Although echocardiography is used as a first line imaging modality, its accuracy to detect acute and chronic myocardial infarction (MI) in relation to infarct characteristics as assessed with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is not well described.One-hundred-forty-one echocardiograms performed in 88 first acute ST-elevation MI (STEMI) patients, 2 (IQR1-4) days (n = 61) and 102 (IQR92-112) days post-MI (n = 80), were pooled with echocardiograms of 36 healthy controls. 61 acute and 80 chronic echocardiograms were available for analysis (53 patients had both acute and chronic echocardiograms). Two experienced echocardiographers, blinded to clinical and CMR data, randomly evaluated all 177 echocardiograms for segmental wall motion abnormalities (SWMA). This was compared with LGE-CMR determined infarct characteristics, performed 104 ± 11 days post-MI. Enhancement on LGE-CMR matched the infarct-related artery territory in all patients .p < 0.001 for all) and associated with higher left ventricular ejection fraction (LVEF) and non-anterior location as compared to detected MI . After multivariate analysis, LVEF and infarct size were the strongest independent predictors of detecting chronic MI . Increasing infarct transmurality was associated with increasing SWMA (p < 0.001).The sensitivity of echocardiography to detect acute MI was 78.7% and 61.3% for chronic MI; specificity was 80.6%. Undetected MI were smaller, less transmural, and less extensive (6% [IQR3-12] vs. 15% [IQR9-24], 50 ± 14% vs. 61 ± 15%, 7 ± 3 vs. 9 ± 3 segments, In patients presenting with STEMI, and thus a high likelihood of SWMA, the sensitivity of echocardiography to detect SWMA was higher in the acute than the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Further work is needed to assess the diagnostic accuracy in patients with non-STEMI. Myocardial infarction (MI) is a major cause of death and disability worldwide . AccuratTwo-dimensional echocardiography has many advantages as a first line, bed-side, real-time imaging modality because it is inexpensive, and rapidly and widely available. Although echocardiography is subsidiary to the electrocardiogram (ECG) in hemodynamically stable patients presenting with ST-segment elevation myocardial infarction (STEMI), its role may be more important in patients with a non-diagnostic ECG. Echocardiography is generally agreed to be very accurate, but the sensitivity to detect acute MI varies widely . SensitiAnimal studies have shown that the extent of echocardiographic SWMA is related to infarct size and transmurality . This isThe current study is a retrospective subanalysis of patients admitted with a first ST-elevation MI (STEMI). Patients were consecutively and prospectively enrolled between August 2006 and March 2008. The purpose of the main study was to investigate infarct characteristics at baseline and follow-up using LGE-CMR . For thiTransthoracic echocardiography was performed at a median of 2 (interquartile range [IQR] 1–4) days (acute) and 102 (IQR 92–112) days (chronic) after admission. Echocardiography was performed according to the American Society of Echocardiography guidelines using a commercially available ultrasound system  . All imaAll 177 echocardiographic studies (patients and controls) were analyzed independently and in random order by two board-certified cardiologists (S.S. and S.B.) with >10 years of experience in echocardiography, who were blinded to patient, clinical and CMR data. Discrepancies were resolved in consensus after review by a third expert (E.C.). Left ventricular ejection fraction (LVEF) was estimated visually. Regional wall motion was assessed visually according to the AHA 17-segment model on a four-point scale  . Since s0, FOV 400mm, matrix 256x256) in the short axis, two-chamber and four-chamber views ).While most studies have focused on the diagnostic accuracy of echocardiography to detect acute MI, less is known about its usefulness in chronic MI. We found that the sensitivity of echocardiography to detect chronic MI was even lower than for acute MI. This was true in the population as a whole as well as in the cohort of 53 patients with serial echocardiograms. This lower sensitivity can be explained by improvement of contractility of initially “stunned” myocardium several months after successful revascularization . It alsoMI was more frequently undetected in patients with higher LVEF, smaller, less transmural and less extensive infarctions and when non-anteriorly located. For undetected acute MI the relationship with infarct transmurality was less strong than for chronic undetected MI, most likely as a result of “stunning” Figure . The relWe also found a significant relationship of the severity of echocardiographic SWMA with increasing infarct transmurality Figure , confirmEchocardiography is a very useful imaging modality in patients with acute chest pain because it can also detect life threatening conditions other than acute MI, such as acute aortic dissection, cardiac tamponade, or pulmonary embolism. It is not our intention to bring echocardiography into disrepute, but rather to call for a cautious approach when it is used as a final test to rule out MI.Although we did not use contrast echocardiography to improve endocardial border definition , we beliWe investigated a homogenous study population, albeit with a modest sample size. Echocardiograms were not available in all patients, and this may have affected our results. At the time of the first echocardiogram , SWMA might have resolved in some patients, lowering sensitivity. However, the process of myocardial stunning after acute MI generally lasts days to weeks . AlthougThe sensitivity of regular echocardiography to detect SWMA in patients initially presenting with STEMI is moderate in the acute phase and even lower in the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Although echocardiography is recommended by current acute coronary syndrome guidelines, excluding MI solely based on wall motion should be done cautiously. When clinical suspicion remains high and all other diagnostic tests are inconclusive, LGE-CMR can be applied.ECG: Electrocardiogram; IRA: Infarct related artery; LGE-CMR: Late gadolinium enhancement cardiovascular magnetic resonance; LVEF: Left ventricular ejection fraction; MI: Myocardial infarction; PCI: Percutaneous coronary intervention; SWMA: Segmental wall motion abnormalities; STEMI: ST-elevation myocardial infarctionThe authors declare that they have no competing interests.All authors have contributed to the conception and design of the study, the interpretation of data, and have critically revised and subsequently approved the manuscript. CJ, SS, EC, MS, ID, PN and SB performed collection and analysis of the data.Undetected chronic inferior myocardial infarction. Corresponding echocardiographic (left) and late gadolinium enhancement cardiovascular magnetic resonance (right) short axis views at mid-ventricular level.Click here for fileUndetected chronic inferior myocardial infarction. Corresponding echocardiographic (left) and late gadolinium enhancement cardiovascular magnetic resonance (right) two-chamber views.Click here for file


The use of ultrasound has expanded enormously over the last two decades in critical care research and practice. Despite the fact that the method has several inherent limitations and is largely operator dependent, it enables clinicians for rapid, by-the-bed, and relatively inexpensive diagnostic evaluation of unstable patients. Point-of-care ultrasound applications such as lung ultrasound are gradually replacing traditional imaging modalities , while the use of ultrasound for procedure guidance has been shown to reduce complications and thus to increase patients' safety –3.In this issue, various papers illustrated the important role of ultrasound in the intensive care unit (ICU). K. Stefanidis et al. applied echogenic technology during ultrasound-guided cannulation of the internal jugular vein (IJV) and of the subclavian vein (SCV), respectively. Both case-control studies included intubated critical care patients and were performed under controlled ICU conditions. Ultrasound-guided cannulation of the IJV was attempted on the transverse axis and cannulation of the SCV on the longitudinal axis via an infraclavicular approach. In both studies, the use of echogenic technology significantly improved cannula visibility and decreased access time and technical complexity optimizing thus real-time ultrasound-guided central venous cannulation irrespective of the technique used.P = 0.007), malignancy , total parenteral nutrition , hypercoagulable state , and obesity . Eight thrombi were chronic, and 28 were acute. Notably, the authors presented a new sonographic sign which characterized acute thrombosis: a double hyperechoic line at the interface between the thrombus and the venous wall. They concluded that the presence of CVC was a strong predictor for the development of UEDVT, while the actual rate of subsequent PE was low. Surely, contrast venography remains a standard diagnostic technique in the evaluation of UEDVT; however, ultrasound has a clear established diagnostic role, while imaging with gadolinium contrast-enhanced magnetic resonance imaging is routinely used but has not been properly validated yet. Moreover, the recognition of gadolinium as a cause of nephrogenic systemic fibrosis has increased interest in noncontrast magnetic resonance venography [Current trends promote the optimization of two-dimensional ultrasound imaging by applying various technologies. Advances in ultrasound software can reduce artifacts and “noise” such as speckle arising from coherent wave interference or clutter arising from beamforming artifacts, reverberations, and other acoustic phenomena, while infusion of contrast agents during imaging facilitates interpretation of various pathologies , 5. In tApart from vascular ultrasound studies discussed above, P. Myrianthefs et al. evaluated whether routine ultrasound examination may illustrate gallbladder abnormalities, including acute acalculous cholecystitis (AAC) in a cohort of critical care patients. The authors evaluated major  and minor  ultrasound criteria. Notably 47.2% of patients showed at least one abnormal imaging finding; however, only 5.7% of cases were identified as AAC. They conclude that diagnosis of AAC requires high levels of clinical suspicion. Nevertheless, this series was small and future larger studies are clearly required to investigate the potential screening role of ultrasound in detecting gallbladder disorders in the ICU.Reading further on, three interesting papers focus on echocardiography emerge. T. Bagger et al. compared conventional and automated speckle tracking echocardiography to determine whether left ventricular (LV) systolic function could be estimated from one single imaging plane. They found a bias of 0.6 (95% CI −2.2–3.3) for global peak systolic strain comparing the automated and the conventional method. Notably, global peak systolic strain of apical 4-chamber cine-loops versus averaged global peak strain obtained from apical 4, 2, and long axis cine loops showed a bias of 0.1 (95% CI −3.9–4.0), and agreement between 4-chamber subcostal and apical global peak systolic strain was 4.4 (95% CI −3.7–12.5). Hence, they found good agreement between conventional and automated methods; moreover, speckle tracking ultrasound applied to single apical 4-chamber cine loops showed excellent agreement with overall averaged global peak systolic strain. In contrast, subcostal 4-chamber cine loops were rather unsuitable for the automated method. Technical issues related to the subjective evaluation of LV function may be solved by the application of advanced echocardiographic methods. Implementing the latter in routine practice remains debatable but represents an option that should be discussed awaiting the validation of currently applied basic echocardiography training programs for noncardiologists. Despite the fact that only basic elements of echocardiography are currently integrated in point-of-care ultrasound training programs, the method represents a “hot spot” of debate in critical care research and practice. J. C. Mandeville and C. L. Colebourn discussed whether transthoracic echocardiography can predict fluid responsiveness in the critically ill following a thorough literature search. They concluded that inferior vena cava analysis and transaortic Doppler signal changes with the respiratory cycle in mechanically ventilated patients were predictors of fluid responsiveness. Fluid responsiveness in the critically ill is a subject of ongoing research. Oftentimes various pathologies which may affect volume status coexist, while the clinical picture can be easily blurred in ICU patients. Recently, suggestions of noninvasive hemodynamic models comprising of lung and cardiovascular ultrasound emerged . DevelopSurely, applying point-of-care ultrasound in the ICU requires formal training. Critical care fellowships offered by European and US residency programs are currently taking on the burden of such responsibility . NotablyRichard HoppmannDimitrios Karakitsos


