We applied these methods to a diverse array of oviparous reptiles , to identify general influences on cardiac rates during embryogenesis. Heart rates increased with ambient temperature in all lineages, but (at the same temperature) were faster in lizards and turtles than in snakes and crocodilians. We analysed these data within a phylogenetic framework. Embryonic heart rates were faster in species with smaller adult sizes, smaller egg sizes, and shorter incubation periods. Phylogenetic changes in heart rates were negatively correlated with concurrent changes in adult body mass and residual incubation period among the lizards, snakes  and crocodilians. The total number of embryonic heart beats between oviposition and hatching was lower in squamates than in turtles or the crocodilian. Within squamates, embryonic iguanians and gekkonids required more heartbeats to complete development than did embryos of the other squamate families that we tested. These differences plausibly reflect phylogenetic divergence in the proportion of embryogenesis completed before  The central biological significance of metabolic rate has spawned a rich literature on this topic, in a wide range of animals from insects to mammals In oviparous amniotes, it is methodologically difficult to measure the physiological functioning of embryos that are enclosed within eggshells. The most widely used measure of embryonic metabolic state is the rate of oxygen consumption, which correlates in interesting ways with variables such as egg mass and incubation temperature Heart rate can be influenced by both intrinsic and extrinsic factors. For example, heart rates of embryos are significantly affected by mode of development  and by egg size in birds 10 values of heart rate were greater at low temperatures than at high temperatures  and 4 , close to significant in tree 1 , but non-significant in tree 2 .Embryonic heart rate increased as test temperature increased. Qeratures . Phyloge2r > 0.15, P < 0.002 for all trees), and clutch size was related to adult body mass  we used the residuals of these variables to further analyze the relationship with heart rates. A multiple regression approach showed that embryonic heart rate was negatively correlated with residual incubation period , and adult body mass , but not residual clutch size , marginally correlated in tree 2 , and 4 , but not correlated in tree 3 . The total number of heart beats differed among lineages: in general, the embryos of crocodiles and turtles required more heart beats prior to hatching than did squamate embryos , as is also the case for other indicators of metabolic rate such as oxygen consumption  of embryonic reptiles were significantly related to egg mass(Em), with larger eggs having embryos with lower heart rates . A similar relationship between heart rate and egg mass is seen in bird embryos also versus egg mass in these two amniote groups exhibit different constants (93.5 in reptiles vs 371.1 in birds), because of the difference in incubation temperatures of reptiles  and birds . Nonetheless, the scale exponent is similar in reptiles (−0.097) and birds (−0.112) Allometric relationships between physiological traits (e.g. metabolic rate and heart rate) and body size are widespread in adult animals; typically, mass-specific reaction rates decrease with increasing body size In addition to this general trend, embryonic heart rate shows among-lineage variation. In reptiles, the greatest among-lineage differences in heart rate were among families, especially within the Squamata . The und6 to 8.5×106, whereas egg mass varied 990-fold from 0.13 g to 128.9 g in our sample. Compared to this dramatic variation in egg mass, the total number of heart beats was relatively invariant. Analogously, several authors have argued that lifespans of post-embryonic stages are characterised by relatively consistent total number of heart beats as well as energy expenditure. The life-span of mammals and birds is roughly fixed when measured in terms of the total number of heart beats  and in energy expenditure  across a 50000-fold variation in body mass The total number of embryonic heart beats during incubation  provides a simple index of cardiac function for interspecific comparisons, although this index could be affected by variations of heart rate during incubation  6) and crocodiles (8.3×106) than in lizards  and snakes . Second, variation in incubation period may stem from the developmental degree of offspring at hatching The among-lineage difference in the total number of embryonic heart beats was related to variation in heart rate and incubation period. Although negatively related to egg mass, heart rate was relatively constant after the effect of egg size was statistically removed in reptiles. This constancy suggests that the among-lineage difference in the total number of heart beats mainly reflects variation in incubation periods. What factors affect incubation period, and thus in turn the total number of heart beats? First, variation in incubation period may stem from different developmental stages of embryos at oviposition. Turtles and crocodiles lay eggs with embryos in early stages of embryogenesis, whereas most squamates complete around 25% of the total period of embryonic development prior to oviposition In conclusion, the heart rate of a reptilian embryo is affected by both intrinsic and extrinsic factors. Intrinsic factors such as phylogenetic lineage and egg size (in turn determined by adult body size) strongly influence rates of cardiac function during embryogenesis, and generate phylogenetic patterns in embryonic heart rates  of an embryo throughout its embryonic development was calculated at any given incubation temperature using the formula THB  =  temperature-specific heart rate × total minutes of developmental time ( =  from oviposition through to hatching) of eggs incubated at that temperature.We measured heart rates of embryos approximately 50 % (range 37 to 62 %) through the total incubation period in all species. As noted above, heart rate is relatively constant throughout embryonic development in reptiles Guide for the Principles of Animal Care. The experiments on Chinese species were conducted under the ethics license from the University of Sydney, which was accepted by the Animal Care and Ethics Committee at Hangzhou Normal University.All experimental procedures were approved by the Animal Care and Ethics Committee at the University of Sydney (L04/7-2007/3/4665) and Iowa State University (3-09-6695-J), and were conducted in accordance with the NIH We analyzed the data using Felsenstein's 10 (25–30°C) and Q10 (30–35°C), the branches to the nodes 2, 3, and 9 were multiplied by −10 in both trees. In tree 3, all branches for maximum body mass, embryonic heart rate, egg mass, clutch size and incubation were set by the method of Grafen 10(20–25°C) all branches were set by Pagel's method, and for Q10 (25–30°C) and Q10 (30–33.5°C) all branches were set to 1, and branch to node 13 was set to −2.5. Branches lengths for total heart beats were set to 1 in all trees. We used PDAP diagnostic charts to verify that these branch lengths adequately fit the tip data, as required by the PIC analysis We reconstructed the ancestral states for the traits we measured . Because some of the x-variables were correlated with each other (see We investigated correlations between the continuous variables by using their standardized PICs in linear regressions through the origin (i.e. intercept equals zero; Felsenstein ther see , we firs


