While TEE is providing a direct assessment of the cardiac function and volume status as a diagnostic tool, until recently it has been impractical to be continuously available for monitoring. A new disposable, monoplanar TEE probe (ImaCor) can remain in the patient for up to 72 hours, allowing repeated measures of ventricular function and volume status, parameters needed to monitor response to therapy.t test.We assessed the benefit these TEE data provided in the assessment of five domains: hypovolemia, right ventricular dysfunction, left ventricular dysfunction, sepsis, and valvular abnormality. Bedside practitioners listed their diagnoses before and after seeing primary TEE images perform by trained physicians. We used a 0 to 5 Likert scale to assess differential diagnosis before and after the TEE, comparing changes using a paired P = 0.054) (Figures All requests for TEE were to access hemodynamic instability. A total of 18 patients were screened and nine were eligible, in which 16 total TEE studies were performed. There were no complications with TEE and all patients tolerated the long-term placement of the probe well. Of the five diagnostic domains studied, right ventricular failure was the most commonly underdiagnosed contributor to the hemodynamic instability among patients prior to TEE ( Figures .Our results suggest that having continuously available TEE for monitoring and management of hemodynamically unstable patients increases awareness of right ventricular dysfunction in the ICU.


In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques.2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference).Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5–7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index . On T2 = −0.63, p < 0.01), while extent of necrosis showed borderline correlation . PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 . At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase.After successful PCI , peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (rIn the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase. Myocardial infarction (MI) causes formation of scar tissue and impairment of regional and global left ventricular (LV) function ,2. TypicFurthermore, assessment of LV regional contraction and dyssynchrony can give valuable insight with regard to cardiac resynchronization therapy (CRT) ,11. To d2-weighted images are responsible for dyssynchronic contractions of the LV in the acute phase. Secondly, the study was designed to investigate the influence of edema and necrosis in the acute phase on changes of LV dyssynchrony during infarct healing.Cardiovascular magnetic resonance (CMR) with myocardial tagging  is a powThe study protocol was approved by the local Ethics Committee and all subjects gave written informed consent before study participation. Between November 2006 and August 2010, 22 patients  were examined at baseline 7.5 ± 4.1 days after first anterior MI and again at follow-up 4 months later (120.8 ± 21 days after MI). Ten patients participated in a previously published study [All measurements were performed on a 1.5 T MRI scanner . All acquisitions were performed during end-inspiration breath-hold periods. After acquiring survey images and reference data for sensitivity encoding (SENSE)  LV short3, matrix size = 28x14x16, receiver bandwidth = 220 Hz/pixel, number of profiles per EPI-segment = 7, number of excitations per heart phase = 4, echo time = 3.3 ms.For the 3D tagging data acquisition an accelerated acquisition scheme was applied ,16. Imag2, pixel size = 1.4 × 1.4 mm2, repetition time = 2 R to R intervals, echo time = 100 ms, slice thickness = 8 mm) in 3 short-axis slices .Edema imaging was performed with a standard T2-weighted (T2w) double-inversion black-blood spin-echo sequence . All MR data, and specifically the T2-weighted and LGE data, were acquired using a cardiac surface coil.LGE short-axis images were acquired in all patients 15 minutes after administration of a bolus of 0.25 mmol/kg body weight of Gadobutrolum . An inversion recovery segmented gradient echo sequence was employed with an inversion time set to null normal myocardium (FOV = 350 × 350 mmcsh in %) was defined as the length change of a contour relative to the original length at end-diastole (first heart phase). For a detailed analysis of csh in 48–66 segments of each LV, each midwall contour was divided into sectors of 60˚ starting at the anterior epicardial junction of the right and the left ventricle on the equatorial level and numbered consecutively from S1 to S6 in clockwise direction as viewed from the apex. The time to maximum csh (Tmax) was automatically determined for each segment. Segments in which Tmax was detected in the first three or in the last acquired time frame where inspected by an observer and corrected manually if necessary. As a measure for mechanical LV dyssynchrony the coefficient of variation in csh (CVcshin %) at end-systole, as well as the circumferential uniformity ratio estimate (CURE)-index were calculated [The 3D tagging data were post-processed with HARP  using anlculated ,24. CURE2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images distributed equally along the LV long axis and was expressed as percentage of LV circumference. This evaluation along the LV mid-myocardial centreline was chosen to avoid the subendocardial region where tissue signals can be difficult to distinguish from signal of stagnant blood of the LV cavity. In analogy, on LGE images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. For this analysis 3 short-axis LGE images were selected from the stack of LGE images according anatomical landmarks that matched those of the T2-weighted images. The salvaged myocardium was calculated as area-at-risk (%LV circumference) minus necrosis (%LV circumference) and is expressed as %LV circumference . For calculations of LV volumes and ejection fraction, endo- and epicardial borders were delineated manually on all acquired SSFP slices. On Te Figure . The tott-test or Wilcoxon test and independent samples t-test or Mann–Whitney test were used to test for differences within and between groups. All tests were two-tailed. The Kolmogorov–Smirnov test was used to test for normality. P-values less than 0.05 were considered statistically significant. The study was powered for the CURE index determined by 3D tagging CMR. A previous study [Statistical analysis was performed by using the SPSS software package release 15.0.1  and MedCalc . Mean values + SD were calculated for all groups. The paired Student’s Table Predictor of LV dyssynchrony in the acute phase of MI:2 = 0.63, p < 0.0001), while the circumferential extent of necrosis showed borderline correlation only  as did the circumferential extent of salvaged myocardium . Necrosis mass  and LV ejection fraction  did not correlate with dyssynchrony in the acute phase of MI.Figure Predictors of LV remodelling and LV dyssynchrony during healing of MIA 4 months follow-up was available for all patients. The main study results are compiled in Table 2 = 0.034, p = 0.41). Thus, the correlation between necrosis and regression of dyssynchrony indicates that LV dyssynchrony persisted in ventricles with smaller necrosis and improved in ventricles with larger necrosis. Extent of necrosis in the acute phase was also positively correlated with an increase in LVEDV  was the extent of edema in the acute phase Figure  a. This MR tagging techniques  well as As was hypothesized, this study could demonstrate a regression of LV dyssynchrony during healing of acute MI Table . HealingFrom a practical point of view the transient nature of the intraventricular dyssynchrony during the acute phase of MI may suggest, that the indication for a CRT should be made with caution during the acute phase and a re-evaluation of dyssynchrony in the chronic phase is recommended when remodelling after MI has occurred. Also, in studies aimed to evaluate responder rates to CRT in patients after AMI, the stage of LV remodeling and the presence or absence of edema in the LV myocardium should be taken into account to enable a comprehensive assessment of the benefit of CRT in this patient population.The extent of tissue edema was measured in 3 short-axis levels only, while tagging and LGE data were acquired over the entire LV. These 3 levels for edema assessment were chosen as the examination time could not be expanded deliberately since cooperation in acute MI patients is often decreasing during long examinations. A fully 3D edema quantification given as percentage of LV mass (and not as percentage of LV circumference) might have yielded tighter correlations with dyssynchrony. As mentioned in the methods section, for edema quantification, the extent of hyperintense tissue along the circumferential midline of each slice was calculated to avoid problems in discriminating edema tissue with high signal from high signal of stagnant blood in the LV cavity. As the edema distribution was typically transmural, this approach might not have affected substantially the correlations found between edema and dyssynchrony. Having these limitations in mind, we included in this study anterior infarcts only in order to study rather large infarcts. Thus, the findings of this study should not be extrapolated to smaller lateral or inferior infarcts.3) with respect to current imaging standards, regional motion changes typically occur on a larger scale in the vast majority of cardiac diseases including coronary artery disease and left bundle branch block. Hence, the achieved spatial resolution appears sufficient for most applications.Application of the accelerated 3D tagging acquisition technique allows assessing detailed 3D motion patterns of the entire LV in only three breath-holds. While the spatial resolution of the final motion parameters is relatively low , however, the positive correlations found are not affected by this fact and show the importance of edema in the viable tissue to cause dyssynchrony. Furthermore, we tried to compensate for a small sample size by selecting a well defined patient population and by applying a strictly standardized imaging protocol.During infarct healing after revascularisation of acute anterior MI, intraventricular LV dyssynchrony regresses. In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis alone does not explain dyssynchrony in the acute phase. Conversely, regression of dyssynchrony during infarct healing is best predicted by the extent of necrosis in the acute phase.From a practical point of view, the indication for CRT in post-infarct patients should consider the potential for improvement of dyssynchrony during infarct healing which is related to necrosis mass in the acute MI. Also, in studies assessing responder rates of CRT in ischemic cardiomyopathy the stage of infarct healing and the presence or absence of tissue edema should be taken into account as these factors have been shown to modify dyssynchrony severity.CMR, Cardiovascular magnetic resonance; AMI, Acute myocardial infarction; CAD, Coronary artery disease; LGE, Late-gadolinium enhancement; FOV, Field of view; CURE, Circumferential uniformity ratio estimate; LV, Left ventricle; BMI, Body mass index; PCI, Percutaneous coronary intervention; CRT, Cardiac Resynchronization Therapy; STEMI, ST-segment elevation myocardial infarction; NSTEMI, Non ST-segment elevation myocardial infarction.The authors declare that they have no competing interest.RM: study design, data acquisition, CMR image analysis, statistical analysis, and manuscript drafting. SK: data acquisition, CMR image analysis, and manuscript drafting. AKR: CMR image analysis, literature research, and manuscript drafting. CS: CMR image analysis and manuscript drafting. PB: study design, literature research, and manuscript drafting. JS: study design, statistical analysis, revision of the manuscript, and guarantator of integrity of entire study. All authors have made revisions to the manuscript and have read and approved the final version.


Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction.The purpose of this clinical trial was to investigate whether molecular magnetic resonance imaging (MRI) of macrophages using ferucarbotran (Resovist®) allows improved visualization of the myocardial (peri-)infarct zone compared to conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction.The clinical study NIMINI-1 was performed as a prospective, non-randomised, non-blinded, single agent phase III clinical trial. Twenty patients who had experienced either an acute ST-elevation or non-ST-elevation myocardial infarction (STEMI/NSTEMI) were included to this study. Following coronary angiography, a first baseline cardiovascular magnetic resonance (CMR) study (pre-SPIO) was performed within seven days after onset of cardiac symptoms. A second CMR study (post-SPIO) was performed either 10min, 4h, 24h or 48h after ferucarbotran administration. The CMR studies comprised cine-CMR, T2-weighted “edema” imaging, T2*-weighted cardiac imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging.The median extent of short-axis in-plane LGE was 28% (IQR 19-31%). Following Resovist® administration the median extent of short-axis in-plane T2*-weighted hypoenhancement  was 0% . A significant in-slice increase (>3%) in the extent of T2*-weighted “hypoenhancement” (post-SPIO compared to pre-SPIO) was seen in 6/16 patients (38%). However, no patient demonstrated “hypoenhancement” in T2*-weighted images following Resovist® administration that exceeded the area of LGE.T2/T2*-weighted MRI aiming at non-invasive myocardial macrophage imaging using the approved dose of ferucarbotran does not allow improved visualization of the myocardial (peri-) infarct zone compared to conventional gadolinium-based necrosis/fibrosis imaging.


The study investigated cardiovascular changes in adult-onset growth hormone deficiency (GHD) and showed that patients with adult-onset GHD have a left ventricular mass index (LVMi) at or below the lower limit of normal, which improves with one year of growth hormone replacement.GHD causes cardiovascular problems, with loss of cardiac response to exercise and increased cardiac mortality, however the underlying processes are poorly understood.Ten patients with adult-onset GHD and age- and sex-matched controls (n=10) underwent CMR. Patients underwent scans before disease treatment and at twelve months after treatment. Cardiac parameters were calculated and indexed to body surface area (BSA). The comparison between groups was done using Mann-U-Whitney test and within the group using Wilcoxon test. The data are presented as median values.2, p=0.315; end diastolic volume index (EDVi) 69.2 vs. 76.3 ml/m2, p=0.1655; end systolic volume index (ESVi) 24.8 vs. 28.3 ml/m2, p=0.3527 and ejection fraction (EF) 64 vs. 63 %, p=0.8197. However, patients had an LVMi beneath the lower limit of normal when compared to published normal ranges (55.4 - 74.0 g/m2).Patients with GHD did not have significantly different left ventricle (LV) mass or volumetric parameters from controls: LV mass index (LVMi) 55.0 vs. 56.6 g/m2, p=0.393), ESVi  and EF  in the GHD group and controls.There were no differences between right ventricular (RV) EDVi  achieving statistical significance compared to pre-treatment values (p=0.0156).Patients with GHD on GH treatment for 1 year showed an increase in median insulin-like growth factor I (IGF-I) SDS from -1.83 to +0.40 (p=0.0068). There was no correlation between LVMi and IGF-I SDS . At one year the median LVMi moved into the previously published normal range (55.0 to 63.0 g/mPatients with adult-onset GHD have an LVMi at or below the lower limit of normal, which improves with one year of growth hormone replacement.Supported by departmental grants by Pfizer and Novartis.


Background: Patients with repaired tetralogy of Fallot (rtoF) are at risk of supra-ventricular tachycardia due to atrial dilatation. To date, the impact of atrial size and function has been poorly studied in this population. Angiotensin-converting enzyme (ACE ) inhibitor are known for their beneficial effects on atrial and ventricular remodelling in patients with cardiomyopathy. A previous study (APPROPRIATE study) has demonstrated their beneficial effect on ventricular longitudinal contraction in patients with rtoF. We aimed to study first the impact atria volume and function and second, the effect of ACE inhibitor ramipril in adults with rtoF.Methods: We studied prospectively 61 patients with rtoF from the APPROPRIATE study cohort (median age 29.5 [interquartile range 22-38] years). A double-blinded, placebo-controlled study of 6 months of ramipril was performed. All patients underwent cardiac magnetic resonance imaging (CMR) with both atria and ventricle volume and function measurements, echocardiography, neurohormonal analysis, and objective cardiopulmonary testing at baseline and follow-up. Values are expressed as median [interquartile range].2/m2. Right ventricle (RV) end-diastolic volume index was (129 [109-144] ml/m2) and RV ejection fraction was 53 [47-49]. It was correlated with age , RV end diastolic volume index , BNP , inversely correlate with right ventricle (RV) ejection fraction . LA size and volume were normal and not correlated with any parameter, probably because there was no associated left heart disease and all our studied patients had normal left ventricle volume and ejection fraction. After 6 months of treatment, no arrhythmia occurred. In the ramipril group, LA maximal volume decreased (p=0.01), anterior septum excursion movement increased, BNP level decreased (p=0.0004) compared to the placebo group.Results: At baseline, all patients were in sinus rhythm. Right atrium (RA) maximal area index was 13.7 [12.2-15.2] cmConclusions: RA size was a marker of RV dilatation and systolic dysfunction. Ramipril appears to have beneficial action on left heart with atrial remodelling in patients with rtoF. However ramipril had no effect on the right heart. Further studies with longer follow-up and larger group are needed.British Heart Foundation Fellowship (SVB-N).French Federation of Cardiology (BB).Unrestricted Actelion educational grant (GD).The study was supported by the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.


We aimed to investigate myocardial lipid content in patients with severe AS and to examine the associations amongst steatosis, energetics and myocardial function.In aortic stenosis (AS), there is impairment of myocardial energetics and a substrate switch with a preference to glucose metabolism and downregulation of fatty acid utilization. Whether or not this results in cardiac steatosis is unknown. We hypothesized that cardiac steatosis is present in severe AS and this can be assessed by 1H and 31P MRS, respectively. Global left ventricular systolic function and mass were assessed using cine cardiac magnetic resonance imaging (CMR) and peak circumferential strain using CMR tagging.Thirty patients with severe AS  and 20 normal volunteers were enrolled. Inclusion criteria were peak aortic valve gradient >50 mmHg, no other significant valvular pathology, normal left ventricular systolic function, no obstructive coronary artery disease and blood pressure <160/90 mmHg. Myocardial lipid content and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were quantified using Clinical characteristics and CMR parameters are presented in Table This is the first study to demonstrate that myocardial steatosis, in addition to impaired energetics, occurs in severe AS regardless of symptoms, and is independently associated with impaired peak circumferential strain. This suggests that myocardial lipid assessment may serve as a useful adjunct to standard clinical information to determine the optimal timing for aortic valve replacement.None.


