The digestion of food is known to alter the hemodynamics of the body significantly. The purpose of this study was to study the postprandial changes in stroke volume (SV), cardiac output (CO) and left ventricular (LV) longitudinal systolic and diastolic functions measured with tissue Doppler imaging, in relation to gastric emptying rate (GER), satiety, and glucose and insulin concentrations in healthy subjects.Twenty-three healthy subjects were included in this study. The fasting and postprandial changes at 30 min and 110 min in CO, heart rate (HR) and blood pressure were measured. Moreover, tissue Doppler imaging systolic (S'), early (E') and late (A') mitral annular diastolic velocities were measured in the septal (s) and lateral (l) walls. Glucose and insulin concentrations, and satiety were measured before and 15, 30, 45, 60, 90, and 120 min after the start of the meal. The GER was calculated as the percentage change in the antral cross-sectional area 15-90 min after ingestion of the meal.This study show that both CO, systolic longitudinal ventricular velocity of the septum (S's) and lateral wall (S'l), the early diastolic longitudinal ventricular velocity of the lateral wall (E'l), the late diastolic longitudinal ventricular velocity of the septum (A's) and lateral wall (A'l) increase significantly, and were concomitant with increased satiety, antral area, glucose and insulin levels. The CO, HR and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting. The satiety was correlated to HR and diastolic blood pressure. The insulin level was correlated to HR.This study shows that postprandial CO, HR, SV and LV longitudinal systolic and diastolic functions increase concomitantly with increased satiety, antral area, and glucose and insulin levels. Therefore, patients should not eat prior to, or during, cardiac evaluation as the effects of a meal may affect the results and their interpretation.NCT01027507ClinicalTrials.gov:  The digestion of food is known to alter the hemodynamics of the body significantly. Following a meal, the blood flow to the gastrointestinal organs increases, affecting the heart rate (HR), blood pressure, and cardiac output (CO). The mechanisms causing the change in heart function after a meal are not known. These postprandial cardiovascular changes have been shown to resemble the effects of vasodilator drugs ,2.The left ventricular (LV) stroke volume (SV) and CO are usually assessed by echocardiography to quantify the total LV function. However, the heart undergoes cyclic mechanical changes in multiple dimensions that result in the ejection of blood. Tissue Doppler imaging (TDI) may be used to quantify different aspects of mechanical myocardial activity. TDI is used to assess both regional and the global ventricular function in systole and diastole, by measuring the tissue velocity at specific locations in the heart. Tissue velocity is determined by the rate at which specific parts of the myocardium move towards or away from the transducer. TDI has been validated and may have a potential role in clinical applications such as the evaluation of myocardial ischemia (at rest and with stress echocardiography) and altered global and regional systolic and diastolic function in cardiomyopathies -11.The systolic longitudinal velocity (S') of a myocardial segment measured with TDI reflects the systolic motion of the LV in the apical direction, which is an important component of systolic function , and is The effect of the digestion of a meal on left ventricular function has not previously been studied in terms of longitudinal velocity measured with TDI. This study was therefore designed to determine whether there are postprandial changes in LV function that can be measured with TDI, and if these changes can be related to changes in glucose and insulin levels, antral area or satiety in healthy subjects.2 [range: 17.0-25.9 kg/m2] without symptoms or a history of gastrointestinal disease, abdominal surgery or diabetes mellitus, were included in this observational study. The mean waist:hip ratio for the women was 0.74 ± 0.02 and for the men 0.87 ± 0.01. The subjects had no connective tissue disease or cerebrovascular or endocrine disease, and none was taking any medication, except four women who were taking oral contraceptives. All subjects were in sinus rhythm. Three men were snuff users, and one was a smoker. Two women were snuff users. All subjects were recruited from the population of southern Sweden.Twenty-three healthy subjects  age: 26 ± 0.2 y [range: 18-33 y]; body mass index: 21.8 ± 0.1 kg/mThe subjects were examined between 7.30 and 11.00 am after an 8-h fast. Smoking and snuff-taking were prohibited 8 h prior to and during the test. The fasting blood glucose concentration of each subject was checked on the day of the examination to ensure that it was normal. If the subjects reported gastrointestinal symptoms (diarrhea or constipation) on the day of the study, the examination was postponed. The test meal consisted of 300 g rice pudding . The total caloric value of the meal was 330 kcal: 10% from protein (9 g), 58% from carbohydrates (48 g) and 32% from fat (12 g). The meal was ingested within 5 min.The gastric emptying rate (GER) was estimated using an ultrasound method described in detail previously . The sonTransthoracic echocardiography examinations were performed with a Sonos 5500 ultrasound system  in the left lateral position, after 15 minutes' rest. On the day of the study, an initial examination was performed to rule out any cardiac dysfunction. A single observer performed all echocardiography measurements three times on separate cardiac cycles, and the mean values were used in the analyses. TDI of the septal (s) and lateral (l) mitral annulus was obtained from the apical four-chamber view, in accordance with current guidelines . Peak syVenous blood samples were taken before and 15, 30, 45, 60, 90, and 120 min after the start of the meal to measure blood glucose and plasma insulin levels. Blood glucose concentrations were measured with the HemoCue Glucose system . The precision of the HemoCue Glucose system was better than 0.3 SD from 0 mmol/L to 22.2 mmol/L. Insulin concentrations were measured using an immunoassay with an alkaline phosphatase conjugate . The sensitivity of the insulin immunoassay was 0.03 mUnit/L (mU/L), and the intra-assay coefficient of variation was below 10% from 0.03 mU min/L to 300 mU/L.A validated satiety scoring scale was used according to the method of Hauber et al., based on a scoring system from -10 (extreme hunger) to +10 (extreme satiety) . SatietyAll subjects gave their written informed consent. The study was approved by the Ethics Committee of Lund University, and performed according to the Helsinki Declaration. The trial is registered in the US National Library of Medicine with the trial registration number NCT01027507.P < 0.05 were considered significant.Results are given as mean values and the SEM unless otherwise stated. The areas under the curves (AUCs) were calculated for blood glucose and insulin concentrations, satiety, CO, HR, SV, systolic and diastolic blood pressure, S's, S'l, E's, E'l, A's, and A'l in each subject using GraphPad Prism software . All other statistical calculations were performed in SPSS for Windows version 14.0, 2005 . The changes in levels of blood glucose, plasma insulin and satiety were calculated as the difference between levels before the meal  and 30 and 120 min after the start of the meal. The changes in HR, SV, CO, systolic and diastolic blood pressure, S's, S'l, E's, E'l, A's, and A'l were calculated as the difference between levels before the meal  and 30 and 110 min after the start of the meal. To determine whether the meal affected a given parameter, the baseline value was compared with the 30 min and 120 min postprandial value using the Wilcoxon t-test. The postprandial values at 30 min and 120 min were also compared using the Wilcoxon t-test. Possible correlations between CO, HR, SV, systolic blood pressure, diastolic blood pressure, S's, S'l, E's, E'l, A's, A'l, blood glucose level, plasma insulin level, GER, and satiety were analyzed with Pearson's correlation. Values of P = 0.003), and the value at 120 min (P = 0.000) . The insulin level at 30 min was significantly higher than at 120 min (P = 0.000) . The mean value of the GER after the meal was estimated to be 43 ± 4%.The mean value of the antral cross-sectional area was significantly larger 15 min after the end of the meal than 90 min after the meal (667 ± 48 mmP = 0.000). The satiety 120 min after the meal was significantly lower than at 30 min (P = 0.000) . The E'l at 30 min was significantly higher than at baseline (P = 0.038), and at 110 min (P = 0.003). The A's at 30 min was significantly higher than at baseline (P = 0.001), and at 110 min (P = 0.006). The A'l at baseline was significantly lower than at 30 min (P = 0.000), and at 110 min (P = 0.005). The A'l at 30 min was significantly higher than at 110 min (P = 0.041) . The HR at 30 min was significantly higher than fasting and at 110 min . The SV at 30 min was significantly higher than fasting and at 110 min (both P = 0.000). The SV at 30 min was significantly higher than at 110 min (P = 0.003) . The diastolic blood pressure at 30 min was significantly lower than at 110 min (P = 0.001)  and antrum area at 15 min . At 30 min there was also a significant correlation between the E's and satiety . A significant correlation was found between E'l at 110 min and antral area at 90 min , and between E's at 110 min and GER . There was a significant correlation between the change in A's at 30 min and the change in satiety . There was also a significant correlation between the change in A's at 110 min and the change in insulin level . A significant correlation was found between the change in E's at 110 min and GER . There was significant correlation between the glucose AUC at 30 min and the AUC for E'l at 30 min . A significant correlation was also found between the satiety AUC at 120 min and the AUC for S'l at 110 min . There was significant correlation between the satiety AUC at 30 min and the AUC for HR at 30 min and the AUC for the diastolic blood pressure at 30 min . A significant correlation was found between the insulin AUC at 120 min and HR at 110 min .At 30 min there was a significant correlation between E'l and glucose level , inotropy and conduction velocity (positive dromotropy), whereas parasympathetic stimulation of the heart has the opposite effects. Changes in HR variability and blood pressure may reflect changes in the balance between the sympathetic and parasympathetic nervous systems. Postprandial hemodynamic changes could be mediated by the innervation of the heart. The vagus nerve mediates the adaptive relaxation of the proximal stomach, the fundic-antral co-ordination (by controlled delivery of the food from the fundus into the antrum), and the peristaltic contractions of the distal stomach after a meal . The endPostprandial changes in heart activity may be influenced by changes in glucose and hormonal signals. It is known that insulin has hemodynamic effects, such as positive chronotropic and inotropic effects on the heart . In thisA limitation of the present study was the fact that it was not possible to perform the echocardiography or gastric empting examinations at the same time, or blinded to the state of food intake. However, both measurements were performed by a single observer thereby avoiding intra-observer variability. The echocardiography examinations were stored digitally and analyzed later in random order in an attempt to avoid bias.This study shows that both postprandial LV global and longitudinal function increase concomitantly with increased satiety, antral area, and glucose and insulin levels. Patients should therefore not eat prior to or during cardiac evaluation because the effects of a meal may affect the results and their interpretation.A's: late longitudinal ventricular velocity of the septum wall; A'l: late longitudinal ventricular velocity of the lateral wall; CO: cardiac output; E's: early longitudinal ventricular velocity of the septum wall; E'l: early longitudinal ventricular velocity of the lateral wall; GER: gastric emptying rate; HR: heart rate; LV: left ventricular; S's: systolic longitudinal ventricular velocity of the septum wall; S'l: systolic longitudinal ventricular velocity of the lateral wall; SV: stroke volume; TDI: Tissue Doppler imagingThe authors declare that they have no competing interests.The authors' contributions were as follows: JH and MD contributed to the design of the study; JH was responsible for recruiting the subjects and carried out the practical aspects of the study. OB performed the ultrasound examinations; MD performed the echocardiographic examinations; JH, SL, and MD conducted the statistical calculations; JH, SL, and MD created the graphs. JH and MD wrote the first draft of the manuscript and SL and OB made critical revisions of the manuscript. All authors read and approved the final manuscript. None of the authors had any personal or financial conflict of interest.