We previously found reduction of cardiac index (CI) in patients with tricuspid regurgitation (TR) due to Ebstein anomaly, but not in patients with comparable right ventricular (RV) volume loading due to pulmonary regurgitation (PR) in patients with repaired tetralogy of Fallot (rTOF). We postulated that the difference may be attributable to impaired left ventricular (LV) filling caused by leftward bulging of the atrialized portion of the RV in Ebstein patients.To measure an index of LV diastolic compression and compare it with CI in different groups.Ebstein and rTOF patients with moderate-severe TR or PR (>20%) measured by cardiovascular magnetic resonance (CMR) without evidence of atrial septal defect or additional haemodynamically significant lesion were included. TR fraction was calculated from RV stroke volume and pulmonary artery forward flow, and PR fraction from pulmonary artery reversed relative to forward flow. The CI was obtained by indexing cardiac output by CMR aortic flow measurement to body surface area. Ventricular volumes were measured from a stack of short-axis cine images. As an index of LV diastolic compression we measured LV width/length at end diastole in 3 chamber long axis cines: the width from septal to lateral wall at basal-mid junction level and the length from mid-mitral valve annulus plane to the LV apex.2 vs 3.2±0.5L/min/m2, p=0.002) but not in rToF, 3.1±0.6L/min/m2, p=ns. LV end-diastolic volume in Ebsteins was less than controls , but comparable in rTOF . LV ejection fraction was similar between Ebsteins and controls  and lower but within normal range in rTOF . RV ejection fraction was decreased in Ebsteins and rToF . LV width/length index was smaller in Ebsteins than controls  but not in rTOF . LV end-diastolic volume correlated with LV width/length index (r2=0.4) and CI (r2=0.6) in Ebstein.Forty patients, 20 Ebsteins  and 20 rTOF  were studied. Sixteen control subjects  were also studied. Regurgitant fractions in Ebsteins and rTOF were similar, TR 44±18% vs PR 38±12%, p=ns. Compared to controls, CI in Ebsteins was reduced (2.5±0.5L/min/mThe findings support the hypothesis that impairment of LV filling by leftward displacement of the septum contributes to the reduction of CI found in Ebstein patients.


Objective: During the last years, left ventricular dysfunction in diabetes was intensely studied and it is recognized as a complication of diabetes, while data regarding the right ventricular dysfunction is still incomplete.The aim of this study was to find a correlation between inflammatory biomarkers, adiponectin and right ventricular strain and strain rate properties in patients with diabetes mellitus type 2.Methods:We studied 29 patients with type 2 diabetes mellitus (DM), with coexisting cardiovascular complications, coronary artery disease and high blood pressure ; and 22 patients with type 2 diabetes and controlled high blood pressure only, with no other coexisting cardiovascular complications . We evaluated the right ventricular (RV) function through Vector Velocity Imaging (VVI)and determined the inflammatory profile through assessment of the following biomarkers: high sensitivity C- reactive protein (hsCRP), tumor necrosis factor-alpha , lipoprotein associated phospholipase A2 (Lp-PLA2) and adiponectin level for each patient. Results:VVI revealed significantly lower values of systolic strain and strain rates (SR) in the basal segment of the RV free wall in group I patients (DM+CV) as compared to group II patients (DM) which indicates higher impairment of RV systolic function in patients with diabetes and other cardiovascular complications. In both groups strain and strain rate values were correlated with Lp-PLA2 activity levels. Conclusions:In Type 2 diabetes mellitus we identified a low-grade inflammatory status correlated with right ventricular systolic dysfunction. Type 2 diabetes mellitus (DM) is characterized by a low-grade inflammatory status and endothelial dysfunction, which substantially potentiates the risk of developing cardiovascular diseases. The impact of diabetes leads to myocardial dysfunction, which is initially sub-clinical and might lead finally to diabetic cardiomyopathy and heart failure (HF).1], while data regarding right ventricular (RV) performance and the impact of different inflammatory factors on its performance, is still incomplete. In the latest years, a lot of evidence has been collected regarding left ventricular dysfunction as a common complication of diabetes mellitus .Right ventricular function, has been recognized as a significant indicator of clinical outcome and prognostic value in heart failure, myocardial infarction, pulmonary embolism and more recent in diabetes, too. [7]. Elevated plasma values of Lp-PLA2 in heart failure with preserved ejection fraction (HFpEF) are consistent with the exacerbated inflammatory status [8].It is already known that lipoprotein-associated phospholipase A2 (Lp-PLA2), is a risk marker for endothelial dysfunction in patients with type 2 diabetes and recent data suggest that Lp-PLA2 might be a biomarker constantly correlated with HF, regardless of aetiology [9].Recent research proved that adiponectin (Adpk) is correlated with the presence of atherogenic dyslipidemia and with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration but not with markers of systemic inflammation such as IL-6 or hsCRP in patients with manifested coronary heart diseases [10].Data collected from current research indicate diabetic disease-specific alterations in the biochemical parameters, Adpk level is inversely correlated with hsCRP in end-stage renal disease patients . Enzymatic activity is expressed through IU/L. Adpk, hsCRP and TNF-alfa, were determined through ELISA.All plasma samples were frozen and stored at -70°C- until analysis. Lp-PLA2 activity was measured using the spectrophotometric method described by Kosaka et al. using the Azwell Auto PLA2-LDL kit . Also, a study done in type 1 diabetes mellitus patients proved that before any development