It remains unknown if LSRdias also related to outcome in these patients.Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain . Global and segmental LSdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors . NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved , global LSRdias , and E/LSRdias  remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S−1 . Global LSRdias <0.85 S−1 predicted a 4-fold increased mortality in CA patients with preserved LVEF.Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5–35 months) follow-up. Baseline mitral annular plane systolic excursion , global LSRSTI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF. Systemic amyloidosis is an uncommon multisystem disease caused by the deposition of insoluble proteins in various tissues and organs. Patients with primary light-chain (AL) amyloidosis have a very poor prognosis with a median survival of 13 months from diagnosis The optimal diagnostic workup for patients with suspected CA includes a combination of medical history, cardiac imaging , electrocardiography, and histopathological examination . Echocardiography is routinely used to detect cardiac abnormalities in suspected CA. The echocardiographic features of advanced CA include concentric left ventricular (LV) and right ventricular (RV) wall thickening, biatrial enlargement, granular sparkling pattern of myocardium, and diastolic dysfunction dias) on mortality risk in CA patients with preserved left ventricular ejection fraction (LVEF).Diastolic abnormalities are generally recognized as the earliest manifestation of CA Written informed consent was obtained from all patients or their guardians. The study was approved by Local Ethics Committee at the University of Würzburg and conducted in accordance to the Declaration of Helsinki.Forty-one patients with biopsy-proven systemic AL amyloidosis and typical echocardiographic features of cardiac involvement A standard 12-lead electrocardiography was recorded. Low QRS voltage was defined as peak to peak QRS amplitudes in each limb lead of less than 0.5 mV, and less than 1.0 mV in any precordial lead 3 – LVEDD3)] +0.6.A standard transthoracic echocardiography was performed . All measurements were performed offline in a remote workstation  by a single experienced operator (DL). Standard two-dimensional (2D) images and Doppler recordings were obtained according to guidelines Pulsed-wave Doppler was performed in the apical 4-chamber view to obtain mitral inflow velocities for LV filling pattern evaluation. Peak velocity of early (E) and atrial (A) diastolic filling and deceleration time of E wave (DT) and isovolumic relaxation time (IVRT) were measured as well as the E/A ratio was calculated. Tissue Doppler early diastolic mitral annular velocity (E′) was acquired at the septal annular site. Diastolic function was graded according to recent guidelines sys) and early diastolic (LSRdias) strain rate as well as peak systolic strain (LSsys) were measured in the basal, mid, and apical segments of septal and lateral walls. Global LSRsys, LSRdias and LSsys of all six segments were calculated . All 2D grey scale images of standard apical 4-chamber view were recorded with a frame rate of 50 to 80 frames per second. A region of interest was created by manually outlining the endocardial border at end-systolic frame on the apical 4-chamber view. The system automatically tracked the tissue within the region and divided the myocardium into six segments. Longitudinal strain rate and strain curves were obtained, and longitudinal peak systolic . Inter-observer variation was done on the same datasets by two observers (DL and KH). The intra- and inter-observer variability was assessed by Bland and Altman analysis and intraclass correlation coefficient.Reproducibility of LSRAll patients were followed by clinical visit or telephone interview. The primary end point was all-cause death.t-test after normalization if indicated. Categorical data were compared across groups using a Chi-square test or Fisher's exact test, as appropriate.Continuous variables were presented as mean ± standard deviation (SD) or median (quartiles) and categorical variables as percentages. Non-normally distributed variables were normalized prior to analysis using a natural logarithm or inverted values. Differences on continuous data between two groups were compared using a Student P<0.05. Statistical analysis was performed using IBM SPSS, version 21 for Windows (SPSS).The optimal cut-off values of deformation variables were derived from receiver operating characteristic (ROC) analysis by maximizing the sum of the sensitivity and specificity. Survival curves were calculated by the Kaplan-Meier method, and compared by log-rank tests. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using univariable and multivariable Cox proportional-hazards regression analysis. The variables with P<0.05 in the univariable analysis were included in the multivariable models. Independent prognostic factors were identified by the multivariable Cox models with the backward stepwise method (likelihood ratio) adjusted for age and gender. Incremental model performance was assessed by changes in the Chi-square value for the regression models. Statistical significance was defined as P = 0.017, P = 0.041, Baseline clinical characteristics and electrocardiographic findings were similar between survivors and non-survivors except that the number of involved organs was significantly higher in non-survivors than in survivors (sys tended to be lower in non-survivors than survivors (P = 0.052). The typical longitudinal apex-to-base strain gradient  was evidenced in 67.5% CA patients but did not discern between survivors and non-survivors . Diastolic strain rate analysis showed that global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (both P<0.05).Among systolic deformation parameters , mid-sepsys, LSsys, and LSRdias were 0.04±0.48 S−1, 0.66±5.48%, and −0.01±0.58 S−1 for intra-observer agreement and 0.02±0.52 S−1, 0.36±5.64%, and 0.04±0.68 S−1 for inter-observer agreement. Intraclass correlation coefficient for LSRsys, LSsys, and LSRdias were 0.877 (95% CI 0.831–0.911), 0.907 (95% CI 0.871–0.933), and 0.913 (95% CI 0.880–0.938) for intra-observer reliability and 0.854 (95% CI 0.800–0.894), 0.903 (95% CI 0.865–0.930), and 0.887 (95% CI 0.844–0.918) for inter-observer reliability.Systolic and diastolic deformation parameters in 120 segments were measured for the intra- and inter-observer variability. Mean differences ±2 SD for LSRsys, global LSRdias, basal-septal LSRdias and E/LSRdias . dias was closely related to global LSRdias (R = −0.712). Therefore, E/LSRdias and global LSRdias were respectively added into two multivariable models (P = 0.010), global LSRdias , and E/LSRdias  remained independently predictive of increased mortality risk (Nineteen patients (46%) died during a median follow-up time of 16 (5–35) months. As shown in ity risk .dias outperformed conventional diastolic parameters (E′ and E/E′) as well as E/LSRdias for predicting mortality in this cohort . CA Patients with global LSRdias <0.85 S−1 was related with a 4-fold increase of all-cause mortality than those with global LSRdias ≥0.85 S−1 . In Model II, adding conventional echocardiographic parameters (MAPSE and E/E′) to Model I enhanced the explanatory power . Adding global LSRdias (Model III) further improved the prognostic performance  including age, NYHA class and number of involved organs were entered in the first step of a multivariable Cox model are predictive of mortality  for predicting outcome and improved the risk stratification in CA patients with preserved LVEF(>50%). Reduced global LSRdias (<0.85 S−1) independently predicted a 4-fold increased mortality in these patients, while mid-septal LSsys only showed borderline significance (P = 0.052) on outcome. Adding global LSRdias to clinical data and conventional echocardiographic variables offered incremental prognostic value.This is the first attempt to explore the prognostic value of STI-derived global LSRsys at apical segments and significantly reduced LSsys at mid and basal segments is a typical strain pattern for CA sys) was evidenced and associated with increased mortality. But MAPSE and mid-septal LSsys are only univariable but not independent predictors of all-cause mortality. The reason for the non-independent predictive value of MAPSE and mid-septal LSsys might originate from the fact that LVEF was preserved and by nature related to a better systolic function in our cohort.It was shown that LV wall thickening and reduced LVEF are associated with higher mortality risk in CA patients IVR) derived by STI is strongly related to hemodynamic indices of LV relaxation both in an animal model and in patients, and E/SRIVR can predict LV filling pressures, particularly in patients with normal ejection fraction IVR with LV stiffness coefficient in heart failure patients with normal ejection fraction by a simultaneous comparison during invasive conductance catheterization IVR was not quantified as with speckle tracking imaging the temporal resolution is not good enough for the detection of change of deformation during this short period. Thus, only global and segmental strain rate during early LV filling were assessed. The study by Wang et al. also reported that strain rate during early LV filling (i.e. SRdias) was negatively correlated to tau (r = −0.56) and pulmonary capillary wedge pressure (r = −0.46) in humans, although this association was weaker than that of SRIVRdias, SRIVR, E/SRdias, E/SRIVR) and LV relaxation, strain rate imaging is not superior in diagnosing diastolic dysfunction in patients with preserved EF as compared with established tissue Doppler parameter E/E′ dias and E/LSRdias remained independent predictor of mortality in these patients. Moreover, ROC analysis showed global LSRdias outperformed conventional diastolic parameters  for predicting mortality in this cohort. In a previous study, Kim et al. reported that LSRdias was related with LV geometric remodeling patterns in hypertensive subjects, and the lowest LSRdias value was evidenced in patients with concentric hypertrophy dias was detected in CA patients with preserved LVEF since concentric hypertrophy is one typical pathological feature of these patients. Our study extends previous findings by demonstrating that LSRdias is not only reduced but also a prognostic marker for poor outcome in CA patients with preserved EF, superior to other diastolic parameters.Diastolic abnormalities are typical features of CA and related to the degree of amyloid infiltration in heart, LV compliance becomes increasingly reduced resulting in a “stiff ventricle” with increasing myocardial amyloid infiltration When focusing on prognosis in CA, three different aspects should be evaluated: 1) Clinical symptoms, 2) general organ involvement, and 3) cardiac stage of disease progression. In our cohort, NYHA class and number of non-cardiac organs involved were related to increased mortality.Kristen et al. found that NYHA class was a risk factor but number of organs involved (including heart) was not associated with increased mortality in AL patients P = 0.012). Adding conventional echocardiographic parameters (MAPSE and E/E′) to Model I (Model II) enhanced the explanatory power (P = 0.009 vs. Model I). Adding global LSRdias (Model III) further improved the prognostic performance (P = 0.020 vs. Model II). Thus, on top of clinical profile and conventional echocardiographic markers, a reduction in global LSRdias serves as an independent and incremental risk predictor of all-cause death in CA patients with preserved LVEF.Our results showed that entering clinical variables including age, NYHA class and number of involved organs in the multivariable Cox regression model are predictive of mortality (Model I, The sample size was relatively small in this study. Future studies with larger patient cohort are warranted to verify the finding in the present study and to compare early diastolic strain rate changes between patients with light chain amyloidosis and non-light chain amyloidosis. Recent studies showed that high sensitive cardiac troponin-T might play an important role for the assessment of prognosis in AL amyloidosis In addition, rapid early diastolic untwist in normal hearts servers as an important component of diastolic suction, and it could be diminished in the earliest stages of diastolic dysfunction dias serves as an independent and incremental risk predictor of all-cause death in CA patients with preserved LVEF.Speckle tracking imaging-derived diastolic deformation improves the risk assessment of CA patients with preserved LVEF. A reduction in global LSR


Edema is an early feature of acute myocardial injury. Signal-intensity based analysis of T2-weighted images is established but known to have a high variability. T2 mapping and, more recently, T1 mapping have been proposed for assessing myocardial edema. We investigated the ability to accurately detect myocardial edema following defibrillation with T2 maps and two different T1 mapping sequences, using histology as a standard of reference.Myocardial damage was induced in ten anesthetized pigs by cumulative electric shocks with a total energy of 1000J. Images were acquired five hours after damage with two different T1 techniques  and T2 mapping. In addition, six pigs underwent the same protocol without injury. After euthanasia, tissue was randomly sampled from segments with injury by at least one of the mapping approaches. At least two random biopsies were also obtained from the control animals. In a blinded fashion, hematoxylin and eosin stains of these samples were assessed for intercellular and interstitial edema using a semi-automatic planimetry technique. Cellular edema was quantified using a mean area of 5-8 muscle fibers in short axis view. To analyze for interstitial edema, a semi-quantitative planimetric analysis of three representative areas of each sample in 20× magnification was performed. ROC curves were generated and compared to histology as the gold standard.There was consistency between MOLLI and SASHA maps vs. histological results of the mean cell area and percentage interstitial space. The comparison of MOLLI to mean cell area was found to have a high negative predictive value with a sensitivity of 0.90 and specificity of 0.71 (p < 0.01). As compared to percentage interstitial space, MOLLI had a sensitivity of 0.95 and specificity of 0.63 (p < 0.01). For mean cell area and percent interstitial space the sensitivity of T2 mapping was 0.91 yet specificity was low .Compared with histology, T1 mapping sequences appear to be more accurate in correctly identifying myocardial edema than T2 mapping.Funding is provided by the Montreal Heart Institute Foundation and the Canadian Foundation for Innovation.