An aging population and better management of various heart diseases explain the exponential growth in incidence and prevalence of chronic heart failure, with poor prognosis and heavy health costs. Medical management is codified in international guidelines. The management of heart failure in over-80 year-old patients follows these guidelines, but no clinical trials have been able to confirm benefit. Moreover, registries show down-prescription of heart failure treatments in the elderly and over-80s.We present the design of the HF-80 ("Is there benefit in optimising heart failure treatment in over-80 year-old patients?") study, which is a prospective randomised open-label clinical trial with blinded end-points, designed to evaluate the effect of optimising management by adhering to guidelines in over-80 year-old heart failure patients. Patients over 80 years of age admitted with acute heart failure will be included. The primary endpoint is to assess quality of life at 6 months on the Minnesota questionnaire. The secondary endpoints are to assess the effect of optimised management on quality of life, mortality, readmission for acute heart failure, cardiac fibrosis and economic data at 12 months. 80 patients will be included, divided into 2 groups: group A, with usual heart failure management by general practitioners; and group B, with optimised management based on international guidelines.It is necessary to assess the benefit of guidelines in over-80 year-old heart failure patients because of the fragility of this population and the elevated risk of iatrogenic complications.NCT01437371.Clinical trials.gov number:  An aging population and improved management of various heart diseases involving ischemic aetiologies explain the growth in incidence and prevalence of chronic heart failure (HF) , with hiAngiotensin-converting enzyme inhibitors (ACEi) ,5 beta-bHeart failure management is now clearly codified for the general population, thanks to several studies and guidelines. Management of over-80 year-old HF patients, however, is simply extrapolated from their findings. No study has specifically assessed optimised HF treatment in the over-80s, where potential benefit could be counterbalanced by co-morbidity and iatrogenic complications. The HF-80 clinical trial was designed as a pilot study to investigate whether optimised management has an effect on quality of life (QOL) in over-80 year-old HF patients.The primary objective of this pilot study is to assess optimised HF management, according to the guidelines of the European Society of Cardiology (ESC) ,12, in tThe secondary objectives are to evaluate the effect of optimised management on:• Quality of life at 12 months• Mortality at 12 months• Readmission for acute HF at 12 months• Cardiovascular events at 12 months• Cardiac fibrosis, evaluated by collagen peptides.The primary assessment criterion is QOL at 6 months, assessed on the Minnesota Living with Heart Failure Questionnaire (LHFQ) .The secondary assessment criteria are QOL at 12 months, measured by both the SF 12  and LHFQThis pilot study will also help lay the groundwork for a French national multicentre study of the management of octogenarian HF patients to find what support is most appropriate.The HF-80 pilot study is a prospective randomised single-centre open-label clinical trial with blinded endpoints. Current lack of knowledge regarding management for this population requires a pilot study, to harvest data before starting a clinical trial to assess mortality. The study population is over-80 year-old patients recently admitted for acute HF. Inclusion and exclusion criteria are listed in Table Dementia will be assessed by the Mini mental state examination (MMSE): patients with scores under 24/30 will not be included. For the very elderly, a preliminary walking test will be performed, to exclude patients with reduced mobility, who are moreover very often subject to dementia.Included patients will be randomly allocated to either arm in a 1:1 ratio. The randomisation list is generated by minimisation  to maintOver-80 year-old patients will be recruited and randomised into 2 groups of 40 Figure :• Group A: "usual care" management by the patient's usual general practitioner (GP) and cardiologist;• Group B: "optimised" management strictly adhering to ESC guidelines ,12, perfPatients will be included in HF-80 at discharge from acute HF care. Before inclusion, trans-thoracic echocardiography will confirm that left ventricle ejection fraction is under 35% and that no exclusion criteria are present. During hospital care, patients of both groups will receive the same treatments, so far as possible using all HF therapeutics; different hospital treatment according to group would not be ethically acceptable. Mean hospital stay is about 10 days, which is too short to induce bias, as medical management optimisation applies only after discharge. Optimised management will be assessed with long-term prognosis.An identical assessment is to be performed at baseline and at 12 months for all patients (groups A and B) ;• Six-minutes walking test (6MWT);• Electrocardiogram (EKG);• Transthoracic echocardiography (TTE);• Blood test  , N-Termi• Renin, aldosterone and collagen peptides , and galectin 3;• Mini mental state examination (MMSE) .During primary hospital care for acute HF and at discharge, both groups will have the same management with initiation of the same treatments, following guidelines ,12.Group A subjects will be followed up by their usual GP and cardiologist without any day-hospital care . The GP and cardiologist will manage treatment optimisation as they are used to doing.Group B subjects will have the same management as group A but will also receive day-hospital care. The first 3 visits will be at 3 weekly intervals, except in case of unstable HF, and then every 6 weeks for 12 months, to optimise treatment.During each day-hospital visit in group B, certain data will be recorded to optimise HF management:• Clinical examination ;• Blood sample , by a single operator , at inclThe following measurements will be taken in each subject:2); RV volume; RV ejection fraction; TEI myocardial performance index; and tricuspid annular plane systolic excursion (TAPSE).2D/MM modes: Right ventricle (RV) diameter (mm); interventricular septum thickness at end diastole and end systole (mm); left ventricle (LV) posterior wall thickness at end diastole and end systole (mm); LV diameter at end diastole and end systole (mm); LV volumes at end diastole and end systole (ml); LV ejection fraction measured by the biplane Simpson method (%); LV mass index (g/m2); inferior vena cava diameter (mm); left and right atrium areas , peak A wave (cm/s), E/A ratio, E-wave deceleration time (m/s); pulmonary venous waveforms, including peak systolic (S) velocity, peak anterograde diastolic (D) velocity, and S/D ratio; VP, Color M-Mode flow propagation velocity; relaxation isovolumic time (m/s); cardiac output, tricuspid E wave; tricuspid regurgitation (none/mean/moderate/severe); systolic pulmonary arterial pressure; mitral regurgitation (none/mean/moderate/severe); and dp/dt for left and right ventricle.Doppler tissue imaging mode: lateral and septal E' wave and A wave at mitral annulus (cm/s), lateral and septal S wave at mitral annulus (cm/s); S' and E' wave at tricuspid annulus (cm/s).2D-Strain mode: Loops obtained by 2D on 3 cycles, with apical 4-cavities, 3-cavities, 2-cavities and parasternal short axis views, with frame rate > 60 frames/s.This will be performed for each patient at inclusion and at 12 months, and also at 6 months for group B . The tesThe usual blood tests made during acute HF hospitalisation will be performed by the hospital biochemistry laboratory: haemoglobin, K, Na, liver assessment, bilirubin, MDRD , NT-pro-It was decided to implement two QOL questionnaires . Termination for futility can thus be considered.With a 2-tailed significance threshold of 0.05, statistical power of 90% and allowing for 15% loss to follow-up, 80 patients will be needed to show a difference of 20 points (σ = 25) in quality of life (LHFQ) at 6 months between the 2 randomisation arms . MorcillThe number of patients included and the curve of the inclusions, the theoretical number of visits for the number of patients included, the number of visits actually made and the ratio will be presented for the 2 groups. The cumulative duration of follow-up and the "total follow-up/expected cumulative follow-up" ratio will be calculated.2 or Fisher-exact tests  and by Student's t tests or Mann-Whitney tests as appropriate (continuous variables). Multivariate analyses to control for confounding effects of variables will be performed.All analyses will be performed on an intention-to-treat basis. Clinically relevant baseline variables and primary and secondary endpoints will be compared between groups by ChiThe survival analysis will be conducted in univariate analysis by log-rank test to compare survival curves following Kaplan-Meier, and in multivariate analysis by the Cox proportional regression model.To measure the evolution of parameters over time points (visits), longitudinal data analysis will be conducted by ANOVA for repeated measures followed by Tukey-Kramer post-hoc test and by random effects models to measure within-subject correlation taking account of effects over time (random intercept and slope). The impact of covariates, such as randomisation group, will be explored to assess the impact of strategies on QOL score.Treatment compliance will be analysed initially in a descriptive step and, if necessary, included in multivariate analysis.A 2-tailed p value of 0.05 will be considered statistically significant . All analyses will be performed by STATAv11 .The aging of the population  is increUnfortunately, clinical trials on HF have recruited young patients. Clinical studies in cardiology, and particularly in HF, recruit young subjects at the expense of seniors who are underrepresented if not excluded -33. ThisA potential bias is present in this design. Patients in the "optimised" group will have more cardiology day-hospital visits; GPs will be in charge of their own management optimisation, as recommended in the ESC guidelines.Divergent data are present in the literature on elderly HF patients, and there is no consensus on managing over-80 year-old patients. The growing size of this population requires clinical trials to confirm that the HF management validated in younger subjects is also effective in those over 80 years of age.HF-80 study is in an activating recruiting phase since October 2011. Institute's committee on human research (CPP Sud Est VI) agreement was obtained in April 2011. Subjects will give their informed consent before being enrolled in the study. AFFSAPS agreement was obtained in May 2011. HF-80 will start enrolling patients in October 2011. Study completion date is estimated at December 2012. Clinical trials.gov number: NCT 01437371.HF: Heart Failure; QOL: Quality of life; LVHQ: Minnesota living with heart failure questionnaire; LV: Left ventricle; 6MWT: 6 minutes walking test; TTE: transthoracic echocardiography; ESC: European society of cardiology; ACEi: angiotensin conversing enzyme inhibitors; NYHA: New York Heart Association; GP: general practitioner.This clinical trial is funded by the support of Laboratoires Servier and Sorin group.The authors declare that they have no competing interests and no other source of fundings than those cited above.RE, FJ, SM, BP, and CV participated in the design of the study. RE and FJ participated in writing the manuscript. BP performed statistical section. VS participated in the biological part of the study. PM, JRL, BC helped to draft the manuscript, and participated in study design and coordination. All authors read and approved the final manuscript.