Detecting and quantifying the severity of mitral regurgitation is essential for risk stratification and clinical decision-making regarding timing of surgery. Our objective was to assess specific visual parameters by cine-magnetic resonance imaging (MRI) in the determination of the severity of mitral regurgitation and to compare it to previously validated imaging modalities: echocardiography and cardiac ventriculography.The study population consisted of 68 patients who underwent a cardiac MRI followed by an echocardiogram within a median time of 2.0 days and 49 of these patients who had a cardiac catheterization, median time of 2.0 days. The inter-rater agreement statistic (Kappa) was used to evaluate the agreement.There was moderate agreement between cine MRI and Doppler echocardiography in assessing mitral regurgitation severity, with a kappa value of 0.47, confidence interval (CI) 0.29–0.65. There was also fair agreement between cine MRI and cardiac catheterization with a kappa value of 0.36, CI of 0.17–0.55.Cine MRI offers a reasonable alternative to both Doppler echocardiography and, to a lesser extent, cardiac catheterization for visually assessing the severity of mitral regurgitation with specific visual parameters during routine clinical cardiac MRI. Long-term outcomes of patients with mitral regurgitation have demonstrated increasing rates of heart failure, atrial fibrillation and sudden cardiac death. There are several MRI methods available to assess the severity of mitral regurgitation. Cine-MRI quantifies mitral regurgitation by comparing the difference between the right and left ventricular volumes in the absence of any other significant valvular regurgitant lesions. Flow velocity mapping and volumetric assessment have been validated in prior studies comparing it to other imaging modalities, however, they require different pulse sequences and/or extra time in post processing. In a high volume cardiac MRI laboratory, this adds extra time to the overall study, thus, validation of the routine sequences used (cine-MRI) on a normal cardiac assessment for left ventricular function would be very beneficial. Higgins et al., validated the assessment of mitral regurgitation via an older gradient echo pulse sequence using the gradient-recalled acquisition by a steady-state (GRASS) technique. Our objective was to assess specific visual parameters by cine-MRI in the determination of the severity of mitral regurgitation and to compare the visual assessment of mitral regurgitation by cine MRI to previously validated imaging modalities: echocardiography and cardiac ventriculography.We hypothesized that the visual assessment of mitral regurgitation by cine-MRI will be similar to the assessment of mitral regurgitation by echocardiography and left ventriculography in patients that have undergone all three imaging techniques for clinical assessment.We retrospectively evaluated patients who had undergone cardiac MRI, echocardiography and cardiac catheterization. A total of 68 patients underwent a cardiac MRI and echocardiogram within a median time of 2.0 days for either congestive heart failure or coronary artery disease. Of these 68 patients, 49 also had a cardiac catheterization, median time of 2.0 days between the cardiac catheterization and MRI. The reason for referral for each study varied greatly, ranging from the assessment of coronary artery disease to the assessment of valvular disease. The patients were chosen based upon retrospective assessment of our database for any patient who underwent both echocardiogram and cardiac MRI within 2 weeks.The Institutional Review Board (IRB) of Duke University Health System approved the study. A written informed consent was obtained from all the study patients.All studies were reassessed for the severity of mitral regurgitation by consensus of three cardiologists at the same time, who were blinded to the patient data. The visual parameters used in assessing the severity of mitral regurgitation via all three modalities are listed in Complete Doppler echocardiography was performed using a Philips Sonos 7500 ultrasound scanning equipment . The standard views were obtained including parasternal, apical, and sub-costal views with color, continuous and pulse wave Doppler. The mitral regurgitation was assessed using the comprehensive data from the echocardiogram including assessment of the color Doppler jet , continuous wave Doppler across the mitral valve and pulse wave Doppler of the pulmonary veins. Cardiac MRI was performed on a 1.5 Tesla scanner (Siemens Sonata) using a 6-element cardiac phase–array receiver coil. Steady-state free-precession (SSFP) cine images were acquired in multiple short-axis  and 3 perpendicular long axis views across the mitral valve. Typical parameters used were: repetition time, 3.0 ms; echo time, 1.5 ms; flip angle, 90°; temporal resolution, 35 ms/phase; in-plane resolution, 1.7×1.4 mm.The characteristics used in the assessment of the severity of mitral regurgitation included: vena contracta size, jet intensity, jet area and length, the left atrial size (using a long axis view) and the left ventricular cavitary size . [12] ThCardiac ventriculography was obtained with a 6 F pigtail catheter inserted into the femoral artery and guided into the left ventricle. A power injector was used to fill the left ventricle. Standard ventriculography in the 30 degrees right anterior oblique position was obtained. For patients with an uncertain degree of mitral regurgitation, LAO views were also obtained. The severity of mitral regurgitation was based on assessment of left atrial opacification by Grossman’s criteria see , determii categories, so that different levels of agreement can contribute to the value of Kappa (K). The K value was interpreted as is shown in The inter-rater agreement statistic (Kappa) was used to evaluate the agreement between echocardiography and cardiac catheterization, cine-MRI and echocardiography, and cine-MRI and cardiac catheterization. Since kappa does not take into account the degree of disagreement between observers and all disagreement is treated equally as total disagreement, for final analysis we chose to use weighted kappa, and assign different weights to subjects for whom the raters differ by The baseline characteristics of the 68 patients are highlighted in There was moderate agreement between cine MRI and Doppler echocardiography in assessing mitral regurgitation severity, with a kappa value of 0.47, confidence interval (CI) 0.29–0.65 . Of the There was fair agreement between cine MRI and cardiac catheterization with a kappa value of 0.36, (CI of 0.17–0.55) . Of the There was good agreement between Doppler echocardiography and cardiac catheterization  . Of the To further consider potential mechanisms for discordance, we stratified patients based on left atrial (LA) size and ejection fraction (EF) in determining the severity of mitral regurgitation. When comparing MRI with echocardiography, there was evidence to suggest that the agreement between echocardiography and MRI improved as the left ventricular function declined and no difference was found when stratified for LA size. There was no difference in the severity of mitral regurgitation between MRI and cardiac ventriculography when stratified by EF (either less than or greater than 20%). However, the correlation was worse when stratified by LA size, with greater LA size having a worse correlation for the severity of mitral regurgitation between the two modalities. There was no difference in the assessment of mitral regurgitation between echocardiography and ventriculography when stratified for larger LA size or a lower EF.The results of our study demonstrate that visual assessment of mitral regurgitation by cine MRI is reasonably comparable to Doppler echocardiography and to a lesser extent cardiac catheterization. There was moderate agreement between MRI and Doppler echocardiography. The correlation between cine MRI and echocardiography was not outstanding, however, cine MRI was able to distinguish severe mitral regurgitation from mild to moderate, which helps in clinical decision making. There was only one patient who was diagnosed with moderate to severe mitral regurgitation by echocardiography who was not determined to have the same severity of mitral regurgitation by MRI. Only one patient with no or mild mitral regurgitation by MRI was found to have moderate mitral regurgitation by echocardiography. There was also a fair agreement between cine MRI and cardiac catheterization in assessing mitral regurgitation severity. Acquisition of multiple 4-chamber long axis views using SSFP in patients with mitral regurgitation seen in any one of the routine views might further increase the agreement.This study found a good correlation between Doppler echocardiography and cardiac catheterization. These findings are consistent with previously published data validating both of these imaging modalities for assessing the severity of mitral regurgitation. MRI identified a higher number of patients with significant (moderate or severe) mitral regurgitation as compared to echocardiography and cardiac catheterization. Of the 39 patients diagnosed as having moderate to severe mitral regurgitation by MRI only 21 of these patients were determined to have similar disease severity by echocardiography. MRI detected all 11 patients who had significant mitral regurgitation by cardiac catheterization. The higher threshold of cine MRI in diagnosing moderate or severe mitral regurgitation as compared to echocardiography and cardiac catheterization may be secondary to the parameters used by MRI. These parameters may need to be adjusted to better correlate with other imaging techniques, as they have not been previously validated. Alternatively, this higher threshold may be more accurate, however outcome data  would be necessary to confirm this alternative explanation. Furthermore, cine MRI provides detailed information about entire mitral valve apparatus, papillary muscle abnormalities and right ventricular morphology, which has both therapeutic and prognostic implications in patients with mitral regurgitation. Cine MRI evaluates the severity of mitral regurgitation through the loss of signal created by the turbulence of protons in blood pool created in the left atrium. In patients who have increased left atrial pressures, there may be less of a gradient between the left ventricle and left atrium, which may lead to more severe mitral regurgitation being underestimated due to the lower turbulence created. However, similar pitfall applies to visual estimation of the regurgitant jet by color Doppler echocardiography. When adjusted for left atrial size, there was worse agreement between MRI and echocardiography and cardiac catheterization, respectively.In left ventriculography, mitral regurgitation severity is assessed visually by the amount of contrast ejected into the left atrium during systole. In echocardiography, the velocity across the valve is assessed to determine the severity of mitral regurgitation. In addition, color Doppler imaging is similar to MRI in that both the modalities are looking at turbulent flow. However, compared to MRI, echocardiography looks at the velocity of both laminar and turbulent flow in assessing the severity of mitral regurgitation.Flow velocity mapping and volume analysis are two other MRI techniques used in assessing the severity of mitral regurgitation. Neuhold et al., evaluated 46 patients with angiographically confirmed regurgitant lesions and found a good correlation with MRI using the volume analysis method. Mitral regurgitation is dependent upon the volume status and blood pressure of patients, which may potentially change in between each imaging study. We were unable to completely account for all loading conditions; however, the close proximity of these imaging tests minimizes this potential limitation.This study is an attempt to validate the proposed visual assessment criteria for the severity of mitral regurgitation and has not been studied previously. We did not use a reference method to look at the reliability of cine MRI. Instead, comparison was made with the standard imaging methods. Larger clinical trials may be required to further validate the criterion before being used in the clinical setting.SSFP sequence utilized to assess severity of mitral regurgitation has an inherently short echo time (TE). Using short TE sequences may not allow for adequate spin dephasing and potentially may decrease the accuracy of the test.Severity of mitral regurgitation was obtained from consensus of three cardiologists, interpreting the images at same time, and we could not obtain the inter-observer variability. Similar method was followed for interpreting cardiac catheterization and Doppler echocardiography images.Another possible limitation may be selection bias in finding patients who had all 3 tests, which included patients with heart failure and those undergoing viability and coronary artery disease assessment, as compared to the general valve disease population. Theses findings may be less applicable to patients not selected for multiple imaging procedures.In order to determine the need and success of medical therapy, as well as, to decide on the correct timing for surgery, prudent assessment of valvular regurgitation is imperative. Cine MRI offers a reasonable alternative to both Doppler echocardiography and to a fair extent cardiac catheterization for assessing the severity of mitral regurgitation with specific visual parameters during routine clinical cardiac MRI.