This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using n = 27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1, 3, 7, and 14 days. PC (n = 27) was performed just after the reperfusion. At the time of the study, 125I-TNC-Ab (1.0 to 2.5 MBq) was injected. Six to 9 h later, to verify the area at risk, 99mTc-MIBI (100 to 200 MBq) was injected intravenously just after the LCA reocclusion, with the rats sacrificed 1 min later. Dual tracer autoradiography was performed to assess 125I-TNC-Ab uptake and area at risk. To examine the ventricular remodeling, echocardiography was performed 2 M after reperfusion in both groups.In control rats (125I-TNC-Ab uptake ratio at 1 day after reperfusion was 3.73 ± 0.71 and increased at 3 days (4.65 ± 0.87), followed by a significant reduction at 7 days  and14 days . PC attenuated the 125I-TNC-Ab uptake throughout the reperfusion time from 1 to 14 days; 2.59 ± 0.59 at 1 day, P < 0.05: 3.10 ± 0.42 at 3 days, P < 0.005: 1.93 ± 0.37 at 7 days, P < 0.05: 1.40 ± 0.07 at 14 days, P < 0.001. In echocardiography, PC reduced the ventricular end-diastolic and systolic dimensions (1.00 ± 0.06 cm to 0.83 ± 0.14 cm (P < 0.05) and 0.90 ± 0.15 cm to 0.62 ± 0.19 cm (P < 0.05), respectively) and prevented a decline of ventricular percentage fractional shortening .In control rats, 125I-TNC-Ab imaging may be a way to monitor myocardial injury, the subsequent repair process, and its response to novel therapeutic interventions like PC by visualizing TNC expression.These data indicate that  Extracellular matrix, in addition to cardiac cells, is essential to maintain the integrity of cardiac tissue and plays an important role not only in providing structural and mechanical support but also in modulating cell function. Cardiac repair after myocardial infarction is regulated through activation and suppression of the acute inflammatory process. Necrosis of cardiomyocytes provokes acute inflammation to remove dead cells and matrix debris, followed by timely infiltration of the infarcted myocardium with myofibroblasts. These secrete large amounts of extracellular matrix proteins, leading to replacement of myocardial dropout with mature collagen-based scar tissue in the infarct. These inflammatory and fibrotic processes are critically involved in the pathogenesis of ventricular remodeling, which is accompanied by changes in the structure and composition of the extracellular matrix and is a significant predictor of left ventricular dysfunction and an adverse prognosis .Tenascin-C (TNC), an extracellular matrix glycoprotein, could provide important biological signaling that influences cell motility, proliferation, differentiation, survival, or apoptosis via cell-extracellular matrix interaction during tissue remodeling of various tissues ,3. TNC aRecently, other groups and we have reported increased serum TNC in heart failure patients, reflecting the severity and progression of ventricular remodeling -15. Of p125I-labeled anti-tenascin-C antibody (125I-TNC-Ab) and left ventricular remodeling in a rat model of acute ischemia and reperfusion.Postconditioning, defined as several repeated cycles of intermittent reperfusion and reocclusion after an index ischemia, is cardioprotective in a canine model of ischemia and reperfusion . Howevern = 54) were anesthetized with an intraperitoneal administration of 40 mg of pentobarbital per kilogram and ventilated mechanically with room air. After left thoracotomy and exposure of the heart, a 7-0 polypropylene suture on a small curved needle was passed through the myocardium beneath the proximal portion of the left coronary artery (LCA), and both ends of the suture were passed through a small vinyl tube to make a snare. The suture material was pulled tight against the vinyl tube to occlude the LCA. Myocardial ischemia was confirmed by regional cyanosis of the myocardial surface and ST-segment elevation on the ECG. In control rats, LCA was occluded for 30 min and reperfusion was obtained by release of the snare and confirmed by the finding of a myocardial blush over the area at risk. In the group of rats with postconditioning, after the 30 min of LCA occlusion, 10 s of reperfusion followed by 10 s of LCA reocclusion was repeated six times at the beginning of the reperfusion. The snare was left loose on the surface of the heart for reocclusion of the LCA just before sacrifice to identify the area at risk (18). Groups of animals with and without postconditioning were studied at 1 , 3 , 7 , and 14 days  after reperfusion. At the time of the study, 125I-TNC-Ab (1.0 to 2.5 MBq) was administered via a tail vein. Six to 9 h afterward, 100 to 200 MBq of 99mTc-MIBI was injected via a tail vein just after the reocclusion of the proximal portion of the LCA for delineation of the area at risk. One minute later, the rat was euthanized and the heart was removed for analysis. The excised heart was rinsed in saline, frozen in isopentane, cooled in dry ice, and embedded in methyl cellulose. Serial short-axis heart sections 20 μm thick were obtained by sectioning on a cryostat to create a series of rings for autoradiography.All experimental procedures involving animals were conducted in accordance with the institutional guidelines set by the Institute for Experimental Animals, Kanazawa University Advanced Science Research Center. Eight to 11-week-old male Wistar rats (n = 6) and without postconditioning (n = 6) was performed. Two months later, echocardiography was performed to evaluate the left ventricular dimensions and function. After echocardiography, 100 to 200 MBq of 99mTc-MIBI was injected via a tail vein. One minute later, the rat was euthanized and the heart was removed for autoradiography.To evaluate the left ventricular remodeling 2 months after reperfusion, 30 min of LCA occlusion followed by reperfusion with  was added to 60 μL of antibody in PBS (0.32 mg/mL). Following mixing, 4 μL of chloramine-T aqueous solution (1 mg/mL) was added. After 15 min at room temperature, the reaction was quenched with 20 μL of Na2H2SO5. The crude product was purified with a PD-10 column  with saline as the eluate. The radiochemical purity of 125I-TNC-Ab was determined by thin layer chromatography (TLC). TLC analyses were performed with silica plates  with saline as the developing solvent. Radiochemical purity was defined as the percent protein-bound activity, which was assessed by dividing the counts at the TLC origin by the total TLC counts. Specificity of the 125I-TNC-Ab was approved by the autoradiography with 125I-labeled nonspecific antibody in the previous study  × 100.Echocardiography was performed in rats with . After purification by PD-10, 125I-labeled anti-TNC antibody showed a radiochemical purity of over 99%.125I-TNC-Ab uptake areas against area at risk in rats without postconditioning at 1, 3, 7, and 14 days after reperfusion tended to decline over time  , with these differences not statistically significant  , followed by a significant reduction at 7 days after reperfusion  and followed by further reduction at 14 days .In the quantitative analysis, 125I-TNC-Ab uptake ratio throughout the time from 1 to 14 days after reperfusion; 2.59 ± 0.59 at 1 day, P < 0.05: 3.10 ± 0.42 at 3 days, P < 0.005: 1.93 ± 0.37 at 7 days, P < 0.05, 1.40 ± 0.07 at 14 days, P < 0.001 . Postconditioning reduced the LVEDD    .Echocardiographic data at 2 months after ischemia and reperfusion are given in Figure 125I-TNC-Ab throughout the entire period until 2 weeks after ischemia and reperfusion.The present study revealed that ischemic postconditioning significantly attenuated TNC expression as demonstrated by the accumulation of Postconditioning also attenuated left ventricular remodeling and reduced infarct size at 2 months after ischemia and reperfusion. These data suggest that attenuation of TNC expression during the acute to subacute phase of tissue healing after infarction by postconditioning might be related to the attenuation of ventricular remodeling at 2 months after myocardial infarction, although whether the relationship is cause and effect or simple association remained to be elucidated.Since the discovery of the cardio-protective effect of postconditioning defined as rapid sequential intermittent interruption of blood flow applied during early moments of reperfusion in a canine model of 60 min of myocardial ischemia and reperfusion , the carOn the other hand, the effect of postconditioning on tissue repair including interstitial signaling and remodeling has been scarcely investigated. After myocardial infarction in the permanent ligation model, TNC is markedly but transiently upregulated during the early phase of tissue repair, is predominantly produced by interstitial fibroblasts in the vicinity of the injured cardiomyocytes but not by cardiomyocytes themselves , and is Although it is difficult to conclude whether TNC is more beneficial or detrimental for tissue healing and reconstruction after myocardial infarction, a timely and proper degree of TNC expression might be beneficial for myocardial tissue repair, whereas prolonged overexpression of TNC might interfere with sound tissue repair and cause inappropriate reconstruction of infarcted ventricle, resulting in so-called ventricular remodeling.In the mice model of permanent ligation of the coronary artery, ventricular remodeling in the TNC knockout mouse was significantly reduced and cardiac function was improved compared with the wild type at day 28 after myocardial infarction . In pati125I-TNC-Ab imaging approach after myocardial ischemia and reperfusion provides an opportunity to monitor the effect of postconditioning, potentially leading to novel therapeutic interventions, directed at the reducing the extracellular matrix remodeling occurring after myocardial infarction.The application of target radionuclide imaging of regional TNC expression as proposed in the present study holds the potential to quantify the extent, amount, and localization of TNC expression and relate the pathophysiological events to the tissue repair and remodeling occurring after severe myocardial ischemia. The current study also demonstrated that the One of the limitations of this study was that the left ventricular function was assessed on only short axis slices in echocardiography, because remodeling and dilation mainly occur on the apical part of the ventricle after anterior myocardial infarction.123I-TNC-Ab is required. Labeling with 123I can easily be performed in the same way as for 125I. In vivo SPECT imaging by 111In-TNC-Ab has already been obtained successfully at 6 h after administration of the tracer in a rat model of 3 days after permanent coronary artery ligation. The biodistribution study of 111In-TNC-Ab showed that target-to-blood, target-to-lung, and target-to-liver ratios were 3.3, 2.0, and 0.35, respectively [125I-TNC-Ab in the infarcted area, resulting in a decent target-to-blood ratio (1.85 ± 0.14 at 5 h and 4.8 ± 1.0 at 24 h after injection) and good target-to-lung ratio (1.97 ± 0.19 at 5 h and 4.9 ± 1.2 at 24 h after injection), indicate the feasibility of in vivo imaging at 5 h or later after tracer injection [111In-TNC-Ab.For future clinical application as a SPECT agent, ectively . On the njection . However125I-TNC-Ab after myocardial ischemia and reperfusion. Postconditioning also attenuated left ventricular remodeling at 2 months after ischemia and reperfusion. The obtained data also implied that radiolabeled TNC-Ab imaging may be useful as a noninvasive way to monitor the changes occurring during the process of myocardial injury and its repair by various therapeutic interventions after ischemia and reperfusion by visualizing TNC expression.The present study demonstrated that postconditioning attenuates the whole process of TNC expression demonstrated by