of systolic dysfunction, the diastolic performance is altered, in both ventricles, suggesting that these alterations in myocardial function could be attributed to ventricular interdependence as well as to the global effect of diabetes on cardiac function [12]. In the last ten years, there has been a lot of evidence accumulated regarding left ventricular dysfunction (systolic and diastolic) in diabetic patients; however, less research has been done for identifying the right ventricular dysfunction. A recent study investigated left ventricular strain and strain rates in diabetic patients. This study concluded that left ventricular longitudinal systolic and diastolic functions were impaired, while the circumferential and radial functions are preserved in patients with uncomplicated type 2 diabetes mellitus [13]. It is worth mentioning that recent research has identified that Lp-PLA2 may be in fact superior to other inflammatory markers, such as hs-CRP, due to its specificity and minimal bio-variation [14]. In addition, Lp-PLA2 is now recognized as a marker of oxidative stress and vascular inflammation which has a relative unique characteristic being independent from BMI and insulin resistance [15]. Until now, none study has been published regarding relation between inflammatory biomarkers and right ventricular strain and strain rate in diabetic patients. We have included in our evaluation the Lp-LPA2 activity enzyme which is considered a link between lipid metabolism and low-grade inflammation and characteristic marker for cardiovascular or metabolic diseases, being considered also a valuable predictor of CVD. The West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated that high levels of Lp-PLA2 were associated with a two-fold increased risk of CHD. This relationship was valid also after taking into account the traditional CV risk factors and other inflammatory markers (including hsCRP) [17], but not all [18].Interestingly, hsCRP did not correlate with any RV echocardiographic parameters, while Lp-PLA2 proved strong positive correlation with all investigated parameters. For group 1 patients ( DM+CVD), Adpk did not correlate with any investigated parameters of right ventricular dysfunction, a finding consistent with other studies [19]; while for group 2, we detected a negative correlation SbasalVR (p<0.05) as well as a negative correlation with Lp-PLA2 (p<0.01). This finding might suggest that for uncomplicated DM, Adpk might be a potential marker of underlying mechanisms linking the diabetic state to cardiac abnormalities [20].In our study, the higher values obtained in group 1 patients (DM+CVD) for Lp-PLA2 (p<0.01) are in correlation with the inflammatory state characteristic of those patients. Furthermore, we found a significant but modest inverse correlation to HDL cholesterol, a finding consistent with many studies . Similar results regarding RV echocardiographic parameters in diabetic patients were recently detected through 3D echo, stating the right ventricular systolic and diastolic dysfunction in diabetic patients [By assessing the inflammatory profile of diabetic patients, it has been revealed that, even those asymptomatic for CVD, have a continuous inflammatory state, together with a decrease in RV systolic function. Due to angle dependent strain measurements, there should be caution in interpretations of strains when tissue direction deviates more than 30° from the beam direction. This could be a significant limitation of this technique, and reposition of transducer might help to correct this issue. Another limitation of this technique is the normal beat-to-beat variation in stroke volume that could explain why strain profiles do not always return to exactly same point of baseline at end diastole. That’s why for this study we averaged three cardiac cycles. Also, this is a cross-sectional study, with data collected at a given time-point, and due to this, it could not provide prognostic value of inflammatory markers. It is necessary to extend the study with a follow-up period.


Hypertension is associated with the development of myocardial fibrosis with a subsequent increase in the myocardial extracellular volume (ECV). T1 measurements pre and post a contrast cardiac magnetic resonance (CMR) study provide a robust non-invasive method for quantification of the ECV. We aimed to determine whether the CMR-derived ECV can differentiate healthy volunteers from patients with systemic arterial hypertension.We performed a CMR study including T1 measurements in 145 patients with hypertension. CMR variables were compared to a group of age-, gender-matched healthy volunteers. Patients with hypertension were followed for the development of adverse cardiovascular outcomes . Values were compared to age- and gender-matched controls.2, and a LV ejection fraction of 61±6%. In comparison to healthy controls, patients with hypertension had elevated LV volumes, LV mass, and left atrial volumes. The ECV was elevated in patients with hypertension as compared to healthy controls . In patients with hypertension, there was a positive association between the ECV and indexed left atrial volume , and the LV mass index  and a negative association between the ECV and early mitral annular relaxation . The ECV was similar in males and females with AH . During a median follow-up time of 18 months, there were 52 events. In univariable analysis, the ECV (hazard ratio (HR) 1.35, 95% CI 1.21-1.51, chi-squared 24.6, p<0.0001), indexed maximal LA volume , and the LV mass index  provided the strongest association with the adverse clinical events. In a multivariate model, the ECV provided the strongest adjusted association with the composite endpoint. Each 10% increase in the ECV was associated with a 24% increased risk of adverse events.Study patients were 66% male with a median age of 58 years (range 36-85), had a BMI of 30±4 kg/m2, a left ventricular (LV) end-diastolic volume of 155±35 ml, an LV mass index of 68±20 gms/mIn comparison to healthy volunteers, the ECV is increased in patients with hypertension, and is associated with structural and functional abnormalities. In follow-up, the ECV provided the strongest adjusted association with a composite end-point of death, heart failure hospitalization and late AF recurrence.Dr. Neilan is supported by an American Heart Association Fellow to Faculty grant (12FTF12060588) and previously by an NIH T32 Training Grant (T32HL09430101A1). Dr. Mongeon receives financial support for research from the Montreal Heart Institute Foundation, Montreal, Canada. Dr. Kwong receives salary support from a research grant from the National Institutes of Health (R01HL091157).Dr. Jerosch-Herold is supported in part by a research grant from the National Institutes of Health (R01HL090634-01A1).