However, sudden cardiac death may be the first clinical manifestation. Hence early detection of myocardial abnormalities before overt left ventricular (LV) dysfunction is warranted for a better risk stratification.Seventeen paucisymptomatic LM carries , 14 paucisymptomatic DCM patients  with mild LV dysfunction (ejection-fraction 40%-55%) and 12 healthy controls  underwent complete clinical, echocardiographic, biohumoral and contrast-enhanced CMR assessment. Cine CMR was used to derive LV volumes, mass and function, and post-contrast CMR to detect late gadolinium enhancement (LGE) as an index of gross fibrosis. Eight LM patients, all DCM patients and all normal controls underwent pre- and post-contrast myocardial T1 mapping with gadolinium partition coefficient calculation, as an index of interstitial fibrosis.LM carriers presented a similar LV end-diastolic volume  and slightly reduced ejection-fraction (61±6% p<0.001) than controls , while in DCM patients LV end-diastolic volume (102±17 ml/m2) and ejection-fraction (49±5%) were worse than both controls and LM carriers (p<0.001). Moreover, DCM patients presented worse diastolic dysfunction , NT-proBNP plasma levels  and Doppler-estimated pulmonary pressure  than LM carriers. Six (43%) DCM patients presented DE, representing 9±3% of LV mass; similarly, seven (42%) LM carriers had DE, but with a larger extension . In LM carries DE distribution was patchy (2 pts) or midwall (5 pt), similarly to DCM patients . GPC reached a steady state 5 minutes after gadolinium injection. In DCM patients GPC was slightly higher than controls , while in LM carriers it was much higher (0.45±0.07) than controls (p<0.01). Even excluding hyperenhanced myocardium, in LM carriers GPC remained higher than controls, while in DCM patients only slightly higher than controls.Myocardial fibrosis occurs early in LM carrier before LV dilatation and dysfunction and may represent an early phenotypic expression of cardiac involvement.


Pulmonary hypertension represents a group of conditions characterized by higher than normal pulmonary artery pressures. Despite improved treatments, outcomes in many instances remain poor. In recent years, there has been growing interest in the use of Cardiovascular Magnetic Resonance (CMR) in patients with pulmonary hypertension. This technique offers certain advantages over other imaging modalities since it is well suited to the assessment of the right ventricle and the proximal pulmonary arteries. Reflecting the relatively sparse evidence supporting its use, CMR is not routinely recommended for patients with pulmonary hypertension. However, it is particularly useful in patient with pulmonary arterial hypertension associated with congenital heart disease. Furthermore, it has proven informative in a number of ways; illustrating how right ventricular remodeling is favorably reversed by drug therapies and providing explicit confirmation of the importance of the right ventricle to clinical outcome. This review will discuss these aspects and practical considerations before speculating on future applications. Pulmonary hypertension (PH) is the term given when mean pulmonary artery pressure (mPAP) is greater or equal to 25 mmHg . It alsoAt the most recent World Health Organisation conference  in 2008, PH was classified into five distinct disease groups Table . Group 1For each patient, a methodical approach is necessary to describe the cause(s) of PH. Alongside right heart catheterisation, multimodality imaging plays a key part in this . EchocarIt is twenty five years since the use of cardiovascular magnetic resonance (CMR) was first reported in PH . Due to The CMR examination is focused on the right heart and pulmonary arteries which undergo characteristic changes in response to elevated pulmonary pressures Table . It is tPatients may be referred with an established diagnosis of PH, with a diagnosis that requires clarification or with PH of unknown aetiology. Conversely, features of PH may be unexpectedly encountered in patients referred with left heart disease (where they should be reported due to its prognostic importance) or in patients with dilated RVs previously thought to have arrhythmogenic right ventricular dysplasia.A minimum data set should allow RV size and function to be assessed by quantifying biventricular volumes, ejection fraction (EF) and mass. RV and LV stroke volume can be derived by flow mapping of the main pulmonary artery and aorta respectively. When reporting cardiac output and index, flow mapping of the aorta should be used  since itIt is not possible to consistently identify a cause by CMR alone. However, in selected cases a specific underlying disease may be suggested by the presence of one or more features Table . It is iIn patients with features suggestive of shunt, dedicated anatomical imaging, cines, flow mapping and angiography should be undertaken. CMR is particularly helpful in the diagnosis of a sinus venosus defect and partial anomalous venous drainage  Figure . If evidChronic thromboembolic disease can be identified using MRA Figure . HoweverIn routine practice, volumetric data is acquired by aligning the short-axis stack to the LV . In PH, It has been suggested that by orientating ventricular acquisition axially  or perpeThere is no consensus as to how RV analysis should be performed. This has become an increasingly relevant issue as enhanced spatial resolution has allowed individual RV papillary muscles and trabeculae to be visualized. Acknowledging that these structures and the interventricular septum hypertrophy in PH, in our centre total RV mass includes the papillary muscles and trabeculae, as well as the 'RV' septum  when theManual analysis offers better control over delineation than semi-automated analysis, reflected in improved interobserver reproducibility . HoweverTo simplify RV assessment, surrogate measurements have been developed. One candidate is analysis of transverse motion, which proved to be more strongly correlated with ejection fraction than tricuspid annular plane systolic excursion .The finding of LGE limited to the insertion regions Figure  has beenThe ability to non-invasively estimate pressures within the right heart is a key objective since it would permit diagnosis and serial assessment without cardiac catheterization. Unfortunately, unlike echocardiography, it is not possible to generate an estimate of RV systolic pressure by measuring the velocity of the tricuspid regurgitant jet. This is because the tricuspid regurgitant jet is dispersed, so it is difficult to isolate the highest velocity in either through-plane or in plane acquisitions  Figure .Pulmonary pressures have been estimated by measuring the effects of PH on the heart. Initial results were encouraging for RV mass  but haveCMR derived flow in the main pulmonary artery has also been used to gauge hemodynamics. For example, pulmonary pressures were shown to be inversely correlated with average blood velocity in the main PA . In addiEnd-organ effects on the PAs themselves can also be assessed since their distensibility is reduced in PH . It has PWV can be calculated directly using the transit time technique by determining flow wave arrival time at two points in the proximal PAs using a high-temporal resolution flow mapping sequence Figure , and divThe sheer number of indices emphasizes the lack of a single, robust non-invasive measure. Indeed in one independent validation , none ofCMR is well suited to longitudinal follow up as it is non-invasive and non-ionizing. Several studies have reported the positive effects medical -49 and sThis has driven interest in the use of CMR to measure efficacy of new therapies. To date, two proof of concept trials ,56 have Using CMR as a trial end-point remains an attractive option since it avoids the limitations associated with the most widely use surrogate in PAH trials; the six minute walk test distance . In addiThe RV has been implicated in clinical outcomes from the earliest right heart catheterization studies which showed parameters which could be related to this ventricle  were relevant to prognosis ,58. HoweThe first outcome study to be reported with CMR  demonstrCMR has offered a number of wide-ranging insights into the pathogenesis of PH through diverse applications Table . By measDuring CMR perfusion with adenosine stress in patients with PH, biventricular vasoreactivity has been found to be diminished. The degree to which this occurs in both ventricles could be predicted from mPAP . DespiteInterventional CMR allows RV pressure-volume loops to be created from which three key measures are extracted: 1) Systolic function  Afterload  and 3) Ventricular-arterial coupling (Emax/Ea). In patients with PAH, Kuehne and colleagues  found thExercise CMR, performed on a recumbent bicycle within the scanner, has been used to demonstrate that exercise-induced increases in cardiac output in patients with idiopathic PAH are due to heart rate changes alone, since stroke volume fails to augment . CMR hasCMR is unlikely to be more widely integrated into a general imaging pathway in PH until its incremental value is proven in routine clinical practice. To determine whether this is the case, clinical trials of CMR imaging should be undertaken comparing standard care in PH with that informed by CMR results. It is also important that analysis become standardized and facilitated by improved software.It has also been suggested that CMR be used to 'screen' potential therapies before they are selected for definitive, long-term studies . Before Like most research in PH, CMR-based work has been mainly applied to Group 1 (PAH). It remains unclear whether the RV in each group behaves differently in the face of similar pulmonary pressures. Through contemporaneous assessment of the RV-PA functional unit, CMR might be able to contribute to an answer, and if this assertion is correct, explain why.Work should continue to define the relevance of flow wave morphology and pulmonary artery stiffness with focus extended to non-invasively determining left atrial pressure. The opportunity to validate this work is offered by the interventional CMR suite. Finally, small animal CMR is being explored although it should be acknowledged that animal models of PAH are unreliable in predicting human responses.CMR permits an accurate assessment of the right ventricle and pulmonary artery flow. In current clinical practice, it is an especially useful tool in patients with a diagnosis of (or suspected of having) PAH associated with congenital heart disease. However it also allows discrimination of other features which might point to an alternative etiology. It is a flexible research tool which has opened new avenues for understanding treatment effects, outcomes and pathogenesis. It appears inevitable that its place in the management of PH will evolve as evidence supporting its use accumulates.CMR: Cardiovascular Magnetic Resonance; CTEPH: chronic thromboembolic pulmonary hypertension; EF: ejection fraction; HASTE: Half-Fourier Acquisition Single-Shot Turbo Spin-Echo; LGE: Late Gadolinium Enhancement; LV: left ventricle; PAH: pulmonary arterial hypertension; mPAP: mean pulmonary arterial pressure; MRA: magnetic resonance angiography; PA: pulmonary artery; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; PWV: Pulse wave velocity; RA: right atrium; RV: right ventricle; SSFP: steady state free procession.The authors declare that they have no competing interests.All authors participated in literature review, manuscript preparation and final approval of the submitted manuscript.