T1 mapping allows quantitative myocardial assessment, but its value in clinical routine remains unclear. We investigated, whether the average native myocardial T1 value can be used as a diagnostic classifier between healthy and diffuse diseased myocardium.Native T1 mapping was performed in 54 persons with healthy hearts and in 150 patients with diffuse myocardial pathologies (coronary artery disease (CAD): n = 76, acute myocarditis: n = 19, convalescent myocarditis: n = 26, hypertrophic cardiomyopathy (HCM): n = 12, dilated cardiomyopathy (DCM): n = 17) at 1.5 Tesla in a mid-ventricular short axis slice using a modified Look-Locker inversion recovery (MOLLI) sequence. The average native myocardial T1 value was measured using dedicated software for each patient. The mean as well as the range of the observed average T1 values were calculated for each group, and compared using t-test. The ability of T1 mapping to differentiate between healthy and diffuse diseased myocardium was assessed using receiver operating characteristic analysis (ROC).The mean T1 value of the group “healthy hearts” (955±34ms) differed significantly from that of the groups DCM , HCM , and acute myocarditis . No significant difference was observed between the groups “healthy hearts” and CAD  or convalescent myocarditis . The average native T1 value varied considerably within all groups  and overlapped broadly between all groups. ROC analysis showed, that the average native T1 value does not allow for differentiating between healthy and diffuse diseased myocardium, except for the subgroup of DCM.The average native T1 value in cardiac MR imaging does not allow differentiating between healthy and diffusely diseased myocardium in individual cases. Due to recent technical developments in cardiac magnetic resonance imaging (CMR), quantitative assessment of the myocardium has become feasible and T1, T2, and T2* times can be measured to quantify tissue properties. Different CMR techniques have been described for quantitative in vivo T1 measurement, which rely either on inversion recovery, saturation recovery, or a combination of both techniques. The sequences employed are called modified Look-Locker inversion recovery (MOLLI), shortened modified Look-Locker inversion recovery (ShMOLLI), saturation recovery single-shot acquisition (SASHA), and saturation pulse prepared heart-rate-independent inversion recovery (SAPPHIRE) . The nat2 (range 17.0–41.3 kg/m2)). Assignment to the above mentioned diagnoses was performed by two experienced cardiologists in consensus using all available clinical information  as well as the CMR results (except of T1 mapping). Subjects, who were referred for CMR as part of a preventive check-up and who did neither show any pathology in CMR nor any clinical cardiac abnormality, were defined as having a “healthy heart”. Diagnosis of myocarditis, DCM, HCM, and CAD was made in accordance to established diagnostic criteria [The retrospective analysis of the data was approved by the local ethic committee of the University Hospital Essen. Only data was analyzed and all patient records/ information was anonymized and de-identified prior to analysis. Between February and June 2015, 401 unselected consecutive subjects referred for CMR were primarily included in this study. Consecutively, 42 of these subjects had to be excluded due to T1 mapping artifacts caused by breathing, off-resonance, susceptibility, and ventricular motion . Additiocriteria –16. Paticriteria ,16,17. A2 to 420 x 380 mm2, flip angle 80°, bandwidth 930 Hz/pixel, GRAPPA R = 2, 24 reference lines, slice thickness 6 mm). Native T1 mapping was performed in end-diastole using a modified Look-Locker inversion recovery (MOLLI) investigational sequence  in a single mid-ventricular short axis slice, as previously described  [2, flip angle 30°, bandwidth 300 Hz/pixel, GRAPPA R = 2, 24 reference lines, slice thickness 6 mm) to assess late gadolinium enhancement (LGE).All MR scans were performed on a 1.5-Tesla MRI system . For cine imaging steady-state free precession (SSFP) images were acquired in standard long and short axis views  ,19. The http://segment.heiberg.se), while after manual definition of the endocardial and epicardial contours, 40% of the resulting myocardial area was excluded to minimize partial volume artifacts  and one radiologist (>10 years of CMR experience) evaluated all CMR studies, except for the T1 mapping, in consensus. Besides qualitative CMR reading, the maximal end-diastolic thickness of the interventricular septum was measured and left ventricular (LV) volumetric quantification was performed using the Argus software , as previously described . AdditioStatistical analysis was done using MedCalc . A D’Agostino-Pearson test was used to test for normal distribution. Normally distributed data are given as mean ± standard deviation (SD). Categorical data are given as absolute numbers or frequencies. Testing for differences of average T1 values and volumetric data between the different groups  was performed using unpaired t-test. Receiver operating characteristic (ROC) analysis was used to test, whether the average native T1 value allows distinguishing between healthy and diffused diseased myocardium. Statistical significance was defined as p < 0.05.Demographic features as well as detailed analysis of LV structural and functional parameters  are given for the group of subjects with healthy hearts and all assessed cardiac pathologies in The average native myocardial T1 value ranged in the group of subjects with healthy hearts between 838 and 1018 ms , and itsSubgroup analysis revealed a significant difference in the mean of the average native T1 value between the group of subjects with healthy hearts and the group of patients suffering from DCM (p < 0.001), the group of patients suffering from HCM (p = 0.035), and the group of patients suffering from acute myocarditis (p = 0.044). No significant differences were observed between the group healthy hearts and the group convalescent myocarditis (p = 0.240) or between the group healthy hearts and the group CAD (p = 0.453). Overall, data analysis revealed six outliners. But as outliner exclusion did not lead to a relevant change in statistical results , these outliners were not excluded to not restrict the general validity of the study.A significant inter-individual variance of the average native T1 values was observed in all analyzed groups ; Table 1This cardiac MR imaging study investigated, whether the average native myocardial T1 relaxation time allows distinguishing between healthy and diffuse diseased myocardium. Our study shows that the native myocardial T1 relaxation time allows distinguishing between certain groups of patients, but that this parameter fails to distinguish between healthy and diffuse diseased myocardium in individual subjects.Although the native T1 relaxation time is a genuine tissue parameter at a given field strength, it is well known, that T1 values measured in clinical routine are affected not only by the type of sequence used but although by sequence parameters as well as by the MR system itself.Therefore, comparison of our data with previous studies is only possible to a limited degree. Messroghli et al., who used a MOLLI sequence at 1.5 T on a Philips Gyroscan Intera MR system, reported a mean native T1 value of 977 ± 63 ms for subjects with healthy hearts . KaramitIn agreement to previously published studies, our results show that the assessment of the average native myocardial T1 relaxation time can be used to differentiate between certain patient groups since we found, that the mean native myocardial T1 value of the DCM, HCM, and acute myocarditis group differed significantly from that of the group of healthy individuals. The higher mean native myocardial T1 value in the DCM and HCM group can be explained by an increased interstitial space in DCM and HCM due to diffuse myocardial fibroses . ConcordIn addition to DCM, HCM, and myocarditis, we assessed the native myocardial T1 values in patients with CAD, whereas we enrolled only patients without myocardial infarction in the mid-ventricular short axis slice used for T1 mapping. Similar to the above mentioned pathologies CAD leads to a diffuse myocardial injury, since it is well known, that coronary micro-embolization frequently occurs in CAD, which results in multiple myocardial micro-infarcts mainly in the mid-myocardial layers . From a Although the calculation of the average native myocardial T1 relaxation time may be helpful to distinguish between certain groups of patients with different cardiac pathologies, our study shows that overall the native myocardial T1 value fails to discriminate between healthy and diffuse diseased myocardium in individual cases. Our ROC analysis showed that only in case of DCM the native myocardial T1 relaxation time allows distinguishing healthy and diffuse diseased myocardium, and even in this case the sensitivity is comparably low. Reflecting individual native myocardial T1 values instead of analyzing mean values in patient groups shows the reason for the