Purpose. Previous studies have underlined the effects of the energy drinks containing caffeine end taurine on the cardiovascular system. The aim of this study was to determine acute changes on echocardiographic parameters assessed by conventional echo-Doppler analysis and by speckle tracking echocardiography after the consumption of an energy drink in a young healthy population. Methods. measurement of blood pressure, electrocardiographic, and echocardiographic examination were performed on 35 healthy subjects , at baseline and one hour after the consumption of a body surface area indexed amount of an energy drink (168 mL/m2) containing caffeine (0.03%) and taurine (0.4%). Results. The analysis of left ventricular function showed a significant increase of mean relative values of MAPSE , global longitudinal strain , and left ventricular twisting  in respect to baseline. Also, right ventricular function parameters appeared significantly increased after energy drink consumption, as TAPSE , global, and free wall right ventricular longitudinal strain . Conclusion. In conclusion, the consumption of the ED in our population showed a significant increase of right and left ventricular myocardial function, suggesting a possible positive inotropic effect related to the substances contained therein. Energy drinks (ED) have increased in popularity among adolescents and young adults, because of the possible ergogenic effects –4 and thTaurine (aminoethane sulfonic acid) is a ubiquitous compound found in very high concentrations in heart and muscle. It has been demonstrated that it has a role in the control mechanism of myocardial contractility and studies in animal models have shown that the lack of taurine induces the onset of dilated cardiomyopathy; the beneficial effect of taurine on heart failure was also reported . MoreoveThe aim of this study was to investigate whether taking a taurine and caffeine containing energy drink determines acute changes in myocardial function assessed by conventional echo-Doppler analysis and by speckle tracking echocardiography (STE), a new technique for assessing myocardial function . The study group included 35 healthy young volunteers . All subjects had unremarkable history and normal findings at physical examination, electrocardiogram, and echocardiography. None of them was taking any drugs. Ten of them were smokers. Eight subjects were usual consumers of energy drinks (no more than a can a week). Only 7 of them practiced sports. Characteristics of the study population are reported in 2  of an energy drink containing caffeine (0.03%), taurine (0.4%), glucuronolactone (0.24%), glucose, and other ingredients, in maximum 5 minutes, and they underwent again echocardiography, electrocardiography, and blood pressure measurements 1 hour after drinking. Each participant was also studied in a control experiment by an equal volume of fruit juice one day after energy drink consumption. All participants were asked to abstain from smoking, coffee, and other food or beverages containing caffeine for at least 12 hours before the examinations. All the examinations were carried out in the afternoon between meals. Baseline clinical, blood pressure, ECG, and echocardiographic measurements were made after 5 minutes of supine rest in a quiet and comfortable environment. After baseline examination, all subjects drank 168 mL/mThe analysis of files recorded was performed offline by a single, experienced, and independent echocardiographer, who did not know if the images refer to those obtained at baseline, after energy drink, or fruit juice consumption, using a commercially available, semiautomated, 2-dimensional strain software . The study protocol was in accordance with the Helsinki Declaration and the ethical standards of our institution, and all participants gave informed consent for participation in the study. Echocardiographic studies were performed using a high-quality ultrasound machine  with the subjects in the left lateral recumbent position. All measurements were made in accordance with current recommendations of American Society of Echocardiography (ASE) . S′) by averaging values measured at septal and lateral mitral annulus [E) and late diastolic (A′) LV filling velocities with trans-mitral pulsed Doppler and by mean E′ and A′ mitral velocity with pulsed tissue Doppler [E/E′ ratio was also calculated [Left ventricle (LV) systolic function was analyzed by calculating left ventricle ejection fraction (LVEF), measured using Simpson's method, and by obtaining left ventricle longitudinal function parameters, as mitral annular systolic plane systolic excursion (MAPSE) with M-mode and mean peak systolic annular velocity with pulsed tissue-Doppler . Right ventricle (RV) systolic function was assessed by calculating tricuspid annular plane systolic excursion (TAPSE) and mean peak systolic annular velocity by pulsed tissue Doppler on tricuspid annulus  software release 11.5. Data are reported as mean ± SD. Changes in the variables observed after ED and fruit juice consumption were compared using the Student's P value of <0.001, 0.004, and <0.0001, respectively  from baseline. The parameters of RV deformation underwent significant changes: TAPSE, global RVLS, and free wall RVLS had a mean relative increase of 15% (P < 0.0001), 8% (P = 0.001), and 5% (P = 0.01), respectively  did not undergo significant variations in respect to baseline. There were no significant changes in either Doppler parameters. Blood pressure and electrocardiographic parameters were showen to be roughly the same between groups, and a mild increase of 6% in diastolic blood pressure after ED consumption was not significant (P = 0.07). There were no significant changes in the parameters measured at baseline and after taking the juice, as shown in All the variables at baseline and after taking ED are shown in ectively . Mitral ectively . TricuspIn addition to standard echo-Doppler analysis, speckle tracking echocardiography (STE) was used in our study to assess cardiac deformation in three spatial directions: longitudinal, radial, and circumferential. STE is a new technique for assessing myocardial function in physiological and pathological settings, and its feasibility and accuracy were tested in comparison with tagged magnetic resonance imaging, the gold standard to study myocardial deformation. It has been proved that STE is able to detect initial ventricular dysfunction in hypertension, diabetes, valvular heart disease, and heart failure, with high sensitivity in analyzing minimal change in myocardial deformation , 16. In our study population of 35 young healthy subjects, taking an ED containing sugar, caffeine (0.03%), and taurine (0.4%) showed a significant change of myocardial function of both LV and RV one hour after drinking it, suggesting a possible positive effect on cardiac inotropism. In fact, the study of LV performance showed an increase of longitudinal function, with an increase of MAPSE and GLS, and a remarkable enhancement of LV Twisting . These mLikewise, the study of RV performance showed an improvement of longitudinal function with a significant increase of TAPSE, and global and free RVLS in respect to baseline . ConversSuch modifications on cardiac mechanics are probably due to the inotropic effect of some substances contained in the ED. In particular, taurine seems to have a similar digital effect by means of the control of myocardial contractility, modulating sarcoplasmic reticular Ca2+ release, and stimulating the pumping rate of Ca2+ activate ATPase pumps , preventIn fact, it has been reported that taurine may reduce left ventricular end-diastolic pressure in patients with heart failure . FurtherIn normal subjects, LV twist represents a mechanism for generating stored energy during systole, which is released during early diastole to produce ventricular recoil, upward annular motion, and suction, confirming the close relation of systolic function to early diastole . In normThe LV twisting motion is a consequence of myocardial fiber orientation, which changes from an approximately longitudinal but slightly oblique orientation in the subendocardium to a circumferential orientation in the mid-wall and to an oblique orientation in the subepicardium , 33. ThuPrevious studies have found that in the setting of LV diastolic dysfunction, torsion is increased in patients with mild diastolic dysfunction but reduced in those with more severe degrees of diastolic dysfunction ; these cMoreover, Tan et al.  showed tSince this study was performed on young healthy individuals at rest, future studies need to focus on whether such benefits persist after long term consumption of energy drinks and what the effects are of consuming these drinks during physical activity; it will also be important to determine which of the effects are induced in patients with cardiac disease to further our understanding of the potential benefits or risks of energy drink consumption. Some limitations should be considered in this study. We evaluated young healthy subjects, so these results cannot be generalized for other populations. The number of subjects of our sample was limited, although it has allowed us to reach interesting conclusions. Moreover, we have investigated the acute changes on myocardial performance only one hour after energy drink consumption. Based on the pharmacokinetics of certain substances of this drink (such as caffeine and taurine), it should be interesting to evaluate the cardiovascular effect at different times from the consumption of these beverages. Lastly, we have used a pear juice as a control, but the same volume of this beverage does not correspond to the same amount of sugar dissolved in the energy drink.


Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.Duchenne muscular dystrophy (DMD) is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV) compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α Duchenne muscular dystrophy (DMD) is an inherited disease of progressive muscle wasting and is the most common form of muscular dystrophy, affecting 1 in 3500 males Clinically, DMD is characterized by skeletal muscle weakness and wasting. DMD presents early in life and is rapidly progressive, resulting in loss of ambulation at approximately 10 years of age and premature death in the early twenties There are significant gaps in knowledge regarding the progression of cardiac involvement in DMD. Increased myocyte passive stiffness secondary to membrane damage in dystrophic myocytes may cause remodeling of LV dimensions early in DMD ex vivo isolated heart preparation, results show, unexpectedly, that isolated mdx hearts have increased whole-organ compliance compared to normal hearts and tolerate considerable LV chamber distension without showing evidence of myocyte damage. To provide further mechanistic insight, we tested other genetic models of dystrophy in which either the DGC or native membrane repair apparatus were disrupted. We found that defective organ level compliance was evident only when the DGC or its extracellular binding partner laminin were disrupted but not in hearts lacking the membrane repair protein dysferlin.In order to build on previous findings in single cardiac myocytes and to gain new mechanistic understanding of the effects of mechanical stress on the dystrophic heart, we tested the hypothesis that isolated dystrophin-deficient hearts have reduced organ level compliance and increased susceptibility to mechanical damage. Using a modified Collectively, these results provide evidence that disruption of the DGC predisposes the LV to dilation via apparent myocyte slippage, a novel and cell death-independent mechanism for the progressive LV dilation observed in DMD.Previously, we have shown that the sarcolemma of single, membrane intact, mdx cardiac myocytes is highly susceptible to passive stretch-induced injury leading to increased stiffness, membrane permeability, aberrant extracellular calcium influx, and myocyte death init, init mdx hearts showed a blunted increase in LVEDP, indicating an increase in whole-organ compliance compared to WT hearts  and mdx hearts were isolated, perfused, and subjected to mechanical stretch using a water filled plastic balloon placed within the LV chamber. WT and mdx mice used in this study were of similar age , had similar body weights  and heart weights . Miniature plastic balloons were first inflated and set at standard physiological LV end diastolic pressure (LVEDP) of 6–8 mmHg x hearts . To visuin vivoinit in isolated mdx hearts, suggesting that the alteration in mechanical compliance we observe are not related to mechanical instability of the sarcolemma  calcium or low (1.75 mM) calcium . Similar to our findings under standard conditions  isolated mdx hearts perfused with high and low calcium showed a similar blunted increase in LVEDP as volume was increased above Vcontrols . To furtcontrols . This iscontrols . The conThe use of non-contracting hearts also allowed for quantitative assessment of end diastolic sarcomere lengths at a set LVEDP. This analysis is confounded in contracting hearts due to obligatory contraction-induced changes in sarcomere length. Accordingly, we measured sarcomere length at a range of set LV pressures to determine the single-cell manifestations of whole-organ stretch in non-contracting WT and mdx hearts. Non-contracting hearts were perfusion-fixed at LVEDP pressures of 8, 80, or 160 mmHg. Immunofluorescent staining for desmin was then used to visualize and measure average sarcomere lengths of the mid-LV free wall . At each2j mice. β-sarcoglycan is a DGC protein normally expressed in the heart, the lack of which causes Limb-Girdle Muscular Dystrophy Type 2E 2j mice carry a mutation in the LAMA2 gene which causes abnormal splicing of the laminin-α2 transcript and expression of a truncated protein 2 heavy chain subunit of the extracellular matrix protein laminin is bound by α-dystroglycan, facilitating the interaction of the DGC with the extracellular matrix. 2j hearts showed reduced LV volumes at normal LVEDP and increased whole-organ compliance compared to WT (C57BL/6) hearts  hearts . Here, sj hearts . To dete2J and β-sarcoglycan-null hearts.The main new finding of this study is that whole-organ compliance is increased in mdx mice and in other genetic models of muscular dystrophy involving DGC disruption, but not in a model of dystrophy caused by defective membrane repair. These results are evidence that the DGC is an important determinant of organ-level mechanical compliance in the heart. This, in conjunction with our findings of similar changes in sarcomere length despite significantly greater excursions in LV volume lead us to speculate that side-to-side translation of myocytes past each other (myocyte slippage) accounts for the increased compliance observed in mdx, dyex vivo stretch and showed no difference between isolated mdx and WT hearts in LV volumes as LVEDP was increased up to 30 mmHg Numerous studies have shown that loss of dystrophin alters the response of striated muscle to mechanical stress. In skeletal muscle, loss of dystrophin alters passive mechanical properties and increases susceptibility to mechanical injury To determine possible mechanisms for the observed changes in the mechanical properties of isolated hearts, perfusate calcium concentrations were altered. Increasing, decreasing, or removing calcium altogether did not alter the enhanced compliance mdx hearts. This is evidence that neither trans-sarcolemmal calcium entry through membrane “micro-tears” nor sarcomeric contraction contributes to the increased compliance of mdx hearts. However, we cannot exclude that alterations in expression or activity of other proteins contributes to the increased compliance observed in dystrophic hearts. For instance, caveolin-3 is upregulated in mdx mice 2J hearts, but not in dysferlin-null hearts, consistent with our hypothesis that disruption of the DGC-mediated linkage of cells with the extracellular matrix promotes enhanced whole-organ cardiac compliance. Collectively, these findings support a mechanism for the increased whole-organ compliance of mdx isolated hearts which is independent of sarcolemma instability and single myocyte compliance. In the broader context of pathophysiological processes associated in DMD cardiomyopathy, the findings presented here suggest a novel mechanism for the pathological ventricular dilation that occurs in DMD and highlight the complex physiological interactions that should be considered when studying diseases at the whole-organ level.To determine the effects of whole-organ stretch on individual myocytes in WT and mdx hearts, we determined sarcomere length at a given LV pressure in non-contracting hearts. Sarcomere lengths were similar at all LV pressures tested despite the considerably larger volumes required to alter LV volume in mdx hearts, suggesting that enhanced stretch of the myocytes does not account for increased compliance in isolated mdx hearts. Since alterations in LV volume expansion are not strictly tracked by proportional changes in sarcomere length, this indicates the mechanical properties of the dystrophic myocardium are not a simple extrapolation of findings from isolated cells. To explain these findings, we propose a model for the accelerated pathological dilation of the ventricle in DMD where disruption of the DGC promotes side-to-side myocyte slippage during whole-organ stretch. A simplified model for this mechanism is shown in When formulating the working model for the increase compliance of dystrophic hearts observed here, we have also considered other possible explanations for our findings. Specifically, previous reports have shown that chronic ventricular dilation is associated with alterations in the collagen I/collagen III content, promoting a more compliant ventricular wall Although LV dilation is associated with numerous disease states of the heart, the basis for this pathological change in organ structure is not well understood. Previous studies suggest that myocyte slippage contributes to LV dilation in numerous disease states including aortic stenosis, acute and chronic myocardial infarction, and end-stage dilated cardiomyopathy ex vivo stretch protocol we observed differences in whole-organ compliance between WT and mdx hearts at LVEDP well above the normal physiological range. We speculate that the processes resulting in increased compliance in isolated hearts at high LVEDP may also occur under normal conditions in vivo, but at a much slower rate. This is in line with the slowly progressive dilation that occurs over the course of years in DMD With regard to the relevance of the findings presented here to the pathogenesis of heart disease in DMD, there are limitations of this study that need to be considered. The retrograde perfused isolated heart preparation used in this study is a well-established and widely used technique for assessing whole-organ cardiac function as measured during isovolumic contraction and relaxation 2J hearts. Mutations in β-sarcoglycan and laminin-α2 cause muscular dystrophy and, importantly, dilated cardiomyopathy 2J mice show muscle wasting, but no evidence of membrane permeability or susceptibility to contraction-induced injury 2J, and β-sarcoglycan-null mice, each of these models shows enhanced whole-heart compliance. We speculate that these mouse models share the phenotype of increased whole-heart compliance due to disruptions of cell-extracellular matrix interactions. Genetic ablation of β-sarcoglycan weakens the interaction of α-dystroglycan with the DGC 2 heavy chain expressed by dy2J mice is defective in its ability to form stable polymers 2J mice are evidence that altering cell-extracellular matrix contacts is a common mechanism for pathological dilation of the heart in diseases which alter cell-extracellular matrix interactions by a variety of different mechanisms. The lack of mechanical defects in the hearts of dysferlin-null mice further supports this hypothesis. Mutations in dysferlin cause muscular dystrophy, but development of dilated cardiomyopathy is rare In addition to our findings in mdx hearts, we also found similar disturbances in the whole-organ mechanical properties of β-sarcoglycan-null and dymdx/J (001801),129-tm1KcamDysf/J (006830), 129S1/SvImJ (002448), B6.WK-dy-2JLama2/J (000524), B6.129-tm1KcamSgcb/1J (006832) were purchased from the Jackson Labs . Mdx carrier females were created by breeding C57BL/10SnJ and C57BL/10ScSnJ-DMDmdx/J mice. Dystrophin-utrophin double knockout (DKO) mice were a kind gift from Dr. Dawn Lowe at the University of Minnesota C57BL/10SnJ (000666), C57BL/10ScSnJ-DMD4, 1.2 mM KH2PO4, 10 mM glucose, 25 mM NaHCO3, 2.5 mM CaCl2, 0.5 mM EDTA, 2 mM sodium pyruvate) while the aorta was isolated and cannulated. Hearts were then retrograde-perfused through with warm buffer bubbled with 95% O2 and 5% CO2 to maintain a pH of 7.4. For experiments in non-contracting hearts, isolated hearts were perfused with a similar buffer lacking calcium and including the contractile inhibitor 10 mM 2,3–butanedione monoxime (BDM).The left atrium was then removed and a plastic balloon was inserted into the LV. An in-line pressure transducer allowed for the recording of pressures within the LV. To assess the mechanical compliance of isolated hearts, balloons were inflated to a physiological left ventricular end diastolic pressure (LVEDP) of 8 mmHg. Volume required to bring LVEDP to this normal range was recorded as Vinit.Mice were anaesthetized with sodium pentobarbital and hearts removed via thoracotomy. Hearts were then immediately placed in ice cold modified Krebs-Henseleit buffer  was applied at a 1∶300 dilution for 1 hour at room temperature. After washing, goat anti-rabbit IgG-AlexaFluor 594  was applied for 1 hour at room temperature. Sections were then washed and mounted with Vectashield for visualization. Slides were visualized using a Zeiss LSM510 META confocal microscope (Carl Zeiss).ex vivo stretch protocol and immediately frozen in liquid nitrogen. 5 µL of perfusate was then added to 200 µL of solution containing 0.12 mM NADH, 2.3 mM pyruvate, and 0.035% BSA in 100 mM sodium phosphate pH = 7.5. Absorbance at 340 nm was then measured in a plate reader  at 1 minute intervals for 15 minutes at a constant temperature of 37 degrees Celsius.Perfusates were collected from isolated hearts immediately before or after the Comparisons between more than 2 groups were made by one-way analysis of variance with a Tukey post-test. When more than one independent variable was tested, two-way analysis of variance with a Bonferroni post-test was used to compare groups. All statistical analysis was carried out using Prism (GraphPad Software).Figure S1P188 does not affect whole-organ compliance and ex vivo stretch does not cause ischemia or impair cardiac function. A) Whole-organ compliance of isolated mdx hearts with and without poloxamer 188 in the perfusate (mdx data is same data used in init of mdx perfused with and without poloxamer 188 perfusate (mdx data is same data used in ex vivo stretch protocol. D) LDH activity in perfusates from WT and mdx hearts taken before and after ex vivo stretch protocol. E) Comparison of LVDP before and after ex vivo stretch protocol. No significant differences between observed between WT and mdx mice by two-way ANOVA. For A, B, n = 7–14. For C, n = 11–14. For D, n = 5–9. For E, n = 8–12.* - p<0.05 vs. all other groups by one-way ANOVA. Values expressed as mean ± SEM.(TIF)Click here for additional data file.Table S1Baseline ex vivo functional data for isolated WT and mdx hearts. Contractile function as shown by LV developed pressure (LVDP) and the maximum derivatives of LV pressure (dP/dt max.) were similar between groups. Lusitropic function as measured by LV end diastolic pressure (LVEDP) and the minimum derivative of LV pressure (dP/dt min.) were also similar between the groups by student's t-test. n = 12–15. Values expressed as mean ± SEM.(TIF)Click here for additional data file.


