , 70. Dat96 mm Hg . The sub96 mm Hg . Early RSecond- and third-generation devices providing rotary continuous flow do not require volume compensation, but the energy transmission is still utilized percutaneously. The ideal MCSD is a fully implantable miniaturized device incorporating a transcoutaneously rechargeable battery. This is technically feasible through a transcutaneous energy transmission system (TETS). The main operation principle of the system consists of the inductive coupling of energy between an external primary and an internal subcutaneously placed secondary coil. An LVAD  and a TAH  are sufficiently supplied by TETS, but neither of these devices, due to other reasons not related to the TETS, is currently clinically applicable .Future development of MCSD technology is being geared to the constantly changing requirements of the patients, who need or will need VAD support. As long the population of patients, who require circulatory support for end stage HF expands, future MCSDs have to be designed for long-term use, safe and less invasive implantation technique, minimizing in that way the associated morbidity. The refinement of the clinical classification, including patient risk profiles like those proposed by the INTERMACS study and the increasing development and use of validated risk stratification models preceded further development of sophisticated therapeutic strategies. These consist in some cases of temporary circulatory support, known as bridge to bridge therapy, in order to “prepare” the patients for permanent LVAD support. The Synergy Pocket Micro-Pump  is the first miniaturized pump constructed to utilize partial circulatory support with a blood flow up to 4.25 L/min. It is implanted superficially in a “pacemaker-like” pocket through a small right thoracotomy. The device is currently undergoing clinical investigation at multiple centers in Europe with favourable initial results, aimed at achieving CE Mark . The inihttp://clinicaltrials.gov - ID NCT01543022). Another minimally invasive implantable assist device is the Symphony by Abiomed . It is the first synchronized implantable heart pump timed to an ECG, providing in that way counter pulsation therapy through a vascular graft anastomosed to the subclavian artery. Symphony was developed to treat patients with moderate HF by improving coronary perfusion and cardiac output and aiming to stimulate the LV remodeling. The device is currently under clinical investigation (Symphony: The Implantable Counter Pulsation Device (CPD) Safety and Feasibility Trial; http://clinicaltrials.gov-ID NCT01452802).The change in the role of LVAD support as DT away from “a last option”—treatment to in some cases an “elective” therapy is under investigation in currently running studies. The one is the Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP) trial, which is a prospective, multi-center, nonrandomized, controlled, observational study to evaluate the effectiveness of the Thoratec HeartMate II Left Ventricular Assist System (LVAS) in comparison to Optimal Medical Management (OMM). The study involves ambulatory advanced HF patients not yet dependent on intravenous inotropic support, who are typically classified as INTERMACS profiles 4–6, within the existing FDA-approved indication for D T. It will include 200 patients at up to 50 sites, including experienced HeartMate II implant centers as well as community centers that care for a large volume of advanced heart failure patients. Apart from the primary above mentioned study-objective, secondary aims of the trial are to determine the accuracy of risk prediction models of a population appropriate for HeartMate II and to establish equipoise, to determine factors related to patient and physician decisions for HeartMate II, to evaluate the frequency of cross-over to other advanced HF therapies, to compare results of early versus delayed LVAD implantation, to determine the feasibility of enrolling target population and to use information to design follow-up studies; randomized trials, or additional observational studies and registries. The trial's estimated completion date is December 2015  trial, is a by the NHLBI-sponsored randomized trial of the HeartWare Ventricular Assist System (VAS) versus best medical treatment in patients with advanced HF and whose illness is not severe enough to qualify them for cardiac transplantation or permanent LVAD therapy according to current guidelines. The hypothesis of the study is that VAD therapy may improve both survival and quality of life in moderately advanced HF patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious complications. The pilot study will include 100 randomly assigned patients in a 1:1 ratio to the HeartWare HVAD, or optimal medical therapy and the estimated completion date is January 2016 .As the available donor hearts for transplantation remain relatively fixed and the number of patients with end stage HF is expanding, the need for long-term circulatory support is expected to increase. Meanwhile, MCS has evolved from a last resort life-saving therapy to a well established viable alternative for thousands of HF patients. The device technology has been evolving rapidly, with both frequent advancements to the particular device types and, more recently, a dramatic shift toward the use of newer generation continuous-flow miniaturized devices. In order to determine the optimal timing when the survival benefit of MCS would be greatest by the lowest surgical risk, further prospective studies are warranted to explore on the one the safety and effectiveness of MCS in less acutely ill HF patients and to develop validated risk stratification models for adequate patient selection on the other.