This can be used to study mechanisms of heart failure development in a longitudinal manner, for example, the potential contribution of myocardial lipid accumulation in the context of ageing and obesity. Similarly, quantifying creatine levels provides insight into the energy storage and buffering capacity in the heart. Creatine depletion is consistently observed in heart failure independent of aetiology, but its contribution to pathophysiology remains a matter of debate. These and other questions can in theory be answered with cardiac MRS, but fundamental technical challenges have limited its use. The metabolites studied with MRS are much lower concentration than water protons, requiring methods to suppress the dominant water signal and resulting in larger voxel sizes and longer scan times compared to MRI. However, recent technical advances in MR hardware and software have facilitated the application of 1H-MRS in humans and animal models of heart disease as detailed in this review.Magnetic resonance spectroscopy (MRS) is the only non-invasive, non-radiation-based technique for investigating the metabolism of living tissue. MRS of protons ( Heart failure, defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body, is a major societal burden due to its high prevalence, poor prognosis and cost. In the United Kingdom, it affects at least one person out of 100, and this number is anticipated to rise in the next few years , 3815, 32), which is the consequence of an imbalance between caloric intake and energy expenditure, leads to triglyceride storage in organs other than adipose tissue, such as muscle, liver, pancreas and also the heart. The ectopic deposition of these lipid droplets in the cytoplasm results in cell dysfunction, a phenomenon called lipotoxicity , [ATP], [Free Cr], [PCr], [H+] indicate the concentrations in ADP, ATP, free creatine, phosphocreatine and protons, respectively.creatine , which eG~ATP) available to drive ATP-requiring reactions, according to the equation:G° is the value of ΔG~ATP under standard conditions of molarity, temperature, pH and Mg2+; R the universal gas constant; T, the temperature (in Kelvin); and [Pi], the concentration in inorganic phosphate.This approach represents, in principle, a unique opportunity to non-invasively measure in vivo the free energy change of ATP hydrolysis  energy availability would improve cardiac function in the failing heart.1H-MRS and cine-MRI, creatine metabolism and cardiac function were monitored over 1 year in these transgenic mice. We found a large variation in creatine elevation between transgenic mice, which then remained constant throughout an individual’s lifetime. To our surprise, very high levels of myocardial creatine  unable to biosynthesise creatine, we confirmed non-invasively the absence of creatine in the myocardium of these mice Fig. c 17]. W. W17]. W1H-MRS has become an invaluable technique to non-invasively assess cardiac lipid and to a lesser extend creatine metabolism in clinical and pre-clinical research; major findings are summarised in Table Over the last decade,


The role of contrast enhanced cardiac MRI (ceMRI) in predicting recovery of left ventricular dysfunction is evolving; yet transthoracic echocardiography (TTE) has not been evaluated in this manner.Patients with acute ST-elevation MI (STEMI) admitted to Mayo Clinic from August, 2007 to September, 2008 who received reperfusion therapy were screened with TTE and ceMRI. Patients with ceMRI evidence of a previous MI were excluded. Left ventricular dysfunction was defined as an ejection fraction (LVEF) < 50%.Of 116 patients screened, 91 met inclusion criteria and 56 patients completed follow-up imaging (3-79 weeks). 89% of both the imaging studies were completed within 3 days of the index MI and 32 (57%) patients had a baseline LVEF <50%. The ability of ceMRI and TTE variables to predict normalization of LVEF was assessed using ROC analysis. Delayed enhancement left ventricular mass index (DEi) (DEi <20% 35/56 (63%) was the strongest  predictor of LVEF recovery with a sensitivity, specificity, positive predictive value, and negative predictive value of 0.79, 0.92, 0.94, and 0.75 respectively. When combined with DEi, wall motion score index (WMSI) significantly correlated with follow-up EF  and overall change in EF . Acute measures of diastolic function did not meaningfully predict LVEF recovery.A DEi of <20%, as assessed by ceMRI, is the strongest predictor of LVEF normalization in patients with acute post-STEMI left ventricular dysfunction. As compared with TTE, ceMRI provides uniquely valuable information for the long-term management of post-STEMI patients.


Standard diagnostic CMR criteria for acute myocarditis have been proposed (ie Lake Louise criteria) based upon the any 2 of 3 approach which includes the presence of myocardial edema (T2), hyperemia/capillary leakage (early Gd enhancement: EGE) as well as fibrosis (late enhancement: LGE). However, there is a lack of prognostic data using these criteria. The aim of this study was to evaluate the diagnostic CMR criteria for the prediction of functional outcome in patients with myocarditis.We studied 24 patients referred for acute myocarditis during the acute phase and 1 year thereafter. CMR studies included T2 weighted and contrast-enhanced T1 weighted (early and late enhancement) with a quantitative assessment of the regional and LGE.In the acute phase, edema  was present in 67%, EGE in 62.5% and LGE in 54%. Edema %LV (2SD) was: 27.3±7.8; LGE %LV (2SD) was 20.5±14.2. At follow-up, EF significantly increased from 57± 5.5% to 60± 4.5% (p< 0.001). In a univariate analysis, LGE% LV was correlated to the change in EF over 1-year , in a multivariate analysis (linear regression), the combination of LGE%LV and regional edema serves as an independent predictor of an increase of EF In our preliminary experience, the combination of LGE with regional edema was an independent predictor of functional recovery during a 1 year follow-up.


Ivabradine may be a valuable option in treatment of patients with atrioventricular conduction disturbances.We present the case of a patient with a heart failure episode induced by acute right ventricular pacing. After reversal of beta-blockers because of chronic obstructive pulmonary disease (COPD) exacerbation, the following sinus tachycardia caused a 2:1 atrioventricular block and consequent continuous right ventricular pacing. He was treated with the selective I Congestive heart failure is a common health problem. The burden of this condition is likely to increase as a result of an aging population and improved survival rates after acute myocardial infarction. In patients with symptomatic chronic heart failure, beta-blockers reduce mortality and hospital admission for worsening heat failure  . HoweverIn January 2010, a 79-year-old man with a ten year history of post-ischaemic dilated cardiomyopathy was admitted with dyspnoea at rest, i.e. NYHA functional class IV, after he reduced bisoprolol dose because of COPD exacerbation. He had received a dual chamber ICD  in July 2009 because of an episode of sustained ventricular tachycardia. Coronary artery disease progression had been ruled out by angiography six months before. Apart from beta-blocker, he received a standard heart failure medication . On physical examination, a grade 2 holosystolic murmur at the left axillary's border at pulmonary auscultation basal rales were detected, blood pressure was 120/80 mmHg, and pulse was regular (105 bpm). Physical examination was otherwise unremarkable. The ECG showed sinus rhythm, with right ventricular pacing and a heart rate at 105 bpm .Chest X-ray demonstrated cardiomegaly with signs of pulmonary congestion. Laboratory test results revealed elevated but stable values of BUN (96 mg/dl) and creatinine (2.01 mg/dl). NT-pro-BNP was 970.9 pg/ml. All other laboratory parameters including thyroid function were normal. Echocardiography demonstrated left ventricular (LV) dilation with an ejection fraction of 39 % calculated by the Teichholz' method. Color Doppler imaging demonstrated mitral regurgitation grade 3. At ICD interrogation 2:1 AV block with a narrow QRS was recognized . We hypoFaster resting heart rates represent per se a risk factor for cardiovascular mortality and HF hospitalization, despite optimal HF therapy. Heart rate may condition left ventricular filling, myocardial oxygen demand and coronary perfusion time. ,3 Beta-bSharma et al. showed in a post hoc analysis of the DAVID trial that DDDR RV pacing >40% was a univariate predictor of death and hospitalization for heart failure .Ivabradine is a specific inhibitor of the If current of the sinus node, that induces a selective and dose dependent HR reduction pure HR lowering agent without effects on atrioventricular conduction or contractility. The SHIFT study has recently assessed that heart rate reduction by direct sinus node inhibition can reduce cardiovascular mortality or HF hospitalization by 18% in patients with chronic heart failure and left-ventricular systolic dysfunction. In particular, this beneficial effect was mainly driven by a favourable effect on HF death/hospital admission RRR 26%) [% [6] Thi