Regional maps of LV dyssynchrony are required for planning LV lead placement.Left ventricular (LV) mechanical dyssynchrony has been proposed as a parameter to select patients for cardiac resynchronization therapy (CRT) [Bax et al JACC 2005].Several recent studies have shown that placing the LV pacing lead in the most delayed regions yields a better response to CRT [Ansalone et al JACC 2002]. However, most imaging-based methods assess global LV dyssynchrony providing a single value for the entire LV. The objective of this study was to develop a method to create a map of regional left ventricular mechanical dyssynchrony based on short-axis SSFP cine images.We examined a series of 13 patients that met standard criteria for CRT . Patients underwent a CMR exam prior to CRT that included acquisition of high temporal resolution short-axis cine images (60 frames/cardiac cycle). The endocardial boundary was delineated in a semi-automated manner, and the boundary contour was sampled at 100 equally spaced points . A time-series of radial motion curves relative to the center of mass was generated for each radial location and over each slice.To detect dyssynchronous regions of the LV, a model of “synchronous” contraction must be identified. Our method to identify a synchronous contraction curve used quality threshold (QT) clustering to identify the radial contraction curves that were most alike and most prevalent in the LV by measuring the “distance” between all of the curves to identify similar trajectories [Heyer et al Genome Research 1999]. The largest cluster of curves was considered to be representative of synchronous contraction of the left ventricle. All curves that belong to this representative cluster were averaged to obtain a reference curve.time shift that resulted in the best correlation with the reference curve . This analysis was repeated for every point throughout the LV and time shift values were projected onto the standard AHA 17-segment model to create a mechanical dyssynchrony map . We were able to successfully generate dyssynchrony maps in all 13 patients.Using cross-correlation, each radial contraction curve was shifted in time to find the We present a robust method to provide a map of regional LV mechanical dyssynchrony that utilizes cross-correlation with a patient-specific reference contraction curve. This method can be used to identify regions of mechanical dyssynchrony for lead placement planning.This research was funded by the National Science Foundation Graduate Research Fellowship and the American Heart Association.


Quantification of myocardial iron overload is critical for the management of patients with hemochromatosis. The effects of excess iron over T2 and T2* relaxation times are well known and both measures strongly correlate with iron concentration. Due to its lower sensitivity to B0 inhomogeneities, T2 has theoretical advantages over T2*, but the latter became the clinical standard as it can be easily obtained in a fast one breath-hold ECG gated multi-echo GRE sequence. T2* is especially challenging at 3T due to greater B0 inhomogeneities at higher field strengths. We aimed to validate a recently developed T2-prepared SSFP sequence that quantifies myocardial T2 times at 3T, compared to standard GRE based multi-echo T2* times at 1.5T.A total of 15 normal volunteers and 7 chronic anemia patients  were prospectively enrolled. Myocardial T2* and T2 times were quantified in the same day, the former using a breath-hold multi-echo GRE sequence at 1.5T  and the latter using a recently developed T2 mapping technique based on a breath-hold T2-prepared SSFP sequence at 3T . All ROIs were placed at mid-interventricular septum, carefully avoiding the blood pool  and T2 times (44.9 ms +/- 2.2 vs. 37.9 ms +/- 6.6 p<0.05 respectively). 3T T2 times strongly correlated with 1.5T T2* times (r=0.91 and Figure Our results show that myocardial T2 values obtained with a T2-prepared SSFP parametric sequence can potentially serve as a valuable tool for quantification of iron overload at 3T.Internal.


Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy.A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function.NCT00841139ClinicalTrials.gov: ISRCTN2887836ISRCTN:  Despite recent advances in the treatment of heart failure (HF), it remains a condition with significant morbidity and mortality having a 5 year mortality rate that rivals most cancers. In the The main determinants of cardiac energetics and energy availability are substrate utilisation. The normal heart relies mainly on fatty acids for its energy requirements, accounting for up to 70% of the total energy requirement in the fasting state. GlucoseThese metabolic changes contribute to the energy starvation state found in heart failure of all aetiologies. Phosphorus-31 (P-31) magnetic resonance spectroscopy (MRS) is used to non-invasively estimate ATP and phosphocreatine concentration and the PCr/ATP ratio. Phosphocreatine is an important short-tem energy store that maintains a high phosphorylation potential under conditions of rapid increased energy demand such as exercise. ATP levels are maintained at steady concentration to maintain energy for muscle contraction and normal cellular function. The myocardial PCr/ATP ratios is reduced in HF and correlates with New York Heart Association (NYHA) class.Perhexline maleate is a metabolic modulating agent that gained popularity in the 1970's as an antianginal therapy until it was linked to both peripheral neuropathy . It has A growing body of studies support the use of P-31 MRS to measure this improvement in myocardial energetics as a response to treatment. Fragasso et al  have demTreatment with perhexiline increases cardiac PCr/ATP ratio, increases cardiac respiratory quotient (indicating relatively greater carbohydrate utilisation), and improves LV mechanical efficiency and left ventricular function in patients with dilated cardiomyopathy.This is a multicentre prospective, randomised, double-blind, placebo-controlled trial of 50 subjects with dilated cardiomyopathy (defined as an ejection fraction (EF) <40% in the absence of evidence of coronary artery disease) who are stable on conventional heart failure therapy. Inclusion and exclusion criteria are detailed in Table All patients will undergo a baseline visit  for accurate estimation of left ventricular cardiac mass.Female subjects of child-bearing potential will be excluded from the study.st order shimming will be performed including the entire heart using the unsuppressed water signal acquired with the body coil as reference. The shimming process involves an automated Hydrogen-1 spectral acquisition to test the quality of the shim that is expressed as a full width at half maximum (FWHM). This is repeated until a FWHM of less than 40 Hz is achieved. A short axis cine scan will be acquired to calculate the trigger delay for ECG triggering and to check quality of shimming and F0 determination. The trigger delay will be calculated such that the spectra is acquired in the diastolic period when the heart is a still as possible. The 3-dimensional ISIS voxel of acquisition will be planned to include most of the septum and apex of the heart within the shimmed area. Care will be taken to minimize blood contamination from the right ventricle, liver and skeletal muscle as much as possible. The voxel size will be kept constant at 89.54 ml (44 × 55 × 37 mm3) to allow comparisons between different subjects and scans. Following this the P-31 spectrum will be acquired with a repetition time of 10000 ms and 512 averages. A repetition time of 10000 ms has found to be optimal for adequate reduction of saturation effects without increasing the scan time greatly. The total scan time will be 23 minutes. The spectra will be analyzed and quantified on the java based Magnetic Resonance User Interface (jMRUI) software. Post-processing will be performed with 15 Hz Gaussian line broadening and Fourier transformation. Phase correction will be performed with PCr peak as the reference peak. Quantification will be performed with AMARES , time domain fitting program, which involves selecting peaks and defining their line width[Cardiac high-energy phosphate metabolism will be measured using P-31 MRS on a 3-Tesla Philips  Achieva whole-body magnet using a linearly polarized transmit and receive P-31 coil with a diameter of 14 cm. Localization will be achieved by image selected in-vivo spectroscopy (ISIS) volume selection. The participants will be positioned supine with the coil directly over the precordium. The coil will be secured in place by straps around the upper body and coil. The participants will then be positioned inside the magnet with the center of the coil at the isocenter of the magnet. Survey images will be obtained to check the position of the coil. The subjects and/or the coil will be repositioned if required to ensure that the distance between coil and septum and apex of the heart is minimized and maximize signal strength. Localized iterative 1ine width. A singlCardiac magnetic resonance imaging will be performed on the same 3 Tesla Philips Achieva system using a cardiac coil with patients in the supine position. Serial contiguous short axis cines will be piloted from the vertical long axis and horizontal long axis images using standard manufacturer supplied sequences. Analysis will be performed offline (Philips ViewForum Ver 4.1) by a single blinded observer for the assessment of ventricular volumes, ejection fraction and left ventricular mass.A standard transthoracic echocardiogram  will be performed with the subject in the left lateral decubitus position by a single experienced echocardiographer using second harmonic imaging and an M3S multi-frequency transducer. All parameters will be measured in triplicate and averaged as per the recommendations of the American Society of Echocardiography. AnalysiGreyscale images for 2-dimensional left ventricular strain will be acquired in cine-loop format in triplicate from the apical 4-, 2- and 3-chamber views and parasternal short axis views at basal, papillary and apical ventricular levels at end expiration at frame rates >70 Hz for offline analysis using commercially available software . The endocardial border will be manually tracked at end-systole and the software generates a region of interest over the myocardium. This enables frame-to-frame tracking of ultrasonic speckles that change position according to surrounding tissue motion throughout the length of the cardiac cycle. Peak systolic velocities, strain, strain rate, rotation and twist will be measured for each myocardial segment in triplicate and averaged.Patients will undergo cardiac catheterisation via the femoral artery and either the femoral or internal jugular vein following appropriate consent. A 7F sheath will be placed in the vein and artery. A Cordis-Webster  7F coronary sinus (CS) thermodilution catheter will be guided into the coronary sinus and 50/50 saline/contrast injections will allow visualisation and confirmation of its position within the right atrium and CS. All catheters will be calibrated prior to utilisation. The catheter is connected to both a Medtronic  temporary pacemaker 5348 and to a specialised Wheatstone bridge coupled to a bank of isolated direct coupled bioamplifiers . The output is subsequently digitised using a Dataq DI720 data acquisition system and both displayed and stored on a laptop computer using Windaq software . The atria will then be paced via electrodes on the catheter in the coronary sinus.plusX mass spectrometer. PV loops will be acquired from the left ventricle with a CFL-512 system (CD Leycom), which allows further offline analysis  for determination of left ventricular stroke work (LVSW), mechanical efficiency, dp/dtmax, dp/dtmin, and Tau (rate of active relaxation).A 7F dual-field conductance catheter  will then guided via the femoral artery sheath through the aortic valve and positioned within the left ventricle. Blood samples will then be taken from the left ventricle and CS for cross heart substrate analysis prior to the administration of heparin. The atria will then be paced at a rate just above baseline to ensure a steady rate. The conductance catheter allows continuous and simultaneous sampling of pressure and volume at 4 ms intervals, allowing the acquisition of pressure-volume loops in real-time. CS thermodilution runs will be performed in triplicate . Samples will then be taken for oxygen and carbon dioxide measurement. Oxygen measurement will be performed using a Bayer Rapidlab 800 series blood gas analyser . Carbon dioxide measurement will be performed by mass spectrometry by the University of Brimingham using a Finnigan MAT DeltaThe steady heart rate will allow for accurate assessment of per beat myocardial oxygen consumption. All of this subgroup will have had CMR studies for accurate assessment of cardiac mass and thus permit correction for myocardial mass.2 by the O2 consumed [Respiratory quotient (RQ) is a unitless value found by dividing the amount of eliminated COconsumed .(1)Mechanical efficiency (ME) can be calculated by dividing work output by work input giving another dimensionless value or percentage .(2)2 is ≈20J will be used[Work input can be calculated from myocardial oxygen consumption measurements according to the Fick principle by multiplying coronary sinus blood flow by the ateriovenous oxygen content difference. To be ul be used.-4 J for the purposes of calculating ME[External work will be estimated from measurements taken from the PV loops acquired from the left ventricle. 1 mmHg × mL equates to 1.33 × 10lating ME.Following baseline investigations ensuring normal liver function tests, participants will be randomised by computer to commence with perhexiline 200 mg oral daily or an identical placebo for one month Figure . RandomiAt one week duration, all patients will have a blood sample taken for serum perhexiline level with the researcher blinded to the subject's treatment allocation. This level will be evaluated by a doctor unblinded to the subject's treatment allocation. The dosage of perhexiline will be adjusted according to the accepted dosing protocol Table . An equaAt the end of one month of therapy, patients will undergo a repeat of baseline investigations and a further perhexiline level will be taken to ensure therapeutic levels were achieved and compliance maintained.The primary end point of the study will be an increase in the PCr/ATP ratio as assessed by MRS after 4 weeks of treatment. This end point has been used in previous studies and is associated with symptomatic class and mortality in heart failure. Seconda2 or repeated measures analysis or variance. Variables not normally distributed will be log transformed prior to analysis to achieve normal distribution or, if this is not achieved, analysed by Mann-Whitney U or Kruskal-Wallis tests.Comparisons will be performed between the groups at baseline and after the 4 week treatment. The normality of distribution of all continuous variables will be determined using a normality plot and the Kolmogorov-Smirnov test. Normally distributed variables will be analysed using unpaired t-tests, χp-value of < 0.05 will be considered statistically significant.Analysis will be by intention-to-treat. A Sample size calculations were based on the primary end point of change in PCr/ATP ratio after 4 weeks of treatment. Pilot work from our group using the same MRS technique and perhexiline revealed a 0.4 improvement in PCr/ATP ratio in the treatment group by comparing means. The response was normally distributed with a standard deviation of 0.5. Using this data, 26 subjects in each arm will provide at least 80% power of detecting a 0.4 change in PCr/ATP ratio using a two-tailed t-test at the 5% significance level. Recruiting 50 patients will allow for withdrawal, drop out or incomplete data.When perhexiline levels are unmonitored, it has been associated with both hepatotoxicity and peripheral neuropathy. All patients will be screened both clinically and biochemically for any sign of these conditions. Perhexiline also lowers serum glucose levels. Patients who are diabetic will be made aware that the medication may cause hypoglycaemic and they will be instructed make frequent blood sugar measurements when starting the study. Perhexiline levels will be tested at one week and at the end of the study as outlined above.All adverse events, including serious adverse events (SAEs), will be recorded and followed up for the duration of the study or until resolution. Assessment of adverse events will be performed by study investigators. All SAEs will be graded and reported to the sponsor. Any suspected unexpected serious adverse reactions will be reported to the sponsor, ethics committee and the Medicines and Healthcare Products Regulatory Agency. This study has been reviewed and approved by the South Birmingham Research Ethics Committee. Written informed consent will be obtained from all study participants.The study is powered for the primary endpoint (an increase in PCr/ATP ratio assessed after 4 weeks of treatment). It is accepted that the study is likely to be underpowered for the secondary endpoint of improvement in LV function. Nonetheless, a similar sized study using perhexiline in heart failure showed a dramatic, absolute increase in ejection fraction of 10% after 2 months of treatment. This imNo similar invasive work of this nature has been performed in human heart failure to allow an accurate power calculation for this component of the trial.The finding that perhexiline improves cardiac energetics by an increase in the PCr/ATP ratio would be an important contribution to support the future work of metabolic manipulation as a treatment for heart failure, even in the absence of coronary artery disease. PCr/ATP ratio has been shown to correlate with mortality, and an improvement in this index may also lead to an improved survival in this patient population.Until now, the proposed mechanism of perhexiline is based on in vitro and animal work. By showing an increase in R/Q we can support the hypothesis of increased carbohydrate metabolism as a result of perhexiline therapy.Improvement in mechanical efficiency would reveal that the above changes contribute, at least in part, to a direct improvement in cardiac function.2,3-DPG: 2,3-diphosphoglycerate; AMARES: advanced method for accurate, robust and efficient spectral fitting; ATP: adenosine triphosphate; CPT: carnitine palmitoyltransferase; BNP: brain natriuretic peptide; CMR: cardiac magnetic resonance imaging; CS: coronary sinus; ECG: electrocardiogram; EF: ejection fraction; FAO: fatty acid oxidation; FWHM: frequency width at half maximum; HF: heart failure; ISIS: image selected in-vivo spectroscopy; jMRUI: java based magnetic resonance user interface; LV: left ventricle; LVSW: left ventricular stroke work; ME: mechanical efficiency; MRS: magnetic resonance spectroscopy; MLWHF: Minnesota Living with Heart Failure; NHYA: New York Heart Association; P-31: phosphorus-31; PCr: phosphocreatine; PV: pressure volume; RQ: respiratory quotient; SAE: serious adverse event; TCA: tricarboxylic acid cycle;The sponsor for this trial is University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. Prof MP Frenneaux holds a patent for the use of perhexiline in heart failure.All authors contributed to the design of the study and were involved in drafting of the protocol and this manuscript. RMB will acquire the majority of the data. All authors will be involved in the statistical analysis and data interpretation. All authors have read and approved the final version of the manuscript.