poor performance of the native myocardial T1 value as discriminator between healthy and diffuse diseased myocardium in individual cases: the substantial inter-individual variance of the native myocardial T1 value both in healthy individuals as well as in diffuse myocardial pathologies. Unfortunately, the majority of studies concerning native T1 mapping in diffuse myocardial pathologies focused on the analysis of differences in the mean value between different groups of patients and healthy volunteers, despite the fact that the differentiation between healthy and diffuse diseased myocardium on individual patient level is from greater clinical interest.However, it must be noted, that some studies reported, that native T1 mapping allows discrimination between healthy and diffuse diseases myocardium in individual cases. Hinojar et al. reported recently, that the native myocardial T1 value allows distinguishing between acute myocarditis and healthy hearts with a sensitivity of 96% and specificity of 100% . While tThe present study has some limitations. First and foremost, like in previous studies we performed T1 mapping for practical reasons in regard to the overall CMR acquisition length only in one mid-ventricular short axis slice ,18. TherIn conclusion, our question, whether native T1 mapping in cardiac MR imaging can differentiate between healthy and diffuse diseased myocardium, must be answered with “yes” and “no”, since the native myocardial T1 relaxation time allows discriminating between groups of patients with certain diffuse myocardial pathologies and a group of healthy individuals, but does not allow differencing between healthy and diffuse diseased myocardium in individual subjects.S1 Table(XLSX)Click here for additional data file.


Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. Heart failure (HF) affects more than 6 million people in the United States, and of those, approximately 10% suffer from advanced HF, requiring evaluation for mechanical circulatory support or heart transplantation (HTx) . As of tThe availability of an acceptable donor heart became the limiting factor for heart transplantation almost two decades ago ,8. This The International Society of Heart and Lung Transplantation (ISHLT) registry reported a total of 4196 adult and pediatric heart transplants performed in 2012 worldwide . The majWhile these numbers are encouraging, they prompt consideration regarding the approximate 1 in 5 subjects who die within 1 year of the transplant, and the 1 in 3 who die within 5 years . This reThe availability of donor organs is clearly the limiting factor in all solid organ transplantation, and the heart is no exception. The donation after brain death (DBD) represents virtually the entire cohort of heart donors  3,8,9].,8,9.3,8,i.e., hypertension and/or diabetes) . Th. Th22]. HTx from DCD is characterized by inherent challenges related to cardiac death and organ harvesting ,25,26,27The main steps of the DCD process are described below and a graphic timeline with the average time intervals for each step is reported in The increasing availability of DCD donors represents a unique opportunity to increase the number of hearts available for transplantation . A recenMechanical circulatory support devices, such as left ventricular assisting devices (LVADs), are often used to temporarily assist patients waiting for heart transplantation . LVADs hThe economic impact of heart transplantation from DCD donors is also quite large . Many paIn order to consider heart transplantation after DCD, it is necessary to characterize the type and degree of cardiac injury occurring during the DCD process and to develop the strategies needed to protect, preserve, and prepare the hearts for re-implantation ,25. A reDonation from living donors is feasible in many forms of solid organ transplantation, but for obvious reasons, it is not an option for HTx . The success of organ transplantation from DBD is inferior compared to the transplantation of organs from living donors, as reported by some studies that suggest brain damage somehow impairs the function of the transplanted organ ,36,37,38Retrospective studies have showed that the time of ischemia inversely correlates with the success of organ transplantation . In DBD,vs. normothermia (36.5–37.5 °C) after brain death had significantly decreased rates of delayed graft dysfunction [A recent randomized study conducted in DBD kidney donors shows that kidneys from donors kept in mild hypothermia (34.0–35.0 °C) function . Ischemia represents one of the challenges of the organ procurement and storage protocols ,44,46,47Unlike other solid organs, however, the heart has a high metabolic need that makes the heart particularly sensitive to ischemia and to reperfusion injury. The use of DBD characterized a giant leap forward in the heart transplant field, leading to surgical success and to a functional transplanted heart. These considerations have historically prevented the use of DCD hearts for transplantation due to the fear of early graft failure . Warm isNeurohormonal activation during DCD heart transplantation contributes to further damage before the cardiocirculatory arrest ,64. RepeFrom the identification of the donor to the transplantation, the donor heart is exposed to several types of injury . Each ofThe explanted heart from DCD is therefore injured before procurement by severe hypoxia and the surge of plasma catecholamines. Once transplanted in the recipient, the explanted DCD heart is exposed to the ischemia-reperfusion injury, leading to cardiac dysfunction. Once the heart is grafted and beating, the transplant faces the additional hurdles of immune-mediated rejection ,8. With the progress of donor-recipients matching programs and immune-suppressive therapies, acute antigen-mediated rejection has become less prominent compared to the past . Howeveri.e., ATP, adenosine, hydrogen and potassium ions, and the release of intracellular alarmins) are referred to as Damage Associated Molecular Patterns (DAMPs) and serve as the initial triggers for the sterile inflammatory response [Pre-clinical and clinical studies have highlighted that the innate immune response, which is an antigen-independent inflammatory mechanism, contributes to organ dysfunction and enhances acute allograft rejection ,67. The response ,69. DAMPresponse ,68,69. PThe inflammasomes are the first-line element of sterile inflammation . They acRecruitment of caspase-1 into the inflammasome favors its autocatalytic activation, a step necessary for the processing of the pro-inflammatory cytokines of the IL-1 family, IL-1β and IL-18 ,71. The ex vivo experiments using human blood have shown contrasting effects of catecholamines on the release of IL-1β. A physiological rise of catecholamines induces IL-1β [The deleterious effects of the procurement process of the donor heart are not well-defined. In DBD, the cardiovascular system has impaired sympathetic and parasympathetic autonomic control, causing changes in the myocardial perfusion and cardiac output, and increasing myocardial levels of adenosine, lactate and catecholamine ,81. Theses IL-1β . Howeveres IL-1β . This dies IL-1β .Recent preclinical studies have shown that in DBD donors the levels of IL-1β are increased in the heart tissue and in the plasma ,91,92. Ai.e., HMGB1 and IL-17A), engaging more neutrophils in the transplanted heart [i.e., Toll-like receptor-4 (TLR-4) for HMGB1  refers to reduced heart function in the early post-operative period, due to left and/or right ventricular impairment requiring inotropes treatment and/or mechanical circulatory assist devices ,99,100. Pro-inflammatory cytokines  have cardiodepressant activity and thus may contribute to PGD ,101. HigGraft failure is the leading cause of death for all heart transplant recipients, followed by infection and multiple organ failure . Hyperacute rejection is an antibody-mediated rejection due to the presence of pre-formed antibodies in the recipient . AntibodTwo different types of acute graft rejection can occur: acute cellular rejection (ACR) and acute antibody-mediated rejection (AMR) . RejectiAMR and ACR also increase the incidence of cardiac allograft vasculopathy (CAV), a type of coronary artery disease associated with late rejection, which increases the risk of graft failure and death ,106. CAVThe improvement in our knowledge on the pathophysiological mechanisms of acute and chronic rejection, CAV, coupled with an increase in the number of heart donors and improved organ preservation during procurement, storage and transplantation may be the key to augmenting the numbers and success of future HTx.T- and B-lymphocytes mediate the rejection mechanisms of ACR and AMR ,106. T-lInnate immunity is a mechanism activated by ischemia and reperfusion injury and considered an alternative to the adaptive, lymphocyte- and antigen-mediated immunity. This innate immune response, together with the systemic inflammation that follows brain injury or death and the adaptive immunity post-transplantation, induces myocardial injury and dysfunction . vs. DCD). Identifying the central nodes in the sterile inflammatory response common to the ischemic injury, to DBD- and to the DCD-associated myocardial damage will help to develop ad-hoc strategies to reduce graft failure. Innate immunity represents a stereotyped mechanism that has evolved to promptly respond to injury occurring as a consequence of invading microbiologic pathogens (infectious inflammation) or in response to non-infectious tissue injury (sterile inflammation) ,69. As sSeveral types of PRRs have been identified; some are involved exclusively in the pathogens associated molecular patterns (PAMPs), and others with dual function of recognizing PAMPs and DAMPs . Interleukin-1α (IL-1α) is expressed on the endothelium of coronary arteries and increases T-cell adhesion to the endothelium . IL-1α bi.e., MyD88, TIRAP, TRAP and TRIF) [The TLR family of receptors is commonly involved in this type of dual recognition of PAMPs and DAMPs, and among other PRRs, TLRs are better characterized ,111. In nd TRIF) ,110,111.nd TRIF) . HMGB1 ind TRIF) . Expression of TLR-2 and TLR-4 increases due to ischemia-reperfusion injury in kidney transplants and the donor TLR-4 mediates ischemia-reperfusion injury ,115. TLRTLR-2 is increased in human transplanted kidneys during acute rejection. Several experimental studies in the mouse support the role of TLRs in