Stimulation of the nitric oxide (NO) – soluble guanylate (sGC) - protein kinase G (PKG) pathway confers protection against acute ischaemia/reperfusion injury, but more chronic effects in reducing post-myocardial infarction (MI) heart failure are less defined. The aim of this study was to not only determine whether the sGC stimulator riociguat reduces infarct size but also whether it protects against the development of post-MI heart failure.18F-FDG-positron emission tomography (PET) were performed to determine infarct size. In the riociguat-treated mice, the resulting infarct size was smaller  and LV systolic function analysed by MRI was better preserved . After 28 days, LV systolic function by echocardiography treated group was still better preserved .Mice were subjected to 30 min ischaemia via ligation of the left main coronary artery to induce MI and either placebo or riociguat (1.2 µmol/l) were given as a bolus 5 min before and 5 min after onset of reperfusion. After 24 hours, both, late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) and Taken together, mice treated acutely at the onset of reperfusion with the sGC stimulator riociguat have smaller infarct size and better long-term preservation of LV systolic function. These findings suggest that sGC stimulation during reperfusion therapy may be a powerful therapeutic treatment strategy for preventing post-MI heart failure. Chronic heart failure (CHF) is a serious consequence of myocardial infarction (MI) and is associated with high mortality and morbidity. Reducing infarct size acutely after an ischemic event is assumed to reduce the risk of detrimental post-MI remodelling S-nitrosylating protective proteins. The NO – sGC - PKG pathway is known to play an important role in the acute protection against cardiac reperfusion injury. We, and others, could show that an increase of cyclic GMP via phosphodiesterase 5 inhibition can afford powerful cardioprotection when applied at the onset of reperfusion. Recently, a new class of drugs, the so-called sGC stimulators, entered the clinical development for the treatment of pulmonary hypertension. Stimulators of sGC have a dual mode of action: they both sensitise sGC to endogenous NO by stabilizing the NO-sGC binding and also directly stimulate sGC independently of NO via a second binding site. The sGC stimulator riociguat, has recently undergone Phase III clinical trials in patients with several subforms of pulmonary arterial hypertension (PAH) and with chronic thromboembolic pulmonary hypertension (CTEPH). Exercise capacity was the primary endpoint for these studies and in all cases riociguat increased the patients' 6-minute-walking-distance. Riociguat also produced positive clinical effects in smaller proof-of-concept studies in patients with pulmonary hypertension secondary to left heart failure, interstitial lung disease and chronic obstructive pulmonary disease. In this study we tested the effects of riociguat on MI size and post-MI CHF development in a mouse model of ischaemia/reperfusion. Gadolinium-enhanced magnetic resonance imaging (MRI) as well as FDG-PET was used to determine the resulting infarct size post-MI, while echocardiogram was used to measure LV function over a 28 day recovery period.All procedures were conducted in accordance with the Animals (Scientific Procedures) Act 1986 (PPL 80/2393) and the University of Cambridge Policy on the Use of Animals in Scientific Research and approved by the Home Office (UK) Animals Scientific Procedures Department (ASPD).Infarct size following ischaemia/reperfusion an in situ open chest mouse model was measured as previously described. Blood pressure was either measured non-invasively using a tail cuff apparatus or through left ventricular catheterization via the right carotid artery using a 1.2 F pressure-catheter .Transthoracic echocardiography was performed on mice anesthetized with 2% isoflurane, using a Vevo 770 ultrasound system . Hearts were visualised in the two dimensional short-axis plane and analysis performed in M-mode in the consistent plane of the papillary muscles. Ejection fraction (EF) was calculated from end-systole and end-diastole measurements in at least three repeated cardiac cycles. Fractional shortening was calculated by the Simpson's method.2) and maintenance (1.5–2% in 1 l/min O2). A pressure sensor for respiration rate was used to monitor anaesthesia depth, rate was maintained in the range 30–45 breaths per minute. Prospective gating of the MRI sequences was achieved with ECG monitoring. Body temperature was monitored using a rectal thermometer and a flowing-water heating blanket was used to maintain animal temperature at 37°C throughout the experiment.Animals were anaesthetised with gaseous isoflurane both for induction . A birdcage coil of 12 cm was used for signal excitation and a 2 cm surface coil for signal reception with the animals positioned prone. After initial localization images, 4-chamber and 2-chamber views were acquired . Using these scans as a reference, short axis slices were arranged perpendicularly to both the long-axis views to cover the left ventricle (LV) . Full LV coverage was achieved with no slice gap with 8–10 slices.DENSE MRI in situ . Within the first 15 min after injection, IR images were acquired .After the acquisition of the standard cine protocol and DENSE, late gadolinium enhancement was performed. 18F-FDG was performed in situ, and list-mode gated PET acquired continuously for 45 min.Animals were transferred on the same bed to the Cambridge PET-MRI scanner. Delineation of the LV at each phase of the cardiac cycle excluded the papillary muscles and trabeculae throughout. The regions from each slice were combined using Simpson's rule to provide LV mass, end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) using Segment v1.9. DENSE MRI images were analysed with in-house code using Matlab: phase images were extracted and unwrapped FDG-PET Images were reconstructed using a 3D filtered backprojection algorithm in 8 cardiac phases and temporal frames of 15 min. The cardiac phase correspondent to end-diastole was selected for each subject. Images from PET and MRI were co-registered manually with a rigid transformation using SPM-Mouse bulk registration tool. et al.Infarct size was assessed in the FDG-PET images by manual delineation in the final frame. Voxels where intensity was below 50% of the maximum heart uptake were considered non-viable, following Stegger Details can be found in the online supplement.All data are presented as mean ± standard error of the mean (SEM). The infarct size is shown as percentage of area at risk. The blood pressure values are plotted as percentage of the respective baselines. Differences among groups were compared by one-way ANOVA with Turkey's post hoc test. A value of p<0.05 was considered significant.Mice treated with riociguat at the onset of reperfusion showed a marked reduction of infarct size after 30 min LCA occlusion followed by 2 h reperfusion. The protection was still present when the NOS inhibitor L-NAME was given prior to the riociguat treatment, while the PKG blocker KT5823 blocked the riociguat effect , suggestFurthermore, FDG-PET was used as an additional technique to assess functional infarct size data. As shown in 2 = 0.85, supplemental Left ventricular ejection fraction (LVEF) was assessed with cardiac MRI 24 h post-MI and with ultrasound 28 days later  were slightly less in myocardium of riociguat-treated mice compared to that in the untreated controls. This may indicate an attenuated fibrotic tissue remodelling process in the ventricle, when sGC activity is stimulated at the onset of myocardial reperfusion. Consistent with reduced expression of extracellular matrix molecules after riociguat treatment, other pro-fibrotic gene activities also tended to be expressed at a lesser extent, i.e. MCP-1 (Ccl2), tenascin C, ST2 (Il1rl1), galectin-3 or lipocalin-2 . Unfortuin vivo mouse model of MI and post-MI CHF. Riociguat not only acutely reduced infarct size and improved LV function but the effect persisted over the 28 days of the study. Infarct size was not only evaluated histologically with TTC staining, but also with novel state-of-the-art imaging techniques. LGE-MRI and FDG-PET were used 24 h after reperfusion and revealed beneficial effects of sGC stimulation on infarct size, cardiac function and morphology. The follow-up over 28 days showed a sustained preservation of mechanical function from the single riociguat treatment at reperfusion indicating that the entire benefit was derived from preventing acute loss of ventricular muscle.In this study we present clear evidence for a strong and long-lasting cardioprotective effect of riociguat, a novel sGC stimulator in an per se does not afford cardioprotection against ischaemia-reperfusion injury NO activates PKG by causing SGC to increase cGMP in the cell. Impairments of the NO-sGC-PKG pathway have been implicated in various cardiac pathologies, including ischaemia/reperfusion injury and CHF development. in vivo cardiac imaging. When we used LGE-MRI to assess infarct size after 24 h of reperfusion there was still a clear benefit in the riociguat-treated animals with smaller infarct sizes and better-preserved LV function. All the techniques used were highly congruent.In recent years, imaging techniques such as MRI and PET became available for the functional and morphological assessment of mouse hearts and allowed non-invasive follow-up studies of MI and CHF. Here we used state-of-the-art techniques to assess myocardial function and morphology with the consecutive combination of LGE-MRI and FDG-PET. While the cardiac MRI provides accurate functional data on the basis of detailed morphology, PET is a highly specific complimentary technique providing functional data on a molecular level. The combination of both techniques overcomes the clear shortcomings of each one alone and represents the current gold standard in Furthermore, DENSE MRI imaging allowed us to determine displacement maps and calculate radial and circumferential strain. These non-invasive imaging techniques allowed us to perform a follow-up of these animals and determine functional parameters after 28 days via echocardiography. Human data suggests that remodelling and CHF development is directly correlated to the extent of the infarcted area after an acute MI. Here we could show that the infarct size reduction due to early riociguat treatment was associated with improved LV function after 4 weeks, suggesting less detrimental post-MI remodelling. This is supported by our observation that many pro-fibrotic genes show a strong trend for lower expression in the treated animals' hearts.Taken together, the present results indicate that a single dose of the sGC stimulator riociguat at the end of a 30 min period of coronary arterial branch occlusion cause an immediate reduction of infarct size and preservation of cardiac function in mice. Furthermore, the beneficial effects on cardiac function and morphology can still be seen 28 days after the ischemic event, leading to a reduction of CHF. The consecutive combination of cardiac LGE-MRI and FDG-PET allowed us to accurately assess infarct size non-invasively in a myocardial infarction model that is very close to the clinical scenario. We conclude that sGC stimulation with riociguat is a promising candidate for preventing post-MI heart failure in acute coronary syndrome patients undergoing reperfusion therapy.File S1Supplemental methods and results.(DOCX)Click here for additional data file.Video S1Merged LGE-MRI/PET video 24 h after infarction of representative heart of control-treated mouse in 2-chamber view.(WMV)Click here for additional data file.Video S2Merged LGE-MRI/PET video 24 h after infarction of representative heart of riociguat-treated mouse in 2-chamber view.(WMV)Click here for additional data file.