In animals and human subjects, an increase in background signal intensity observed on late gadolinium enhanced (LGE-SI) images is associated with a decrement in left ventricular ejection fraction (LVEF) during receipt of anthracycline chemotherapy. Moran's I statistic is a measurement of spatial dispersion of hyperenhanced voxels relative to the mean myocardial LGE-SI, ranging from highly clustered I=+1) to highly diffuse (I=-1)  scheduled to receive 3 to 4 months of potentially cardiotoxic chemotherapy (anthracycline or trastuzumab) for treatment of breast cancer or hematologic malignancy. Before and then 3 and 6 months after chemotherapy initiation, participants underwent cardiovascular magnetic resonance (CMR) assessments of LVEF, LGE-SI, and Moran's I statistic determined by personnel blinded to participant identifiers and all other aspects of the analyses. Results were analyzed using paired Student's t-tests to test for a difference between baseline and subsequent examinations, and one-way ANOVA to test for trending change. All values are reported as mean ± standard deviation with p-values<0.05 considered statistically signficant.37 participants were treated for breast cancer and 14 for hematologic malignancy. A declining LVEF from baseline (58±6%) was observed three months (54±7%) and six months (53±7%) after beginning chemotherapy  occurs in a diffusely distributed pattern within the myocardium concurrent with a declining LVEF. Moran's I statistic is a novel method to discriminate processes related to a diffuse increase in myocardial T1  from those related to a clustered increase in myocardial T1 (infarct); further investigations are warranted to study the utility of Moran's I statistic with T1 and T2 mapping.This work was supported in part by the National Institutes of Health grant R33CA12196 (Hundley), American Heart Association Predoctoral Fellowship 09PRE2210050 (Jordan), and a grant from the Susan G. Komen Foundation BCTR07007769 (Hundley).


This study evaluates the association between microvascular obstruction and myocardial salvage, determined by cardiac magnetic resonance performed both in the acute stage of myocardial infarction and after 4 months.In patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention, myocardial salvage, infarct size, left ventricular volumes, and ejection fraction were assessed by early (1–4 days) and follow-up (4 months) cardiac magnetic resonance. These variables were related to the presence or absence of microvascular obstruction at early investigation. Myocardial salvage was determined by: (1) myocardium at risk and infarct size measured in the acute stage and (2) myocardium at risk, measured acutely, and infarct size measured after 4 months. Multivariate analyses were performed, adjusting for clinical confounders at baseline.Microvascular obstruction was present in 49 of 94 included patients, (52%). Myocardial salvage was significantly reduced in patients with microvascular obstruction, compared to those without: 23% vs. 38%, measured acutely, and 39.8% vs. 65.4%, after 4 months (p<0.001). The presence of microvascular obstruction was significantly and independently associated with large infarct size, lower left ventricular ejection fraction, and larger left ventricular end-systolic volume.The presence of microvascular obstruction demonstrated by cardiac magnetic resonance early after infarction was associated with impaired myocardial salvage. This association was more marked when based on measurement of infarct size after 4 months compared to assessment in the acute stage. Timely reperfusion by primary percutaneous coronary intervention (PCI) is the preferred treatment for patients suffering from acute ST-elevation myocardial infarction (STEMI) In recent years, cardiac magnetic resonance (CMR) imaging has become an important tool in characterization of myocardial injury following an acute infarction. By different CMR modalities, variables like myocardial edema, infarct size, myocardial haemorrhage, and the presence of MVO, can be assessed early in the course of an acute myocardial infarction. From a clinical point of view, identification of reliable markers of long-term left ventricular (LV) function defined early in the course of STEMI could potentially have important implications regarding patient follow-up and treatment strategies. The demonstration of MVO by CMR has been shown to be associated with an adverse outcome regarding early and final infarct size, LV remodeling, and clinical long-term prognosis In the present study we determined myocardial salvage in 2 ways, based on CMR performed in the acute stage of STEMI as well as after 4 months. First, calculation of salvage was based on myocardium at risk and infarct size measured in the acute stage and, second, salvage was calculated from myocardium at risk, measured acutely, and final infarct size, measured at 4 months. Our aims were to compare myocardial salvage at the two time points and relate the results to the presence or absence of MVO at early CMR.The study population consisted of patients with STEMI treated by primary PCI within 6 hours, consecutively recruited from the ongoing POSTEMI study Patients with previous myocardial infarction, renal failure, collateral flow to the ischemic myocardium, unstable patients in cardiogenic shock and patients with pulmonary congestion or severe hypotension were excluded. An occluded IRA [Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1] with successful recanalization (TIMI flow 2 or 3) after first balloon inflation had to be demonstrated. All patients received aspirin 300 mg, clopidogrel 600 mg, and heparin 70 IU/kg (maximum 7000 IU) before or during PCI and the glycoprotein IIb/IIIa inhibitor eptifibatide was given during and after angioplasty, using a standard regimen of weight-adjusted bolus followed by infusion for minimum 12 hours CMR was performed on a 1.5 T scanner , using five element synergy-cardiac coil and vector-based ECG. LV was scanned in two and four chamber long axis view using balanced fast field echo sequences for functional analysis, and short axis images were acquired for complete LV volume analysis. The scanning parameters were set to slice thickness 8 mm, slice gap 0 mm, and 25 heart phases.T2 weighted imaging was performed in cardiac short axis plane using black blood inversion recovery fast spin echo sequences. To improve signal-to-noise ratio, a slice thickness of 15 mm was chosen and in total 5 slices were scanned from the apex to the basis of LV The late gadolinium enhancement (LGE) study was performed 15 minutes after contrast injection in two and four chamber long axis view and in short axis view, using 3D T1 enhanced gradient echo technique with inversion prepulses, covering the whole LV. A dose of 0.15 mmol/kg, gadolinium-DTPA 469 mg/ml  was injected using Spectris power injector. Slice thickness was 6 mm and slice gap was set to 0. After performing a “Look-Locker sequence”, optimal inversion time was chosen to suppress signal of normal myocardium.Image analysis was performed on View Forum workstation . Left ventricular ejection fraction (LV EF) was calculated by assessment of the volumes of the endocardial contours in diastole and systole of the short axis images. The included slice closest to the mitral valve plane had myocardium in at least 2/3 of the LV circumference. To obtain the volume of LV myocardium, epicardial tracing was done in diastole.T2 weighted images were used to quantify the myocardium at risk. Myocardium with a signal intensity (SI) of more than 2 standard deviations above the SI in remote non-infarcted myocardium was considered as the “myocardium at risk”. The area indicated was also manually traced and compared to the area of the whole short axis slice.On LGE images the size of the infarction was assessed, drawing the contour of the infarcted area in all short axis slices. The volume of the infarction was related to the total LV myocardial volume. Further, short axis slices corresponding to the slices used in the T2 study were chosen and the hyperintense area  in these slices was traced. This hyperintense, infarcted area was then related to the myocardium at risk seen at T2 imaging.MVO was defined as a dark area in the centre of the hyperintense area in infarcted myocardium, assessed in late enhancement images. On manual tracing of infarcted area, the MVO dark area was included. Myocardial salvage (%) was defined as [(myocardium at risk –infarct size): myocardium at risk] x 100 Continuous variables are presented as median values with interquartile range. Categorical variables are presented as proportions. Differences between groups were analyzed by Mann-Whitney test for continuous variables and chi-square test for categorical variables in univariate analyses.The study design was a prospective cohort with exposition, the presence of MVO or not, and different endpoints determined by early and late CMR .For the endpoint “large infarct size”, defined as relative infarct volume ≥25.4% of LV myocardial volume (≥75 percentile) at 4 months, we estimated the crude odds ratio (OR) for the association between presence of MVO and this endpoint. Stratification analysis using the Mantel-Haenszel method was used to highlight potential effect modification by Breslow-Day test of heterogeneity and to quantify potential confounders. A multivariate logistic regression analysis on the association between MVO and the risk of developing a large final infarct size, including a backward elimination procedure, was performed to adjust for multiconfounders The association between the presence or absence of MVO and the changes in EF and in LV volumes was analyzed by the covariance model (ANCOVA), controlling for baseline variables and confounders Analysis of a possible association between the presence of MVO and myocardial salvage was performed by a multivariate linear regression model, controlling for potential confounders 2 = 0.38) was attributable to a linear relationship between myocardial salvage and MVO. The association between MVO and myocardial salvage was highly significant also after adjustment for covariates [β/SE (β)] = −6.93, p<0.001.A flow-chart of consecutive STEMI patients included in the present study is shown in Measured early as well as after 4 months, LV volumes were significantly larger, whereas LV EF was lower in patients with, compared to patients without MVO, respectively . We alsoThe crude OR for developing a large myocardial infarction, measured after 4 months, in patients with MVO compared to patients without MVO at early CMR was 17.5 . In order to adjust for covariates influencing the association between MVO and risk of large infarct size, we performed a multivariate analysis. No effect modification was found. The following variables were identified as potential confounders: anterior wall infarction, gender, door-to-balloon time, and myocardium at risk, and all except gender were included in the final model. The adjusted OR for developing a large infarction in the presence of MVO was 14 . A strong association between MVO and LV ESV as well as LV EF was shown, ([β/SE (β)] = 3.20, p<0.0001 and [β/SE (β)] = −5.48, p<0.0001) respectively, when adjusted in the ANCOVA model for the possible confounding effects of door-to-balloon time, anterior infarction, myocardium at risk, gender, and baseline LV ESV. However, there was no significant association between the presence of MVO and 4 months LV EDV after adjustment for the same covariates [β/SE (β)] = 1.04, p = 0.299.During 4 months follow-up, none of the patients had re-infarction or stroke. Ten patients were re-hospitalized for congestive heart failure or unstable angina, 7 in the group without MVO and 3 in the group with MVO (p = 0.13).In the present study, we found a strong, independent, and robust association between MVO and impaired myocardial salvage. Previously, an association between impaired myocardial salvage and MVO in STEMI patients has been reported, based on a single, early CMR Our results confirm and extend previous reports on the association between MVO and variables of LV function after PCI-treated STEMI Some investigators have calculated the size and extent of MVO and related this to LV outcome variables By CMR the presence of MVO can be assessed by first pass perfusion from early gadolinium enhancement or from the LGE imaging phase (“persistent MVO”) Myocardial salvage assessed by CMR has been identified as a predictor of clinical outcome The patients included in this study were recruited from an ongoing trial, investigating the effect of postconditioning during primary PCI on final infarct size. Thus, they were selected according to the inclusion and exclusion criteria of the trial In summary, in PCI-treated STEMI patients we have demonstrated that the presence of MVO was associated with reduced myocardial salvage in the acute stage and the reduction was more marked when based on measurement of infarct size after 4 months. Thus, a CMR study early in the course of STEMI may yield information useful for the treatment and follow-up strategies of such patients.