Diabetes mellitus may alter cardiac structure and function independently of underlying coronary artery disease or hypertension. This so called “diabetic cardiomyopathy” is associated with myocardial fibrosis and is characterized by a long and silent phase of progressive left ventricular (LV) remodeling before the occurrence of contractile dysfunction and heart failure symptoms. In the preclinical stage, with normal LV ejection fraction, new echocardiographic techniques reported subtle myocardial dysfunction with a decrease in systolic strain.Recently, myocardial T1 mapping has been proposed to detect interstitial fibrosis early in the disease course.to evaluate whether myocardial T1 mapping could detect abnormalities in type 2 diabetic patients with normal standard parameters of LV function and normal LGE imaging.Type 2 asymptomatic diabetic patients with no history of heart disease, a normal LV assessed by conventional echocardiography  and normal LGE imaging were compared to matched healthy volunteers.T1 quantification was performed using a Modified Look-Locker Inversion -recovery (MOLLI) sequence at 1.5T (Siemens), on a short axis of the LV, before, 5 and 15 min after 0.2 mmol/kg gadolinium injection. Imaging protocol included also standard Cine-SSFP imaging, and LGE imaging. Regional strains were assessed using Displacement Encoding with Stimulated Echoes (DENSE) imaging. Left ventricular diastolic function  was further assessed using echocardiographyTwenty-four diabetic patients (51±4 years old) and 16 matched volunteers (47±7 years old) were included. Despite normal ejection fraction, global circumferential strain was decreased in diabetic patients compared to volunteers .Mean myocardial T1 relaxation time was significantly shorter in diabetic patients than in volunteers both at 5  and 15 minutes  after gadolinium injection.Echocardiography displayed abnormal diastolic LV filling with an impaired LV relaxation in 55% of patients and in 25% of volunteers. Interestingly, post-contrast myocardial T1 time was shorter in case of impaired relaxation than in case of normal mitral inflow pattern .T1 relaxation time is decreased in asymptomatic type 2 diabetic patients with normal ejection fraction. T1 abnormalities are associated with impaired myocardial circumferential strain and early diastolic dysfunction suggesting that interstitial fibrosis may be implicated in diabetic cardiomyopathy. In the future, T1 quantification may contribute to detect subclinical stage of diabetic cardiomyopathy.


Anabolic steroids are known to induce left ventricular hypertrophy (LVH). The pathologic LVH due to hypertrophic cardiomyopathy, hypertension, and aortic stenosis has been associated with myocardial perfusion abnormalities. However, the effects of anabolic steroid misuse on myocardial blood flow (MBF) are unknown.Twenty one body-builders were studied - 14 anabolic steroid users and 7 controls matched for age and training history. First pass CMR perfusion imaging was performed on a 1.5T Avanto  after adenosine-induced hyperemia (140 mcg/kg/min) and at rest using a hybrid echo-planar imaging sequence. Images of the base, mid-ventricle and apex were acquired and the myocardium was divided into 16 segments as well as endocardial and epicardial layers. After image registration, a modified Fermi-constrained deconvolution algorithm was applied pixel-wise to quantify absolute MBF. Late gadolinium enhancement (LGE) imaging was performed as well as standard assessment of ventricular volumes, function and LV mass. Data were analysed using a linear mixed effects model.Anabolic steroid-using subjects had significant LVH both in terms of maximum wall thickness and indexed LV mass Table . For theHyperemic MBF was similar in strength-trained bodybuilders using anabolic steroids compared with non-users. However, steroid use appeared to exacerbate resting differences in the transmural distribution of perfusion independent of the effects of wall thickness. Further work is required to delineate the mechanisms responsible for these differences in microvascular function.This work is supported by the NIHR Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College. Dr Ismail is supported by the British Heart Foundation. Dr Arai and Dr Hsu are supported by the National Institutes of Health.


Cardiac MR (CMR) is the accepted gold standard for the assessment of myocardial scar and biventricular systolic function. Bright blood cine imaging with phase-contrast mitral inflow assessment has shown promise for the evaluation of left ventricular (LV) diastology. The purpose of this study is to evaluate the accuracy of LV diastolic function grading by CMR, using Doppler echocardiography as the reference standard. We hypothesize that quantitative CMR analysis of diastolic function coupled with left atrial volume (LAV) assessment is accurate in characterizing LV diastology.83 patients without mitral valve disease  underwent CMR imaging on a 1.5T scanner for evaluation of myocardial viability or infiltrative heart disease. All patients underwent 2-D phase-contrast (PC) imaging of the mitral valve . Bright-blood (BB) 4- and 2-chamber cine imaging was performed  for lateral mitral annular and left atrial volume (LAV) assessment. Peak E and A velocities were obtained from PC data. 4-chamber BB cine images were analyzed using prototype software evaluating deformation fields to automatically identify and track the mitral base plane at the lateral and septal insertions, extracting lateral e' values . LAV was obtained using the length-area method. LV diastolic function was graded using established echocardiographic criteria. Differences in means were assessed using the student's t-test.Echocardiographic LV diastolic function was indeterminate in 30 patients (36%). CMR correctly categorized 95%, 80%, 50%, and 50% of patients with normal, grade I, grade II, or grade III LV diastolic dysfunction by echocardiography with an overall accuracy of 77% Table . CMR undQuantitative CMR assessment of LV diastolic function is clinically feasible and accurate when using the LAVi to distinguish normal and pseudonormal patterns. Additional work is ongoing to improve CMR grading of LV diastolic dysfunction in the context of an elevated LAVi.Dr. Collins is supported by the RSNA R&E Foundation and the SIR Foundation. Dr. Markl is supported by the NIH on a R01 as well as NUCATS.