The diagnosis of PH should be based on clinical suspicious and specific complementary tests. CMR has no acoustic window limitation, it is the gold standard for quantification of right ventricular (RV) function, it is the main test for congenital heart disease (CHD) and finally it gives more comprehensive information.To show how useful the CMR was for patients referred for heart failure (HF), regarding the identification and severity of pulmonary hypertension (PH) not previously assessed by other non-invasive techniques.We reviewed patients referred to our institution from January 2008 to March 2010 for further evaluation of HF who were firstly diagnosed of PH by CMR. The study was performed on a 1.5T Avanto scanner and included: cine images, phase-contrast sequence, time-resolved angiography for aorta and pulmonary artery, and inversion recovery sequence. The data analyzed was: ventricular volumes and functions, flows, interventricular septum (IVS) motion, and assessment of late gadolinium enhancement (LGE).20 patients were included. Eleven (55%) were female and the mean age was 47. Following the Dana Point classification 2008: 10 belonged to group 1; 4 to group 2; 1 to group 3; 1 to group 4; and 4 patients had mixed conditions. All patients presented high RV volumes . The RV ejection fraction (RVEF) was 41 ± 16 %. The RV outflow tract was enlarged (30 ± 5 mm) and pulmonary artery (PA) too . RV wall thickness was 4,2± 1,4 mm. Pulmonary peak velocity was 105,7 ± 76,8 mmHg, with moderate regurgitation. IVS motion classified as: 50% flattening, 35 % D-shaped, normal only in 1. The left ventricular (LV) overall function was related to the baseline disease. The systolic RV/LV volume ratio was 1,9 ± 0,8 and the diastolic one was 1,6 ± 0,6. LGE was present in 60%, mostly in basal RV and LV insertion points; additionally in LV inferior wall in one patient suggesting myocardial infarct, and another patient presented transmural LGE in inferior apical wall. CMR angiography was of value as it allowed orthogonal measures of PA and showed features of chronic thromboembolic disease, pulmonary vein stenosis and discovered CHD.CMR is able not only to diagnose PH but also provide its severity and etiology, offering prognosis and guiding management / follow-up within a single examination.


T1 imaging based on pixel-wise quantification of longitudinal relaxation has the potential to differentiate between normal and abnormal myocardium. The accuracy of T1 measurement has not been established nor systematically tested in the presence of health and disease.Intra-observer, inter-observer and inter-study reproducibility of T1 imaging was assessed in subjects with left ventricular hypertrophy  or dilated cardiomyopathy . Thirty-eight subjects with low-pretest likelihood of cardiomyopathy served as a control group. T1 values were acquired in a single mid-ventricular short axis slice using modified Look-Locker imaging prior and after the application of gadolinium contrast at 1.5 and 3 T. Analysis was performed with regions of interest (ROI) placed conservatively within the septum or to include the whole short axis (SAX) myocardium.Intra-observer, inter-observer and inter-study repeated measurements within the septum showed smaller mean differences and narrower 95% confidence intervals than repeated short axis ROI measurements. Native T1 values were higher in septal ROIs compared with SAX values at both field strengths . Native T1 values revealed significant mean differences between controls and patients with LVH for both septal  and SAX ROIs  with greater differences observed at 3 T versus 1.5 T field strength. Native T1 values revealed significant mean differences between controls and patients with DCM for septal ROI  at both 1.5 T and 3 T, but only for SAX ROIs at 3 T . There were no significant differences in post-contrast T1 values or partition coefficient (λ) between controls and patients.Conservative septal ROI T1 measurement is a robust technique with excellent intra-observer, inter-observer and inter-study reproducibility for native and post-contrast T1 value and partition coefficient measurements. Moreover, native septal T1 values reveal the greatest difference between normal and abnormal myocardium, which is independent of geometrical alterations of cardiac chamber and wall thickness. We propose the use of native T1 measurements using conservative septal technique as the standardized approach to distinguish health from disease assuming diffuse myocardial involvement. Quantification of longitudinal relaxation by T1 mapping provides tissue specific values in line with their composition and magnetic field strength -6. HowevIn addition to native and post-contrast myocardial T1 measurements, the calculation of hybrid measures, such as partition coefficient λ have been reported ,13. FurtConsecutive subjects referred for clinical Cardiovascular Magnetic Resonance (CMR) were invited to participate in this study. Groups of unrelated subjects were composed to examine the influence of LV chamber size and wall thickness :1. LV hypertrophy .-2, end-systolic volume index (ESV/index) > 37 ml.m-2, reduction in global systolic function (ejection fraction (EF) of < 56%), but no increase in wall thickness).2. Dilated LV cavity  > 100 ml.m3. Thirty-eight normotensive subjects with low-pretest likelihood of cardiomyopathy, normal LV volumes, mass, and global systolic function, as well as absence of myocardial Late Gadolinium Enhancement (LGE) and no regular medication served as a control group.Exclusion criteria for all subjects were the generally accepted contraindications to CMR  or history of renal disease with a current eGFR < 30 mL/min/1.73 m2. The study protocol was reviewed and approved by institutional ethics committee and written informed consent was obtained from all participants.We integrated native and post-contrast myocardial T1 mapping with MOLLI into our routine imaging protocol for the determination of the underlying etiology of cardiomyopathy as previously described . StudiesAll routine CMR analysis was performed using commercially available software . Endocardial LV borders were manually traced at end-diastole and end-systole. The papillary muscles were included as part of the LV cavity volume. LV end-diastolic (EDV) and end-systolic (ESV) volumes were determined using Simpson’s rule. Ejection fraction (EF) was computed as EDV-ESV/EDV. All volumetric indices were normalized to body surface area (BSA).For each subject T1, relaxation values were measured separately by two independent observers. Chosen regions of interest (ROIs) were automatically propagated across all eleven images in the MOLLI sequence with a prior image- co-registration step for motion-correction . Care waTwo main approaches to place myocardial ROIs within the mid-SAX slice were examined: Septal and SAX myocardial ROI Figure . An addiStatistical analysis was performed using SPSS software . Departures from normality were detected using Kolmogorov-Smirnov test. Mean differences were examined by one-way and repeated measures ANOVA with Bonferroni post-hoc tests, as appropriate. Comparisons of values between two field strengths, and post-processing approaches were performed using paired and unpaired t-tests and one-way analysis of variance, as appropriate. Agreements between two methods, different observers, and repeated measurements of a single observer were determined by linear regressions, mean differences (bias), 95% confidence interval, and relative differences  according to the methods of Bland and Altman. Values are reported as mean±SD and a p-value of less than 0.05 was considered statistically significant.Subject characteristics are presented in Table There were significant regional differences between the septal and lateral ROIs for nativeT1, but not for post-contrast values. At both 1.5 T and 3 T field strengths, native septal T1 values were higher than SAX or lateral T1 values : 1.5 T: 976 ± 37 vs. 952 ± 41 vs. 943 ± 45, p < 0.01; 3 T: 1108 ± 67 vs. 1087 ± 60 vs. 1052 ± 72, p < 0.01). The partition coefficient λ was lower at 1.5 T than 3 T and showed no regional variation at either field strength . We observed a wide variability of native blood T1 values in all sub-groups with a coefficient of variability (CoV) of 21-28%.Table Table Table Inter-study reproducibility was performed in subgroups of normal subjects (n = 12), patients with dilated cavity (n = 6) and subjects with increased LV wall thickness (n = 5) who underwent a second CMR study within up to 1-month interval with no interim change in clinical status or medication. Septal and SAX approaches showed excellent reproducibility and agreements in both field strengths whereas post-contrast T1 measurements showed high variability irrespective of sequence or field strength. Reproducibility of partition coefficient λ was inferior to that observed with native T1 measurements.Results of our study reveal that the choice of septal vs. SAX approach matters with respect to reproducibility of measurements and detection of effective difference between health and disease assuming diffuse myocardial involvement. We demonstrate that using a conservative septal approach is the more reproducible within and between observers compared with evaluation of the complete SAX slice. Our results also reveal that using septal approach is also most robust for measurements in repeated studies within the same subject. We further show that septal T1 measurements in native myocardium reveal the greatest difference between health and disease, irrespective of the field strength or geometrical changes due to cardiac pathology. Results of our study provide a proof of concept that T1 measurement derived conservatively within the septal myocardium should be adopted as the standardized approach in measurement of T1 values when assuming diffuse involvement. Using this approach, we further propose the native T1 as the best discriminatory measure between health and disease.Several studies report on excellent reproducibility of T1 measurements prior to or after administration of the contrast agent ,9,12,13.We also show that whereas post-contrast measurements are relatively observer-independent, these measurements are less reliable when cross-correlated between different studies within the same subject. These findings concord with the previous postulations indicating the relatively dynamic post-contrast evolution of T1 myocardial values and an ~150-200 ms change within the usual time-frame between 10–25 minutes when most of contrast-enhanced studies are performed . A more The ultimate goal of T1 imaging is a robust clinical application for differentiation between normal and abnormal myocardium -5,22-25.Several limitations pertain this study. The small sample size may limit the generalization of present findings as well as assessment of multifactorial influences on T1 measurements. For routine clinical application of T1 mapping, studies with larger subject samples are required to determine normal standard ranges for T1 values. Clinical outcome data must then be assembled to confirm clinical relevance of these measurements. T1 sampling in the septum of a single short axis slice is based on assumption that it is representative of a diffuse myocardial process. Future studies using whole-heart acquisitions with lower susceptibility to regional variations in T1 values are needed to determine and understand the relevant regional variation. Inferior inter-study reproducibility of the partition coefficient λ may be explained by changes in hematocrit between scans. We did not collect blood samples for determination of hematocrit from these healthy volunteers. As this study was based on sampling from clinical environment, individuals have not undergone parallel assessments on both field strengths, thus, our study lacks the comparative data between the two field strengths. Finally, T1 values obtained by our group in control and patient subgroups are relatively lower than those reported by other groups ,13, indiConservative septal ROI T1 measurement is a robust technique with excellent intra-observer, inter-observer and inter-study reproducibility for native and post-contrast T1 value and partition coefficient measurements. Moreover, native septal T1 values reveal the greatest difference between normal and abnormal myocardium, which is independent of geometrical alterations of cardiac chamber and wall thickness. We propose the use of native T1 measurements using conservative septal technique as the standardized approach to distinguish health from disease assuming diffuse myocardial involvement. The superior performance is afforded by the ability to eliminate measurement errors, sampling of voxels straddling the myocardial-blood pool interface, and reduced signal in the lateral wall.The authors declare that they have no competing interests.TR, EN, VP – study design, TR, DD, IM, VP – data acquisition, analysis, manuscript preparation. TV, TS, EN, VP – sequence validation. All authors read and approved the final draft of this manuscript.