Hemorrhage is a frequent hallmark of large acute reperfused myocardial infarctions (rMI). Recently, there has been a growing interest in CMR for noninvasive detection of hemorrhage in rMI. While T2*- and T2-weighted CMR have been used for this purpose, there is a lack of consensus on which of these methods is the most appropriate and reliable. We investigated the relative abilities of T2 and T2* CMR for detecting hemorrhage in rMI in a canine model and patients.Canines (n=14), subjected to ischemia-reperfusion (I/R) injury (3 hrs of LAD occlusion followed by reperfusion), underwent CMR (1.5T) studies on day 5 post reperfusion. T2*-weighted ), T2-weighted , T2-STIR (TE=64 ms) and Late Enhancement (LE) images covering the LV were acquired. Imaging resolution of all the scans was 1.3x1.3x8 mm3.Patients (n=14) underwent CMR (1.5T) on day 3 post angioplasty for STEMI after providing informed consent. T2*-weighted (TE=2.6-13.8ms (6 echoes)), T2-STIR (TE=61ms) and LE images covering the LV were acquired. Imaging resolution of all the scans was 1.4x1.4x10 mm3.T2* and T2 maps were constructed by fitting the multi-echo data to monoexponential decay. A threshold-based signal analysis was used to identify hemorrhagic (Hemo+) and non-hemorrhagic (Hemo-) infarcts. T2-STIR signal intensity (STIR-SI), T2* and T2 values, measured from Remote, Hemo- and Hemo+ regions, were compared. Statistical significance was set at p<0.05.Representative T2* and T2 maps, and T2-STIR and LE images (acquired from a canine on day 5 post I/R injury) are shown in Fig. Representative T2* map, T2-STIR and LE images, acquired from a patient (day 3 post angioplasty) are shown in Figure 2. Consistent with the animal studies, mean T2* of Hemo+ was lower than the mean T2* of both Remote and Hemo- , while no differences were observed between T2* of Remote and Hemo- (p=0.61). Mean STIR-SI of both Hemo- and Hemo+ were greater than that of Remote , with the mean STIR-SI of Hemo- greater than that of Hemo+ (p<0.001).This work was supported in part by grants from American Heart Association (SDG 0735099N) and National Heart, Lung, And Blood Institute (HL091989).


Gray-zone imaging for VT/VF is markedly predictive for both ischmic and non-ischemic patients as related to the incidence of post-implantation shock delivery.Sudden cardiac death in patients is predominantly caused by ventricular tachycardia (VT)/ventricular fibrillation (VF). Patients who have a low left ventricular ejection fraction (LVEF) and inducible VT during electrophysiologic study (EPS) are at risk of sudden death and may benefit from an implantable cardioverter-defibrillator (ICD) as do patients with low LVEF. However, LVEF's primacy in predicted SCD has been questioned. Recently, cardiac MRI (CMR) has shown that a determination of myocardial core scar via late gadolinium enhancement (LGE) may predict VT/VF with greater precision than LVEF presumably due its ability to define likely sources of macro-rentry by delinieating the 'gray-zone' myocardium.We hypothesize that LGE depiction of gray-zone scar is more predictive of VT/VF than LGE core scar assessment.A consecutive, retrospective chart review was performed of patients with both a CMR exam for LGE and with post-CMR ICD implantation from 2006-2010 within 30 days. Demographic and clinical events were collected from patient charts and ICD interrogation. Standard LGE (>2SD) and gray-zone  was manually determined and related as a percent of LV mass to arrhythmic events and ICD therapy.A total of 45 subjects met our inclusion criteria. These included patients with both ischemic (n=28) and non-ischemic (n=17) cardiomyopathy. In this population, LVEF was not predictive of ICD therapy in univariate or multivariate analysis (p=NS). In contrast, LGE strongly predicted future ICD therapy (combined anti-tachycardia pacing and defibrillation) in the multivariate logistic model (p=0.02), as well as defibrillation alone (p=0.03). LGE gray zone showed a similar trend for defibrillation but did not reach statistical significance (p=0.06).LGE via CMR is markedly predictive for future ICD therapy delivery in patients with non-ischemic and ischemic cardiomyopathy alike. This marker may prove to be an important stratification variable that will greatly enhance current approaches that have traditionally relied soley on LVEF.Internal.


Late gadolinium enhancement (LGE) cardiac MR can identify injured or scarred myocardium. However its prognostic implication remains unclear.We sought to quantify the risk of major adverse cardiovascular events (MACE) among patients with LGE and CAD.Two reviewers conducted a systematic search of electronic databases (MEDLINE and EMBASE) and hand searched bibliographies. Reviewers extracted data in duplicate, evaluated the quality of the studies based on a 4 point scale, and calculated pooled estimates. Out of 579 unique records screened, 115 full-text articles were assessed for eligibility. We then performed a meta-analysis on 18 eligible studies which reported on the occurrence of MACE in patients with LGE detected after a myocardial infarction.2, 83.5%). Furthermore, there was a continuous relationship between risk and the amount of LGE detected. For every 10% of the left ventricular mass with LGE, the risk of MACE increased by 56% . Pre-specified meta-regression analyses revealed that the HR for MACE decreased with declining ejection fraction (p=0.02) when LGE was continuous, and was inversely related to age (p<0.001) when LGE was binary.A total of 4,438 patients were included in the analysis. The overall hazard ratio (HR) for MACE was 2.65  for the presence of any LGE, with large amounts of heterogeneity between studies (IStudies were heterogeneous with respect to patient characteristics and the definition of MACE, which may limit interpretability and generalizability.The presence and extent of LGE are independent predictors of MACE in patients with prior myocardial infarction.Nil.


To evaluate left and right myocardial performance at rest and after maximal exercise by conventional and Tissue Doppler Imaging (TDI) echocardiography.Iron Overload Cardiomyopathy (IOC) is the main cause of death in thalassemia major (TM) patients but conventional Echocardiography fails to predict early cardiac dysfunction. As TDI is able to demonstrate regional myocardial dysfunction and stress test may reveal abnormalities which are not evident at rest, we wondered if echocardiographic parameters may reveal abnormalities when applied first at rest and then after a physical effort.We enrolled 46 consecutive beta-TM patients and 39 control subjects without evidence of cardiac disease; two echocardiograms, at baseline and at the end of maximal exercise on supine bicycle ergometer, were done. All TM patients had a liver iron assessment by SQUID (Superconducting Quantum Interference Device) and a cardiac iron one by MRI (T2*) evaluation.38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S’ waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. Pulmonary artery systolic pressure (PAPs) values were greater than in control subjects both at rest and after exercisein our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results. Some previous studies reported interesting results about the utility of Tissue Doppler Imaging for the echocardiographic evaluation of patients with beta-talassemia major.TM patients are prone to iron overload due to chronic blood transfusion and increased intestinal absorption.6With our study we evaluated the effectiveness of TDI in TM patients without clinical or instrumental signs of heart failure in early detection of regional myocardial dysfunction at rest and after maximal exercise.From January to October 2011 we examined 46 consecutive patients with beta-thalassemia major (TM) on regular blood transfusion and iron chelation. Inclusion criteria were a recent Biosusceptometry SQUID (Superconducting Quantum Interference Device) to quantify liver iron concentration (LIC) and a cardiac iron assessment by MRI T2* technique in the previous year. Exclusion criteria were: clinical signs of heart failure, pulmonary hypertension, arrhythmias, left ventricular ejection fraction (LVEF) <55%, ongoing pregnancy, age <18 years, reduced exercise capacity or dyspnea at six minutes walking test (6MWT).We also examined 39 healthy age-, and sex-matched volunteers. The study protocol was approved by local ethics committee/boards, and all patients and control subjects were enrolled after informed consent.Transthoracic echocardiography was performed 4–9 days after blood transfusion to ensure hemodynamic stability, using a Aloka Prosound Alfa 10 ultrasound system (2.5–3.5 MHz), by a single expert investigator that was blinded to clinical information about patients until the end of the study. Cardiac cycles were stored in a digital format. Chamber dimension were determined by standard proceduresPulmonary arterial systolic pressure (PAPs) was derived from the tricuspid regurgitation velocity and an estimation of the right atrial pressure based on the dimension of inferior vena cava.10For all measurements, intervals from 3 consecutive cardiac cycles were measured and averaged.8During the same session all patients underwent a complete echocardiographic examination (standard and TDI) after maximal exercise performed on a supine ergometer ER-900, Bitz-Germany, increasing workload by 25 Watts every 2 minutes, until they experienced fatigue or symptoms or until 85% of the age-predicted maximum heart rate was achieved.t test or Fisher’s exact test. The degree of association between clinical and laboratory variables were determined using the Pearson’s correlation coefficient. Differences were considered significant at a probability value of p<0.05.Data are expressed as mean ± standard deviation for continuous variables or count (%) for categoric variables. Variables between the 2 groups were compared using the unpaired Student The characteristics of patients and control subjects are summarized in Echo at rest (4): in patients with TM the morphological data were within normal ranges, with a mild atrial dilation compared to control group . Left atria’s area had a significantly negative relation with mean haemoglobin levels of the previous year . at rest  and 4: isystolic function, in TM patients EF was normal, left S’-waves by TDI were comparable to controls and the average value of Tricuspid Anular Plane Systolic Excursion (TAPSE) was normal (23.9±3 mm).As regards Diastolic parameters were in ranges of normality in both groups, even if right isovolumic relaxation time (IVRT) was higher in TM patients (59.6±19.6 ms) then in the control group .PAPs value was within normal limit even if higher in TM patients than in control subjects (24.38±3 mmHg vs 20.8±4.8 mmHg), due to different tricuspid regurgitation jet velocity (TRV) between the two groups . There were no remarkably echocardiographic differences at rest between patients with and without cardiac iron overload detected by MRI  as showed in Right S’ wave increased more in TM cases than in controls (p<0.0001); also TAPSE, used to evaluate the systolic function of the right ventricle, followed this way, although without statistic significance (p=0.14). TAPSE values significantly differed between patients with and without cardiac iron overload .PAPs value increased in both groups, due to TRV rising after exercise (2.63±0.18 m/s in TM patients vs 2.27±0.28 m/s in control group) and remained higher in TM patients (p<0.0001).2+ metabolism abnormalities.14Heart disease is till today the major cause of mortality in thalassemic patients.Cardiomyopathy from iron toxicity has a silent course, with late onset of symptoms of congestive heart failure,In clinical practice echocardiography provides a fast bedside and relatively cheap technique to study heart function; however, conventional echocardiographic parameters remain normal until late, mainly due to the anemia-related hyperdynamic state. Pulsed Doppler tissue imaging is a relatively new technique which allows the assessment of ventricular regional function, myocardial velocity, time intervals of the cardiac cycle and, most importantly, is preload independent.There is evidence that long axis function measured by TDI is a more sensitive index of myocardial contractility than conventional echocardiographic parameters. Impairment of longitudinal fiber motion is therefore a sensitive and early marker of myocardial dysfunction, with prognostic value.Conversely, in our work only 17.4% of patients had some evidence of cardiac iron and 38 of 46 (82.6%) had no evidence of cardiac iron overload. They underwent physical exercise to highlight by stress a contractile dysfunction that is not evident at rest, because this may potentially be an early sign of cardiomyopathy. The exercise capacity of this group of patients was comparable to that of healthy controls. The absence of ventricular hypertrophy and dilation may be due to the good clinical care, while dilation of the atria (50% of patients) is probably a consequence of residual anemia with transfusional regimens that keep the haemoglobin between 9.5 and 13.5 g%.As expected in patients whose iron overload cardiomyopathy is presumably in very early stages, the global and segmental LV systolic functions were normal at rest.The most interesting data on the systolic function came from TDI. The average values of S’ waves measured on the basal septum and on the lateral mitral ring were normal at rest in TM. As expected, the S’ waves increased with exercise, in both groups, but in TM patients it achieved significantly lower values than in the control group .Our data show a weak correlation between LV S’ waves values after exercise and LIC and also with mean ferritin values . A signiSubgrouping patients according to the presence of cardiac iron at MRI, we did not found any significant difference in the echocardiographic values, except for TAPSE. Even for the TDI parameters of systolic velocity we did not showed a significant difference, although a trend to lower values was present in patients with T2 * <20 .The possible explanation for this finding could be that the group of patients with cardiac iron accumulation is too small to have sufficient statistical power and moreover the range of cardiac iron load is moderate-mild . We should also keep in mind that some patients presenting without accumulation on MRI have had heart iron accumulation in the past then regressed after regular chelation therapy over the years. Finally, it is possible that the reduced systolic regional performance detected by TDI and likely to be attributed to iron damage, could be due to other factors, such as chronic anemia, that all patients with TM have in common.Nevertheless, systolic S’ velocity at TDI evaluation done after a physical exercise were lower also in TM patients without evidence of cardiac iron overload when compared to a healty group: this is a new result, not yet described in TM patients, and further studies are needed to understand if the reduced shortening of longitudinal fibers could represent a very early sign of initial myocardial dysfunction.The preservation of global systolic function could be explained by the patchy iron deposition in the heart,Conversely, in RV, systolic function - measured with TAPSE, FAC and S’ wave - is preserved, with a pattern similar to control group. The only difference we found is about the S’ wave measured at the tricuspid ring: under exercise, it increases more in TM patients than in control group. This difference recalls what described by Hamdy et al.Doppler analysis of flows through the AV valves shows normal average values of both mitral and tricuspid E/A ratio. The response to stress is normal, with filling velocities increase and non-significant decrease in E/A ratio bilaterally. According to Kremastinos et al.,23We have not yet provided an adequate follow-up to validate the clinical impact of our findings. Because of the need to acquire data quickly after stopping the exercise, we could not conduct a full assessment of all myocardial segments to the TDI, but only the basal ones. However, these are generally considered the most reliable.8Our study shows that patients with beta thalassemia major, without clinical signs of heart failure and with normal EF under exercise stress may have a reduced response to exercise of left ventricle longitudinal fibers that could be detected with TDI echocardiography, even without MRI evidence of iron overload. To our knowledge this is a novel finding and we hypothesize that it may be a very early sign of initial myocardial damage by iron. Further investigations are warranted to confirm this hypothesis, in order to clarify if it could influence the clinical and therapeutic choices. A follow-up with the same technique could also confirm the stabilization, the exacerbation or regression of the dysfunction, and therefore the response to therapies.From our data we conclude that stress echocardiography with TDI may be a non-invasive and repeatable imaging technique to assess the efficacy of chelation therapy and to identify early signs of myocardial involvement, even when MRI is not indicated or is negative for cardiac iron overload.