Hemodynamic monitoring has been part of the routine management of intensive care patients and high risk surgical patients since the advent of the pulmonary artery catheter (PAC) more than thirty years ago. The growing availability of new less invasive devices over the past decades has now made it possible to monitor cardiac output (CO) more often in the operating room, as well as in new clinical settings such as the emergency department. In this special issue papers have been arranged that discuss different aspects of hemodynamic monitoring, from technical issues to new clinical applications.Perioperative intravascular fluid assessment and monitoring: a narrative review of established and emerging techniques” is a review on perioperative intravascular fluid assessment and monitoring. How cardiovascular physiology can be monitored is explained, and different technologies are presented.The first paper titled ““Cardiac output assessed by invasive and minimally invasive techniques” is a review on all available technologies to monitor CO. The authors start from the PAC and carry on to present the more recent less invasive devices. The review covers technical aspects as well as clinical validation and use.The second paper titled The effect of a hyperdynamic circulation on tissue Doppler values: a simulation in young adults during exercise” presents research done on healthy individuals undergoing strenuous exercise, using left ventricular tissue Doppler velocity (TDI), giving us new data on the use of TDI in hyperdynamic circulation.The third paper titled “The effect of airway pressure release ventilation on pulmonary catheter readings: specifically pulmonary capillary wedge pressure in a swine model” investigates the effect of the airway pressure release ventilation (APRV) on the PAC readings in an animal model. This papers gives new insights into the heart-lung interaction when using this new mode of ventilation. The fourth paper titled “Clinical applications of heart rate variability in the triage and assessment of traumatically injured patients” heart rate variability (HRV) is explored. HRV represents a way of looking at the function of autonomic nervous system during stress conditions and has been studied in different areas as a predictor of morbidity and mortality. In this paper the authors focus on the use of HRV in trauma patients.In the fifth paper titled “Recommendations for haemodynamic and neurological monitoring in repair of acute type A aortic dissection” gives a perspective on how hemodynamic monitoring should be used in conjunction with other clinical strategies. In this review the authors describe how hemodynamic monitoring can be combined with neurological monitoring in order to optimize the circulation guaranteeing adequate cerebral blood flow. The sixth paper titled “Assessing the left ventricular systolic function at the bedside: the role of transpulmonary thermodilution-derived indices” is a review on the use of transpulmonary thermodilution to measure CO and other derived variables. The authors focus on how these variables can be used to assess the left ventricular function in different clinical situations.The seventh paper titled “Maurizio CecconiJamal A. AlhashemiMaxime CannessonChristoph K. Hofer


Progressive heart failure due to remodeling is a major cause of morbidity and mortality following myocardial infarction. Conventional clinical imaging measures global volume changes, and currently there is no means of assessing regional myocardial dilatation in relation to ischemic burden. Here we use 3D co-registration of Cardiovascular Magnetic Resonance (CMR) images to assess the long-term effects of ischemia-reperfusion injury on left ventricular structure after acute ST-elevation myocardial infarction (STEMI).Forty six patients (age range 33–77 years) underwent CMR imaging within 7 days following primary percutaneous coronary intervention (PPCI) for acute STEMI with follow-up at one year. Functional cine imaging and Late Gadolinium Enhancement (LGE) were segmented and co-registered. Local left ventricular wall dilatation was assessed by using intensity-based similarities to track the structural changes in the heart between baseline and follow-up. Results are expressed as means, standard errors and 95% confidence interval (CI) of the difference.Local left ventricular remodeling within infarcted myocardium was greater than in non-infarcted myocardium . One-way ANOVA revealed that transmural infarct thickness had a significant effect on the degree of local remodeling at one year (P < 0.0001) with greatest wall dilatation observed when infarct transmurality exceeded 50%. Infarct remodeling was more severe when microvascular obstruction (MVO) was present  and when end-diastolic volume had increased by >20% .The severity of ischemic injury has a significant effect on local ventricular wall remodeling with only modest dilatation observed within non-ischemic myocardium. Limitation of chronic remodeling may therefore depend on therapies directed at modulating ischemia-reperfusion injury. CMR co-registration has potential for assessing dynamic changes in ventricular structure in relation to therapeutic interventions. Since the advent of primary percutaneous coronary intervention (PPCI) to treat acute myocardial infarction immediate survival has improved but at the expense of a rising incidence of progressive heart failure . IschemiIn this paper we apply techniques previously developed in neuroscience research to align and co-register Cardiovascular Magnetic Resonance (CMR) images of the heart to map the effects of remodeling in three dimensions . This frThe aim of this study was to use 3D co-registration techniques to determine how the LV remodels after reperfused acute ST-elevation myocardial infarction (STEMI) and the relationship to ischemic injury.The study was approved by the Hospital’s research ethics committee and all patients gave written informed consent. To be included in the study each patient had to have been admitted within 24 hours of the onset of chest pain with an ECG diagnosis of acute STEMI and angiographically proven partial or complete coronary occlusion of the infarct-related artery. Exclusion criteria were contraindications to CMR, previous MI or heart failure, clinical instability, significant arrhythmias, pregnancy or lactation. In total MR images from 46 patients were analyzed . A baseline CMR was performed within 1 week of PPCI and the follow-up study at one year.Coronary catheterization was used to identify and treat the infarct-related artery and all patients received either a bare-metal or drug-eluting stent. Standard medical treatment was provided. Flow in the infarct-related artery was graded using the Thrombolysis in Myocardial Infarction trial (TIMI) criteria prior to and after intervention .The CMR studies were performed on a 1.5 T Philips Achieva system  using a 32-channel coil. Myocardial edema was imaged with a navigator-gated black blood T2-weighted turbo spin echo sequence with spectrally selective inversion recovery (SPIR) fat suppression using the following parameters - field of view 350 x 280 mm; matrix, 256 x 123; repetition time msec/echo time msec, 2 R-R intervals/100; in-plane resolution, 1.4 x 2.3 mm; section thickness, 8 mm. An intravenous bolus of Gadobutrol 1.0 mmol/ml  was administered at a dose of 0.15 mmol/kg. Early enhancement imaging was performed to assess microvascular obstruction (MVO) with a single breath hold 3D inversion recovery sequence within 1 minute of contrast injection using the following parameters - field of view, 350 x 290 mm; matrix 252 x 135; repetition time msec/echo time msec, 4.4/1.3; in-plane resolution, 1.4 x 2.1 mm; section thickness 8 mm. Late Gadolinium Enhancement (LGE) was performed to assess infarct size 10 minutes after contrast injection with a 2D inversion recovery sequence using the following parameters - field of view, 320 x 