Many experimental and clinical studies have confirmed a continuous cross-talk between both sympathetic and parasympathetic branches of autonomic nervous system and inflammatory response, in different clinical scenarios. In cardiovascular diseases, inflammation has been proven to play a pivotal role in disease progression, pathogenesis and resolution. A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals' processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers. However, a lot of open questions remain to be addressed, regarding the existence of a true association between heart rate variability and autonomic nervous system output or its adoption for risk stratification and therapeutic monitoring at the bedside. Finally, potential therapeutic implications will be discussed, leading to autonomic balance restoration in relation with inflammatory control. Systemic inflammation is a normal response to altered homeostasis and has an important role in several pathophysiological processes, such as infection or trauma. It is characterized by the endocrine release of different cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1), IL-4, IL-6, IL-10, and many others, normally confined to paracrine regulation of a local inflammatory response Koj, . Apart fRecently, it has been demonstrated that subclinical inflammation and the con-centration of inflammatory markers, such as cytokines, correlate strongly to cardio-vascular mortality and morbidity in both healthy subjects and in those with known coronary artery disease (CAD) .In the healthy state there is some degree of stochastic variability in physiologic variables, such as heart rate (heart rate variability). This variability is a measure of complexity that accompanies healthy systems and has been suggested to be responsible for their greater adaptability and functionality related to pathologic systems Buchman, . StudyinOn the contrary, it has been repeatedly demonstrated that various “biomarkers” such as cytokines, exhibit marked interdependence, pleiotropy (multiple effects) and redundancy (multiple cytokines with the same effect)  and the immune-regulated inflammation is the capability of the brain to monitor and to affect at the same time the immune status. The first mechanism relies upon activation of vagus nerve afferent fibers that signal the brain that inflammation is occurring. Different kind of mediators such as cytokines can activate visceral vagus afferent fibers which terminate within the dorsal vagal complex (DVC) of the medulla oblongata. The DVC consists of the nucleus tractus solitarius (NTS), the dorsal motor nucleus of the vagus (DMN) and the area postrema (AP) , whereas stimulation of β2-subtype adrenoreceptor-cAMP-protein kinase A pathway is associated with an inhibition of pro-inflammatory cytokines' production  and parasympathetic nervous system. The SNS activation during the early stages of stress induces local inflammatory response through αIn conclusion, there is strong evidence that CNS controls body's systemic response to inflammation. Recently, different clinical studies investigating a possible association between ANS outflow and various inflammatory indices in patients with heart diseases have appeared in the literature ; that is, the variability of R-R series in the electrocardiogram (ECG), and its frequency components  intervals  are calculated. Other time domain variables include the mean NN interval, the mean heart rate or the difference between the longest and the shortest NN interval, as well. The simplest of these metrics is the standard deviation of the NN intervals (SDNN), which is the square root of the variance. However, it should be emphasized that SDNN becomes less accurate with shorter monitoring periods. The most commonly used time domain methods are the square root of the mean squared differences of successive NN intervals (RMSSD), the number of interval differences of successive NN intervals greater than 50 ms (NN50) and the proportion derived from dividing NN50 by the total NN intervals (pNN50)  and auto-regressive modeling. FFT displays in a plot the relative contribution (amplitude) of each frequency. This plot includes at least three peaks.Fast periodicities in the range 0.15–0.4 Hz [high frequency (HF)] are largely due to the influence of the respiratory phase on vagal tone. Low-frequency periodicities (LF), in the region of 0.04–0.15 Hz, are produced by baroreflex feedback loops, affected by both sympathetic and para-sympathetic modulation of the heart, whereas very low frequency periodicities (VLF), in the frequency range between 0.003 and 0.04 Hz and ultra low frequencies  have been variously ascribed to modulation by chemoreception, thermo-regulation and the influence of vasomotor activity. The area under the power spectral curve (power) in a particular frequency band is considered to be a measure of HRV at that frequency, whereas the LF/HF ratio has been suggested as an indirect index of sympathovagal balance  the central oscillator theory   and estimated possible relationships on repeated measures at 4 months in recovery (n = 51). They found modest negative correlations between all inflammatory biomarkers and mainly SDNN, VLF and LF power. The strongest associations were seen between WBC and SDNN (r = −0.351). However, relationships did not persist on multivariate analyses after a 4-month period. According to the authors, the correlations were observed largely among HRV indices reflecting sympathetic activity, suggesting that the inflammatory response in acute coronary events may be associated with sympathetic activation instead of vagal withdrawal. Furthermore, leukocytosis observed in these patients seems to be a potential source of pro-inflammatory cytokines within the atheromatous plaque and might induce a potential rupture.Hamaad et al.  tested tIn another study, Lanza and colleagues  assessedIn a study including patients with suspected CAD, Madsen et al.  enrolledIn a similar study , with total power of heart rate signals and ULF . No correlation was found between IL-6 and time (pNN50 and RMSSD) or frequency domain (HF power) indices of vagal activity.In 2001, Aronson et al.   , IL-6 (r = −0.233) and WBC (r = −0.292). Moreover, depression was associated with high IL-6 serum levels and increased cardiovascular mortality risk. In conclusion, in patients without heart disease depression seems to be associated with HRV imbalance and inflammation.In a recent study of Kop and colleagues (2010) who recruited 908 patients, free of CAD, for a median follow-up period of 13.3 years, it was demonstrated that among depressed participants, HF power of HRV was negatively correlated with CRP , have been reported from different research groups  and the second group included patients with septic shock . This study found in the group of patients with SOFA > 10, statistically significant inverse correlations between CRP and LF/HF ratio (r = −0.61), . At the same time, IL-10 proved to be significantly correlated with HF and SOFA score in a positive way and with LF, LF/HF and SDNN in a negative way. Finally, the total variability of heart rate signals (SDNN) was found to be negatively correlated with both CRP (r = −0.79) and SOFA score (r = −0.84)  Figure . IL-6 wa) Figure .These findings suggest that reduction in HRV and LF/HF is related with an augmented pro- and anti-inflammatory response during sepsis, especially in more severely ill patients. Furthermore, severity of illness is positively associated with HF and IL-10 serum concentrations and changes inversely with variability of heart rate signals. In this respect, elevated levels of IL-10 have also been found in trauma patients who developed sepsis and multiorgan failure  have pleiotrophic mechanisms in patients with heart failure, such as ANS output modulation Lefer, . ExperimDifferent experimental studies have shown that catecholamines, except from increasing cardiac contractility and heart rate via interaction with beta adreno-receptors, may induce myocardial damage by calcium overload and subsequent cell necrosis, upon excessive β-adrenoreceptor stimulation (Opie et al., Since heart failure is associated with a sympathetic up-regulation and parasympathetic withdrawal, β blockers have been used to modify the effects of augmented sympathetic tone and restore autonomic imbalance. In this respect, Goldsmith et al.  showed tRecent evidence suggests that a primary site of attenuated vagal control on the heart occurs at the level of the parasympathetic gaglion (Bibevski and Dunlap, Based on the results of VNS in animal models of HF, Schwartz et al.  and De FAs a consequence of such preliminary results, a pivotal multicenter international clinical trial, the INOVATE-HF study, has been recently designed to assess safety and efficacy of VNS in 650 CHF patients from 80 sites, with NYHA class III symptoms, sinus rhythm and QRS width less than 120 ms, using the CardioFit system (Hauptman et al., Different experimental studies have established an inter-relation between ANS output and inflammatory regulation, whereas the discovery of the “cholinergic anti-inflammatory pathway” has expanded our understanding of how the nervous system modulates the inflammatory response through an immunoreflex. Furthermore, clinical data from large epidemiological studies involving patients with CAD, heart failure and healthy subjects with increased risk factors for heart diseases suggest that there is a rather weak or moderate association between inflammation and ANS activity, estimated through HRV analysis. Finally, investigation of HRV alterations during critical illness, such as sepsis and MODS, has demonstrated loss of variability of heart rate signals that is inversely correlated with immune response, particularly in most severe cases.Early and more accurate monitoring of cardiovascular patients, particularly in the early stages of life-threatening illnesses through continuous automated detection of abnormal variability of heart rate signals, could alert clinicians to impending clinical deterioration and allow earlier intervention. In this respect, the combination of structural indices, such as the left ventricular ejection fraction, with autonomic function indices derived from heart rate variability analysis has been proposed as the state-of-the-art method for risk assessment among patients with acute myocardial infarction or severe congestive heart failure (Priori et al., In conclusion, the enormous complexity of neuro-immunological interactions cannot be captured by simple measurements, such as HRV analysis. A rather multi-parameter monitoring of ANS, through different estimators of heart rate variability and complexity has been suggested for assessment of ANS output (Goldberger, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The underlying myocardial injury in early forms of dilated cardiomyopathy (DCM) is unclear. Cardiovascular magnetic resonance (CMR) myocardial T1-mapping monitors the enlargement of the cardiac extra-cellular space and thus offers a non-invasive tool of quantitative measurement of myocardial fibrosis. We used T1-mapping techniques to explore the hypothesis that diffuse myocardial fibrosis is related to DCM.We investigated 77 DCM patients  and 46 healthy controls . Significant coronary artery disease was excluded invasively. All CMR examinations were performed using 1.5 T CMR scanner (Philips Achieva). Short axis slices covering the LV were acquired using SSFP sequence to measure volumes and ejection fraction. T1-relaxation times were measured before and 15 minutes after Gd-DTPA (Magnograf) injection (0.2 mmol/kg). T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times  using a single breath-hold modified Look Locker inversion recovery sequence  in late diastole. Early DCM with mild reduction of LVEF was defined as EF between 45-55% while severely depressed LVEF was defined as EF<30%. Delta-T1 was calculated as non-contrast myocardial T1-post-contrast myocardial T1.Mean LVEF was 43 ± 12% in DCM and 62 ± 4 in controls. Compared to controls, deltaT1 was significantly higher in 42 early DCM patients . Patients with advanced DCM (n=10) had the highest delta-T1-values (634 ± 71 ms). Non-contrast-T1  and post-contrast-T1 (1018 ± 40 ms vs. 1037 ± 45 msp=ns) were not significantly different between controls and patients with advanced DCM. ANOVA analysis showed significant differences between the groups  appear to be a more reliable parameter in the assessment of myocardial fibrosis than a single time-point measurement.none