acute rejection . Gene siThe inflammasome has a key role in the early sensing, activation and amplification of inflammation in response to tissue injury. The activation of the inflammasome in the heart requires two independent processes, the priming and the triggering; one without the other is insufficient to induce cardiac dysfunction . in vivo and in vitro [In vivo, purines seem to be important triggers of NLRP3 activation. Inhibition of the ATP-activated purinergic receptor P2X7R, the adenosine receptor AdoR2B, or their individual gene silencing are mechanisms sufficient to blunt caspase-1 activation and to induce cardioprotection [Ischemia triggers the activation of the NLRP3 inflammasome both in vitro ,120. In otection ,75,121. otection . + T-lymphocytes, macrophages and neutrophils. The inflammasome regulates acute graft versus host disease in an experimental model of hematopoietic cell transplantation [versus host disease [Data on the role of the inflammasome during organ procurement, storage, or reperfusion due to transplantation are currently lacking. A recent report showed that IL-18 blockade using IL-18 binding protein (IL-18BP) improved graft survival in a mouse model of syngeneic heterotopic heart transplantation . IL-18BPantation . In the  disease . In the  disease . A recen disease . ASC pos disease . Interes disease .in vitro and in vivo, but it has not been tested in animal models of cardiac diseases [Inflammasome inhibitors to be used in clinical practice today are lacking . A smalldiseases . TargeteReduced NLRP3 activation can be reached by inhibiting the P2X7 receptor . In fact2S, a hydrogen sulfide donor, has also shown promising effects on ischemia-reperfusion injury and inflammasome inhibition [Additional strategies that reduced myocardial ischemia-reperfusion injury by inhibiting caspase-1 in the mouse were alpha-1 antitrypsin (AAT) or derived small peptides. Plasma-derived or human recombinant AAT, or genetically engineered small peptides designed to recapitulate the anti-inflammatory effects of the C-terminal peptide of AAT and other serine protease inhibitors , have shown to significantly reduce infarct size in myocardial ischemia-reperfusion injury in the mouse ,135. Na2hibition .NF-κB signaling, mediated by the TLR or other PRRs and/or cytokine/chemokine receptors, is also an important determinant of inflammasome activation . NF-κB dStudies to characterize the functional role in injury, organ dysfunction and tissue rejection of the inflammasome in the heart, however, are lacking.versus host disease in mice [IL-1β blockers are considered the standard of care for the clinical treatment of inflammasome-mediated diseases ,139,140. in mice . The 3 b in mice ,146,147.Anakinra is currently tested in clinical trials to evaluate its anti-inflammatory and cardioprotective effects in patients with acute myocardial infarction (AMI) and/or heart failure ,150,151.Heart transplantation success is influenced by the intrinsic damage linked to the ischemic and inflammatory injuries during all phases of organ procurement and transplantation. Unfortunately, myocardial injury starts in the donor and continues in the recipient. Understanding the mechanisms of the innate immune responses is vital to reduce graft injury and corroborate the strategies to reduce activation of the adaptive immunity. Progress toward this knowledge will support the development of targeted therapies to be used to preserve or minimize the myocardial injury during heart transplantation, and also to potentially increase the pool of transplantable donor hearts by considering DCD hearts. A better understanding of the innate immune response of the transplanted heart may lead to novel therapeutic strategies to protect the graft from ischemic and inflammatory injury.


CMR can be used to assess the structure and function of athletes' hearts. However, diastolic function is not routinely measured with CMR. Mitral annular (MA) motion, commonly assessed by tissue Doppler imaging, is an important element of diastole that may help to distinguish physiological remodeling from pathological processes of the heart. CMR has been shown to play a useful role in evaluating MA motion. This study aims to characterize the global left ventricular diastolic function in endurance athletes by 3D volume tracking of the MA, using conventional cine-CMR images.CMR studies of 24 high-level endurance athletes (age 22 ± 3) were retrospectively selected from a database. Routine CMR studies from 39 patients with normal hearts (age 42 ± 16) and 29 hypertrophic cardiomyopathy (HCM) patients (age 52 ± 17) with normal ejection fractions were included for comparison. Using normalized cross-correlation, feature-tracking of the atrioventricular junctions was performed over the cardiac cycle, in routine long-axis 2-, 3-, and 4-chamber cine-CMR views. This resulted in 6 spatial MA points per cardiac phase, which were interpolated with a spline for 3D MA reconstruction. The 3D volume swept out by the MA was then calculated; the net sweep volume at a given cardiac phase was derived from the sum of the incremental volumes starting from end-diastole.E) and atrial systole (PSRA), normalized by end-systolic sweep volume (ESSV). Sweep volume acceleration time (ATSV) and deceleration time (DTSV) (relative to the PSRE time). 50% diastolic sweep volume recovery (DSVRT50), defined as the time required in diastole for the MA to recover 50% of its ESSV, normalized by RR interval. Analysis of variance with post-hoc test and binary logistic regression were used for statistical analyses.The resultant 3D MA sweep volume curve and its first derivative were calculated. The following diastolic variables were used Figure : Peak swE, followed by the normal group and then the HCM group ; PSRA was the lowest in athletes, higher in the normal group, and the highest in the HCM group ; DSVRT50 was the shortest in athletes, followed by the normal group and then the HCM group . No statistical differences were observed in ATSV and DTSV between athletes and the normal group. Lastly, the PSRE:PSRA ratio was a significant independent predictor of athletes over the normal group when controlling for age (P = 0.035).As seen in Figure 3D MA sweep volumes derived from cine-CMR demonstrated that athletes had significantly faster early diastolic relaxation, followed by reduced MA motion in atrial systole, and faster diastolic MA sweep volume recovery, when compared to normal subjects and HCM patients.NIH R21-HL108218.


In a systematic review and meta-analysis, Kazem Rahimi and colleagues examine the burden of heart failure in low- and middle-income countries.Please see later in the article for the Editors' Summary Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57%  of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies , and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care  and 11 studies on the management of chronic heart failure in primary care or outpatient settings . The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted  develop heart failure, a life-threatening condition in which the heart no longer pumps enough blood to meet all the body's needs because it has become too weak or too stiff to work properly. Heart failure can affect the left, right, or both sides of the heart, and it can develop slowly (chronic heart failure) or quickly (acute heart failure). Its symptoms include swelling (edema) of the feet, ankles, and legs, tiredness, and shortness of breath. Heart failure, which is most commonly caused by coronary heart disease (blockage with fatty deposits of the blood vessels that supply the heart) or high blood pressure (hypertension), cannot be cured. However, lifestyle changes  and various medications can control heart failure and improve the quality of life of patients.In high-income countries (HICs), heart failure is a common condition that typically consumes 1%–2% of healthcare resources. Experts believe that heart failure may soon become a major public health issue in low- and middle-income countries (LMICs) because fewer people are dying of infectious diseases in these countries than in the past. LMICs need to plan for this eventuality, but little is known about the current burden of heart failure in LMICs. Here, the researchers undertake a systematic review and meta-analysis of published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis uses statistical approaches to combine the results of several studies.The researchers identified 49 published studies and four unpublished databases that provided information on nearly 240,000 hospitalizations for acute and chronic heart failure in 31 LMICs. Across these LMICs, the average age of patients admitted to hospital for heart failure was 63 years, more than ten years younger than the average admission age in HICs. Differences in mean age at presentation, which ranged from 42 years in Cameroon and Ghana to 75 years in Argentina, largely correlated with the human development index  of individual LMICs. Notably, acute heart failure accounted for 2.2% of all hospital admissions in the LMICs for which data were available. Hypertension was the main cause of heart failure in Africa and the Americas, whereas ischemic heart disease was the main cause in all other regions. More than two-thirds of patients were prescribed diuretics for heart failure, whereas only 57% of patients were treated with angiotensin-converting enzyme inhibitors, only 34% were treated with beta-blockers, and only 32% were treated with mineralocorticoid receptor antagonists, the three treatments currently recommended in guidelines for managing heart failure. Finally, on average, patients admitted to hospital for heart failure in LMICs spent ten days in hospital, and 8.3% of them died in hospital .These findings show that the presentation, causes, management, and outcomes of heart failure vary substantially across LMICs. Importantly, however, these findings reveal that heart failure is already a major burden in LMICs and that the use of recommended medications for heart failure is currently suboptimal in these countries. Because the studies included in this systematic review and meta-analysis set out to answer different research questions and used different methods to diagnose heart failure, the estimates of the burden of heart failure in LMICs provided here may not be completely accurate. Moreover, because the data were derived mainly from urban tertiary