320 mm; matrix 200 x 147; repetition time msec/echo time msec, 5.5/2.5; in-plane resolution 1.6 x 2.2 mm; section thickness 8 mm. Balanced-steady state free precession (b-SSFP) images in the left ventricular short axis plane were acquired using the following parameters - field of view 320 x 320 mm; matrix, 160 x 151; repetition time msec/echo time msec, 3.0/1.5; shot duration, 50 ms; in-plane resolution, 2.0 x 2.2 mm; number of cardiac phases, 30; section thickness, 8 mm.Our approach was to co-register the cine and LGE images onto an atlas template, and then use intensity-based similarities within the heart to track local expansion of the LV in the first year after acute STEMI Figure . The atlA 3D mesh reconstruction of the endocardial and epicardial surfaces was created from the baseline segmentation ,14. To mThe presence of MVO was defined as a region of low signal intensity within the infarcted region on early enhancement images . Left veData were analyzed with IBM SPSS statistics . Remodeling data are presented as mean and standard error of the mean. Comparisons were made using two tailed t-tests and reported as a P value with the 95% confidence interval (CI) of the difference of the mean. The effect of infarct thickness on remodeling was evaluated with a one-way analysis of variance (ANOVA). A P value < 0.05 was considered significant. As this was a preliminary study no correction for multiple tests was made.Baseline characteristics for all patients are shown in Table The mean surface-to-surface distance between manual and automatic segmentations was 1.2 mm ± 0.3 for the endocardium and 1.5 mm ± 0.2 for the epicardium.Remodeling within infarcted myocardium was greater than in remote myocardium . One-way ANOVA revealed that infarct thickness had a significant effect on the degree of local remodeling at one year (P < 0.0001) Figure  with walMean wall thickness averaged throughout the acutely infarcted region decreased significantly during the first year  and was unchanged in the remote region . There was no difference in infarct wall thickness when either global left ventricular remodeling , or MVO was present .In this study we have used image-registration to map in three dimensions where the left ventricular wall dilates in the first year following STEMI and to relate this to the extent of local ischemic injury. Our findings show that following PPCI with standard medical therapy infarct transmurality and MVO have a significant effect on local ventricular wall remodeling while only modest dilatation is observed within non-ischemic myocardium.Image co-registration is an emerging technique for the statistical analysis and quantification of cardiac motion and geometry . In thisA limitation of conventional imaging is that assessment of cavity volumes does not reflect the dynamic regional changes in myocardial structure that occur in response to ischemia-reperfusion injury. In animal studies of remodeling there is an acute phase of lateral slippage of the myocardial planes within the infarct leading to progressive left ventricular dilatation . In the In our cohort remodeling in the non-ischemic territory was modest compared to the infarcted region. The late phase of ventricular remodeling has been shown to be amendable to medical therapy, as chronic administration of angiotensin-converting enzyme inhibitors (ACEIs) are associated with a reduction in the extent of ventricular dilation ,31 and pImage registration offers a more refined model of left ventricular adaptations to infarction than can be derived from global measures of cavity volume. The potential clinical applications include interventional studies of cardio-protective therapies where the physiological effects of remodeling within infarcted and remote myocardium may be separately measured and compared to imaging markers of ischemic injury. The approach may also be helpful for predicting the complications of ischemic remodeling such as ventricular aneurysm formation and the development of ischemic mitral regurgitation. Developments in parallel imaging also make 3D acquisition of both cine images and LGE appealing for registration techniques as they avoid section mis-registration -36.We do not have inter-study reproducibility data for the registration technique as the patients were only scanned once at each visit. We used the segmentation of the myocardium to guide registration so the final transformation is weighted to geometric changes within the myocardium. We also used an initial non-rigid transformation to limit the influence of local structures other than myocardium. However, as the mutual information between images is not explicitly defined the registration may also be influenced by structures immediately adjacent to the heart. EM segmentation provided an accurate segmentation of the myocardial boundaries, but the influence of signal intensity differences in acute and remote myocardium was not evaluated. Mean wall thickness in infarcted myocardium at follow-up was 8.9 mm and so there were typically at least 4 voxels across the width of the LV to perform the non-rigid registration However, accuracy of registration may be limited by severely thinned myocardium. We did not use follow-up LGE images in the remodeling analysis as we wanted to distinguish expansion of remodeled myocardium from expansion of the zone of necrosis. We also did not segment the T2 images due to the relatively low signal to noise ratio of these sequences.In our cohort the mean baseline LVEF was not significantly impaired and this is likely to have been influenced by the exclusion of subjects with acutely impaired left ventricular function who were not suitable for CMR within 7 days of PPCI. However, the observation that local remodeling may be observed despite a normal ejection fraction supports the premise that global indices of function may mask the regional effects of ischemic damage. Further research is needed to explore whether local morphological changes affect long-term outcome or are independent predictors of heart failure. GMM has not been formally assessed for infarct segmentation although the methodology is similar to validated techniques for pixel-weighted infarct quantification . Our finThe severity of ischemic injury has a significant effect on local ventricular wall remodeling while only modest dilatation is observed within non-ischemic myocardium. This indicates that revascularization and standard medical therapy may be effective at preventing structural changes in the remote myocardium, and that further limitation of chronic remodeling may depend on therapies directed at modulating ischemia-reperfusion injury.Co-registration of CMR images acquired in longitudinal studies is an analysis technique which has potential for assessing dynamic changes in ventricular structure in relation to therapeutic interventions.AAR, Area-at-risk; ACEI, Angiotensin-converting enzyme inhibitor; CMR, Cardiac magnetic resonance; LGE, Late gadolinium enhancement; MVO, Microvascular obstruction; NYHA, New York Heart Association Functional Classification; PPCI, Primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; T2-SPIR, T2 weighted spectrally selective inversion recovery; TIMI, Thrombolysis in Myocardial Infarction trial grading.The authors declare that they have no competing interests.DPO’R conceived of the study design, performed the statistical analysis and drafted the manuscript. WS developed the co-registration methods and analyzed the data. BA participated in the coordination of the study and revising the manuscript. AJB contributed to the manual data analysis and revising the manuscript. GD scanned the patients, contributed to data analysis and revised the manuscript. DR participated in the study design and in developing the image analysis methods. SAC conceived of the research program, coordinated the study and revised the manuscript. All authors read and approved the final manuscript.