In this study we determined the normal range of high-pass filtered image phase values in a group of normal subjects for all sixteen segments of the heart. The range and standard deviations varied significantly across the heart, with less variance in septal segments. In a group of acute myocardial infarction patients, phase values in hemorrhagic myocardial infarction were significantly less than normal segments and well depicted as hypointense lesions in filtered-phase images.Myocardial hemorrhage in patients with acute myocardial infarction (AMI) is a form of severe reperfusion injury. Detection has been shown with T2-weighted (T2W) and T2*-weighted magnitude images and is closely associated with microvascular obstruction (MVO). Limitations of the T2W technique include the prerequisite of myocardial edema as well as adequate visualization of myocardial edema to detect a hypointense infarct core. Overall quality of T2*-weighted images across all segments of the myocardium limits its usage for evaluation of the entire left ventricle. Susceptibility-weighted phase images have been shown to be sensitive for the detection of hemosiderin in microbleeds of the brain and should be an effective means of detecting myocardial hemorrhage.15 healthy control subjects and 11 AMI patients were studied at 1.5 T. The comprehensive study protocol included cine, T2-weighted, T2*-weighted, resting perfusion and late gadolinium-enhanced imaging. High-pass filtered phase images were reconstructed from breath-hold multi-echo T2*-weighted acquisitions (Echo delay time(TE) =2.4-15.5ms, 2.2ms spacing) over the entire left ventricle. ROIs were drawn for each subject in each of the 16 AHA myocardial segments and the mean phase and standard deviation were recorded. Normal variations in myocardial phase across echo delay time and anatomical segment were compared in the control group using ANOVA and normal ranges as mean+-2*standard deviations were calculated. Analysis of the phase measured with the same control group protocol across echo times in AMI patients was plotted and compared to normal ranges.Filtered phase in the control group was small, on average across echo times and patients being zero in all segments with variance significantly increasing with echo time p<0.001). There was a difference between anatomical segments (p<0.001), with less variation in septal segments compared to a cyclic variation due to myocardial fat in other segments (Figure . There wHigh pass filtered myocardial phase is small and normally varies by anatomical myocardial segment and echo delay time. Myocardial hemorrhage causes a significant phase decrease beyond these normal variations. High-pass filtered phase imaging represents a quantitative, high quality method for the detection of myocardial hemorrhage without the need for the presence or high quality visualization of myocardial edema.American Heart Association Scientist Development Grant, 0635029N.


Transthyretin (TTR) is the major constituent of severe systemic amyloid diseases with a broad spectrum of genotypes and heterogeneous phenotypes. Data on risk stratification is lacking. We evaluated the impact of different imaging tools for risk assessment in TTR patients.® Philips Medical Systems, Best, The Netherlands), and 99mTechnetium-DPD scintigraphy. EDV, ESV, EF and myocardial mass were analyzed on a standard workstation (Philips Viewforum). Longitudinal function was assessed by mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursion. Atrial septum thickness was measured on SSFP-4 chamber views. Gadolinium contrast-enhanced CMR (CE-CMR) was assessed semi-quantitatively  in an AHA modified 16 segment model of the left ventricle as well as for the right/left atrium and right ventricle. Nuclear DPD-retention was assessed semi-quantitatively using a region of interest technique by comparison of counts in the heart at 3 hours after injection with whole body counts at 5 min after injection.30 patients  with diagnosis of TTR amyloidosis  were evaluated by cardiac MRI . By MRI LV mass was 166  g, LV ejection fraction 59  %, MAPSE 8  mm, and TAPSE 14  mm). Thickness of atrial septum was 7  mm. Late gadolinium enhancement was present in 26 patients (87%). Mean sum of semi-quantitative CE-CMR was 27.0±2.7 . By 99mTechnetium-DPD scintigraphy heart retention was 6.5  %, heart-to-body retention was 8.0  %.Median troponin T 0.02  µg/l, NT-proBNP 1217  ng/l, and MDRD 76  ml/ months. Multivariate analysis revealed median of MDRD, LV ejection fraction, and NT-proBNP as independent predictors of survival, but not CE-CMR or scintigraphic heart retention.99mTechnetium-DPD scintigraphy for risk stratification of patients with TTR amyloidosis.This is the first report comparing different diagnostic tools for risk stratification of patients with TTR amyloidosis. This preliminary study demonstrates the potential impact of cardiac MRI and laboratory findings, but not None.


We report the case of a 68-year-old man suffering from incremental hepatic and renal failure one month after anterior myocardial infarction. Cardiac MRI showed a pronounced apical post-AMI aneurysm, a moderate to severe mitral and tricuspid regurgitation as well as a hemodynamically highly significant 12 mm apical ventricular septal defect with a left-to-right ventricular shunt of almost 63% as the underlying cause. Heart X-ray revealed a severe LAD in-stent restenosis. CAPD catheter drainage of hydroperitoneum due to congestive liver and renal failure was provided in combination with intensified CAPD hemodialysis. Heart surgery was performed where the apical aneurysm was excised, the mitral valve was reconstructed, the IVSD was closed and the subtotally in-stent occluded LAD was bypassed. Post-surgery, the ascites were significantly reduced, and CAPD hemodialysis therapy could be terminated since the renal function gradually improved (MDRD = 25 mL/min). To our knowledge, for the first time we report successful CAPD catheter drainage of hydroperitoneum in combination with CAPD hemodialysis. A 68-year-old man who lived in Venezuela for the last four decades presented to our clinic with inexplicably incremental renal and hepatic failure with an obviously reduced general and nutritional condition for further diagnostic and therapy. Due to severely reduced creatinine-clearance (MDRD = 14 mL/min), he was scheduled for continuous ambulatory peritoneal dialysis (CAPD) both to drain his up to six litre nonmalignant, persistent hydroperitoneum as well as for dialysis. Patient's history was inconspicuous apart from a single vessel coronary heart disease that had lead to an acute myocardial infarction (AMI) interventionally treated by implantation of a bare metal stent into the LAD three years ago. One-month post-AMI, the patient complained of progressive abdominal heaviness and pressure as well as shortness of breath, which was nebulously explained by hepatic failure due to thienopyridine treatment. In contrast to the assumed hepatic cirrhosis, multiple abdominal ultrasound studies did not reveal cirrhotic hepatic tissue texture as well as excluded a veno-occlusive Budd Chiari disease. Shortly before the admission to our hospital echocardiography study was conducted externally with reduced acoustic windows to exclude an underlying cardiac disease and showed a moderately reduced left ventricular function, a mild aortic and mitral regurgitation as well as anterior hypo- to akinesia with potential apical adhesions. These findings were in far contrast to a holosystolic harsh loud murmur accompanied by a thrill being present in the third and fourth left intercostal space. For further clarification of morphology, function, the extent of myocardial scar, and exclusion of constrictive pericarditis, a gadolinium contrast enhanced and cine MRI was conducted. Cine short axis, two- and four-chamber MRI imaging showed a dilated right and left ventricle with an almost severely reduced left and right ventricular function (LV ejection fraction = 35%), a pronounced apical post-AMI aneurysm with transmurally infarcted myocardial tissue  as thin The overall incidence of post-AMI IVSD is hard to assess because clinical and autopsy series differ considerably . A largeIn our case, due to right-sided heart failure with increased right atrial pressure and tricuspid regurgitation, subsequent congestive hepatomegaly associated ascites was extensively treated with diuretics and consequently led to hepatorenal syndrome. Although echocardiography might not always suggest IVSD due to reduced acoustic windows, simple and inexpensive auscultation is almost pathognomonic. An IVSD is characterized by the appearance of a new harsh, loud holosystolic murmur at the lower left sternal border and is usually accompanied by a thrill. Although biventricular failure generally ensues within hours to days, in our case the patient astonishingly survived more than three years with accretive signs of hepatic and renal failure. Operative intervention is mostly successful and should not be delayed in patients with a correctable lesion .Our case report has two important issues. To our knowledge, for the first time we report successfully practiced CAPD catheter drainage of hydroperitoneum due to congestive liver and renal failure in combination with CAPD hemodialysis. Secondly, simple auscultation of the heart lead to the diagnosis of IVSD that, if correctly performed earlier, could have greatly relieved the patient's symptoms, his reduced physical state, and his commencing hepatic and renal failure. Furthermore cardiac TEE or MRI as not invasive and radiation-free methods should be considered in case of limited acoustic windows for echocardiography to exclude an IVSD.


Approximately 300.000 patients might be treated in Hungary because of heart failure. Out of this 900-1000 might be affected by end stage heart failure. These patients should be potentially treated by heart transplantation (HTX). The etiologic reasons of heart failure among transplanted patient are mainly cardiomyopathic or ischemic in origin (48%-44%). The valvular or congenital origin is rear (4%-2%). The prevalence of Marfan syndrome is 1-2/10.000; it means that we can calculate with 1000-2000 Marfan patients (MP) in Hungary. As it is mentioned in the literature MPs are often affected by a left ventricle dysfunction due to the characteristic Marfan cardiomyopathy, which may show a rapid progression in case of concomitant longstanding aortic or/and mitral regurgitation.Among the 243 patients underwent HTX in Hungary, there was only one Marfan patient. The 12 year-old male patient underwent previously a total aortic root replacement and after that a mitral valve implantation 4 and 2 years earlier. The symptoms of a left ventricle dysfunction were developed just a year after the second open heart procedure, but the progression was extremely fast resulting with a very severe heart failure. The MR imaging raised even the etiologic role of the Marfan cardiomyopathy in developing of this type of heart failure. The child, who was accepted to high urgent list of Eurotransplant got a donor heart after 31 days. After the operation he recovered uneventfully.Despite of the successful HTX, it remains controversial, how the longstanding immunosuppressive treatment will affect and damage later on the wall structure of the aorta (arch and the descendent) predisposing a later dissection of the descending aorta.