In patients with severe aortic stenosis, left ventricular hypertrophy is associated with increased myocardial stiffness and dysfunction linked to cardiac morbidity and mortality. We aimed at systematically investigating the degree of left ventricular mass regression and changes in left ventricular function six months after transcatheter aortic valve implantation (TAVI) by cardiovascular magnetic resonance (CMR).Left ventricular mass indexed to body surface area (LVMi), end diastolic volume indexed to body surface area (LVEDVi), left ventricular ejection fraction (LVEF) and stroke volume (SV) were investigated by CMR before and six months after TAVI in patients with severe aortic stenosis and contraindications for surgical aortic valve replacement.2 at baseline to 69.4±18.4 g/m2 at six months follow-up (P<0.001). LVEDVi , LVEF  and SV  did not change significantly.Twenty-sevent patients had paired CMR at baseline and at 6-month follow-up (N=27), with a mean age of 80.7±5.2 years. LVMi decreased from 84.5±25.2 g/mBased on CMR, significant left ventricular reverse remodeling occurs six months after TAVI. In patients with severe aortic stenosis, left ventricular hypertrophy is a frequent pathophysiological adaptation to pressure overload . HoweverHemodynamic changes that occur after TAVI have been generally evaluated by echocardiographic methods ,15. CardTwenty-seven patients who underwent successful TAVI using the Medtronic CoreValve  or Edwards SAPIEN  bioprostheses were assessed with CMR before the procedure and at six-month follow up Figure . The insLeft ventricular mass indexed to body surface area (LVMi), left ventricular end diastolic volume indexed to body surface area (LVEDVi), stroke volume (SV), left ventricular ejection fraction (LVEF) and mass/volume ratio were assessed at baseline and six months. The occurrence of subendocardial fibrosis was assessed in terms of late gadolinium enhancement (LGE) at baseline and six months.3 ; reconstructed voxel-size = 1.25 × 1.25 × 8 mm3 acquisition; sensitivity encoding (SENSE)-factor = 2) were acquired after the acquisition of true two- and four- chamber planes for the assessment of left ventricular ejection fraction (LVEF %).The CMR images were analyzed off-line using a commercial software  by a blinded experienced CMR reader unaware of patients’ clinical data. For assessment of left ventricular function, the end-diastolic and end-systolic cine frames were identified for each slice and the endocardial and epicardial borders were manually traced. The end-diastolic and end-systolic volumes were then calculated using the Simpson’s rule  and indexed to body surface area. LVEF was calculated as (end-diastolic volume - end-systolic volume)/end-diastolic volume. LVMi was derived via the Simpson’s method multiplied by the specific gravity of myocardium (1.055 g/ml) and indexed to the body surface area. LVMi was divided by the LVEDVi to obtain the mass/volume ratio. Normal values used in this study for both LV systolic function and mass were those reported by Maceira et al. [All CMR studies were performed with a 1.5 Tesla Magnetic Resonance Imaging scanner  with a flexible cardiac five-element phased-array coil and a vector electrocardiogram for R wave triggering using a standard MRI imaging protocol. In brief, multiple short axis (SAX) cine images using a breath-hold steady state free precession sequence with parallel imaging ; Repetition time (TR)/Echo time (TE) = 3.1/1.56 ms; slice thickness 8 mm; matrix 180 x 175 ; flip angle 60°; acquisition voxel-size = 1.78 × 1.82 × 8 mma et al. . Left veTo evaluate LGE, an intravenous bolus dose of 0.2 mmol/kg body weight of gadobutrol  was administered at a rate of 3 ml/s by a power injector . Ten minutes after gadolinium injection, a ‘Look Locker’ sequence was performed to obtain the most appropriate inversion time to null the signal intensity of normal myocardium. LGE images were then acquired using the following parameters: fast gradient echo, repetition time 6.1 ms, echo time 3 ms, flip angle 25°, field of view 320 mm, slices thickness 10 mm, acquired in the left ventricular short axis over 2 RR intervals and no interslice gap. LGE was evaluated by visual assessment in short-axis slices and further characterized by spatial location, pattern, and LGE quantification  [2) and LVEF (< or ≥ 55%) were dichotomyzed as previously described [Quantitative data were presented as mean ± standard deviations and were compared using the Student t paired test. Univariate and multivariate correlates of left ventricular reverse remodeling were analyzed by logistic regression. To explore their significance as baseline predictors, LVMi  patients had a proibitive Logistic EuroSCORE, 1 (3.7%) patient had a porcelain aorta, 3 patients (11.1%) had received thoracic radiation therapy for lung cancer, 1 (3.7%) had a severe form of diabetic lipodystrophy, 1 patient (3.7%) had cirrhosis and 5 patients (18.5%) refused surgery. All patients were in New York Heart Association class III-IV and 37% of them were previously hospitalized for congestive heart failure (Table 2 to 69.4±18.4 g/m2 (P<0.001). Conversely, LVEDVi, SV and LVEF did not change significantly  Table . Figure 2vs 69.5± 22.3 g/m2, P <0.001), with no significant changes for other parameters . At baseline, evidence of LGE was present in 10 (41.6%) of 24 cases. Causes for LGE were ischemic in 8 cases, and non-ischemic in 2 cases Figure . At follAlthough limited by the small sample size, our study enables a deeper understanding of left ventricular reverse remodeling occurring after TAVI in a complex clinical cohort, by means of a reliable and accurate technique as CMR. In particular, at six months, we observed a statistically significant reduction of LVMi.2, p < 0.005) and continued to further trend downward at 4 years . Lamb et al. [Regression of myocardial hypertrophy due to the decrease of ventricular afterload after surgical aortic valve replacement is a well-recognized phenomenon ,22,23. Ib et al.  showed tStudies based on echocardiography seem to confirm that after TAVI the left ventricle undergoes a similar reverse remodeling process -30. In aThe significant reduction of the left ventricular mass observed in our study was not accompanied by a corresponding significant increase in LVEF and SV. Several studies demonstrated improved LVEF after surgical aortic valve replacement, particularly in patients with low preoperative ejection fraction . HoweverWe did not collect CMR data regarding post-TAVI aortic regurgitation that could have influenced left ventricular remodeling. However, based on trans-thoracic echocardiography, no patient had a residual severe aortic insufficiency, while a mild to moderate insufficiency was present in 4 patients, a mild insufficiency in 7 and no hemodynamically significant regurgitation in the remaining population. Moreover, another major limitation of this study is the lack of information on diastolic dysfunction, flow, and changes in gradients and aortic valve areas pre and post TAVI. Finally, our study demonstrated the absence of periprocedural myocardial infarction potentially caused by the deployment of the prosthesis and possible calcium embolization.This CMR study explored the mid-term hemodynamic effects of TAVI. Our results expands on previous findings from echocardiography studies by means of a more precise and reliable imaging technique. A significant left ventricular reverse remodeling was shown at 6 months from TAVI. The implication of this finding remains unclear and should be explored in large dedicated studies with clinical endpoints.CMR: Cardiovascular magnetic resonance; LVEDVi: Left ventricular end diastolic volume indexed to body surface area; LVMi: Left ventricular mass indexed to body surface area; LVEF: Left ventricular ejection fraction; SV: Stroke volume; TAVI: Transcatheter aortic valve implantation.Non-financial competing interests.ALM conceived and designed the study, participated in data analysis, interpretation and manuscript drafting and was responsible for the final manuscript draft. AS participated in study design, data analysis and interpretation, statistical analysis and manuscript drafting. DC participated in data analysis and interpretation, statistical analysis and manuscript drafting. AS, AC, IC, GP, MF and RP performed additional data analysis. CP and CT participated in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.