Myocardial PVM may be used to assess peak velocities and the times to those peaks (TTP) in order to characterise healthy and pathological regional heart motion . HoweverAn efficient navigator-gated spiral trajectory PVM sequence  was used to scan basal, mid-ventricular and apical short-axis slices in ten healthy volunteers on two separate occasions. Retrospective cardiac gating was implemented, allowing analysis of all major velocity peaks throughout the cardiac cycle, including atrial systole. The reproducibility of peak velocities and their TTP values was assessed by Bland Altman analysis. Analysis of TTP vales was repeated after normalisation to a fixed systolic and diastolic length.Reproducibility data are shown in Table High temporal resolution myocardial PVM with retrospective cardiac gating is a highly reproducible technique for measuring all peak velocities in the cardiac cycle, including those in atrial systole. Absolute and normalised systolic TTP values have comparable reproducibility. However the reproducibility of diastolic TTP values is improved following normalisation to a fixed systolic and diastolic length. This is particularly apparent for the late diastolic peak representing atrial systole.The authors acknowledge the support of Heart Research UK, Imperial College London and NIHR Royal Brompton Cardiovascular Biomedical Research Unit.


In patients with a small heart, defined as an end-systolic volume (ESV) of ≤20 mL calculated using the Quantitative Gated SPECT (QGS) program, underestimation of ESV and overestimation of ejection fraction (EF) using gated myocardial perfusion imaging are considered errors caused by inappropriate delineation of the left ventricle (LV). The aim of this study was to develop a new method for delineation of the LV and to evaluate it in studies using a digital phantom, normal subjects and patients.The active shape-based method for LV delineation, EXINI heart (ExH), was adjusted to more accurately process small hearts. In small hearts, due to the partial volume effect and the short distance to the opposite ventricular wall, the endocardial and the epicardial surfaces are shifted in the epicardial direction depending on the midventricular volume. The adjusted method was evaluated using digital XCAT phantoms with Monte Carlo simulation , a Japanese multicentre normal database (69 patients) and consecutive Japanese patients (116 patients). The LV volumes, EF and diastolic parameters derived from ExH and QGS were compared.p = 0.0058), but ExH gave comparable EFs . QGS gave higher EFs in subjects with a small heart than in those with a normal-sized heart (74.5 ± 5.1 % vs. 66.1 ± 4.9 %), but ExH gave comparable values . In consecutive patients, the average EFs with QGS in patients with ESV >20 mL, 11–20 mL and ≤10 mL were 57.9 %, 71.9 % and 83.2 %, but with ExH the differences among these groups were smaller .The digital phantom studies showed a mean ESV of 87 % ± 9 % of the true volume calculated using ExH and 22 % ± 18 % calculated using QGS. In the normal database, QGS gave higher EFs in women than in men (71.4 ± 6.0 % vs. 67.2 ± 6.0 %, The volume-dependent edge correction algorithm was able to effectively reduce the effects on ESV and EF of a small heart. The uniform normal values might be applicable to both men and women and to both small and normal-sized hearts. Electrocardiography (ECG)-gated myocardial perfusion single-photon emission computer tomography (SPECT) is a standard technology used today, and composite information on perfusion and function has been utilized for both diagnostic and prognostic purposes –3. A numThe purpose of this study was first to develop a new method for delineation of the LV that more accurately quantifies small hearts. The new method was then evaluated using digital XCAT phantoms with Monte Carlo simulation, a normal database produced by the Japanese Society of Nuclear Medicine (JSNM) Working Group, and a clinical series of consecutive Japanese patients. EF, end-diastolic volume (EDV), ESV and volume curve differentiation (dV/dt) parameters calculated with the new method and with widely used cardiac quantification software were compared.In this study, a small heart was defined as a heart with an ESV of ≤20 mL as calculated using Quantitative Gated SPECT (QGS) software  , 14. PatThe SIMIND Monte Carlo program together with the XCAT phantom were used to generate projection data , 16. A p99mTc -labelled hexakis-2-methoxy-isobutylisonitrile (MIBI) and tetrofosmin were included. Wall motion determined by gated SPECT was considered to be normokinetic. Patients who had a normal coronary angiogram as well as those without an indication for coronary angiography because of a low likelihood of ischaemic heart disease were included. Low-energy collimators were used in all subjects. The acquisition angle for each projection was 4–6° per step with a rotation of either 180° or 360°. No attenuation correction was used in any of the hospitals. Patients with ESV <10 mL were excluded.A standard database created in 2007 by the JSNM Working Group for Standardization based on myocardial SPECT studies was used . Patient99mTc-MIBI and 99mTc-tetrofosmin were used in 94 and 22 patients, respectively. The indications for stress myocardial imaging included evaluation of known coronary artery disease (45 %), screening for ischaemia due to multiple risk factors, preoperative evaluation of abdominal aortic aneurysm and peripheral vascular disease (38 %), chest symptoms and ECG abnormality (13 %) and other cardiac diseases including cardiomyopathies (4 %). The patients were classified into the three groups  based on the ESV determined by QGS software. The SPECT data were acquired with steps of 6° over 360°. ECG gating was performed with 16 frames per cardiac cycle. Since the purpose of the study was not to detect ischaemia, only resting gated SPECT data were used in the subsequent analysis.Consecutive patients with suspicion of ischaemic heart disease and who were undergoing a stress–rest gated myocardial perfusion study were included. The studies were performed from October to December 2011. Of 116 patients, 79 men (mean age 59 ± 11 years) and 37 women (mean age 71 ± 11 years) were included. Gated SPECT data were processed using a standard software package to reconstruct short-axis images. Butterworth and ramp filters were used for filtered back projection reconstruction. To quantify LV function including EF, EDV and ESV, a standard method using QGS software was applied. QGS also calculates the dV/dt parameters as discussed below .The new method for delineation of the LV, EXINI heart (ExH) software , was based on a previously described method in which a heart-shaped LV model and an active shape algorithm are used instead of geometrical approximations such as ellipsoid or hybrid cylindrical/spherical models . After aThe method was adjusted to more accurately process small hearts. In small hearts, due to the partial volume effect and the short distance to the opposite ventricular wall, the ventricular volume appears to be smaller than the actual volume. Therefore, the endocardial and the epicardial surfaces are shifted in the epicardial direction before LV volumes are calculated. The size of the shift is calculated using the mid-ventricular volume of the LV using a univariate polynomial equation of the second degree. The equation was adjusted to give an increasing shift rate for decreasing volumes and a smooth transition to volumes above which no adjustment was performed. The parameters of the equations were determined empirically based on experience from a previous study  and analDiastolic dV/dt parameters were calculated , 17, 19.t test and analysis of variance. Differences in the data between the software algorithms were evaluated using a paired comparison test. Contingency analysis of categorical variables was also performed, and Fisher’s exact test and the Pearson test were used. Linear regression analysis of LV functional parameters was also performed. In the consecutive patients, comparison among multiple groups was performed for all pairs using the Tukey-Kramer method. A p value <0.05 was considered significant.All data are expressed as means ± standard deviation (SD). Differences between groups were tested using the The digital phantom images were processed using ExH and QGS. The LV delineations for the phantom with a true EDV of 40 mL and EF 65 % are shown in Fig. p = 0.027, Fisher’s exact test). None of the parameters  differed significantly between the two software programs . LV volumes determined using both methods were smaller in women than in men. The dV/dt parameters PFR and 1/3MFR determined using QGS were higher in women, but did not differ significantly with ExH.In the normal database, a small heart with an ESV of ≤20 mL was observed in 17 of 33 women (52 %) and in 9 of 36 men , but it was similar with ExH. The dV/dt parameters 1/3MFR, TPFR and TPFR/RR did not differ significantly between the groups.The functional parameters in the NH and SH groups were compared Table . EF dete R = −0.421, p = 0.0003), but no significant correlation was seen with ExH  . The average EFs in the NH, SH20 and SH10 groups were 57.9 %, 71.9 % and 83.2 % with QGS , with a difference of 25.3 % between the NH and SH10 groups. However, using ExH, the average EFs were 65.2 %, 67.8 % and 71.5 % , with a difference of only 6.3 % between the NH and SH10 groups. An example of edge tracing in a patient with a small heart is shown in Fig. Among the 79 men, the NH, SH20 and SH10 groups comprised 50 63 %), 21 (27 %) and 8 (10 %) patients, respectively, and among the 37 women the groups comprised 6 (16 %), 16 43 %) and 15 (41 %) patients, respectively. Four patients who had an outlier EDV of ≥250 mL were excluded from the comparison of volumes and EF among the three groups  were excluded . HoweverSome methods for overcoming the effect of heart size have been suggested. A high cut-off frequency of the Butterworth filter during processing could help improve visualization of the endocardial border , 8. ThisThe effect of a small heart may differ depending on the algorithm used for ventricular edge determination , 10. ComThe initial application of this algorithm to the clinical setting indicated that EF seemed to be more independent of ventricular volumes. In other words, when QGS software is used, whether or not the studied patients have a small heart should be considered to best judge the abnormality. Although additional studies are required, the results with the ExH algorithm indicate that the correction for a mean volume of <85 mL will work effectively in various populations.There were some limitations to this study. The true volume was not determined from the patient data. Probably MRI might have been the first choice for this purpose, but it was not performed routinely in our hospital. Second, the algorithm for a small heart could have been improved by adjusting the range of volume for correction. Since the original images were blurred, various methods for improving the resolution might have been added, but this requires further investigation.The LV volume-dependent correction algorithm for subjects with a small heart provided a more uniform EF between genders as well as between small and normal-sized hearts. Normal values of EF and dV/dt variables were also stable. The application of this software to the clinical setting shows promise.