The structural heterogeneities provide a substrate for triggered activity from which ventricular arrhythmias can be initiated. Pathological alterations in ion channel properties and gap junction intercellular communication lead to changes in the action potential profile and cellular excitability, serving as a trigger for arrhythmias. Although extensive pharmacological therapies have been developed for the treatment of arrhythmias, efficacy of the drugs remains limited due to the complex remodeling processes underlying heart failure.Arrhythmias are a common and often fatal complication of heart failure accounting for 50% to 70% of cardiac deaths due to tachyarrhythmic mechanisms.If) and the hyperpolarization‐activated cyclic nucleotide gated (HCN) channels is emerging. The subject has been addressed by Kuwabara et al2 in this issue of Journal of the American Heart Association.Among the ionic mechanisms that contribute to ventricular arrhythmias, the role of the pacemaker or funny current . For instance, increasing cAMP levels via β‐adrenergic stimulation causes a rightward shift in If activation meaning that the current is activated at more positive voltages without affecting the maximum current amplitude. This mechanism participates in the relationship between β‐adrenergic stimulation and regulation of heart rate.3If in nonpacemaker cells and its potential role in triggering ventricular arrhythmias in both patients and various experimental animal models.Over the last 20 years, much attention has focused on If is abundantly present in ventricular myocytes and progressively declines during maturation.4 Thus, in the adult heart, If can be detected only in a minority of ventricular myocytes, and the current is significantly reduced compared with neonatal myocytes. Under certain pathological conditions If is able to recover its “fetal” phenotype with an increase in the numbers of ventricular myocytes in which the current can be recorded and also with greater current amplitude. This has been demonstrated extensively during cardiac hypertrophy in both humans and several animal models of heart failure, such as pressure overload and postmyocardial infarction.6 Interestingly, there is a strong degree of correlation between the severity of hypertrophy and If density in ventricular myocytes; the expression of the HCN channels responsible for If is most pronounced in regions with the greatest overload,7 raising the possibility that this mechanism is mechano‐sensitive. The nature of the initial injury also seems a determining factor in this phenomenon. Ischemic cardiomyopathy for example leads to a greater If current density in ventricular myocytes compared with dilated cadiomyopathy.8 Moreover, the link between β‐adrenergic stimulation and If may have a role in these differences and could provide a potential arrhythmogenic mechanism in a setting of enhanced sympathetic drive such as heart failure, with an increased contribution of the current during diastole in ventricular myocytes.During fetal and neonatal development If in both healthy and diseased hearts are the HCN channels responsible for generating the current. There are 4 known isoforms identified in mammals (HCN1 to 4) of which HCN1, HCN2, and HCN4 are differentially expressed throughout the myocardium but with the highest levels in the sinoatrial node. The adult ventricle has low levels of HCN2 and HCN4 which subsequently increase at both the mRNA and protein levels as a result of heart failure.7 The specific overexpression of HCN1 has also been reported recently in heart failure.9 It is possible that increases in the different HCN isoforms that are normally present at low levels could potentially interact and give rise to heterotetramers with unique biophysical and regulatory properties compared with homomers. Posttranscriptional mechanisms may also contribute to HCN expression through microRNA.10 Collectively this increase in HCN subunit expression is likely to be the underlying cause for the gain of function in If recorded from diseased ventricle.The molecular determinants of If and HCN channel expression during cardiac remodeling, yet the precise involvement of If in arrhythmias remains to be fully determined. The paper by Kuwabara et al2 provides insight into the role of If in the initiation of triggered activity in a bradycardic model of heart failure. By using genetically modified mice that express a dominant negative form of the transcriptional repressor neuron‐restrictive silencing factor (dnNRSF‐Tg), the authors generated a model of heart failure11: NRSF, a regulator of the fetal cardiac gene program, activates the reexpression of HCN2 and HCN4 to induce dilated cardiomyopathy. Kuwabara et al tested the hypothesis that expression of HCN channels predisposes ventricular myocytes to enhanced automaticity. The major findings of the study are the increase in If density and the high incidence of ventricular tachycardia, premature ventricular contractions, and sudden cardiac death in the dnNRSF‐Tg mice. β‐adrenergic stimulation increased the susceptibility of myocytes to early after‐depolarizations and spontaneous action potentials through increased cAMP production. These findings were confirmed in myocytes from mice with cardiac specific overexpression of HCN2, demonstrating a link between HCN and arrhythmias. These results are also in agreement with another study9 showing that HCN activity increases the proarrythmogenic potential in the failing myocytes through prolongation of the repolarization phase in ventricular action potentials.The majority of studies have focused on the modifications in functional and molecular properties of 2 used ivabradine, a selective heart‐rate–reducing agent, to inhibit channel activity. Ivabradine blocks HCN activity by entering the pore of the channels when they are in open state thereby reducing the slope of diastolic depolarization.12 A major clinical trial to demonstrate the beneficial effects of ivabradine is the BEATUTIFUL  study treating 10 917 patients with stable coronary artery disease and left ejection fraction <40%. Although ivabradine treatment did not affect the primary composite outcome, it reduced the need for hospitalization due to myocardial infarction and coronary revascularization in patients with baseline heart rates >70 bpm.13 This work was followed by the SHIfT  trial (6558 patients), which confirmed that treatment with ivabradine significantly reduced hospital admission for worsening heart failure by 18% and cardiovascular deaths due to heart failure.14 In both trials the favorable effects of ivabradine were greatest