Myocardial T1 and T2 mapping using cardiovascular magnetic resonance imaging (CMR) is promising to improve disease detection and monitoring. We applied T1 and T2 mapping at 3T to study the technical feasibility and provide reference values in healthy volunteers.3). For T1 maps, Modified Look-Locker Inversion Recovery (MOLLI) technique with 11 single shot SSFP images was used before and after injection of gadolinium contrast . T1 and T2 relaxation times were quantified for each slice and each myocardial segment.Sixty healthy volunteers  underwent T1 and T2 mapping of the left ventricle in 3 short axis slices. For T2 maps, 3 single shot steady state free precession (SSFP) images with different T2 preparation times  were acquired .


We investigated age related remodeling and associated changes in systolic and diastolic function and myocardial mechanics using cardiac MRI and echocardiography.Aging is associated with left ventricular (LV) remodeling. However, relationships between age related remodeling, changes in systolic and diastolic function and changes in myocardial mechanics are not well characterized.Sixty-five normal volunteers aged 23-85 years were carefully screened by history, ECG and echocardiography. All were free of obesity, diabetes, hypertension, cardiovascular and valvular disease. Participants underwent cardiac MRI and echocardiography on the same day. LV structure and global systolic function were assessed using SSFP cine imaging. LV systolic and diastolic torsion and strain were assessed from tagged gradient echo cines using HARP software. Diastolic function was also assessed using echocardiographic mitral inflow and tissue velocity.o/cm, 1.31 ± 0.4 o/cm, 1.83 ± 0.6 o/cm, p=0.02) while LV global systolic function was unchanged  and circumferential strain tended to decrease with aging . Diastolic function was consistently reduced with aging evident by decreased mitral medial e’  decreased mitral inflow E/A ratio  but increased mitral E/e’ . There was also a significant decrease in early diastolic strain rate . Women demonstrated greater declines in diastolic function than men.Mean age was 53.6 ± 14 years, 52% female. The cohort was divided into 3 subgroups by age: ≤ 44, 45-60 and ≥ 61 years. Comparing younger to older age groups, LVEDV decreased with aging  with unchanged LV mass , resulting in an increased mass/volume ratio  consistent with concentric remodeling. Torsion increased significantly in the oldest group (1.41 ± 0.4In this carefully screened normal cohort, age dependent concentric remodeling was associated with significant decline in diastolic global function and mechanics, increased systolic torsion with preserved LVEF and a mild trend toward reduced systolic strain. Age related changes in diastolic function were more pronounced in women than in men.


With interest we read the article by Esposito et al. about a female child with myopathy and left ventricular hypertrabeculation / noncompaction (LVHT) carrying a mutation in two different genes, the integrin-α7 gene and the myosin heavy chain 7B gene (MYH7B) . We haveThe authors mention in the discussion that MYL2 and MYL3 mutations were found in patients with LVHT . Among tLVHT has not only been found in association with mutations in the TAZ, DTNA, ZASP, lamin A/C, MYH7, ACTC1, TNNT2, TNNI3, MYBPC3, and TPM1 genes but also in association with mutations in the dystrophin, DMPK, ZNF9, LAMP2, GAA, mtDNA, AMPD1, GBE1, RYR1, COL7A1, PMP22, MMACHC, beta-globin, and DNAJC19 genes .The index patient underwent echocardiography at age 1 month but LVHT was diagnosed not before the next echocardiographic examination at age 17 months. Which is the reason why LVHT was not detected at the initial examination? Was LVHT missed because of poor image quality, absent awareness of the pathology, ignoring the abnormality, left ventricular hypertrophy at the initial investigation, severe dilation of the left ventricle, or did LVHT truly develop during the period between the two examinations (acquired LVHT)? Did the authors review the initial echocardiographic examination? Did the presence of a patent arterial duct and patent foramen ovale prevent LVHT from being diagnosed at the initial examination?Myopathy is often subclinical at an early stage and may be detected or suspected only upon creatine-kinase (CK) screening, needle electromyography or muscle biopsy at this stage . Were thThe patient obviously died from sudden cardiac death, which is a frequent complication in patients with LVHT. Were there any other family members of the 5 generation family in whom sudden cardiac death has been reported? Since ECGs had been recorded in all family members it would be interesting to know if QTc was prolonged in any member other than the index patient? Was implantation of an implantable cardioverter defibrillator ever considered in case V/4?Since LVHT may be also complicated by cardioembolic events, death could be attributable also to fatal cerebral or cardiac embolism . Did theThe authors mention that the index patient underwent cardiac MRI at age 10y. Was any late enhancement observed and if there was late enhancement how was it distributed?Overall, the interesting paper by Esposito et al. evokes a number of questions, which require further discussion. Currently, there is no proof that LVHT is causally linked to any of the mutations so far described in association with LVHT.


While conventional temporal resolution on the order of 30-50 ms is sufficient for calculating LV functional metrics such as global ejection fraction (EF), it is insufficient to accurately capture subtle regional wall motion dyssynchrony. A higher frame-rate cine imaging, e.g., 100 fps imposes an undue burden on the manual segmentation, precluding more sophisticated analyses, e.g., measurement of SLWM delays. A robust algorithm that inscribes papillary and trabeculae as LV cavity is a necessary pre-requisite for such an analysis.To present a high-temporal resolution cine MR imaging method, as well as an ultra-fast, inline M-Mode analysis tool that can measure SLWM delays interactively on the scanner console.All imaging and analysis was done on a standard clinical 1.5T scanner  with a 32channel coil.16 asymptomatic volunteers and 10 clinical patients.voxel: 2x2x8 mm3, temporal resolution 5.6-12 ms; TR/TE/flip=2.8-3 ms/1.4-1.5 ms/55deg; time=18 heart-beats/slice, SENSE-factor=3.The processing and analysis steps included: 1) automatic endocardial LV contour delineation for all the cine phases ; 2) M-mode representation of the LV with overlay of: end-systolic(ES) phase, the onset of peak contraction for septal and lateral wall, and LV centroid.The user interactively probes the SLWM by prescribing a line, and the corresponding M-mode display is automatically marked with various indices such as time to ES, onset of peak contraction for septal and lateral wall, and percent radial contraction  even in asymptomatic volunteers.