Cardiovascular Magnetic Resonance CMR has provided the opportunity to quantify right ventricular (RV) parameters with excellent reproducibility and accuracy. The role of the RV is gaining ground in thalassemia major (TM) patients and this population could experience different “normal” RV values due to chronic anemia and eventually pre-existing iron burdens. In literature, there are no data on the ranges for “normal” RV volumes and ejection fraction (EF) in TM patients. The aim of this study was to establish the ranges for normal RV volumes, mass and ejection fraction normalized to the influence of body surface area (BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.Among the 923 TM patients enrolled in the Myocardial Iron Overload (MIOT) network who underwent CMR for the assessment of cardiac iron overload, function and fibrosis, we selected 142 patients with no known risk factors or history of cardiac disease, normal electrocardiogram, no myocardial iron overload  and no myocardial fibrosis. All patients had been regularly transfused and chelated since early childhood. Moreover, we studied 71 healthy subjects matched for age and sex. RV function parameters were quantitatively evaluated in a standard way by SSFP cine images using MASS® software. RV end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) were normalized by body surface area .Table In a large cohort of well-treated TM patients males showed significantly higher RV EF compared to controls. Appropriate “normal” reference ranges normalized to BSA, sex and age should be used to avoid misdiagnosis of cardiomiopathy in the clinical arena in TM patients.


Presenting electrocardiograms of intermittent left bundle branch block in a 60-year-old female. A 60-year-old female with a history of intermittent left bundle branch block (LBBB), hypertension, and dyslipidemia underwent a routine outpatient colonoscopy. On the morning of the procedure she was afebrile and normotensive. Electrocardiogram revealed sinus bradycardia at a rate of 54 and a narrow QRS A. PropofOne minute later the patient became asystolic and CPR was initiated. After a minute of CPR her pulse was reestablished with a rate of 63. At this time, LBBB was observed on the monitor B. MyocarOn examination the patient was anxious but completely asymptomatic. Other than bradycardia, with rates varying between 47 and 52, and mild hypertension (blood pressure 150/71), physical exam was unremarkable.Three and a half hours after the administration of metoprolol, heart rate increased to 64 and EKG revealed intermittent LBBB, with both narrow and wide QRS complexes, despite a stable heart rate . FifteenThe patient was monitored overnight and no further events were noted. Except for a negligible rise in troponins to 0.017  and mild renal insufficiency (creatinine 1.24), her blood tests, including complete blood count and biochemical profile were normal. Echocardiogram showed a mildly dilated left ventricle with normal wall thickness and systolic function but reduced left ventricular compliance. No significant valvular abnormalities were detected.Three weeks earlier she underwent evaluation for atypical chest pain. At that time a narrow QRS and inferior and anterior T-wave inversions were noted, while the heart rate was 49 . When thBecause of baseline bradycardia she had been initially discharged on 12.5 mg of metoprolol twice daily. However, she had been erroneously taking 25 mg of metoprolol twice daily, aggravating her bradycardia on the morning of the arrest. The arrest was attributed to propofol-induced bradycardia  and possIntermittent, rate-dependent LBBB occurs due to prolongation of the refractory period of the main left bundle branch or both the anterior and posterior fascicles together. Once the heart rate slows and the RR interval is longer than the refractory period of the conduction pathway, normal conduction can occur.It was once felt that this prolongation of the refractory rate is usually due to intrinsic disease of the cardiac conduction pathway. However, other causes, such as myocardial dysfunction secondary to myocarditis, cardiomyopathy, left ventricular hypertrophy, valvular disease and ischemic causes need to be considered .Intermittent LBBB is usually seen at higher heart rates. Interestingly, in our patient it occurred at rates as low as 61. It is important to recognize intermittent, rate-dependent LBBB and to differentiate it from ST elevation myocardial infarction or a ventricular arrhythmia.


Speckle tracking-derived strain and strain rate are recently available parameters to assess left atrial (LA) deformation. We hypothesized that such new parameters could be of interest to evaluate the risk of LA stasis among patients with atrial fibrillation (AF).Single-centre study enrolling all patients with non-valvular AF lasting longer than 48 hours for whom no therapeutic anticoagulation was given in the preceding 3 weeks and who were assessed through transesophageal and transthoracic echocardiogram during a 6 month time interval. LA deformation was assessed by transthoracic echocardiogram through speckle tracking analysis, whereas LA stasis parameters were sought on transesophageal echocardiogram.P <0.001) and peak positive strain rate and maximum filling velocity of the LA appendage . Peak negative strain rate was also found to be associated with both maximum emptying velocity  and maximum filling velocity of the LAA . AF duration, peak negative strain rate and time-to-peak positive strain were independent predictors of LAA thrombi or sludge on multivariate analysis logistic regression. The area under the curve for the estimated probabilities using the obtained logistic regression model was 0.89 .Among the 82 assessed patients, LA appendage thrombi or sludge were found in 16 (19.5%). A moderate positive correlation was found between peak positive strain rate and maximum emptying velocity (r = 0.589; Our findings suggest that LA mechanical dysfunction assessed through speckle tracking may be of interest to predict LA stasis in the setting of AF. Non-valvular atrial fibrillation (AF) is associated with stroke and peripheral embolism of cardiac origin  and overTransesophageal echocardiogram is the gold-standard for the detection of thrombi in the LAA  and its Transthoracic echocardiography is now a highly versatile technique that provides solid structural and functional information about the atria. Its potential role in the risk stratification of AF and prediction of left atrial stasis has been overlooked . SpeckleWe hypothesized that speckle tracking derived strain and strain rate could be of interest to evaluate the risk of LA stasis among patients with atrial fibrillation (AF).All patients during a 6 month time interval undergoing transthoracic and transesophageal echocardiogram were assessed for the presence of criteria allowing admission into the study. Patients with an AF episode lasting for longer than 48 hours and without effective anticoagulation in the preceding 3 weeks were considered eligible for the study except if any of the following exclusion criteria were met: lack of adequate endocardial border definition of the left atrium, presence of prosthetic heart valve or previous valve repair, significant aortic or mitral valve disease  and previous closure of the LAA.This study was conducted with the approval of our Institution’s Ethics Committee, Comissão de Ética da Faculdade de Medicina da Universidade de Coimbra. All subjects provided their informed consent to undergo the necessary investigations and to allow the usage of their data for research purposes, preserving their anonymity.Preliminary transthoracic echocardiography was performed using standard views (GE Vivid 7 echocardiograph with a M4S probe). The frame rate was set > 60 frames per second. Since all patients were in AF at the time of procedure, all measurements were obtained from an average of 3 cycles. Left atrium volume was measured using the bi-plane area length method. Left ventricle ejection fraction was calculated with the Simpson method. The ratio between indexed left atrial volume and left ventricle ejection fraction, which has shown to be highly accurate at excluding the presence of an LAA thrombus in patients with AF who are candidates for AF catheter ablation or cardioversion [Pulsed-wave Doppler at the tips of the mitral valve was used for measuring early diastolic filling velocity (E). The early diastolic tissue velocity (E’) was measured with tissue Doppler imaging of the lateral mitral annulus. E/E’ ratio was calculated. Mitral regurgitation was semi-quantitatively assessed by color Doppler across mitral valve and graded as none/trace (0), mild (I/IV) and moderate (II/IV). Individuals with moderately severe (III/IV) and severe (IV/IV) mitral regurgitation were excluded from analysis.Global longitudinal strain and strain rate of the left ventricle were assessed as previously described by other authors ,9.Transthoracic images were processed for assessing left atrial deformation through speckle tracking imaging using the GE Health Care EchoPac Dimension software, PC version 108.1.4 (featuring a software for speckle-tracking of the left ventricle) by two cardiologists who were blinded for the transesophageal echocardiogram results and clinical information of the patients.The left atrium endocardial surface was manually traced using a point-and-click approach in apical four-chamber view, which allowed the automatic definition of a region of interest. This was manually adjusted, if necessary, to better suit the atrium anatomy. The cardiac cycle was demarcated by indicating QRS onset. The region of interest was divided into 6 segments by the software Figure  and the Transesophageal echocardiogram was performed without anaesthesia or sedation using a 6 T phased array multiplane transesophageal probe (frequency 7.0 MHz). The left atrium and LAA were imaged in different tomographic planes to detect the presence of LAA thrombus and spontaneous echocardiographic contrast, which was graded according to the classification (1 to 4+) proposed by Fatkin et al. . When deLAA flow velocities were assessed with a pulsed Doppler sample placed 1 cm from the entry of the LAA into the body of the left atrium. Emptying and filling velocities were estimated from an average of five well-defined emptying and filling waves.Patients were divided into 2 groups, according to the type of findings on transesophageal echocardiogram: group I, with LAA thrombus or sludge and group II, without any of these changes.Comparisons were performed between the two patient groups. Chi-square was used for nominal variables and Student’s t-test was used for comparison of continuous variables, where appropriate; the Levene’s test was used in order to check the homogeneity of variance; equivalent non-parametric tests were used when Kolmogorov-Smirnov was in favor of absence of normal distribution. Pearson’s r correlation coefficient was used for quantifying the degree of association between two quantitative variables. Results with p < 0.05 were regarded as significant.Univariate analysis was performed using the chi-square test. Predictors from univariate analysis were used for obtaining logistic regression models  that could predict the presence of left atrial thrombi or sludge. Continuous variables which statistically differed between group I and II (or presented a non-significant trend: P < 0.1) were converted into qualitative variables and then used in the logistic regression analysis. Cut-off values