referral hospitals, these findings may not reflect the broader picture of heart failure in the community in LMICs. However, although additional studies are needed to completely assess the burden of heart failure in LMICs, the present findings nevertheless highlight the need to implement better strategies for the management of heart failure in LMICs.http://dx.doi.org/10.1371/journal.pmed.1001699.Please access these websites via the online version of this summary at PLOS MedicinePerspective by Druin BurchThis study is further discussed in a heart failureThe US National Heart, Lung, and Blood Institute provides information for patients about heart failureThe UK National Health Service Choices website provides information about all aspects of heart failure for patients and their carersThe American Heart Association, a not-for-profit organization, also provides detailed information about heart failure, including a personal story about heart failure; further personal stories about heart failure are provided by the not-for-profit organization HealthtalkonlineThe British Heart Foundation, a not-for-profit organization, provides additional information about Heart Failure Matters provides practical information about heart failure for patients, families, and caregivers in several languages; its website includes an animated journey through heart failure and several personal stories about the conditionheart failure (in English and Spanish)MedlinePlus provides links to further resources about  In high-income countries (HICs), heart failure is a well-recognized public health problem representing a significant burden for patients and healthcare systems With demographic changes and the epidemiological transition to non-communicable diseases Therefore, we sought to conduct a systematic review of both published and unpublished data regarding the patterns of heart failure presentation, management, and outcomes in LMICs.This systematic review was designed and undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines In order to capture a comprehensive overview of heart failure in LMICs, a wide range of studies, each with differing objectives and designs, were included. Studies meeting the minimum quality requirement, as specified below, for inclusion were analysed for both methodological limitations and reporting quality, using items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines I2 statistic and tested using Cochran's Q test. Means were rarely reported with an estimate of variability, and, consequently, we weighted individual means by study size in pooled analyses, and present the pooled mean and the range of means.Study-specific data on percentages are presented as forest plots with exact binomial 95% confidence intervals (CIs). These percentages were pooled, by World Health Organization region  and acroPatients presenting acutely to hospitals may differ in many respects from those that are seen in clinics for chronic management. When pooling the data we therefore indicate the setting of each study in all forest plots. Studies from community primary care or outpatient clinics were designated as non-acute, and studies from inpatient populations, acute. Studies reporting both inpatient and outpatient data were included in the non-acute category. Additional subgroup analyses were performed by level of country income and by study time period. For income level analyses, studies were divided into low-income, low-middle-income, and upper-middle-income groups according to World Bank Statistical analyses were done using R version 3.0.2 and Stata version 11.2.Overall, 49 published studies Most studies were based in a single hospital, although 21 datasets documented multi-centre studies in Algeria The studies together included 237,908 episodes of heart failure hospitalisation. The median number of cases across all studies was 386 . Diagnosis of heart failure was established according to the Framingham criteria r = 0.71, p<0.001) (The demographic characteristics of patients and outcomes by region are shown in p<0.001) .I2 99%, p for heterogeneity <0.001) and 33% , respectively. In Africa, 8%  of heart failure is due to IHD, with hypertension the dominant cause, responsible for 46%  of cases. Cardiomyopathies cause 24%  of heart failure cases across LMICs taken together  of cases of heart failure across LMICs  and hypertension, are the leading causes of heart failure . Howevertogether . Idiopatss LMICs .I2 100%, p<0.001) of individuals in LMICs worldwide  of cases, beta-blockers in 34% , and mineralocorticoid receptor antagonists in 32%   –12.Across LMICs, patients admitted with heart failure remained in hospital for a mean of 10 d . The meaI2 99%, p<0.001)   across tData relating to heart failure as a proportion of total hospital admissions were available for five countries. Across these countries, heart failure accounted for 2.2% (range: 0.3%–7.7%) of total admissions. Brazil was the only LMIC with nationwide registry data compiled for all patients with heart failure treated by its public health system In sub-Saharan Africa, the total number of cardiovascular admissions was reported, rather than total hospital admissions. In Nigeria, heart failure accounted for 31% of cardiovascular cases presenting to hospital Population-level data regarding the prevalence of heart failure were available in only one study, from Turkey Meta-regression was performed to investigate the potential effect of the time period in which each study was undertaken on between-study heterogeneity in the causes, management, and outcomes of heart failure.p<0.001) between 1990 and the late 2000s   –17.p<0.001) (p = 0.56) for ACEI use and 0.67%  for mineralocorticoid receptor antagonist use, with loop and/or thiazide diuretic use changing by −0.49% per year   . Corresp = 0.49) –21.p = 0.042)  .Our study presents, to our knowledge, the most comprehensive review to date and the first pooled analysis of the burden of heart failure in LMICs worldwide, collating data on over 230,000 episodes from 31 countries, with representation from all world regions. We found that heart failure is already a major burden to populations and health services in LMICs, where it makes up an average of 2.2% of hospital admissions, affecting more men than women. Reflecting the broad range of countries included and their differing levels of socio-economic development, there are wide variations in patient characteristics and the causes of heart failure and its management. Nonetheless, noticeable similarities can be discerned both between the included LMICs themselves and between these LMICs and HICs.Across all LMICs from which data were available, the mean age of patients was 63 y, which is over a decade younger than in studies from HICs Substantial inter-regional variation is present in the causes ascribed to individual cases of heart failure. Heart failure is a syndrome made up of a constellation of signs and symptoms, with additional features present on further investigation. Given that a number of its aetiological underpinnings are often potential co-morbidities, disentangling one from the other is fraught with challenges, particularly in low-resource environments without recourse to a broad range of investigative tools Current guidelines worldwide stress the importance of ACEIs, beta-blockers, and mineralocorticoid receptor antagonists in the management of heart failure with reduced LVEF, with loop/thiazide diuretics given for symptom relief. Across the 29 studies from which management data were available, few studies reported the LVEF of patients, and fewer still separated data by LVEF. Overall mean LVEF was 40%: 38% amongst inpatients and 48% amongst those in non-acute settings. Consequently, it is not possible to make strong conclusions about the adherence of practice to evidence-based practices worldwide, but it is evident that management diverges considerably between regions and remains suboptimal on average. Data from the EuroHeart Failure Survey II of 30 high-income European countries also demonstrated poor medical management p = 0.27). On average, the in-hospital mortality rate was 8.3% in LMICs, compared to 6.7% in the EuroHeart Failure II Survey Across represented LMICs, patients admitted with heart failure had a poorer immediate prognosis than those in many HICs. However, as is the case for HICs, the estimates from LMICs varied substantially, although we found the difference between the two outlying regions in terms of prognosis, the Americas and South East Asia, was not statistically significant Click here for additional data file.Checklist S1PRISMA 2009 checklist.(DOC)Click here for additional data file.


Women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD) evidenced by the Women's Ischemia Syndrome Evaluation (WISE) studies , 2. CMD CMD subjects (n=14) from symptomatic women with objective evidence of myocardial ischemia enrolled in the NHLBI-sponsored WISE studies were evaluated. Subjects with evidence of obstructive CAD , left ventricular dysfunction, left ventricular hypertrophy, or valvular/structural heart disease were excluded.T1 mapping using a vendor-provided MOLLI sequence for the mid-ventricular slice was performed at 1.5T . The MOLLI acquisitions were ECG-triggered and obtained during an 11-heartbeat breath-hold and T1 maps were generated following on-line automatic motion correction , 4. The The mean age of WISE subjects with CMD was 57±11 years with an average BMI of 23.9; 34.7% had hypertension, 7.1% had diabetes. All subjects had preserved ejection fraction (mean EF: 63%). No focally elevated native T1 region was observed in any of the subjects. A representative T1 map is shown in Figure Native T1 values in women with signs and symptoms of ischemia and no obstructive CAD were significantly elevated compared with normal values reported in the literature. Our initial findings suggest presence of diffuse myocardial fibrosis in this population. Future studies using age and gender matched normal controls are needed to confirm these initial findings. The presence of diffuse myocardial fibrosis may elucidate a potential underlying mechanism leading to heart failure and other adverse events in patients with CMD, with important therapeutic implications.Grant sponsors: NIH National Heart, Lung and Blood Institute grant nos. K99 HL124323-01 and R01 HL090057-01; and the Barbra Streisand Women's Cardiovascular Research & Education Program, CSMC.