Exposure to anthracyclines (ANT) during childhood represents a high risk for development of late cardiotoxicity. Cardiotoxicity is usually detected only when clinical symptoms or progressive cardiac dysfunction have already occurred. Early detection of cardiotoxicity may lead to better therapeutic outcome. N-terminal pro-brain natriuretic peptide (NTproBNP) has been hypothesized to reflect increased left ventricular wall stress before development of echocardiographic abnormalities. The aim of this study was to detect cardiac abnormalities using plasma NTproBNP and echocardiography in asymptomatic childhood leukemia survivors treated with or without cardiotoxic anthracycline therapy.Serum levels of NTproBNP were determined in 69 asymptomatic survivors of childhood leukemia treated with or without anthracyclines and in 44 apparently healthy controls. The survivors were divided into two treatment groups: 36 patients after chemotherapy containing anthracyclines (ANT) and 33 patients after chemotherapy without anthracyclines (nonANT). Levels of NTproBNP were measured by using the Elecsys 2010 immunoassay analyzer (Roche Diagnostics). Echocardiography using M-mode, two-dimensional and Doppler measurements were performed on the same day as blood samples were obtained for NTproBNP analysis in survivors.Serum levels of NTproBNP were significantly higher in the ANT group than in controls . Survivors exposed to ANT had significantly increased levels of NTproBNP compared with patients treated without ANT . Female exposed and unexposed survivors had significantly higher NTproBNP levels than males. Four of the 36 survivors (11%) treated with ANT and two of the 33 patients (6%) not exposed to ANT had abnormal NTproBNP levels. Although no patient had echocardiographic abnormalities, significant differences were found in values of left ventricular ejection fraction (LVEF) and deceleration time (DT) between survivors treated with or without anthracyclines.Higher levels of NTproBNP detected in childhood leukemia survivors after low anthracycline cumulative doses might reflect an initial stage of ANT cardiotoxicity before the development of echocardiographic abnormalities. Although the current studies support NTproBNP as one of the best available biochemical markers of late anthracycline cardiotoxicity, a possible strategy toward further improvement and combination with other cardiac biomarkers and novel echocardiographic methods should be explored in additional studies. Childhood cancer survivors exposed to anthracyclines are at increased risk for premature cardiac morbidity and mortality-8. For 3Diagnosis of cardiac dysfunction and heart failure after anticancer therapy is based on medical history, physical examination and is further confirmed by other tests, mainly echocardiography. Nevertheless, clinical misdiagnosis is common, particularly in early stages of heart failure. Current monitoring techniques, such as MUGA (Multi Gated Acquisition Scan) or echocardiography, have substantial limitations and detect LV dysfunction only after it had occurred. Cardiotoxicity is usually diagnosed only upon manifestation of clinical signs and symptoms or progressive cardiac dysfunction. Thus new diagnostic tests are required to confirm ventricular dysfunction induced by anticancer therapy .Novel echocardiographic techniques are promising in evaluating the presence of myocardial structural alterations and subtle myocardial dysfunction induced by anticancer therapy, yet they are not used in routine clinical practice.Although new cardiac imaging techniques, such as quantitative assessment of ventricular function through measurement of myocardial strain and strain rate can more precisely assess heart structure and function during and early after cardiotoxic therapy, it remains to be proven whether they have the ability to detect early treatment-induced cardiac injury in long-term cancer survivors several years after completion of malignancy therapy. Morevover, the definition of reference range of ventricular strain and strain rate values in normal adults and description of the variability among systems and observers are debatable,11.Early and accurate diagnosis of ventricular dysfunction in asymptomatic cardiac patients may permit a prompt onset of therapy of subclinical cardiotoxicity before the development of life-threatening complications.This study aims to detect cardiac abnormalities using plasma N-terminal pro brain natriuretic peptide (NTproBNP) and echocardiography in asymptomatic childhood leukemia survivors treated with or without cardiotoxic anthracyclines (ANT).Childhood acute leukemia survivors without any cardiac symptoms were consecutively recruited in the out-patient clinic of the National Cancer Institute, Bratislava, Slovak Republic, from January 2006 to October 2010. A total of 69 survivors of acute leukemia were involved, aged 17–31 years, whose chemotherapy completion dated back for at least 5 years. They had been treated between 1985 and 2005 in a single center – at the Children´s University Hospital, Bratislava. Survivors were divided into two treatment groups: 36 patients who had received chemotherapy containing cardiotoxic anthracyclines (ANT) and 33 patients after chemotherapy without anthracyclines (nonANT)  without any known cardiovascular risk factors and no clinical evidence of heart, lung, renal, liver or systemic disease. A blood sample was drawn and stored under the same conditions as in the patients. In this study, our normal values of NTproBNP were different for females (<105 pg/mL) and males (<75 pg/mL) (below 97.5th percentile from controls).All participants or their guardians gave their written informed consent. The study was approved by the Ethics Committee of the National Cancer Institute and the Faculty of Medicine, Comenius University in Bratislava, Slovak Republic.All patients were examined by a general cardiologist. The blood samples for immunochemical analysis were obtained at the same day as the echocardiographic measurement was performed.EDTA-anticoagulated blood (5 ml) was collected by venous puncture. Fasting was not a prerequisite before sampling. The whole blood was centrifuged for 10 minutes (3500 rpm) within 2 h after sampling. Centrifuged plasma (500 μL) was aliquoted to labeled eppendorf tubes before freezing and stored at −20°C until assayed.The cardiac biomarker NTproBNP was measured at the Clinical Biochemistry Department, National Cardiovascular Institute, Bratislava, Slovak Republic, within two months after collection. Hemolyzed samples were excluded. Venous blood samples were obtained in the morning and serum concentrations of biomarkers were measured by electrochemiluminescence immunoassay on Elecsys analyzer (Roche Diagnostics). The detection limit for the NTproBNP assay is 5 pg/mL.We compared the NTproBNP levels between the studied groups exposed and unexposed to ANT and our age- and sex-matched control group.Echocardiography using a GE VIVID 7 machine (GE Ultrasound Europe) was performed in all patients included in the study. Assessment was done by one experienced cardiologist who was unaware of the participants’ treatment status and the NTproBNP value.Standard techniques were used to obtain M-mode, two-dimensional and Doppler  echocardiograms.Left ventricular (LV) end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD) and left atrium dimension were measured using standard M-mode methods from parasternal LV long axis images. LV ejection fraction (EF) was calculated by Teichholz formula (M-mode) as well as by the Simpson method from apical view . Systolic LV dysfunction was defined as EF less than or equal to 50%.Quantification of metric and functional echocardiographic parameters was based on the recommendations of the American Society of Echocardiography´s Guidelines and Standards Committee and the Chamber Quantification Writing Group.Pulsed Doppler traces of the mitral valve inflow were used to extract the ratio of peak early to peak late flow velocities (E/A), E-wave deceleration time (DT), LV isovolumetric relaxation time (IVRT) and were assessed as standard parameters of LV diastolic function. Diastolic LV dysfunction was defined as E/A inversion and DT above 220 ms on the transmitral Doppler curve (impaired relaxation).The tissue Doppler imaging (TDI) of the mitral annulus from apical four-chamber view provided additional parameters reflecting the global systolic and diastolic function of the LV. Early diastolic velocity (Ea) of the mitral annulus was considered a good indicator of LV myocardial relaxation and diastolic function, and so was the ratio of early diastolic myocardial velocity (Em) and late diastolic myocardial velocity (Am).Peak systolic velocity at myocardial segments (Sm) was used to assess systolic function. The ratio of early diastolic LV inflow velocity (E) to Ea of the medial mitral annulus (E/Ea) was used for estimation of the LV filling pressure.Continuous variables (echocardiographic parameters) are presented as mean ± SD (standard deviation) and the cardiac biomarker NTproBNP as median and interquartile range. Comparisons between continuous or categorical variables were performed using the Student t-test, Mann–Whitney and Wilcoxon test. Correlations were evaluated with Spearman correlation coefficient. A p-value less than 0.05 was considered statistically significant.Serum levels of NTproBNP were significantly higher in survivors treated with anthracylines than in controls . Survivors exposed to ANT had significantly increased levels of NTproBNP compared with survivors treated without ANT . Levels of NTproBNP in survivors not exposed to ANT compared with controls were not significantly different   survivors in the ANT group and in 2/33 (6%) in the nonANT group.Women exposed to anthracyclines had significantly higher values of NTproBNP than exposed men: median (25th-75th percentiles): 82.6 (51.5-99.1) vs 38.1 (22.2-53.7) pg/mL; p = 0.0031.Unexposed female survivors had significantly higher values of NTproBNP than unexposed male survivors: median (25th-75th percentiles): 44.6 (21.6-83.2) vs 17.6 (12.5-24.7) pg/mL; p= 0.0039 : 28.8 (17.1-44.5) vs 17.2 (10.3-33.9) pg/mL; p = 0.12.Although no patient had echocardiographic abnormalities, significant differences were found in values of left ventricular ejection fraction (LVEF) and deceleration time (DT) between survivors exposed and not exposed to anthracyclines Table.NT proBNP values positively correlated with ANT dose  but failed to correlate with LVEF  and DT .Measurement of natriuretic peptides (NP) is routinely used in diagnosis and management of cardiac dysfunction and heart failure. NatriurNTproBNP is a promising candidate marker for the exclusion and detection of ventricular dysfunction after potentially cardiotoxic anticancer therapy,13,15-28In the present study, this finding was extended to show NTproBNP levels not only in survivors after ANT therapy but also in patients unexposed to anthracyclines. The NTproBNP values in unexposed survivors were found to be comparable to those determined in the control group. According to our information, only one other study reported recently NTproBNP levels in survivors who received ANT compared with patients not receiving these agents. These a2). So far only few studies have been published that assessed cardiotoxicity after such ANT doses[In the present study, the detection of cardiotoxicity was performed in childhood leukemia survivors after a low cumulative ANT dose  and 6% of patients previously unexposed to anthracyclines had abnormal NTproBNP levels. In the study of Mavinkurve-Groothius et al.[In the study we found that 11% survivors treated with ANT (with median cumulative dose 221 mg/ms et al., abnormas et al.. The appSimilarly as in some studies, NTproBNP levels were significantly related to cumulative ANT dose in our survivors, yet these concentrations were not correlated with LVEF and DT,26.Given the young age of our survivor population and the rarity of other diseases in young patients, the increased values of NTproBNP found in survivors may provide an useful information on late ANT subclinical cardiotoxicity.Higher levels of NTproBNP detected in childhood leukemia survivors after low anthracycline cumulative doses might reflect an initial stage of ANT cardiotoxicity before the development of echocardiographic abnormalities. Although the current studies support NTproBNP as one of the best available biochemical markers of late anthracycline cardiotoxicity, a possible strategy toward further improvement and combination with other cardiac biomarkers and novel echocardiographic methods should be explored in additional studies.A:: Peak flow velocity of late filling; Am:: Late diastolic myocardial velocity; ANT: Group: patients previously treated with anthracyclines; DT:: Deceleration time; E:: Peak flow velocity of early filling; Ea:: Early diastolic annular velocity; EF:: Ejection fraction; Em:: Early diastolic myocardial velocity; IVRT:: Left ventricular isovolumetric relaxation time; LA:: Left atrium dimension; LV:: Left ventricular; LVEDD:: Left ventricular end-diastolic diameter; LVESD:: Left ventricular end-systolic diameter; MUGA:: Multi Gated Acquisition Scan; nonANT:: Patients previously treated without anthracyclines; NTproBNP:: N-terminal pro-brain natriuretic peptide; RV:: Right ventricular dimension; Sm:: Systolic velocity at myocardial segments; TDI:: Tissue Doppler imaging.The authors indicated no potential conflicts of interest.Conception and design: BM Collection and assembly of data: DU, IS Data analysis and interpretation: ER, PS Manuscript writing: BM, DU Final approval of manuscript: All authors.