Cardiac magnetic resonance (CMR) myocardial feature tracking (FT) is emerging as a sensitive and reproducible method for measuring myocardial strain parameters without the need to acquire additional images. Up until now adult CMRFT studies have primarily focussed on the reproducibility of the software,with very few studies addressing disease states beyond ischaemic cardiomyopathy. The aim of this pilot study was to assess the feasibility of cine-images derived quantitative CMR FT strain parameters to differentiate between normal individuals and patients with Left ventricular non-compaction (LVNC).Patients were identified retrospectively from an established clinical CMR database. 8 LVNC patients with negative invasive angiography or stress CMR myocardial perfusion imaging were compared to 21 normal controls. LVNC was defined according to the Petersen criteria,with an end-diastolic ratio of non-compacted to compacted layer (NC/C) >2.3. LV morphological and functional parameters were performed off-line on a dedicated workstation. CMR 4-chamber(4CH) and mid-ventricular short axis(SAX) cine-images were analysed in systole(S) and diastole(D) using dedicated FT software.There was no difference in age (p=0.87) or weight (p=0.84) between LVNC and normals. LV end diastolic volumes(ml): 232±81 vs.151±45 p=0.004; LV end systolic volumes(ml): 149±87 vs.70±30 p=0.038; Mean LV ejection fractions(%): 39±10 vs.55±8 p=0.002; Significant differences were identified between LVNC vs. normals in all measures of circumferential strain(cs): ScsSAX(%) -8.1 vs.-12.3 p=0.01, DcsSAX(%) -5.6 vs.15.2 p=0.01. All radial strain(rs) in SAX and 4ch views showed either significance or trends towards significance: SrsSAX(%)14.4 vs.20.9 p=0.05, DrsSAX(%) 9.10 vs.14.0 p=0.07; Srs4CH(%) 10.1 vs.14.7 p=0.07, Drs4CH(%) 7.6 vs.13.5 p=0.04. No significant differences in longitudinal strain were seen. Where significant strain differences were seen between LVNC vs. normals, significant correlation with EF across all subjects was seen: ScsSAX r=-0.88 p<0.001, DcsSAX r=0.55 p=0.004; SrsSAX r=0.84 p<0.001; Drs4ch r=0.68 p<0.001, but within the LVNC cases alone, significant correlations with EF were only demonstrated in the SAX: ScsSAX r=0.89 p=0.03, DcsSAX r=-0.723 p=0.04; rsSAX r=0.836; p=0.01. These same three parameters also correlated with NC/C: ScsSAX r=0.622 p=0.10, DcsSAX r==0.61 p=0.11; SrsSAX r= -0.694 p=0.056.This is the first study to our knowledge that confirms the ability of CMRFT to identify abnormal rs and cs, but not longitudinal strain parameters in the presence of LV non-compaction. As expected strain correlated with EF. NC/C ratio also correlated with strain. The use of CMRFT in future studies could help establish whether cs and rs are able to differentiate between normal individuals and LVNC patients with normal EF and therefore potentially identify a prognostic marker for the development of LV dysfunction in LVNC.Ian Stone has received a research grant from GlaxoSmithKline


Peripartum cardiomyopathy (PPCM) is a rare but potentially lethal complication of pregnancy occurring in approximately 1 : 3,000 live births in the United States although some series report a much higher incidence. African-American women are particularly at risk. Diagnosis requires symptoms of heart failure in the last month of pregnancy or within five months of delivery in the absence of recognized cardiac disease prior to pregnancy as well as objective evidence of left ventricular systolic dysfunction. This paper provides an updated, comprehensive review of PPCM, including emerging insights into the etiology of this disorder as well as current treatment options. Peripartum cardiomyopathy, the development of systolic heart failure in the puerperium, is a rare but serious complication of pregnancy. Diagnosis requires objective evidence of left ventricular (LV) dysfunction with no other explanation for heart failure signs and symptoms , 2. In tThe incidence of PPCM in the United States is difficult to estimate as overlapping diagnosis codes make chart review both tedious and potentially inaccurate. Until recently, only small studies reporting the experience of single centers were available to estimate the incidence of this rate disorder. Two large studies in the United States reviewed ICD-9 codes and performed chart reviews to better report an estimate of incidence. Charts from discharges from the National Hospital Discharge Survey database (1990–2002) were reviewed to identify cases of PPCM. This study reported an estimated incidence of 1 : 3,189 live births in the US with the highest incidence occurring in African-American women . This stThe strongest risk factor for PPCM appears to be African-American ethnicity  [2; (3) no evidence of pre-existing heart disease prior to peripartum symptom onset; (4) no other identifiable causes of heart failure [The National Heart, Lung and Blood Institute (NHLBI), with the National Institutes of Health (NIH), published diagnostic criteria for PPCM to direct more accurate research on epidemiology, pathophysiology, and outcomes. The criteria include: 1) onset of heart failure signs and symptoms in the last month of pregnancy or within 5 months postpartum; (2) LV systolic dysfunction with ejection fraction (EF) measured ≤45% or LV end diastolic dimension ≥2.7 cm/m onset of failure . However failure . An obje failure  as many The clinical presentation of PPCM is most often dyspnea (90%), tachycardia (62%), and edema (60%) . Some caα and IL-6) are elevated in women with PPCM compared to pregnancy controls [Cardiac biomarkers, including B-type natriuretic peptide (BNP), are elevated in patients presenting with PPCM although these markers are not unique to PPCM. Elevations of troponin T (TnT) appear to have prognostic significance in this group. A TnT level ≥0.04 ng/mL at presentation predicts persistence of systolic dysfunction with a sensitivity of 55% and specificity of 91% . Inflammcontrols , 16. HowECG abnormalities are often noted on presentation, most commonly sinus tachycardia, nonspecific ST-T segment changes, LV hypertrophy, premature ventricular contractions, and bundle branch block . HoweverEvaluation of suspected PPCM should include an echocardiogram. Average EF at diagnosis is often reported in the range of 20–30%; however, some women present with severe systolic dysfunction and an EF <20% . SeveralInvasive evaluation, such as cardiac catheterization or endomyocardial biopsy, is often unnecessary for diagnosis or treatment. The pathology identified on endomyocardial biopsy is often nonspecific edema, inflammation, hypertrophy, and fibrosis . InflammRecovery of systolic function occurs in roughly half of affected women and usually occurs within 6 months of symptom onset . A rapidA proposed, but unlikely, etiology is nutritional deficiency. Selenium deficiency has been investigated given its association with heart failure in the third world independent of pregnancy. Forty percent of women with PPCM had low levels of selenium, but no correlation was found between selenium levels and the severity of cardiomyopathy . AnotherA genetic predisposition is plausible in PPCM; however, little data exist to confirm this theory. Familial clustering has been reported , and regHormonal abnormalities could contribute as women with PPCM have been found to have lower levels of progesterone, prolactin, and estrogen during pregnancy, all hormones with a vasodilatory response preventing hypertension in the face of intravascular volume expansion . WhetherAlterations in the immune response are normal in pregnancy as immunosuppression is necessary to ensure the safety of the fetus during development. A potential maladaptive response to pregnancy which may account for the development of PPCM is an autoimmune response to the cardiomyocyte. Antibodies recognizing unique cardiac tissue proteins have been described in the sera of patients with PPCM. In this same study, the sera from patients with other cardiomyopathies did not recognize the same cardiac tissue proteins .Infectious agents invading the cardiomyocyte resulting in myocarditis have been described in PPCM. Given the immunosuppressed state of pregnancy, it is logical that pregnant women are more susceptible to infection or viral reactivation. Endomyocardial biopsy specimens from some patients demonstrate inflammatory changes consistent with myocarditis, as well as the presence of viral DNA in some patients with PPCM , 21, 27.stat3 develop PPCM. Deletion of stat3 results in enhanced oxidative stress which is associated with the generation of a 16 kDa prolactin derivate. This protein appears to be a key factor in the development of PPCM, leading investigators to treat patients with bromocriptine with early promising results [The most exciting recent insight into the etiology of PPCM involves a mouse model. Female mice with a deletion of  results , 28–30.Standard heart failure treatment is recommended for PPCM until the EF recovers. Medications include angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs), beta blockers, and diuretics. However, caution must be exercised as ACE inhibitors and ARBS are contraindicated in pregnancy. In addition, patients are advised regarding nonpharmacologic approaches such as salt restriction and the avoidance of offending medications . Select patients may eventually benefit from cardiac resynchronization therapy, internal defibrillators, or cardiac transplantation. If systolic function normalizes, patients can discontinue heart failure medications without subsequent decompensation .An important therapeutic option to consider is anticoagulation. Pregnancy conveys a hypercoagulable state that extends approximately 3 months postpartum. During this time, patients with PPCM and depressed systolic function are at high risk for thrombus formation and thromboembolic events . Warfariα levels and increased EF in patients with PPCM [No specific treatment has been identified to significantly alter the morbidity of PPCM. Small trials have reported benefits of pentoxifylline, intravenous immunoglobulin, and bromocriptine. Pentoxifylline decreased TNFith PPCM  althoughith PPCM . More reith PPCM . Case reith PPCM , 28–30. Transplant requirements in small series are reported to be 6 to 10% , 34, 35.In addition to prescribing standard heart failure treatment, appropriate management of the patient with PPCM involves counseling regarding subsequent pregnancies. Women with persistent LV dysfunction are advised not to pursue further pregnancies. How to advise women with recovered LV function is more challenging. Some studies report good outcomes , and othAlthough rare, when a woman is diagnosed with PPCM, only 50% will be expected to fully recover cardiac function. Obstetricians should suspect the diagnosis, particularly if the patient has risk factors, including African-American ethnicity. Evaluation should include an echocardiogram to assess the LV systolic function. Treatment includes ACE inhibitors or angiotensin receptor blockers, beta blockers, and diuretics. Consideration should be given to anticoagulation. A number of causes are being investigated, including nutritional, infectious, and genetic, which, hopefully, lead to more targeted treatments.