Coronary slow-flow phenomenon (CSFP) is an angiographic diagnosis characterised by a low rate of flow of contrast agent in the normal or near-normal epicardial coronary arteries. Many of the patients with CSFP may experience recurrent acute coronary syndromes. However, current clinical practice tends to underestimate the impact of CSFP due to the yet unknown effect on the cardiac function. This study was performed to evaluate left ventricular (LV) and right ventricular (RV) diastolic and systolic functions, using two-dimensional (2D) longitudinal strain and strain rate, in patients with CSFP, and to determine the relationships between the thrombolysis in myocardial infarction (TIMI) frame count (TFC) and LV and RV diastolic and systolic functions.Sixty-three patients with CSFP and 45 age- and sex-matched controls without CSFP were enrolled in the study. Diagnosis of CSFP was made by TFC. LV and RV diastolic and systolic functions were assessed by 2D speckle-tracking echocardiography.P = 0.01). LV peak systolic longitudinal strain (LS) and LV peak systolic longitudinal strain rate (LSRs) were lower in patients with CSFP than in controls . There was no difference in LV ejection fraction. RV peak early diastolic longitudinal strain rate (RSRe) was lower in patients with CSFP than in controls (P = 0.03). There were no differences in RV peak systolic longitudinal strain (RS), RV peak systolic longitudinal strain rate (RSRs), or RV fractional area change among the groups. The mean TFC correlated negatively with LSRe and RSRe in patients with CSFP .LV peak early diastolic longitudinal strain rate (LSRe) was lower in patients with CSFP than in controls (LV diastolic and systolic functions were impaired in patients with CSFP. CSFP also affected RV diastolic function, but not RV systolic function. Coronary slow-flow phenomenon (CSFP), initially reported by Tambe et al.  in 1972,This study was performed between June 2010 and October 2013. Over a 3-year period, of 4328 consecutive patients who underwent coronary arteriography in the cardiology department of our hospital, 108 patients with normal or near-normal (<40% stenosis) coronary arteries were enrolled in the study. We performed coronary angiography in these patients because they had typical angina and coronary risk factors. CSFP was defined as a corrected thrombolysis in myocardial infarction (TIMI) frame count (TFC) exceeding 27 in one or more vessels based on the recommendations of Gibson et al. . Among tCoronary angiography was performed by the femoral approach using the standard Judkins technique. Coronary arteries were demonstrated in the left and right oblique planes and on cranial and caudal angulations. The same contrast medium was used in all patients. All injections were performed manually in all patients and control subjects. Coronary flow rates of all subjects were documented using the TFC. The TFC was determined for each major coronary artery of each subject included in the study, according to the method first described by Gibson et al. . The numEchocardiographic examination was performed within 72 hours after the coronary angiography. By using a Vivid 7 Dimension ultrasound system  with a 2- to 4-MHz phased-array probe, images were acquired in the left decubitus position during normal respiration. Right and left heart images and measurements were acquired from standard views according to the recommendations of the American Society of Echocardiography by two experienced cardiologists who were blinded to any clinical data . At leasLeft atrial anteroposterior dimension was measured during LV end-systole immediately before mitral valve opening from the parasternal long-axis view. LV end-diastolic dimension, interventricular septal thickness, and posterior wall thickness were measured during LV end-diastole immediately before aortic valve opening from the parasternal long-axis view. LV ejection fraction (LVEF), the index of global LV systolic function, was computed from apical two- and four-chamber views. LVEF was measured using the biplane modified Simpson method. Right atrium long-axis and minor-axis dimension and RV end-systolic area (RVESA) were measured during RV end-systole immediately before tricuspid valve opening in the apical four-chamber view. RV basal cavity diameter, RV mid cavity diameter, RV longitudinal diameter and RV end-diastolic area (RVEDA) were measured during RV end-diastole in the apical four-chamber view. The RV fractional area change (RVFAC), the index of global RV systolic function, is calculated as follows: RVFAC (%) = (RVEDA − RVESA)/RVEDA .Pulsed-wave Doppler was performed in the apical four-chamber view to obtain mitral inflow velocities for the assessment of LV filling. Early diastolic mitral inflow velocity  and late diastolic mitral inflow velocity  were recorded. Pulsed-wave TDI images were acquired by activating the TDI functions of the echocardiography unit. From the apical four-chamber view, the sample volume should be positioned at the septal and lateral corner of the mitral annulus to record the longitudinal excursion of the mitral annulus. Primary measurements included the systolic (S’), early diastolic (E’), and late diastolic (A’) velocities. The tissue Doppler average signal of the septal and lateral sides of the mitral annulus was acquired to assess LV global function. The following measurements from the mitral annulus were made from the TDI recordings: mitral S’, E’, A’, E/A, E/ E’. Similar to Doppler-derived LV analysis, early diastolic tricuspid inflow velocity (tricuspid E) and late diastolic tricuspid inflow velocity (tricuspid A) were recorded. The following measurements from the lateral corner of the tricuspid annulus were made: tricuspid S’, E’, A’, E/A, E/ E’.Dynamic 2D ultrasound images of three cardiac cycles from apical two-, three-, and four-chamber views were acquired using conventional ultrasound, with a frame rate of 57 to 72 frames per second. To measure strain and strain rate, the image analysis was performed off-line using customized software within the EchoPAC work station . The endocardial boundary of the left ventricle was delineated manually, after which the software automatically drew the epicardial boundary. The widths of the regions of interest were adjusted manually to match the actual endocardial and epicardial boundaries. Automatic frame-by-frame tracking of speckle patterns during the cardiac cycle yielded a measure of strain and strain rate at any part of the myocardium. The LV myocardium was divided into six segments in each apical view, and each segment was individually analyzed. Subjects with inadequate tracking of more than one segment in at least one apical view were excluded from the study. By averaging all LV segmental values in all views, LV peak systolic longitudinal strain (LS) and strain rate (LSRs), LV peak early diastolic longitudinal strain rate (LSRe), and LV peak late diastolic longitudinal strain rate (LSRa) were calculated and obtained. Similar to STE-derived LV analysis, the longitudinal strain and strain rate of the basal, middle, and apical portions of RV free wall were obtained in apical four-chamber view. By averaging these segmental values, RV peak systolic longitudinal strain (RS) and strain rate (RSRs), RV peak early diastolic longitudinal strain rate (RSRe), and RV peak late diastolic longitudinal strain rate (RSRa) were calculated. The peak systolic longitudinal strain and strain rate represent ventricular longitudinal systolic function; the peak early diastolic longitudinal strain rate and peak late diastolic longitudinal strain rate represent ventricular longitudinal diastolic function.t-test was used to compare normally distributed continuous variables. Categorical variables were compared using the chi-square test. For all parameters, a value of P<0.05 (two-tailed) was considered statistically significant.Statistical analysis was performed using the SPSS 17.0 software package. Continuous data were expressed as mean ± standard deviation, and categorical variables as frequency and percentage. The Shapiro-Wilk test was used to evaluate whether the distribution of variables was normal. The Student One patient with CSFP and one control were excluded because of inadequate tracking quality of more than one segment in at least one apical view during the analysis of images by 2D-STE. In the remaining 106 subjects (62 CSFP patients and 44 control subjects), there were potentially 1,862 segments that could be tracked to obtain strain measurements. Of these, 46 segments (2.43%) were excluded from analysis because of inadequate tracking quality.P<0.001), LCx , and RCA , as well as mean TFC  than those with normal coronary flow. The LAD, LCx, and RCA were involved in 89%, 70%, and 56% of the patients, respectively. There was one-, two-, and three-vessel involvement in 24%, 36%, and 40% of the patients, respectively.The baseline characteristics and angiographic findings of the CSFP and control groups are shown in The conventional 2D echocardiography and Doppler echocardiography parameters of the LV and RV are compared in P = 0.003). LSRe was significantly lower in the patients with CSFP than in control subjects (P = 0.01) (P = 0.004 and P = 0.03)   . LS and  = 0.03) . There w = 0.04) .P = 0.01). RSRe was significantly lower in the patients with CSFP than in control subjects (P = 0.03)  (Tricuspid E/ E’ of patients with CSFP was found to be higher than that of controls ( = 0.03) . RS and  = 0.03) . There w = 0.01) .The main objective of this study was to evaluate LV and RV diastolic and systolic functions in patients with CSFP. The main findings of our study were as follows. (1) CSFP affected RV diastolic function, but not RV systolic function. (2) The degree of deterioration of LV and RV diastolic functions had close relationships with the mean TFC.CSFP is an angiographic diagnosis characterized by a low rate of flow of contrast agent in the normal or near-normal epicardial coronary arteries. In our study we chose to use the simple, reproducible, and validated means of the TFC to evaluate coronary flow. Previous studies showed that TFC in arteries with CSFP is significantly increased , 18], , .CSFP mimics various clinical presentations such as unstable angina, acute myocardial infarction, and ventricular tachycardia . The preThis study measured 2D longitudinal strain and strain rate, and demonstrated that both the LV diastolic and systolic functions were impaired in patients with CSFP. Nevertheless, TDI in previous studies demonstrated disagreements on the effect on LV diastolic and systolic functions in patients with CSFP. Altunkas et al.  found thStudies evaluating RV function in patients with CSFP in the published literature are limited. In our study we found that CSFP affected RV diastolic function, but not RV systolic function, on assessment of longitudinal strain and strain rate using 2D-STE. In contrast to the left ventricle, only RV diastolic function was affected in patients with CSFP. Obviously the degree of impairment of LV and RV functions in the patients with CSFP was different. A probable explanation may be the difference in anatomy, mechanics, and function between the LV and RV . The RV Our study showed the negative correlation between the mean TIMI frame count with LV and RV diastolic functions. The myocardial diastolic performance markedly decreased as the mean TIMI frame count increased. This finding emphasizes the importance of close attention to the patients with a larger number of TIMI frame count. However, there was no association between the mean TIMI frame count with myocardial systolic performance. An explanation for these findings may be that diastolic dysfunction is more sensitive to the severity of inadequate supply of the myocardium .In view of the deterioration of ventricular function in patients with CSFP, clinical intervention should be timely employed in these patients to improve symptoms and patients’ quality of life. The conventional antianginal therapy was once one of the common treatment modalities for patients with CSFP, but its value was limited. It has been shown that resting coronary microvascular resistances are abnormally high and the unique calcium T-channel blocker mibefradil influence functional obstruction in arteries <200 μm . We willThe sample size of the study population may not have been adequate. We are expanding the sample size and performing a follow-up of these patients.LV systolic and diastolic functions were impaired in patients with CSFP. CSFP also affected RV diastolic function, but not RV systolic function. The degree of deterioration of LV and RV diastolic functions had close relationships with the mean TFC.