were obtained through receiver operating characteristic (ROC) curves which allowed us to define the optimal cutoff point, which was the value combining the higher value of specificity plus sensitivity (Youden index). The Hosmer-Lemeshow summary statistic was used to assess the goodness-of-fit of the models. The coefficients from the obtained model  were used for estimating the probability of event in each patient. Then, the discriminative capability of the obtained probabilities was also assessed through a ROC curve.PASW Statistics version 18.0 was used for descriptive and inferential statistical analysis.Inter-observer variability was assessed using Bland-Altman plots with data from the first 7 included patients in the study (average for each of the 6 segments shown), that were separately assessed by the two operators. MedCalc for Windows version 9.2.0.1 was used.During the pre-specified inclusion period, 133 patients were assessed during an AF episode of longer than 48 hour duration and with no effective anticoagulation in the preceding 3 weeks. Of these, the following were excluded from analysis due to the presence of exclusion criteria: inappropriate endocardial border definition of the left atrium (n = 11), previous closure of the LAA (n = 3), valve repair or presence of prosthetic heart valve (n = 10) and significant valvular disease (n = 27).2 and CHA2DS2-VASc scores were 2.0 ± 1.1 and 3.2 ± 1.6, respectively. Information on demographics, clinical data and anti-thrombotic medication are provided on Table Out of the remaining 82 patients, most were male (65.9%) and the average CHADSThrombus or sludge in the left atrium or LAA was found in 16 patients (19.5%) (group I). No differences were found for baseline variables when comparing these patients with the remaining (group II), except for the estimated AF duration, which was more often longer than 1 month in group I.As regards standard transthoracic echocardiographic parameters, no differences were found between the two groups Table . Also, n6  and Seg11 . In all the remaining segments, a satisfactory definition of the endocardial borders and tracking was possible .Adequate tracking of all 6 segments was possible in most patients . The segments which were more frequently excluded from analysis were Seg-1; 95%CI -0.54; 0.51), PNSR  and TPPS .Bland-Altman analysis for inter-observer variability of speckle-tracking derived data is shown in Figure Lower values of peak positive and peak negative strain rate, as well as a lower peak-to-peak strain rate, were observed in group I patients. Patients with sludge or thrombi had a trend for higher indexed left atrial volume and left atrial dyssynchrony, as assessed through the standard deviation of time to peak positive strain Table .A moderate positive correlation was found between peak positive strain rate and maximum emptying velocity  and peak positive strain rate and maximum filling velocity of the LAA . Peak negative strain rate was also found to be associated both with maximum emptying velocity  and maximum filling velocity of the LAA . No significant correlation was observed between peak negative strain and LAA flow velocities and only a trend for a very slight association was observed between peak positive strain and both LAA maximum emptying velocity  and LAA maximum filling velocity .On univariate analysis, body mass index, AF episode duration, indexed left atrial volume, peak positive strain rate, peak negative strain rate, peak-to-peak strain rate and time to peak positive strain were predictors of thrombus or sludge on transesophageal echocardiogram. However, only AF duration, peak negative strain rate and time-to-peak positive strain remained significant on multivariate analysis Table . The areOur data suggest that left atrial mechanical dysfunction, as assessed through peak negative longitudinal left atrial strain rate and time-to-peak positive strain, are associated with the presence of LAA thrombus or sludge. These findings are important not only due to their possible application in the selection of patients for transesophageal echocardiogram before catheter ablation or cardioversion of AF, but also for risk stratification of AF. These parameters may relate to prognosis and clinical endpoints, since LAA thrombus ,13, sludThe described association may be explained by the following: higher left atrial dyssynchrony and lower deformation (compromised contraction and relaxation) may predispose to stasis (as shown by the correlation with flow velocities in the LAA) and subsequently to increasing severity of spontaneous echocardiographic contrast, sludge and thrombus formation. Furthermore, it has been suggested that left atrial wall fibrosis, assessed through delayed enhancement magnetic resonance imaging is inversely related to the strain and strain rate derived from vector velocity imaging echocardiography . TherefoThe average strain and strain rate values in our population of patients with AF may be considered low compared to the standard values proposed by Cameli et al. ,19. HoweIn our sample, left atrial size  was not an independent predictor of left atrial stasis, after adjustment to other echocardiographic parameters and AF episode duration. This may mean that previously described associations between atrial size ,22 and t2 score ≥ 2) [2 score (≤ 1 assessed prior to cerebrovascular events) suggested that reduced peak negative left atrial strain might identify those at risk for stroke [Previous investigations support the assessment of left atrial strain and strain rate in patients with AF, with promising results ,25,26 coore ≥ 2) . A recenBesides this preliminary clinical evidence, data concerning a possible association between left atrial strain and strain rate with left atrial stasis are scarce. A study using tissue Doppler imaging has shown a moderately strong positive association  between mean left atrial systolic strain and LAA appendage emptying velocities , contrarUnlike previous studies, our investigation includes only patients that were assessed during an AF episode. Using speckle tracking for the quantification of left atrial deformation and dyssynchrony we have provided the first evidence towards the association of these novel parameters with the presence of LAA thrombus or sludge. However, one point of our investigation must be highlighted: due to its cross-sectional design, we can only conclude towards an association of compromised left atrial deformation with left atrial stasis. Therefore, since no follow-up was performed, no causal association between left atrial dysfunction and thrombus or sludge formation can be inferred.Most data of a possible association between compromised left atrial deformation and a pro-thrombotic state in AF are based on strain. Some reasons may explain why in our sample the association was found for strain rate: Unlike other studies where most patients were assessed in sinus rhythm , all paComparison of groups with a discrepancy in size may be associated with some issues. First, a small group of patients may be more prone to being affected by the presence of outliers and therefore, the average value of some variables may not be truly representative. However, in this sample of patients, standard deviations of the assessed echocardiographic variables were smaller in the group of patients with thrombi or sludge, which render the chance of selection bias or outliers less likely. Second, small samples may sometimes lack statistical power to demonstrate the presence of smaller significant statistical differences. For example, patients with thrombus or sludge display lower absolute values of left atrial strain, which fail to achieve statistical significance possibly due to insufficient power of the sample.6) and the total percentage of patients where tracking in the 6 apical 4-chamber segments was achieved.Our data were obtained using software that was designed for the assessment of the left ventricle, but still allowed the automatic definition of a region of interest and tracking of speckles in the left atrium. We do not know if using dedicated software to the left atrium would have changed our observations. However, we think it would likely improve the quality of tracking (namely in SDue to deficient endocardial border definition of the left atrium in 2-chamber view in a significant number of patients, we have chosen not to evaluate these segments. We acknowledge that having a global evaluation of the left atrium, ideally with 3D echocardiography, may provide more accurate and precise data. However, this could lead to a more complex and time-consuming procedure.Left atrial mechanical dysfunction assessed through speckle tracking seems to be associated with a higher prevalence of the different markers of left atrial stasis. These findings suggest a possible application of this technique in the selection of patients with AF for transesophageal echocardiogram. Moreover, there may be a rational for assessing left atrial deformation in the context of risk stratification of AF, but this should be further explored in future trials.AF: Atrial fibrillation; LA: Left atrial; LAA: Left atrial appendage; E: Early diastolic filling velocity; E’: Early diastolic tissue velocity.The authors declare that they have no competing interests.RP designed the study, performed the analysis of data along side with AF and wrote the first draft of the manuscript. MJF, LG and SBo discussed and revised the study design. Data was acquired by AF, JT and AB. All authors actively revised the first draft of the paper, providing suggestions and corrections. Input from reviewers was used for preparing a new version of the paper, which was prepared and revised by all authors. SBa provided all the necessary English language support for the preparation of the final version. All authors read, revised, accepted the final version of the manuscript and confirm the accuracy or integrity of data.


We focused our study on patients with severe compromised ischemic left ventricle and functional mitral regurgitation to understand how mitral valve replacement versus repair affects survival and provide the predictors of hospital and long-term mortality.870 patients  from 2000 to 2012, with coronary artery diseases and significant ischemic mitral regurgitation (>2) were operated – in 787pts CABG+MV repair were performed and in 83 pts MV replacement were combined with CABG. Groups were matched by propensity score using demographics dates, co-morbidity, LV remodeling and MR grade by quantitative echocardiography. Survival  and NYHA functional class were compared. The impact of mitral valve replacement versus repair on survival by comparing theses propensity matched subgroups was analyzed.Follow-up was 100% complete. Before matching 10-year survival was significantly worse in replacement group . After propensity matching 1:2 we’ve received homogenous cohort of 99 pts with severe compromised LV  and severe MR. The fact of mitral valve replacement versus repair did not influence survival  and overall in 1- and 5-year it were 91,8±0,14% and 69,2±0,48% respectively. The independent risk factors for an increased mortality within the five years of surgery in multivariate propensity-matched analyses were found LV ESD , chronic renal disease , use of IABP during hospital period  and age .The mitral valve replacement versus repair did not seem to affect survival in patients with severe damaged ischemic LV and it mostly depends on factors related to the patient’s condition at the time of surgery.