The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities.Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated.Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients.Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM. Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death. About one third of DCM cases are familial. During the past few decades, several DCM disease genes have been identified, many of them limited to individuals or families -3. The lCarriers of LMNA mutations causing cardiomyopathy should be recognised at an early stage so that regular cardiologic follow-up can be arranged; affected individuals have a high risk of sudden cardiac death or severe heart failure by middle age . HoweverEchocardiography is regarded as the standard method to clinically study DCM; however, cardiovascular magnetic resonance (CMR) plays an important role in the characterisation and risk stratification of patients with DCM. Late gadolinium enhancement (LGE) CMR with standard cine-imaging is an accurate and reproducible method both to demonstrate myocardial fibrosis and to measure wall thickness as well as global and regional function of both ventricles ,8.The main purpose of this study was to characterise myocardial fibrosis, regional wall motion abnormalities, ventricular dilatation, longitudinal LV systolic function and global function with LGE CMR in asymptomatic or mildly symptomatic carriers of LMNA mutations causing DCM. In addition, we investigated the possible association between the localisation of myocardial fibrosis and the conduction abnormalities documented with electrocardiography (ECG).2) recruited for this study between 2004 and 2008. Each subject was a heterozygote for one mutation. A summary of the mutations, symptoms and ECG findings are presented in Table The LMNA mutations had originally been identified in DCM patients who participated in an earlier molecular genetic study of DCM carried out in collaboration between the Helsinki University Hospital and the University of Kuopio ,3. The sAll participants gave written informed consent. The project was approved by the local institutional ethics committee.CMR was performed with a 1.5 T MR imager  using a multi-channel body-array coil as a receiver. Breath-hold cine CMR was performed using retrospectively electrocardiographically gated segmented true fast imaging with steady-state free precession (SSFP). Cine MR images were obtained in vertical and horizontal long-axis, and a stack of images in short-axis plane covering both ventricles was acquired. The imaging parameters were TR/TE 3.0/1.6 msec, flip angle 52 degrees, 256 × 256 matrix, 240 × 340 mm field of view. Slice thickness was 6 mm and interslice gap 20%. The temporal resolution was 42-49 msec.ve to fifteen minutes after the injection of a contrast agent  LGE images were acquired in the same views as for cine images, using inversion recovery turbo fast-low angle shot (FLASH). The imaging parameters were TR/TE 2.58/2.3 msec, flip angle 50 degrees, 256 × 256 matrix, 240 × 340 mm field of view. Slice thickness was 8 mm and interslice gap 0%. Inversion time was optimised for each measurement to null the signal intensity of normal myocardium (240-360 msec).FiThe images were analysed in consensus by two experienced (> 10 years experience) cardiac radiologists . In each patient, the three LV short axis sections were divided into 17 segments according to American Heart Association (AHA) guidelines . The plaOn the cine images, segmental wall motion was visually assessed and scored as 1 = normal, 2 = hypokinesia, 3 = akinesia and 4 = dyskinesia.Measurement of volumes and ejection fraction of both ventricles were segmented semi-automatically by tracking the endocardial borders of both ventricles with a segmentation tool developed for this purpose .To assess longitudinal LV systolic function, mitral annular displacement (MAD) was measured as the difference (between end-diastole and end-systole) of the distance from apex to the lateral and septal sites of the mitral annulus in the horizontal long-axis view, and apex to the anterior and inferior sites in the vertical long-axis view. The mean value of MAD at all four sites was then calculated.Statistical analysis was performed using NCSS version 2007 software. Chi-Square test and Fisher's Exact test were used to calculate for correlation between the percentage of LGE and wall motion abnormalities. Volumetric results of both ventricles were compared to normal values published earlier by Maceira et al ,12 whoseOut of 17 patients, 15 exhibited LGE. Among the total of 289 segments, LGE was observed in 47 (16%). The extent of LGE was less than 50% in 36/47 enhanced segments  and two with atrial fibrillation showed enhancement of the basal and mid-ventricular septum. Conduction abnormalities correlated significantly with presence of LGE in the LV septum (p = 0.01). Four patients had a normal ECG recording, and two of them had enhancement of the basal septum. Table A volumetric analysis of one female subject was excluded because of poor cine image quality due to arrhythmia. When compared with the age, sex and BSA standardised normal values published earlier by Maceira et al ,9, ventrLongitudinal LV systolic function was decreased in nine patients when compared to normal values published by Nikitin et al . DecreasMAD was significantly lowered when EF was decreased (p < 0.03) Figure . MAD corThe present study demonstrates that 88% of asymptomatic or mildly symptomatic carriers of LMNA mutations causing cardiomyopathy had typical myocardial fibrosis, predominantly in the mid-myocardium of the basal septum. This was observed in all individuals with an AV conduction defect. The pattern of enhancement was typically linear and less than 50% of the area of the segment. Enhancement was associated with wall motion abnormalities at LV basal segments, where the degree of enhancement had a significant correlation with decreased motion. Minor systolic dysfunction without ventricular dilatation, preserved systolic function with mild LV dilatation or systolic dysfunction with mild dilatation of LV, or of both ventricles, was observed in 69% of LMNA mutation carriers. In our patients as an early marker of the disease longitudinal LV systolic function was decreased in nine patients when compared to normal values . In addiEarly studies show that even a very small amount of myocardial scar tissue is visible with routine LGE CMR sequences . MyocardAssomull et al reported that mid-wall myocardial fibrosis in DCM patients predicted both ventricular tachycardia and sudden cardiac death . CardiomPrevious autopsy studies have shown the location of fibrosis near the region of the conduction system and this has been postulated to be the cause of the AV blocks in LMNA-related cardiomyopathies ,25. In cZimmermann et al concluded that enhancement is a typical feature on CMR carried out in DCM patients but it did not correlate with myocardial biopsy findings . Since aIn conclusion, in the early stage of DCM caused by a LMNA gene mutation, AV conduction defects are common with or without a minor depression in LV systolic function. Usually the suspicion of DCM caused by LMNA mutations is based on the presence of conduction system disturbances in an ECG and by clinical exclusion of other aetiologies. However, other inflammatory or infiltrative cardiomyopathies may resemble DCM caused by LMNA mutations. If the typical pattern and location of myocardial fibrosis, mild LV dilatation and systolic ventricular dysfunction can be accurately observed with LGE CMR in the early stage of the disease, the diagnosis can be confirmed by DNA analyses. Myocardial scarring is known to provide a substrate for ventricular dysfunction, conduction abnormalities and ventricular arrhythmias. The disease is known to have a malignant course, and the combination of ECG recordings and LGE CMR will help to recognise these patients. LGE CMR can also be used to differentiate between LMNA-related cardiomyopathy and cardiac sarcoidosis, both of which can cause AV conduction defects and arrhythmias. Although no specific medical treatment exits so far to prevent the development of LMNA-related cardiomyopathy, sudden cardiac death may be prevented by a timely placement of a pacemaker or an implantable cardioverter defibrillator.LGE CMR is also a reproducible method to monitor the progression of the disease and therefore we have an ongoing follow-up study with DE-MRI to obtain further information about the progression of the familial form of DCM caused by a LMNA mutation.We had a limited number of patients, all of them carriers of a rare familial form of DCM caused by a LMNA mutation (14 out of the 17 Lamin A/C mutations in the population are due to either a ser143pro mutation (n = 10) or an arg190trp mutation (n = 4)). Wall motion abnormalities were visually graded as well as the percentage of enhancement in LV segments. As both cine volumetry and LGE imaging are widely used as gold standards in cardiac research, we did not collect any new data of healthy subjects. Global volumetric CMR results and longitudinal systolic function were compared with previously published normal values obtained from healthy volunteers.The authors declare that they have no competing interests.MH, SK, KL have carried out cardiovascular magnetic resonance imaging studies, performed image analysis and participated drafting the manuscript. MA have been involved in cardiovascular magnetic resonance imaging and analyzing images. TH have participated in the study design and coordination, performed clinical examinations and echocardiography's of the patients and have been involved in drafting the manuscript. RJ, MK, ER, JK, SK and KP have participated in the design of the study, performed clinical examinations and echocardiography's of the patients and the control group. They have been involved in revising the manuscript. JK and JT have participated in analyzing magnetic resonance images. All authors have read and approved the final manuscript.