To investigate the haemodynamic effects of an alveolar recruitment manoeuvre in intubated patients with diastolic dysfunction compared with patients with normal diastolic function in a mixed ICU.2O for 30 seconds. Haemodynamic parameters of cardiac output (CO), stroke volume (SV), heart rate (HR), pulse pressure variation (PPV), and cardiac cycle efficiency (CCE) were continuously recorded during the manoeuvre using the MostCare pulse contour method.Between October 2011 and February 2012, 16 mechanically ventilated patients admitted to the ICU with normal systolic function and without inotropic support were enrolled. A transthoracic echo-cardiography was performed to assess diastolic function: E/A, isovolumic relaxation time (IVRT), deceleration time (DT), E/e' were assessed. Eight patients  were identified in diastolic dysfunction group (Group 1) and eight were included in the normal diastolic function group (Group 2). A recruitment manoeuvre was performed by applying a PEEP of 40 cmHP <0.05), SV (P <0.01), systolic pressure (P <0.04) and PPV (P < 0.04) occurred in Group 1 during the remaining part of the manoeuvre. No significant decrease in the same haemodynamic parameters were noted when only E/A was used to discriminate the diastolic dysfunction. See Table No significant haemodynamic changes happened in the first part of the recruitment t0 to t15 seconds). A significant decrease in CO (5 secondsThe recruitment manoeuvre can compromise left diastolic filling by increasing the transpulmonary pressure. In patients with diastolic dysfunction a significant decrease in SV can be observed during the recruitment manoeuvre with no compensatory mechanisms evoked determining a significant decrease in CO. The E/A ratio is not able to discriminate between the two groups, confirming the power of tissue Doppler imaging to recognize the correct diastolic pattern.


Non-tropical non-hypereosinophilic left ventricular endomyocardial fibrosis (EMF) is a rare condition, not associated with defined substrates, about which there is a paucity of data in the literature. We describe a series of EMF patients presenting to our institution over 4 years in a high-volume CMR service.Retrospective review of 4156 clinical CMR studies (May 2006 to August 2010) was undertaken to identify cases of undifferentiated restrictive cardiomyopathy, confirmed on echocardiography and not otherwise meeting current classification guidelines. CMR had been ordered to further elucidate the etiology of restrictive cardiomyopathy. Obtained metrics were compared to a cohort of age-matched controls.CMR was performed on 1.5T system, and dual-read by a cardiologist and radiologist with SCMR level 3 experience. LV volumes, EF, segmental wall thickness, and late gadolinium enhancement were quantified with MASS software. Cases consistent with endomyocardial fibrosis (EMF) were identified and compared to age-matched controls. No patients had history of hypereosinophilia and none were from endemic areas in subtropical Africa.2 vs 46 ±12 g/m2 , p=0.012), LV length was significantly shorter , and LV apical wall thickness was significantly increased . All cases of EMF demonstrated extensive, high-signal subendocardial enhancement in the left ventricle on LGE images. Apical thrombus was present in all cases, but only seen on echo in two. Two patients underwent surgery with histological confirmation of CMR findings. Figure 5 cases 0.12%) of undifferentiated restrictive cardiomyopathy with distinctive features of EMF were identified. ECG was non-diagnostic in all cases, and echocardiography thought to represent the apical form of HCM. Mean age 43 years (range 16-60), 40% female. Mean EF 50% (range 39-59%), controls 61%±2.1(p=0.020). Indexed LV mass was significantly increased (65.6 ±2.6 g/m2% of undNon-tropical EMF is distinguished by contracted left ventricular length, increased apical wall thickness, abnormally intense subendocardial fibrosis and presence of apical thrombus. The ventricular architecture and pattern of enhancement differed from the major alternative diagnoses, such as apical hypertrophic cardiomyopathy, left ventricular noncompation and infiltrative myocardial disorders. CMR adds value in the diagnosis of restrictive cardiomyopathies, over-and-above ECG and echocardiography, and can be recommended in cases where ECG and echo data are discordant.


Heart transplantation is the therapy of choice for advance heart failure. Our group developed two transplant programs at Instituto Nacional del Torax and Clinica Davila. We report our clinical experience based with generic immunosuppression with may have lower costs and may allow more patients to be transplanted.Fifty-three consecutive patients were transplanted between November 2008 and April 2013, representing 51% of all Chilean cases.Ischemic or dilated cardiomyopathy were the main indications (23(43%) each), age 48+13 years and 48(91%) were male. Transplant listing Status: IA 14(26%)(VAD or 2 inotropes), IB 14(26%)(1 inotrope) and II 25 (47%) (no inotrope). Mean waiting time 70+83 days. Twelve (24%) were transplanted during VAD support (median support: 36 days). Operative technique: orthotopic bicaval transplant with ischemia time: 175+54 min. Operative mortality: 3 (6%), all due to right ventricular failure. Re-exploration for bleeding 2 (4%), stroke 3(6%), mediastinitis 0(0%), pneumonia 4(8%), and transient dialysis 6 (11%). Mean follow-up was 21+14 months. Three-year survival was 86+6%. One patient died of Pneumocystis Jirovecii pneumonia and the other died suddenly (non-compliance). Freedom from rejection requiring specific therapy was 80+7% at 3 years of follow-up. Four hundred eighty four endomyocardial biopsies were done: 11(2.3%) had 2R rejection. All survivors are in NYHA (New York Heart Association) functional class I and all but one has normal biventricular function.Mid-term results are similar to those reported by the registry of the International Society for Heart and Lung Transplantation. Rejection rates are low in spite of generic immunosuppression.