Disturbances of interatrial conduction have been proposed as one of the contributing mechanisms of postoperative atrial fibrillation (AF). P-wave dispersion has been recognized as a sensitive tool for detecting interatrial conduction disturbances. Doppler myocardial imaging (DMI) has been validated as a non-invasive tool to indirectly reflect electrical atrial activation and therefore is used in this study to detect possible interatrial electromechanical disturbances after cardiac surgery.30 patients  admitted for coronary bypass surgery with no prior history of AF were included in this investigation. Echocardiography and electrocardiograms (ECG) were obtained on the day before and after surgery. In addition to standard echocardiography, DMI-loops were acquired from the apical window. The following time intervals were derived off-line from the free right atrial (RA), left atrial (LA) lateral and LA posterior wall: onset P-wave to start (P to A’start), to peak (P to A’peak) and to end of atrial deformation . These intervals were compared to each other and to P-wave dispersion derived from the recorded ECGs.All patients were in sinus rhythm during their postoperative assessment, but 11 patients presented episodes of AF within the first three postoperative days. Atrial electromechanical activation was earliest in the RA and latest in the lateral LA. In patients with AF, P-wave dispersion was significantly prolonged postoperatively : 12.1–25.2 ms; p < 0.001) compared to non-AF patients . P dispersion was closely correlated to P to A’start intervals . Prolonged right to left conduction interval was associated with an elevated risk for AF (from RA to LA lat.: odds ratio 1.13 (CI:1.03-1.24); p: 0.007.DMI enabled detection of interatrial conduction disturbances in concordance to findings of prolonged postoperative P-wave dispersion. Equally effective to P-wave dispersion, this simple and reproducible tool might help to early identify the risk for postoperative AF, thus extending the informative value of routine postoperative echocardiography. Atrial fibrillation (AF) remains a common phenomenon in patients undergoing cardiac surgery, and is associated with increased morbidity and longer hospital stays-3. AmongThe aim of this investigation was to assess the use of DMI for atrial electromechanical activation before and after cardiac surgery, and to evaluate its use as a possible predictor of postoperative AF.2) and/or impaired left ventricular systolic function (ejection fraction (EF) ≤ 50%) were excluded. Requirement of atriotomy , atrioventricular or intra-ventricular conduction disturbances and (corrected) congenital cardiac malformations were regarded as further exclusion criteria. Cardio-pulmonary bypass (CPB) was deployed in all patients using Bretschneider’s crystalloid cardioplegic solution for myocardial protection.This investigation was approved by the local ethics committee of the RWTH Aachen University (EK 228/12). After giving their written consent, 30 patients (23 men) with a mean age of 62 ± 10 years with isolated coronary artery disease with no prior history of AF who were referred to our department for isolated coronary artery bypass grafting (CABG). Patients with (bi-)atrial dilatation  length ≤ 4.5 cm, LA Area ≤ 20 cm12-channel Electrocardiogram (ECG) recorded on the day before surgery and on the first postoperative day were considered for this investigation. P-wave Standard two-dimensional (2-D) and Doppler-echocardiograms were digitally recorded using a Vivid E 9 ultrasound machine  with a 2.5-5 MHz matrix phased array transducer . Image sequences were acquired in parasternal (long/short axis), apical  as well as subcostal (short/long axis) acoustical windows in two consecutive cardiac cycles for off-line analysis with simultaneous ECG-recording in lead II. Left veAn independent professional statistician processed the presented data . The precision of the derived parameters is expected to be around 2–5 ms. To increase accuracy of the presented data, all measurements were repeated in triplicate and means were subsequently calculated. Data were rounded to full milliseconds. Continuous variables are presented as mean ± standard deviation (SD).t-test for paired data.Data were evaluated with and without adjustment for heart rate variability. The appropriate tests used were: linear regression analysis, Spearman’s ranking coefficient, logistic regression, All patients survived surgery without any serious adverse events. The results of left ventricular systolic function, right ventricular systolic longitudinal function and atrial sizes are summarized in Table Postoperative left ventricular systolic function as well as atrial sizes did not differ to preoperative values. There was a significant postoperative decrease of right ventricular systolic longitudinal function measured by TAPSE.The results of pre-and postoperative DMI-derived values are summarized in Table According to the electromechanical activation, peak atrial longitudinal deformation, measured by P to A’peak intervals, was also earliest in the mid regions, starting with the RA followed by the IAS, posterior LA and latest in the lateral LA respectively .We observed a significant postoperative decrease of P to A’peak intervals within and between the atrial walls and regions, i.e. peak mechanical atrial longitudinal deformation occurred earlier postoperatively. In particular, peak atrial longitudinal deformation was reached earlier by far in the RA ; p < 0.001).Preoperatively, total electromechanical activation was comparable in all atrial regions and walls . Due to this phenomenon we calculated the measured time intervals with and without heart rate adjustment in order to reveal a possible influence of the increased heart rate. However, heart rate adjustment did not alter the significance of pre- to postoperative comparison of the measured time intervals.preoperative: 40.5 ± 8.5 ms vs. P-wave dispersionpostoperative: 59.5 ± 6.1 ms; p < 0.001).All patients were in sinus rhythm during the 12-channel ECG-recording at the third postoperative day. Eleven patients had brief (<1 day) episodes of AF, recorded by continuous monitoring during the first three postoperative days. Mean heart rate was significantly higher postoperatively . No patient presented postoperative atrioventricular or inter-/intra-ventricular conduction disturbances . Mean P-wave dispersion and duration was within normal ranges prior to surgery in the entire cohort with no significant postoperative changes . However, in eleven patients who presented temporary postoperative AF, a significantly prolonged P-wave dispersion was observed  compared to non-AF patients . P dispersion was closely correlated to p to A’start intervals  in patients presenting postoperative AF as shown by P-wave dispersion in surgical and invasive electrophysiology in non-surgical AF,8.Proper tracking of the respective atrial wall with small regions of interest (ROI) as used in this study is very time-consuming taking up to 30 minutes and, after a learning curve of several exams, approximately 15 minutes. The chosen region of interest (e.g. base or mid portion) within the atrial wall did alter our measurements significantly. This coincides with the findings of Quintana et al., which showed that electromechanical intervals were longer near the atrio-ventricular ring than in the mid regions of the atria. On the Our findings of interatrial electromechanical coupling by DMI correlate well with findings of Quintana and Zhang, where electromechanical coupling was the earliest in the RA, followed by the IAS and the latest in the lateral LA,14. Ther.Postoperative reduction of P to peak A’-wave intervals coincides with postoperative reduction of peak diastolic longitudinal deformation velocities, but not with TEMA. We noticed a significant postoperative reduction of right atrial TEMA while left atrial TEMA stayed fairly unchanged. Due to the fact that postoperative heart rates were significantly increased, we adjusted our measurements accordingly. This postoperative reduction of right atrial TEMA lead to a significantly increased difference between postoperative right and left atrial TEMA in the entire cohort. These findings might indicate decreased right atrial refractoriness as described in the literature by electrophysiologic studies.Three recent echocardiographic studies assessed the predictive value of pulsed-wave (PW)- DMI in patients prior to cardiac surgery-25. HereIn all three studies frame-rates of PW-DMI were not described: Pre-settings in PW-DMI of the leading echocardiography machine vendors only show very low frame rates of approximately 35 frames per second, if the whole four chamber sector is used. Using 35 frames per second at a heart rate of 80/min means that 21 frames per cycle are recorded.To increase frame rates the scanning sector must be reduced to the region of interest and frame rates per se increased on the respective machine setting in order to achieve frame rates higher than 90 frames per second. Looking at the figures of these studies, where in DMI-Mode the full apical four chamber view was used for pulsed-wave Doppler assessment, one must assume that frame rates were too low for measuring these brief electromechanical time intervals.Nevertheless, PW-DMI with adequate frames rates measuring respective atrial electromechanical coupling (onset P-wave to onset A’-wave) should allow a more clinical application to detect interatrial conductance disturbances rather than carrying out the measurement off-line in quantitative analysis.The findings described in this study were obtained from a small group of patients. Larger consecutive studies might underline the postoperative phenomenon of interatrial conduction disturbance and shortened right atrial refractoriness. Furthermore, long-term follow-up has not been performed in this investigation where the development of atrial electromechanical (conduction time) and mechanical (peak systolic velocities) over time as well as the observation of heart rhythm in operated patients would be interesting.From a methodological point of view, the surface ECG of ultrasound machines could be improved in order to identify the exact onset of P-wave due to the fact that the observation of atrial electromechanical activation takes place in just several milliseconds.DMI was able to detect disturbances in atrial electromechanical coupling in concordance to findings of prolonged postoperative P-wave dispersion. This simple, easy to obtain, reproducible, and clinically useful tool might help quantifying atrial electromechanical function, thus extending the informative value of routine postoperative echocardiography. Equally effective to P-wave dispersion, DMI derived atrial electromechanical activation may help to early identify the risk for postoperative AF.DMI can be a helpful non-invasive tool to detect IACD. DMI might be a good predictor for postoperative AF. However, further investigations with larger numbers of patients are required to evaluate its value as a prediction tool.AF: Atrial fibrillation; AV: Atrio-ventricular; CABG: Coronary artery bypass grafting; CI: Confidence interval; CPB: Cardio-pulmonary bypass; DMI: Doppler myocardial imaging; IACD: Interatrial conduction disturbance; IAS: Interatrial septum; ECG: Electrocardiography; LA: Left atrium; LAA: Left atrial appendage; OR: Odds ratio; PA-TDI: onset P-wave to peak A’wave of lateral LA (from 24); PW-DMI: Pulsed-wave Doppler myocardial imaging; RA: Right atrium; ROI: Region of interest; SD: Standard deviation; TAPSE: Tricuspid annular plane systolic excursion; TEMA: Total electromechanical activity; 2-D: Two-dimensional.The authors declare that they have no competing interests.NH, AA and AG wrote the manuscript and interpreted statistics. NH and AA performed echocardiography and subsequent analysis. RH supervised study design and echo analysis. He also participated in the design of the study. NH, AA and EK recorded all ECGs and interpreted all monitor recordings. NH, AA and EK measured P-wave dispersion. KM supervised ECG interpretation and P-wave dispersion measurements. RA participated in the study design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.