Periostin was proved to play an important role in extra-cellular matrix remodeling after acute myocardial infarction (AMI). Myocardial periostin was markedly up-regulated after AMI and participated in the maladaptive process of cardiac remodeling. However, few researches focused on the circulating periostin and its significance. This study aims to investigate the association of serum periostin level with cardiac function and short-term prognosis in AMI patients.We totally recruited 50 patients diagnosed as ST-elevation myocardial infarction. Blood samples were taken within 12 hours after the onset of AMI before emergency coronary revascularization procedures. Serum periostin was measured using enzyme-linked immunosorbent assay. All patients received echocardiography examination within one week after hospitalization. Correlations of serum periostin with echocardiography parameters, Killip class and myocardium injury biomarkers (CK-MB/troponin T) were investigated. AMI patients were divided into two groups by serum periostin level (higher/lower periostin group) and followed up for six months. Primary endpoints included cardiovascular mortality, nonfatal stroke/transient ischemic attack, chest pain occurrence and re-hospitalization. Secondary endpoint referred to composite cardiovascular events including all the primary endpoints.p<0.01) and left atrium diameter (LAD) . Positive correlation was found between serum periostin level and Killip class . There was no association between serum periostin and CK-MB or troponin T (p>0.05). After six months follow up, patients in higher periostin group showed increased composite cardiovascular events (*p<0.05). Patients showed no significant difference in primary endpoints between the two groups.Serum periostin was in negative association with left ventricular ejection fraction (LVEF) (r = −0.472, *Serum periostin was in negative correlation with LVEF and LAD, in positive association with Killip class and higher serum periostin level may be predictive for worse short-term disease prognosis indicated as more composite cardiovascular events six months post AMI. Acute myocardial infarction (AMI) remains as a worldwide public health problem with an increasing rate of incidence and causes irreversible cardiomyocytes impairment in vitro and in vivo. Delivery of recombinant periostin into the heart of MI rat improved cardiac systolic function, reduced fibrosis and hypertrophy as well as enhanced myocardium repair Periostin was a 90-kDa extra-cellular matrix protein secreted by fibroblasts, which acted as an important regulator in ventricular remodeling process such as pathological hypertrophy or fibrosis after myocardial injury. Periostin was proved to be related closely to the onset and development of coronary artery disease Although the net effect of periostin on ventricular remodeling after acute myocardial infarction has not reached a consensus, there is no doubt that this molecule acts as an important regulator in this process. Myocardial periostin was significantly up-regulated after AMI and participated actively in cardiac remodeling. However, few researches focused on the change in circulating periostin after AMI. This study was designed to investigate the association of serum periostin level with cardiac function and short term disease prognosis in acute myocardial infarction patients. Our study found that serum periostin was in negative association with left ventricular ejection fraction and left atrium diameter as well as in positive association with Killip class in acute myocardial infarction patients. Higher serum periostin level was related to increased composite cardiovascular events after six months follow up post AMI.Clinical researches were approved by the Ethics Review Board for Clinical Studies of the First Affiliated Hospital of Soochow University . All clinical studies confirmed to ethics guidelines of the 1975 Declaration of Helsinki. All patients were informed with and signed written consent of this study. We did not conduct research outside of our country of residence.We totally enrolled 50 patients of acute myocardial infarction (ST elevation) in our study. All patients were in consistent with the following diagnostic standards for ST-elevated acute myocardial infarction: i Clinical history of ischemic type chest pain; ii ECG changes. New ST elevation at the J point in at least 2 contiguous leads of 0.2 mV in men or 0.15 mV in women in leads V2–V3 and/or of 0.1 mV in other contiguous chest leads or the limb leads; New or presumably new left-bundle branch block; iii Evidence of myocardial injury or necrosis indicated by elevated serum cardiac biomarker, especially troponin T . All patients received coronary revascularization procedures and standard drug therapy for coronary artery disease after hospitalization. Basic clinical characteristics including gender, age, coronary heart disease history, hypertension history, diabetes history, smoking history were collected and fasting blood sample were taken for measurement of glucose, cholesterol, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglyceride and renal function. Blood sample for periostin and myocardial injury biomarkers evaluation was taken within 12 hours after the onset of AMI before emergent coronary revascularization procedures. All blood tests were performed in the hospital’s laboratory.Serum periostin was measured using the DuoSet® ELISA kits (R&D Systems) according to manufacture’s instructions. Briefly, plates were coated with 100 µl of capture antibody and incubated overnight. After blocking with PBS containing 1%BSA overnight, 100 µl of diluted serum samples or recombinant periostin standards at different concentrations were added and incubated for 2 h at 37°C. Then 100 µl of detection antibody was incubated for 2 h at 37°C and streptavidin-HRP for 20 min. Plate washing were performed with 400 µl of washing buffer (0.05% Tween-20 in PBS) after every incubation for at least three times. Wells were incubated with 100 µl substrate solution for 20 min and stopped by adding 50 µl stop solution (2 N H2SO4). The optical density was measured at 450 nm and 570 nm using a micro-plate reader  and the absorbance at 570 nm was subtracted from the absorbance at 450 nm. Each experiment was performed in duplicate wells and averaged for statistical analysis.Trans-thoracic echocardiography was performed to assess cardiac function of acute myocardial infarction patients. All patients finished echocardiography examination within one week after hospitalization. A trained echo-cardiologist blinded to the experiment performed all the measurements with GE Vivid 7 system . Left ventricular M-mode spectrum was performed in standard parasternal long-axis view to measure LV diameter at end cardiac diastole (LVDd) and systole (LVDs). The Teicholz method was used to calculate left-ventricular volumes and left-ventricular ejection fraction. Index including left ventricular posterior wall thickness (LVPWT), inter-ventricular septal thickness at diastole (IVSTd), left atrial diameter (LAD) and aorta dimension (AoD) were measured. All measurements were repeated for three consecutive pulsation cycles and averaged for statistical analysis.Patients involved in this study were followed up for major cardiovascular events six months after the onset of acute myocardial infarction. We set primary and secondary clinical endpoints for evaluation of major cardiovascular events. Primary endpoints included cardiovascular mortality, nonfatal stroke or transient ischemic attack, typical chest pain occurrence and re-hospitalization due to unstable angina pectoris, re-infarction or heart failure. Cardiovascular mortality was defined as death due to fatal myocardial infarction, coronary intervention procedure, congestive heart failure, stroke, sudden cardiac death or other cardiovascular causes. Secondary endpoint was defined as composite cardiovascular events including all the four primary endpoints.p value of <0.05 (two-tailed) was considered significance. All analyses were performed using SPSS 17.0 software .All continuous variables were expressed as mean ± SD. Comparisons between two groups were performed with unpaired Student’s t-test and comparisons among three or more groups were assessed by one-way ANOVA with Dunnett’s post-test. Categorical variables were expressed as percentages. Chi-square test was used for comparisons of categorical variables. Spearman correlation was used to analyze the relationship between serum periostin level and other parameters. A The authors have full access to the data and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.The average age of patients was 63.30±12.78 years. AMI patients showed an average serum periositn level of 203.35±16.90 ng/ml. We analyzed the relationships of serum periostin level with patients’ clinical characteristics by spearman correlation. Baseline characteristics including gender, CHD history, hypertension, diabetes mellitus, smoking history, age, heart rate, triglyceride, cholesterol, HDLc, LDLc, venous glucose, creatinine and blood urea nitrogen (BUN) showed no correlations with serum periostin level .p<0.01) and left atrium diameter  (p<0.01) (p<0.05). Correlation of periostin with coronary and echocardiography parameters was shown in p<0.01) but neither of them showed significant correlation with serum periositn   A–B. Fur(p<0.01) . Patienteriositn . Detailep<0.05, In order to assess the effect of serum periositn on short-term prognosis, we followed up patients for major cardiovascular events six months after the onset of AMI. All patients were divided into two groups based on median periostin level (188 ng/ml), named as higher periostin group (N = 25) and lower periostin group (N = 25). Basic clinical characteristics including gender, age, hypertension, diabetes, smoking history, blood glucose, cholesterol, HDLc, LDLc, triglyceride and renal function showed no difference between the two groups . There wAcute myocardial infarction is one of the lethal diseases in the world, with an increasing morbidity and threatens the public health. The local ischemia and hypoxia conditions after AMI caused irreversible cardiomyocytes death or apoptosis and these cardiomyotes were gradually replaced by interstitial fibrosis through ventricular remodeling process. As scar and fibrosis structure lacked the ability of contractility and electric activity, systolic function and electric coupling of the heart were impaired and these finally led to deteriorated cardiac function Periostin is an extra-cellular protein proved to play an important role in cardiovascular development and disease This study investigated the association of serum periostin level with cardiac function, coronary situation, biomarkers and clinical characteristics in acute myocardial infarction patients. The six month prognosis was also assessed. We found that serum periostin level was in negative association with left ventricular ejection fraction and left atrium diameter, in positive correlation with Killip class and showed no relationship with serum CK-MB or troponin T. Patients with higher serum periostin level exhibited increased composite cardiovascular events after six months follow up.in vitro and acted as a cardio-protective factor In our study, serum periositn level showed negative correlation with LVEF, suggesting that patients with lower left systolic function had higher circulating periostin level. Killip class represented left ventricular failure degree in the acute period after AMI. Serum periositn level was in positive correlation with Killip class. This was in consistent with the results of periostin and LVEF, suggesting a relationship of higher periostin level with worse left ventricular function. CK-MB and troponin T are well documented serum biomarkers for myocardial infarction and reflected myocardium injury According to our results, we concluded that periostin showed good correlation with cardiac systolic function and short term prognosis in ST elevation acute myocardial infarction patients. Higher serum periostin level was associated with worse left ventricular function and deteriorated short term prognosis. In the present study, we visited patients for six months and this was a relatively short period for myocardial infarction patients. Long term observation for cardiovascular major events and clinical prognosis would be needed in the further study. Our present study enrolled myocardial infarction patients with ST elevation and did not include non-ST elevation myocardial infarction patients or unstable angina patients. As these patients shared the similar pathological process as unstable plaque, the serum periostin level in these patients would better be analyzed in further experiments.Table S1Echocardiography Parameters of AMI Patients. LVEF: left ventricular systolic ejection fraction; LVDd: left ventricular end diastolic diameter; LVPWT: left ventricular posterior wall thickness; IVSTd: inter-ventricular septal thickness in diastole; LAD: left atrium diameter; AoD: aorta dimension. Date presented as mean±SD.(DOC)Click here for additional data file.