P < 0.001, r = 0.83). In this pilot study TEE successfully answered the questions raised by the anesthesiologists. Larger cohort studies are needed to address this issue.A pilot study aimed to introduce intraoperative monitoring of liver surgery using transoesophageal echocardiography (TEE) is described. A set of TEE measurements was established as a protocol, consisting of left atrial (LA) dimension at the aortic valve plane; mitral velocity flow integral, calculation of stroke volume and cardiac output (CO); mitral annular plane systolic excursion; finally, right atrial area. A total of 165 measurements (on 21 patients) were performed, 31 occurring during hypotension. The conclusions reached were during acute blood loss LA dimension changed earlier than CVP, and, in one patient, a dynamic left ventricular (LV) obstruction was observed; in 3 patients a transient LV systolic dysfunction was documented. The comparison between 39 CO paired measurements obtained by TEE and PiCCO2 revealed a statistically significant correlation ( In major surgery haemodynamic complications are likely to occur; hence for this reason monitoring is necessary to trace physiological parameters. There are several commercially available monitoring systems, but transoesophageal echocardiography (TOE) was not as extensively studied in noncardiac  as it wa The questions faced by anaesthesiologists in noncardiac surgery are quite different from those in cardiac surgery, where valvular diseases, prosthesis placement and complications are the most relevant. Questions on LV function or acute change in volume status and hypotension are more concerning in noncardiac surgery. Good candidates for such monitoring are patients submitted to major surgery, especially those undergoing liver surgery or even transplantation –8. DurinIn our centre, the usual means for monitoring include the continuous monitoring of the central venous pressure (CVP) and, in selected cases, the continuous monitoring of cardiac output (CO) through the use of the PiCCO system. Pulmonary artery catheters, used more often in the past, are now seldom used. As resident anaesthesiologists felt an increasing need for a more accurate monitoring, a pilot study aimed to introduce intraoperative monitoring of liver surgery using TOE was performed. This study was aimed to evaluate the place of TOE for liver surgery monitoring and to compare efficiency of TOE measurements with PVC and PiCCO to diagnose hemodynamic instability causes. A set of TOE measurements was established as a protocol, after previous discussion with the anaesthesiology staff about the required information. A comparison between the information derived from the monitoring devices used was also performed.This was a 1-year prospective study, which included patients submitted to liver surgery and enrolled without previous selection, although limited to the availability of the anesthesiologists (FP and AO), intensive care specialist with expertise in the area (PM), and echocardiography equipment. This pilot study was open with the anaesthesiologists being aware of TOE information. All data was digitally recorded for later visualisation, if deemed necessary.Patients were characterized by age, gender, and body surface area. Main diagnoses  and comorbidities were also collected. The main demographic and clinical characteristics of the enrolled patients are presented in The study protocol was reviewed by the local Ethics Board, and an informed statement was obtained previous to surgery.During liver surgery, hypotension and liver manipulation (reported by the surgeons) were the most regarded situations. Hypotension was considered when mean arterial blood pressure was 60 mmHg or lower, and data was thoroughly analysed. Blood loss was considered either by the reports from the surgeons or by a decrease in haemoglobin levels of more than 2 gr/dL. Other possible aetiologies were evaluated according to the available monitoring devices.Patients were anaesthetised using a general balanced anaesthesia, having been intubated after anaesthesia induction.CVP monitoring was performed continuously using a central venous line connected to a Philips M4 monitor, where the arterial pressure and heart rate were also registered. The arterial pressure was monitored invasively using an arterial catheter inserted into a radial or femoral artery. The invasive CO, when used, was determined using a PiCCO 2 system, for which a central venous line and a femoral arterial line were inserted and then calibrated according to the manufacturer's instructions.The TOE monitoring was performed using a Siemens ACCUSON X300 and a General Electric LOGIC P6, both equipped with a multiplane transoesophageal probe.Before the study started, a consensus was established with the anaesthesiologists to determine the information needed for monitoring. The information considered necessary was previous surgery knowledge of the heart anatomy and function; CO; left ventricular (LV) performance; data on volume status; right heart chamber evaluation. Special concern was addressed to the TOE parameters; they needed to be easily obtained, not time consuming, in order to permit quick therapeutic decisions. It was also established that intragastric views should not be used so as to avoid interference with the surgical field. The choice of invasive monitoring was carried out by the anaesthesiologist's judgement and independent of study purposes.After anaesthesia induction, a transoesophageal probe was inserted and the first images obtained. A global examination was first performed and global and segmental wall motion abnormalities were evaluated, as well as valvular regurgitations. The following sets of measurements were chosen in order to obtain the information previously required by the anaesthesiologists. The CO was obtained through the mitral velocity time integral (VTI), measured as follows. First the left ventricular influx by evaluation of the mitral E/A ratio in the 4-chamber view was analysed. Secondly, left ventricular CO was assessed by measuring the mitral VTI, calculating the stroke volume index (SVI) and multiplying it by heart rate . Necessa2. LA and RA dimensions were considered the TOE surrogates for volume status and preload determination and regarded as changes from the previous measurements.An LV systolic dysfunction was considered whenever MAPSE was <15 mm, and CO <2,4 L/mr) and P value, which were considered significant if <0.05. The statistical program used was an SPSS for Windows, version 18.0 . Comparisons were made between data from TOE and usual monitored parameters. The parameters compared were CO analysis by PiCCO and TOE whenever available and preload assessment comparing CVP with LA and RA measurements, as well as its changes during acute phenomena.All variables are presented as mean and standard deviations. To compare continuous variables, parametric and nonparametric statistical tests were used, calculating the correlation index  were due to hemorrhage, 9 (5 patients) without obvious cause, and 6 (4 patients) due to liver manipulation.n = 29), TOE modifications preceded CVP changes by 10 to 15 minutes. In  In the haemorrhage evaluation the LA and RA dimensions decreased in all patients, as well as CVP, but it occurred simultaneously in only two occasions. In the remaining measurements , a hypotensive episode was documented without blood loss. Within this group, in two cases a typical change in volume status was detected by TOE, but not by CVP; in one case, a decreased volume status was identified by both methods; in two cases there was no change observed by the two methods; in three episodes (3 patients) a systolic dysfunction was detected by TOE (decrease in CO and MAPSE) in patients with previous normal LV contractility. This LV dysfunction was transient and, due to global LV hypokinesia, the recovery was observed within a few minutes. No apparent cause for this phenomenon was detected.Only one patient presented an LV dysfunction, detected previous to surgery, suffering from ischemic heart disease. During surgery, hypotension was detected during a massive blood loss, and LV dysfunction exacerbated, along with exacerbated wall motion abnormalities. Vasopressor and inotropic support was started, some recovery of LV contractility was observed but the patient remained hypotensive. This patient died in the early postoperative period in the Intensive Care Unit.P = 0.001). However no relevant information could be obtained from this parameter during surgery, even during hypotension/blood losses.Overall, TOE-derived CO varied more markedly than PiCCO2-derived; the mitral E/A wave form changed during anaesthesia induction and remained less than one during most part of the surgery. The first obtained mean values for this parameter were 0.99 ± 0.47 and for the remaining 0.83 ± 0.36 (P = 0.001), but not between CVP and LA dimension (P = 0.07).By linear regression analysis, considering CVP as a dependent variable and LA dimension and RA area as independent variables, a significant association was found between CVP and RA area . Interestingly, the same changes were observed during liver manipulation, which results in decreased preload due to vascular compression. This information is important and allows the anaesthesiologist to anticipate adequate therapeutic actions. To our knowledge, this finding has not yet been described in the literature. However, RA area was the parameter with a statistically significant association with CVP, not the LA dimension.The present study evaluated preload not preload dependency, using comparative data from static parameters. Among the possible parameters, left ventricular end diastolic area (LVEDA) could not be considered as transgastric views were not obtained . DynamicP < 0.001), with r value of 0.83. Although the methods are different the importance of this parameter is its changes during acute events, and in this regard both methods were reliable, although TOE-derived CO presented greater variability than PiCCO-derived CO.CO has gained particular attention as a way of accessing the global circulatory status, but how accurately this variable measures the adequacy of circulatory flow is yet to be established. Perhaps the usefulness of CO consists in detecting changes in this variable during surgery, especially during episodes of instability. Considering this as the main use of CO monitoring, the changes are more important than its absolute value. Using TEE, CO was monitored through the mitral pulsed-Doppler influx, an occasionally used method , 15. In Left ventricular function was monitored through mitral valve annular plane systolic excursion, a method widely used and tested , 17. TheOther possibilities of TOE were not observed in this study, for example, the detection of right heart overload and alterations in cardiac chambers, mainly due to gas embolism or thrombus formation. In a larger cohort study they could possibly be observed.In this pilot study the preload determination was considered rather than preload dependency. The invasive counterpart for preload dependency estimation can be the systolic volume variation, and several TOE parameters can be used to evaluate, such as the analysis of superior vena cava, an easy procedure to carry out during TOE examination. This need was not particularly expressed by anaesthesiologists, more focused on acute and life-threatening phenomena and LV function. But in future protocols this item can be used. Some other measurements could be considered but, as we limited the information to a non-time-consuming acquisition in order to describe an easy-to-use tool during anaesthesia, most information was limited. More complex data can be obtained through this technique which, yet due to time constraints typical of an operating theatre, went beyond the scope of this study.In the future it is also necessary to enrol patients who present atrial fibrillation, in order to fully understand the limitations of TOE monitoring.Another question regards TOE possibilities. Right heart dysfunction and/or overload could not be detected in the patients studied, but it can be an advantage in the use of TOE. Other conditions resulting from the cardiac imaging  can also present an advantage, not observed in the studied patients.The use of a TOE monitoring was possible during liver surgery, in order to assess volume status, LV function, and CO. In five patients monitored with the PiCCO system, a statistically significant correlation between CO obtained by mitral valve VTI was obtained. TOE was also useful during episodes of hypotension, detecting changes in volume status earlier than invasive tools.TOE is a possible and valuable tool in monitoring liver surgery, and its use by anaesthesiologists should be encouraged. More data is needed to establish its role in other noncardiac surgery monitoring.