Accurate analysis of T2-weighted magnetic resonance images (MRI) is crucial for myocardial edema (ME) assessment. In view of frequent artifacts from motion, slow flow and field inhomogenities affecting infarcted and remote myocardium (ReM), several approaches can be used to evaluate ME: 1) visual assessment, 2) signal intensity (SI) > 2 SDs of ReM or 3) normalizing myocardial SI to that of a skeletal muscle: T2 Ratio. Currently, there is no standardized approach to a (semi-) quantitative edema assessment using T2-weighted imaging.The purpose of this study is to compare different approaches for the analysis of T2-weighted images in patients with late reperfused myocardial infarction (MI) for reproducibility and agreement with the extent of MI, using LGE as a standard of truth.Thirty patients with acute late reperfused MI (time to reperfusion > 200 minutes) who underwent cardiac MRI at 1.5 T within 5 days from onset of symptoms were retrospectively studied. The MRI protocol included b-SSFP cine, T2-STIR imaging using a body coil and Late Gadolinium Enhancement (LGE) imaging. Ten patients demonstrated microvascular obstruction (MVO) on LGE images and were analyzed separately. Infarct size was determined on LGE images using a threshold of 2SD and 5SD above the SI of ReM. Regions of interest were traced manually; edema size was measured using thresholds of 2, 3 and 5SDs above the SI of ReM, as well as using the T2 Ratio.When using LGE with a cutoff of 2SD, the LGE area with high signal intensity was larger than the area with high T2 signal intensity (2SD). There was a very good agreement between LGE/5SD and T2 ratio in both, patients without MVO  and with MVO . Infarct size defined by LGE/5SD was significantly smaller than edema size using thresholds of 2SD and significantly larger using a 5SD threshold (both p<0.001).In contrast, there was no correlation between LGE/2SD and T2 measurements. Figure Using LGE/5SD in patients with late reperfusion acute myocardial infarction, a normalized T2 signal intensity ratio appears to be the most accurate approach for the evaluation of the size of infarct-related edema.


Approximately one third of patients treated with cardiac resynchronization therapy do not derive any detectable benefit. In these patients, acute invasive hemodynamic evaluation can be used for therapy optimization. This report describes the use of systematic invasive hemodynamic measurements for clinical decision making in a patient who experienced severe ventricular arrhythmias and clinical deterioration following a biventricular upgrade. Cardiac resynchronization therapy (CRT) has been established as an effective treatment for heart failure patients with severe left ventricular (LV) systolic impairment and electrical dyssynchrony . UnfortuA 65-year-old male patient with non-ischemic dilated cardiomyopathy, left ventricular ejection fraction of 20%, intra-ventricular conduction delay with a QRS duration of 148 ms, and NYHA class 3 was scheduled for upgrade of an implantable cardioverter defibrillator (ICD) to a cardiac resynchronization therapy - defibrillation (CRT-D) system. The ICD had previously been implanted for primary prevention. Echocardiography prior to the BiV upgrade demonstrated myocardial scarring of the LV lateral wall and showed no evidence of mechanical dyssynchrony. Unfavorable coronary venous anatomy required epicardial LV lead placement in the lateral position via minimal lateral thoracotomy. Four weeks later, the patient was admitted with multiple ICD discharges due to incessant ventricular tachycardia (VT) . He was An invasive hemodynamic pacing study was performed to evaluate the hemodynamic effect of conventional BiV pacing and to explore whether LV endocardial pacing could effectuate hemodynamic improvement. For this purpose, a temporary pacing electrode and a RADI pressure wire were positioned within the LV cavity, another temporary pacing electrode was placed in the right atrium . The RADNeither LV, RV or BiV pacing with the implanted system nor LV endocardial pacing at different sites improved LVdP/dtmax as compared to baseline . FurtherPatient selection plays an important role in CRT response. According to the ESC heart failure guidelines available at the time of device implantation, our patient had a class I indication for CRT . HoweverThe presence of myocardial scar at the area targeted by the LV lead is an important determinant of CRT response . Lead poIn a small percentage of patients, CRT may potentiate ventricular tachyarrhythmias. The exact mechanisms of proarrhythmia remain largely unclear but our findings suggest that pacing in the region of myocardial scar may facilitate its development. This conception is supported by the morphology of the VT which suggested a lateral exit site close to the LV epicardial pacing lead. A suggested underlying mechanism is a potential increase in local myocardial oxygen demand by pacing, precipitating ischemia in the peri-infarct zone and making it vulnerable to re-entry ,9. The cThis case report illustrates the potential contribution of acute invasive hemodynamic evaluation to clinical decision making in CRT. Acute hemodynamic testing may also be considered as a step-up approach to justify implantation of a LV endocardial lead and to guide lead positioning optimization. Finally, this case underlines the importance of considering the possibility of CRT related proarrhythmia, whenever CRT treated patients develop new ventricular tachyarrhythmia's.


The FAST method for measuring left ventricular twist has been expanded to semi-automatically measure torsion, peak systolic twist rate, peak diastolic untwisting rate, time to peak twist, and duration of untwisting using FAST+CSPAMM.Alterations in left ventricular (LV) twist are important for many pathologies including aortic stenosis, diastolA spoiled gradient echo pulse sequence was modified to support CSPAMM and used to acquire short-axis images in healthy volunteers (n=13) at the LV base and apex with the following parameters: 360-300x300-280mm FOV, 5-6mm slice thickness, 192x144 acquisition matrix, 501 Hz/pixel receiver bandwidth, TE/TR=3.5-3.7/4.7-6.5ms, 10mm tag spacing, 7-8 ky-lines per segment, 3/4 partial Fourier imaging, 14-16 cardiac phases, 15° FA and two averages for SPAMM imaging, and non-linearly ramped imaging flip angles  for CSPAMM[The comparison of FAST+CSPAMM to FAST+SPAMM for twist, torsion, twisting rates, time of peak twist and duration of untwisting are summarized in Table The FAST+CSPAMM is a semi-automated method that provides a quick and quantitative assessment of systolic and diastolic left ventricular twist, torsion, and twisting rates. When FAST is used in conjunction with CSPAMM duration of untwisting can be measured, which may provide further insight into left ventricular diastolic dysfunction.AHA to MLR.


Leaflet malcoaptation in ischemic mitral regurgitation (IMR) is thought to be caused by a combination of annular dilatation and leaflet tethering due to subvalvular ventricular remodeling. Despite this, little is known regarding leaflet dynamics in IMR. Using high temporal resolution MRI we describe, for the first time, the influence of post infarction ventricular remodeling on leaflet motion.A porcine model of IMR was used. Using direct coronary ligation, five animals were subjected to a posterior myocardial infarction. Eight weeks post infarction animals underwent 4D time-resolved, flow sensitive MRI imaging, 3D MRI cine imaging and 2D phase contrast, high temporal resolution imaging of the mitral valve, left ventricle and aortic outflow tract. Three naïve animals underwent identical imaging protocols to serve as controls. Net mitral and aortic transvalvular flows were determined as well as left ventricular volumes and ejection fraction. Anterior to posterior mid-leaflet tip distances were measured throughout the cardiac cycle for quantification of temporal leaflet dynamics. Statistical significance was computed by ANOVA.Average net flow through the aortic valve was equal to average net flow through the mitral valve in both cohorts. Regurgitant fraction was 11.0 ± 2.3% in the ischemic group. End diastolic volumes for the ischemic group (compared to controls) were 125.6 ± 29.0 ml  Similarly, end systolic volumes increased for the ischemic group 87.8 ± 25.9 ml . Ejection fraction decreased substantially from 57 ± 5.5% at baseline to 31.2 ± 7.7% (P=0.002) with the development of IMR. Analysis of temporal leaflet dynamics revealed that the early diastolic peak leaflet separation at the A2-P2 scallop was wider in the ischemic group . Both cohorts demonstrated interval leaflet closure through mid diastole followed by a blunted enlargement of the opening area during atrial contraction. Figure Ventricular dilatation in IMR leads to significant increases in leaflet separation during diastole. The use of high temporal resolution MRI for assessing dynamic leaflet motion can serve as an important addition in future studies looking at the effects of various therapeutic options on valve physiology.This work was supported by grants from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD . R. Gorman and J. Gorman are supported by individual Established Investigator Awards from the American Heart Association, Dallas, TX.


Intra-ventricular pressure gradient along the direction of the outflow tract is generated by the impulse response of the myocardial contraction. This spatial pressure gradient, derived from the maximal acceleration estimates within the left ventricular (LV) ejection flow, has been validated in vitro by using MRI and was found strongly related to the inotropic state of the LV as demonstrated in animal and human echocardiographic studies. This acceleration may be less dependant on load conditions than others LV systolic function parameters, especially LV ejection fraction (LVEF).Aim: (1) to evaluate the feasibility of LV ejection flow acceleration (Acc) estimates by spatial and temporal derivative of velocities recorded by CMR using phase contrast sequence, (2) to compare the acceleration values to LVEF in patients with Dilated Cardiomyopathy (LVEF<50%) and in control subjects.Ten DCM patients  and 14 age-matched controls underwent CMR with cine sequences to determine LV volumes and LVEF. Through plane phase contrast acquisitions were obtained in breathhold  at 2 consecutive levels, at the level of aortic valve and 10 mm below through the LV outflow tract. Total Acceleration  and its two components, Temporal (TempAcc) and Convective (ConvAcc) Acceleration were derived from velocities at phase contrast sequence by using our home-made previously validated semi-automatic software Art Fun.-2, p<0.001) and TempAcc  but not ConvAcc  were significantly lower in DCM.Acceleration measurement was feasible in all DCM and controls. Overall, TempAcc  but not ConvAcc  correlated with LVEF. Nevetheless, TotalAcc was better correlated to LVEF  than TempAcc derived from velocities obtained at the level of the aortic valve alone. Compared to control, mean LVEF  TotalAcc (880±463 vs 1909±637 cm.sThis preliminary study demonstrated the feasibility of LV ejection flow acceleration measurement derived from velocities at phase contrast sequence by CMR. TotalAcc is highly correlated to LVEF, better than TempAcc alone underlying the incremental value of ConvAcc.none