Patients who survive either ventricular fibrillation or sustained ventricular tachycardia carry a high risk of further episodes, which could be fatal. Anti-arrhythmic drugs were the standard treatment for patients with malignant ventricular arrhythmias, but despite using the best appropriate medical treatment, arrhythmia recurrence rates remain high at 40-50% at five years. Implantable cardioverter defibrillators (ICD) are effective at treating ventricular arrhythmias and there has been clear evidence that they reduce mortality. Cardiac resynchronization therapy (CRT) improves symptoms and reduces morbidity and mortality in patients with advanced heart failure. In addition, many patients have indications for combined ICD and CRT therapy.While the number of ICD/CRT implantations in the developed world has increased, device utilization rates are less in low- and middle-income countries, despite having higher incidence of risk factors for sudden cardiac death and heart failure. The primary obstacle to the growth of this therapy in developing nations is its cost - ranging from $8000 to $16,000 depending on the model and the features available. Due to its cost, this therapy is currently accessible only to the affluent in developing countries, whereas the subset of patients who requires this therapy is increasing rapidly. According to available data, only a few hundreds of patients in India which has a population of over 120 million receive ICD implants every year, whereas in developed countries with much smaller population the number is at least in thousands.In this context, devices donated for use by charitable organizations, industry or devices harvested by physicians/industry for reuse, becomes extremely important to patients in low- and middle-income countries. Reuse of devices poses risks such as infection, device malfunction and premature battery depletion. But, recently published studies have shown that there is no increase in morbidity or mortality associated with device reuse, if implanted with good technique and proper sterile precautions. However, there is no proper data or registry available regarding the availability of devices with potential for reuse in the developing or even in the developed world.The HRS guidelines recommend that physicians seek patients' consent for post-mortem device retrieval while they are alive. In routine practice, informed consent for device implants rarely includes a discussion regarding post-mortem handling of devices. A survey of patient preferences showed that 87% of patients did not know how devices were handled after their death despite the fact that majority were willing to have their devices retrieved for reuse . MoreoveIn an interesting study published in this issue, Iyer IR and Mackall J tried to unravel veterans' preferences regarding post-mortem handling of devices and also to create some data on reuse potential of these expensive devices . In thisThis is an important study considering that data regarding reuse or reuse potential of these expensive life saving devices are so scarce and its implications especially in developing countries are many. Major limitations of this study are small sample size and retrospective nature for assessing reuse potential of devices. Devices and battery technology analyzed in this study are different from currently used devices; recent generation devices show longer battery life and therefore may offer greater reuse potential. A larger study utilizing large datasets maintained by device manufacturers and multiple centers may give a better estimate of number of devices with significant reuse potential in order to formulate a health policy on this rather important issue.


Duchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease. We previously identified myocardial disease by late gadolinium enhancement (LGE) in DMD subjects at various stages of disease, but the true prevalence is unclear. Cardiovascular magnetic resonance (CMR) is well established for both assessment of ventricular function and myocardial fibrosis by LGE. We sought to establish i) prevalence and distribution of LGE in a large DMD population and ii) relationship among LGE, age, LVEF by CMR and current living status.Current living status, demographic and CMR data including ventricular volumes, LVEF and LGE from 314 DMD patients undergoing evaluation at a single large tertiary referral center were analyzed.113 of 314 (36%) of DMD subjects showed LGE positivity with prevalence increasing from 17% of patients <10 years to 34% of those aged 10–15 years and 59% of those >15 years-old. Patients with LVEF ≥55% were LGE positive in 30% of cases; this increased to 84% for LVEF <55%. LGE was more prevalent in the free wall  vs. septal segments . Patients with septal involvement were significantly older and had lower LVEF than those with isolated free wall LGE. Ten percent (11/113) patients who had LGE died 10.8 months after CMR. Only one patient from the LGE negative group died. Patients who died had higher heart rate, larger left ventricular volume and mass, greater number of positive LGE segment and increase incident of septal LGE compared to those who remained alive.In DMD patients, LGE occurs early, is progressive and increases with both age and decreasing LVEF. Segmentally, the incidence of the number of positive LGE segments increase with age and lower LVEF. Older patients and those who died during the study period had more septal LGE involvement. The current studies suggest that the time course and distribution of LGE-positivity may be an important clinical biomarker to aid in the management of DMD-associated cardiac disease. Duchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting approximately 1 in 5000 males is the most common inherited muscular dystrophy . The disFibrosis of the left ventricle in DMD has been observed at autopsy ,17 and dCurrent living status as of December 2012 and demographic data were analyzed from records of DMD patients who underwent clinical CMR studies including LGE between September 2005 and September 2012 at a single large tertiary referral center. Only patients with a known diagnosis of DMD confirmed by a skeletal muscle biopsy showing absent dystrophin and/or DNA analysis demonstrating a characteristic dystrophin mutation in all patients. The Institutional Review Board at Cincinnati Children’s Hospital approved the study.CMR was conducted either on a Siemens 3 Tesla Trio , Philips 3 Tesla Achieva  or on a 1.5 Tesla GE Signa Excite . Machine type was based solely on clinical availability, independent of the patient’s clinical status. Cardiac functional imaging was performed using a standard retrospective ECG-gated, segmented steady state free precession (SSFP) technique and includes a short axis stack of cine SSFP images from cardiac base to apex as previously described ,21. TypiLGE imaging was performed via a FLASH inversion sequence recovery protocol 5–8 minutes after 0.2 mmol/kg) gadolinium-based contrast agent injection as previously described ,23. The Study results are expressed as mean ± SD for continuous data and as percentages and numbers for categorical data. Continuous variables were compared using two-sample t-test and categorical variables were compared using Fisher exact-test. LGE data were classified as being positive or negative and analyzed using a logistic regression model to estimate the odds ratio (OR) and 95% confidence interval (CI) between the patient aged: 10–15 years and > 15 years as compared to the reference age group of < 10 years. Similar model was used to estimate the OR (95% CI) between the LVEF of subjects with LVEF < 55% compared to those with LVEF ≥ 55%. Segments were summarized across the above age and LVEF groups. All tests were 2-sided, and a p-value < 0.05 was considered statistically significant. SAS version 9.2  was used for all analyses.2, p < 0.0001), ventricular mass , lower LVEF  and greater number of positive LGE segments  compared to those who remained alive  and normal LVEF (≥ 55%) or reduced LVEF (< 55%) Table . Among pA multivariable model with LVEF (<55 versus ≥55 percent) as the main clinical outcome using a logistic model was performed. An un-adjusted model with +/-LGE in the model as a covariate which resulted in estimated OR for +/-LGE of 12.3  in predicting reduced EF was performed. Then age (as continuous variable) was added into the model resulted in an adjusted OR for +/-LGE of 7.6  in predicting reduced EF. Similar analysis using +/-septal LGE as a covariate in the model and LVEF as the main clinical outcome was conducted and this resulted in un-adjusted estimated OR for +/-septal LGE of 7.0  in predicting reduced EF. Then age (as continuous variable) was added into the model with resulted in an adjusted OR for +/-septal LGE of 5.2  in predicting reduced EF.Figure Septal LGE-positivity was never found in isolation and only in association with LGE positivity in other free wall segments. Patients with septal LGE involvement were older than those without septal LGE involvement , though heart rate and BSA were not statistically different between the two groups. Among patients age < 10 years (n = 14) the incidence of septal LGE was 7.1% , for those age 10–15 years (n = 51) the incidence of septal LGE of 7.8% 95% CI, 2.2-18.9) and increased to 25%  for patients > 15 years of age (n = 48)  evidence of myocarditis. All 6 patients with LGE had histologic evidence of myocarditis and rapid deterioration of LVEF was noted in those patients in 1 year follow up CMR ,41. WansThis was a retrospective study and as a result is subject to accepted limitations of this design. There is no correlation with LGE findings with medications such time on steroid and ACE inhibition, however patients are typically on steroid by age 5 years and typically remain on the steroid regimen for life. ACE inhibition is typically added by age 10 years or when there are signs of left ventricular dysfunction is evident by echocardiogram and independent of LGE findings. Although we have mortality data the numbers were small and since all patients died out of the hospital, we do not have the cause of death. The purpose was to define the natural history of LGE presence in the DMD population; future studies should focus on correlations with clinical outcomes  and genotype-phenotype correlations. It is acknowledged that this would be valuable information and warrants additional future investigation. In addition, the data was accrued from a single center which could be seen as a limitation or a strength as it facilitated consistent image acquisition and interpretation. Only qualitative assessment of LGE is available for this study. We found it difficult to perform quantitative assessment of LGE in our patient population using either threshold or full width at half maximum (FWHM) methods, nature of the disease and epicardial LGE location bordering on epicardial fat compared to those reported in ischemic heart disease. T1 mapping, an emerging technique for characterization of the myocardial extracellular space, was not used in this work and warrants ongoing evaluation in DMD cardiomyopathy .This study documents evidence of scar burden at an age earlier than has been previously described for DMD-associated cardiac disease . As suchDMD: Duchenne muscular dystrophy; BSA: Body surface area; CMR: Cardiovascular magnetic resonance; LVEDV: Left ventricular end-diastolic volume; LVEF: Left ventricular ejection fraction; LGE: Late gadolinium enhancement; SSFP: Steady state free precession; OR: Odds ratio; CI: Confidence interval.The authors declare that they have no competing interests.KNH, WM and DWB contributed to all aspects of the manuscript conception, design, data analysis, collection, critical revision and final approval. MDT, SVR and LHC participated in the design and coordination of the study and helped to draft the manuscript. HRA provided statistical support and helped to draft the manuscript. JLJ and ROD helped draft, reviewed and revised the manuscript. All authors read and approved the final manuscript.