Previously a myocardial tissue classification algorithm has been developed to locate and quantify infarct in a given myocardial region-of-interest specified on late gadolinium enhancement (LGE) MR images . To compThe proposed deformable contour algorithm addresses these challenges by minimizing an energy function that: 1) incorporates intensity overlap into the deformable model by applying Bhattacharyya coefficient ; 2) elimThe average perpendicular distance between manually drawn and automatically detected contours was 1.03 ±0.4 mm and 0.92±0.32 mm for endocardial and epicardial contours, respectively. The average Dice coefficient was 0.95±0.02 for endocardium and 0.97±0.01 for epicardium and 0.85±0.05 for the myocardium. Representative results in Figure Our method provides a high degree of automation and accuracy. The results for the proposed automated segmentation technique indicate that it will streamline accurate quantification of myocardial infarct on LGE MR infarct images in clinical practice.MaRS Innovation 2011 Medical Sciences Competitive Proof of Principle (MSCPoP) for Medical Devices and Ontario Research Fund, (Imaging for Cardiovascular Therapeutics)


We assessed the value of speckle tracking imaging performed early after a first ST-segment elevation myocardial infarction (STEMI) in order to predict infarct size and functional recovery at 3-month follow-up.44 patients with STEMI who underwent revascularization within 12 h of symptom onset were prospectively enrolled. Echocardiography was performed 3.9±1.2 days after myocardial reperfusion, assessing circumferential (CGS), radial (RGS), and longitudinal global (GLS) strains. Late gadolinium-enhanced cardiac magnetic imaging (CMR), for assessing cardiac function, infarct size, and microvascular obstruction (MVO), was conducted 5.6±2.5 days and 99.4±4.6 days after myocardial reperfusion.GLS was evaluable in 97% of the patients, while CGS and RGS could be assessed in 85%. Infarct size significantly correlated with GLS , RGS , CGS , ejection fraction , wall motion score index (WMSI) , and left atrial volume . Baseline ejection fraction and GLS were independent predictors of 3-month infarct size. MVO mass significantly correlated with GLS , WMSI , and ejection fraction . In multivariate analysis, GLS was the only independent predictor of MVO mass (p = 0.015). Longitudinal strain >−6.0% within the infarcted area exhibited 96% specificity and 61% sensitivity for predicting the persistence of akinesia (≥3 segments) at 3-month follow-up.Speckle-tracking strain imaging performed early after a STEMI is easy-to-use as a marker for persistent akinetic territories at 3 months. In addition, GLS correlated significantly with MVO and final infarct size, both parameters being relevant post-MI prognostic factors, usually obtained via CMR. Echocardiography is a useful tool for risk stratification and prognosis assessment following acute myocardial infarction (AMI). Several echocardiographic parameters, such as left ventricular (LV) volume, ejection fraction (EF), wall motion score index (WMSI), presence of mitral regurgitation, and left atrial volume, have been shown to provide prognostic information CMR is currently considered to be the most reliable method for determining microvascular obstruction (MVO) in the first days after reperfusion In the present study, we sought to prospectively assess the value of speckle tracking imaging performed within the first days after successful reperfusion in ST-segment elevation myocardial infarction (STEMI) patients in order to predict initial microvascular obstruction (MVO) and infarct size at a later time point.i.e., proximal or mid-left anterior descending coronary artery, proximal dominant circumflex coronary artery, or proximal right coronary artery; thrombosis in myocardial infarction (TIMI)-flow Grade 0 or 1 prior to PCI, and successful revascularisation with TIMI-flow Grade 2 or 3 after stenting. Diagnosis of STEMI was defined by chest pain for at least 30 minutes, ST-segment elevation ≥0.1 mV in at least two or more limb leads, or ST-segment elevation ≥0.2 mV in two or more contiguous precordial leads. Exclusion criteria were cardiogenic shock, history of myocardial infarction or aorto-coronary bypass surgery, contraindication to CMR and cardiac arrest before PCI.Patients with STEMI admitted to the Angers university hospital were prospectively enrolled. Inclusion criteria were as follows: primary or rescue percutaneous coronary intervention (PCI) for first STEMI within 12 hours of symptom onset; age above 18 years; culprit coronary artery with proximal occlusion, Baseline echocardiography was performed within 5 days after myocardial reperfusion. CMR was performed at baseline, within 10 days after myocardial reperfusion in order to assess MVO, with the examination repeated at 3-month follow-up in order to quantify infarct size and infarct transmurality.The protocol was approved by the Institutional ethics committee at the University Hospital of Angers (France), and the study was conducted in accordance with the Declaration of Helsinki and French regulatory requirements. Prior to being included into the study, the patients gave their written informed consent.Images were obtained in the left lateral decubitus position with a commercially available VIVID 7 system  using a 2.5 MHz transducer at a depth of 14 to 16 cm. Standard data on bi-dimensional echocardiography was collected according to American Society of Echocardiography (ASE) guidelines For 2D-strain analysis, apical four-, three-, and two-chamber views, and parasternal short axis view at papillary muscle level were stored in cine-loop format, triggered to the QRS complex during one heart cycle with frame rates between 55 and 70 frames/sec. These cine loops were then analyzed off-line on the EchoPAC  system, based on frame-by-frame tracking of natural acoustic markers For 2D-strain analysis, inter-observer and intra-observer agreements were determined based on recordings obtained from twenty random patients.CMR scans were performed with 1.5-T imager  using an 8-element phased-array cardiac receiver coil. Localization was carried out using breath-hold real-time and steady-state free precession images of true anatomical axes of the heart.LV function was assessed by means of cine imaging using a segmented steady-state free precession pulse sequence in multiple short-axis, long-axis, and four-chamber views covering the entire LV. Typical in-plane resolution was 1.6×1.9 mm, with a 7.0 mm section thickness and the following parameters: repetition time (TR)/echo time (TE): 2.6 ms/1.3 ms; flip angle: 80°; matrix: 256×208; temporal resolution: 35–50 ms. Receiver bandwidth was set to 930 Hz/px and adapted to the shorter echo spacing (3.1 ms).Late gadolinium enhancement (LGE) was performed 10–12 minutes following initiation of gadoterate meglumine , administered in cumulative dose calculated at 0.2 mmol/kg of body weight, along with a two-dimensional segmented inversion-recovery gradient-echo pulse sequence. Typical in-plane resolution was 1.68×1.68 mm, with a 7.0 mm section thickness and the following parameters: TE: 4.66 ms; flip angle: 30°; image acquisition triggered at every other heartbeat; matrix: 256×208. Inversion time was set to null the normal viable myocardium signal and typically ranged from 240 ms to 300 ms.All deidentified images were analyzed at the central core laboratory by two experienced observers who were blinded to the patient data. Commercially available software  was used for the analysis. Endocardial and epicardial borders were outlined manually on all end-diastolic and end-systolic short-axis cine slices. LV end-systolic and end-diastolic volumes, EF, and LV myocardial mass were then calculated in a standard manner.The recommended 17-segment system was employed LV segmental motion was assessed visually using a three-grade scale: 0 = normal; 1 = hypokinesia; 2 = akinesia, dyskinesia, or systolic expansion.Transmural myocardial LGE extension was assessed visually. The segmental extent of LGE was assessed as follows: 0 = 0%; 1 = 1%–25%; 2 = 26%–50%; 3 = 51%–75%; 4 = 76%–100% hyperenhancement. We considered myocardium non viable if LGE exceeded 75% of mural extent. LGE area was manually defined on all segments, and infarct size was defined as the total LGE mass. Microvascular obstruction (MVO) was identified by the presence of a central hypoenhancement within the bright signal A segment was considered as part of the infarcted area if LGE was present in more than 50% of the circumferential extent for that segment The mean value of longitudinal strain was calculated within the infarcted area (infarct LS) so as in the remote myocardium area.th;75th percentiles) in cases of non-normal distribution, with categorical data expressed as frequencies and percentages. We compared baseline with 3-month CMR data using McNemar test or a Chi-squared test, as appropriate. Baseline echocardiographic and CMR data obtained at 3-month follow-up was compared using Pearson’s correlation test. P-values <0.05 were considered statistically significant.Data was presented as mean±standard deviation or median .We calculated the specificity, sensitivity, as well as positive and negative values of different parameters for predicting myocardial contractility recovery at 3-months (absence of recovery was defined by ≥3 akinetic segments at 3 month). ROC curves were generated.Inter-observer agreement was studied in a blinded fashion using echocardiographic and CMR scans randomly selected from 20 patients, which were analyzed on EchoPac and QmassMR software by two different observers. Intra-observer agreement was also tested in a blinded fashion using 20 speckle tracking examinations, which were analyzed at two different times on EchoPac. Inter-and intra-observer agreements were assessed using the Bland and Altman method In total, 44 patients were included in the study between February 2009 and March 2010. Of these, three were excluded from analysis, one because of surgically treated significant ischemic mitral regurgitation at 1-month follow-up, another because of significant aortic stenosis, and the remaining patient because of pace-maker implantation prior to the second CMR. Characteristics of the remaining 41 patients are summarized in No patient was excluded from analysis due to insufficient apical acoustic windows. Longitudinal global strain data was assessed in 40 (97%) patients, and radial and circumferencial strain data in 35 (85%).Bland and Altman tests for longitudinal, radial, and circumferential global strains and LVEF are illustrated in LGE mass evaluated at 3 months significantly correlated with the following echocardiographic data: longitudinal global strain (GLS) , radial global strain (RGS) , circumferential global strain (CGS) , LV EF , WMSI , and left atrial volume .In multivariate analyses, as illustrated in When studying transmural extension of LGE at 3 months, LVEF and CGS were related to LGE above 75% of transmural extension .MVO was reported in 24 patients (58.5%), and MVO mass significantly correlated with the following echocardiographic data: GLS , WMSI , and EF .In multivariate analyses, GLS was the only independent predictor of MVO mass .Mean GLS was −13.9±3.4%. Mean LS in the remote and infarcted segments was −15.7±3.7% and −10.5±4.6%, respectively. Concerning the infarcted myocardium, mean LS of viable and non viable segments was −14.8±4.6% and −9.1±4.7%, respectively.Overall, 23 patients presented an akinesia affecting at least three segments at baseline, 10 having recovered at 3-month follow-up.ROC curves for predicting akinesia ≥3 segments at follow-up are displayed in In the present study, 2D-strain echocardiography conducted within the first days after successful reperfusion in STEMI patients was feasible and provided relevant prognostic information. GLS was a marker of 1) MVO mass assessed a few days after reperfusion and 2) infarct size at 3-month follow-up, while 3) infarct LS >−6.0% measured at the acute phase showed good specificity for diagnosis of a persistent akinesia (≥3 segments) at 3-month follow-up but a poor sensitivity (61%).i.e., a few days after reperfusion, the examination is instrumental in detecting and quantifying MVO Cardiac imaging techniques at the acute myocardial infarction phase mainly aim to provide prognostic factors. Infarct size is well-recognised as a strong outcome predictor following myocardial infarction New echocardiographic modalities, such as strain imaging, provide new insights into cardiac mechanics, with 2D-strain echocardiography being a highly promising tool GLS has recently been studied in AMI, being shown to exhibit a predictive value for infarct size and LVEF recovery Our CMR study provided additive information on MVO, another post-MI prognostic factor, as GLS was shown to significantly correlate with MVO mass. To the best of our knowledge, MVO’s influence on myocardial strain is still unclear, although MVO was shown to exhibit a significantly negative impact on regional function at the segmental level This was a prospective, monocentric study, with echocardiography and CMR required to be performed within the first days after reperfusion. Therefore, including a large patient number proved difficult, and the main limitation of our study is its small sample size, essentially due to limited CMR accessibility. As a consequence, we were not able to assess initial strain imaging values so as to predict later LV remodeling, although encouraging results were obtained with surrogate markers, notably myocardial infarct size and MVO.Our study was exclusively based on 2D strain analysis, itself limited to the quality of view acquisition and to its 2D nature. In-plane and out-of-plane motion may, in fact, pose a problem for strain analysis, which not encountered when using the 3D or MR-tagging approach It is worth mentioning that although the cut-offs and corresponding sensitivity, specificity, and predictive negative and positive values were specific to our dataset, they were nevertheless of particular interest in terms of defining how GLS relates to akinetic territory. However, when computing the limits of agreements for GLS see  and the 2D-strain echocardiography carried out as a bedside test within a few days after reperfusion in STEMI patients provides indices similar to those obtained using CMR. Further studies involving larger patient series and registries are needed to confirm the parameters’ prognostic value in terms of LV remodeling and clinical patient outcome.