in those patients with a higher heart rate. The most striking finding of the SHIfT trial, obtained from the echocardiographic substudy, was the reversal of cardiac remodeling in the left ventricle with pronounced increase in left ventricular ejection fraction and reduced left ventricular systolic volume.15 Effects of ivabradine in preventing arrhythmias were also investigated in a small group of patients (21) with inappropriate sinus tachycardia. Ivabradine reduced 70% of symptoms reported at baseline and in 50% of patients all symptoms were eliminated highlighting its potential use in the treatment of arrhythmias.16 Beneficial effects of chronic treatment with ivabradine have also been shown in rodent models of heart failure with improvements in whole heart systolic and diastolic function, reduction in interstitial and perivascular fibrosis, increase in angiogenesis and myocardial perfusion, improved calcium handling, decreased mortality and ventricular excitability, and reversal of myocardial structural remodeling.19To confirm the contribution of HCN overexpression in the development of arrhythmias, Kuwabara et al20 However, there are studies showing that some of the effects may be mediated by different mechanisms. We have recently shown that the reduction in myocardial fibrosis induced by ivabradine is not due to heart rate reduction, as the β‐adrenergic blocker metoprolol did not reduce fibrosis in a rodent model of heart failure, despite a similar reduction in heart rate.19 Kuwabara et al2 also studied the remodeling effects on arrhythmias independent of heart rate reduction by using a nonbradycardic dose of ivabradine. With this strategy they clearly demonstrated the reduction in If amplitude and occurrence of spontaneous action potentials in the presence of isoproterenol and improved survival rate in the dnNRSF‐Tg model. Other effects of ivabradine independent of heart rate include the attenuation of the renin–angiotensin aldosterone system (RAAS) through a reduction in angiotensin‐converting enzyme and angiotenisn II type I receptor (AT‐1) transcript expression.17 All these studies support the notion that ivabradine can have direct effects on ventricular structure and electrophysiology independent of the sinoatrial node.The mechanisms of ivabradine, however, remain controversial. Most clinical and experimental evidence points to a primary role of heart rate reduction. Ivabradine‐driven cardiac remodeling has been extensively studied at doses that lower heart rate and the reduction in heart rate is thought to be the likely cause of remodeling by optimizing energy consumption while simultaneously reducing cardiac work load.2 contributes to the significant progress that has been made in establishing the role of If and HCN channels as markers of pathological remodeling and identifying the cardioprotective effects of ivabradine in the failing heart. However, there are key questions that remain unanswered: (1) Is the overexpression of HCN channels and augmented If in the ventricle an adaptive response with specific functional consequences or is it simply part of a global remodeling process? (2) What is the role of the different HCN isoforms and how do the isoforms contribute to the clinical and pathological scenario? (3) What are the effects of ivabradine on the fibrotic pathways, in particular the RAAS system and the local regulation of ECM? (4) Are the effects of ivabradine on arrhythmias secondary to the reversal of remodeling rather than a direct effect on the HCN channels? (5) What are the reasons for the variability in the effects of ivabradine in different HF models and at different stages of disease?The paper by Kuwabara et alPharmacological inhibition of the HCN channels remains a potentially useful strategy in heart failure as there are already significant encouraging results from large clinical trials and accumulating positive laboratory studies. However, more specific clinical trials should address the efficacy on treating arrhythmias in heart failure and it is also essential that the specific mechanisms involved are investigated in the laboratory in order to understand the pathways involved and refine this novel and promising approach.


To evaluate myocardial feature tracking (FT) as a potential novel quantitative analysis tool for the assessment of myocardial viability using LDDSMR.Low dose dobutamine stress magnetic resonance imaging (LDDSMR) is a widely accepted technique for assessment of hibernating myocardium in patients with ischemic cardiomyopathy (ICMP). It is particularly helpful in patients with intermediate transmurality of scar where prediction of functional recovery by late gadolinium enhancement imaging (LGE) alone is difficult. Analysis of LDDSMR is usually based on visual assessment and is therefore considerably operator dependant. Recently myocardial feature tracking (FT) has been introduced. It tracks tissue voxel motion of cine-MR images to assess circumferential and radial myocardial strain independent of additional sequences.15 consecutive patients with ICMP referred for viability assessment were studied at 3 Tesla (Philips Achieva) at rest and during LDDSMR. ICMP was defined as: angiographically established coronary artery disease, LV-EF ≤45% and ≥2 segments with wall motion abnormalities at rest. Myocardial function was studied by steady state free precession (SSFP) cine imaging in 3 short axis slices covering 16 myocardial segments, excluding the apex.The same segments were studied with dedicated FT software  to assess subendocardial and subepicardial circumferential (Ecc) and radial (Err) strain.subendocardial r=0.84, Ecc subepicardial r=0.72 and Err r=0.7.208 of 240 segments (87%) were analysed by two independent observers. 32 segments were excluded because of insufficient image quality or visualization of the outflow tract. Interobser-variability was: Ecc -1· min-1) there was improvement in Ecc subendocardial, Ecc subepicardial  and Err  and Ecc subepicardial (p=0.008) while Err remained unchanged with stress. Hypokinetic segments without scar (n=75) improved in all three strain values . Hypokinetic segments with non-transmural scar (n=60) showed improved Ecc subendocardial , Ecc subepicardial and Err up to 75% transmurality while transmurally scarred segments (n=6) remained unchanged with stress.During LDDSMR (5 and 10 µg · kgFT is a novel technique, which reliably detects quantitative wall motion derived from SSFP CINE imaging. It seems useful for quantitative analysis at rest and during low dose dobutamine stress for viability assessment in patients with ischemic cardiomyopathy.


Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography. Advances in cardiovascular interventional techniques have allowed percutaneous treatment of conditions that either previously required open operations or have not been amenable to any treatment.Aortic stenosis (AS) is the most common valvular abnormality in the western world and it is more frequent in elderly patients with comorbidities. Transcatheter Aortic Valve Implantation (TAVI) offers an alternative to patients with severe symptomatic AS and contraindications for surgery or high risk for surgery .Mitral regurgitation (MR) has a prevalence of 1-2% in the general population and there are several percutaneous techniques for the treatment of it, such as direct annuloplasty, indirect annuloplasty-coronary sinus and ventricular remodeling, however only repair by using Mitraclip has been extensively evaluated  and theiAtrial fibrillation (AF) is the most common cardiac arrhythmias. At present, percutaneous left atrial appendage (LAA) occlusion may be an acceptable option in selected high-risk patients with AF who are not candidates to oral anticoagulation .Para-valvular leaks (PVLs) represent a complication of cardiac valve replacement and their surgical repair is associated with a high mortality and morbidity rate, thus, in selected cases, percutaneous repair can be performed . This reThe severity of AS is usually assessed by TTE according to AHA/ACC  and to ETo date, there is a lack of pharmacological therapies to prevent the progression of AS and unfortunately, balloon aortic valvuloplasty has revealed limited long-term efficacy .TAVI can be considered an alternative to surgery for patients with symptomatic severe AS and with contraindications or at high risk for surgery Table  1]. Pat. Pat1]. Echocardiography is not mandatory to guide TAVI. Intraprocedural TEE may play a role with the SAPIEN series in guiding valve implantation and in early post implantation assessment . During After TAVI, survival at 30 days is 92.9%, at 1 year it is 78.6% and at 2 years it is 73.7%, so midterm to long-term survival is encouraging in high-risk patients, although a substantial proportion of patients died within the first year . During MR can be divided into primary, or organic, and secondary, or functional categories . OrganicWhen regurgitation across the valve is the consequence of inappropriate leaflets coaptation, one surgical approach is to create a double orifice by suturing the free edges of the middle leaflet segments, the edge-to-edge, or Alfieri stitch . This teThe Clip Delivery System (CDS) has the MitraClip, an implantable clip, attached to its distal end Figure  29,30].,30.29,30In the EVEREST I study, MitraClip had a low incidence of morbidity and mortality and reduction in MR (less than 2+) was observed in the majority of patients . There wAfter percutaneous mitral valve repair, mitral valve area decreases without evidence of clinically significant mitral stenosis .The EVEREST II is the first randomized trial which compares MitraClip device with open mitral valve surgery. Although percutaneous repair was less effective in to reducing MR than conventional surgery, it was associated with superior safety and similar improvements in clinical outcomes at 12 months .TTE follow-up is recommended at 1 and 12 months .The final step of development of interatrial septum Figure  during fThe prevalence of a PFO has been reported to be 24% in the general population and increases to 38% in patients with cryptogenic stroke, suggesting an association between PFO and stroke . Two proClinical and echocardiographic indications and controindications to PFO percutaneous closure are reported in Table ASD is a common form of congenital heart disease accounting for approximately 10% of all congenital heart defects . There aThe TTE protocol to imaging ASD is the same applied during the study of PFO Figure  3,51].,51.3,51]TTE can evaluate ASD rims although, especially in adults, TEE is mandatory Figure  51]. Ri. Ri51]. ASD closure is indicated in presence of hemodynamic significance  or after a paradoxical embolic event Table  4]. Lar. Lar4]. During the procedure for PFO, echocardiography is not usually required, although TEE guidance has been described extensively in adult patients . ICE hasPercutaneous PFO and ASD closure is a safe and effective treatment in adults patients, even in case of thrombophilia or pulmonary hypertension, also during a long-term follow-up, up to 11 years ,7. EarlyA early or late post-procedure relatively rare complication is device embolization . ResiduaErosion has been described, as late complication, in patients with multiple devices, deficient antero-superior rims and oversizing devices that, also, can cause superior vena cava occlusion ,55.Device thrombosis appears to be more common with devices containing uncoated metal arms, within the first month after device implantation . FinallyDuring follow up, TTE is recommended at 6, 12 and 24 months .Patients with AF have an increased risk of thrombembolic stroke  and in nLAA has a tubular form and is attached by a narrow junction to the left atrium , it is nWarfarin is the gold standard treatment to prevent embolic stroke, but benefits of anticoagulation do not come without risk of bleeding ,63 and, At present, percutaneous LAA closure is an acceptable option in selected patients with AF at high-risk of stroke who are not candidates to oral anticoagulation Table . In addiClinical and echocardiographic indications and contraindications to percutaneous LAA closure are reported in Table Independently of the type of device, the actual deployment methodology is similar. First, standard transeptal puncture is performed for left atrial access. Next, the sheath is advanced up to the LAA orifice and a pigtail catheter is inserted into LAA. Then, TEE and fluoroscopic evaluate size (length and diameter), shape, and angulation of the orifice and body of the LAA. The device is then sized and is advanced into the LAA orifice .Currently, three devices for LAA occlusion have been specifically designed: the Percutaneous LAA Transcatheter Occlusion (PLAATO), the WATCHMAN LAA system and Amplantzer Cardiac Plug Device. The PLAATO device was the first device, consisting of a self-expandible nitinol cage covered with a nonthrombogenic occlusive expanded polytetrafluoroethylene membrane and currently it is not available because of economic reasons. The WATCHMAN LAA System  consists of a parachute-shaped device with a self-expanding nitinol frame structure with a permeable polyester membrane over the atrial side and mid-perimeter fixation barbs to secure it in the LAA; it is permeable to blood, thus patients require conventional thromboembolic prophylaxis with 6 weeks of warfarin, at which time device endothelialization is confirmed by TEE . More reTEE is also used to determine any residual flow in the LAA and to examine device stability . AdequacTo date, LAA percutaneous closure, in particularly with Amplatzer device, have proved to be a procedure with a high success rate (96%) and low rate of serious complications (7%) .Complications include: ischemic stroke; pericardial effusions; tamponade; LAA tear/rupture and device embolization ,67,69 F. To veriPVLs indicates a regurgitation between the prosthetic ring and the native valvular annulus -72 prediTTE is the first diagnostic approach to PVLs Figure  70,73].,73.70,73Patients with severe PVLs and/or haemodynamic instability with symptoms of congestive heart failure or severe hemolysis are candidates to leak correction ,76. SurgTEE is commonly used for image guidance ; ICE mayPVLs percutaneous closure is a feasible procedure in selected patients, with a reasonable degree of technical and clinical success, complete or partial PVL occlusion in 70% of patients, with concomitant clinical improvements and an acceptable level of serious complications (10%) .Early complications associated with device closure of PVLs include incomplete closure, impairment of valvular function, embolization and onset of new haemolysis .A major limitation of perivalvular leak closure is the frequent persistence of leak, often due to the semilunar shape of the defects. In such cases, it may be prudent to plan a staged procedure, first implanting one device and after this has fibrosed, deploying another, rather than risking dislodgement or embolization of the first device with immediate implantation of a second ,79. AfteTo ensure that device has not migrated, the leak has been closed follow-up with TTE is generally adequate at 1, 6 and 12 months.Significant advances in percutaneous repair of many heart diseases have highlighted the importance of a systematic approach for selection, guidance and follow up of patients undergoing these procedures.Echocardiography plays a critical role in patient selection, particularly in choosing the appropriate size of the prosthesis to be implanted. To date, TAVI is targeted at high-risk patients but it may be extended to the lower risk group in the future, if the initial promise holds true after careful evaluation.A combination of TEE and supplemental TTE has been used for MitraClip procedure. Its safety profile is similar to other percutaneous procedures and now it is attractive for high-risk surgical candidates, in future randomized trial results will define the role for surgical candidates.Understanding correlation between anatomy and echocardiography is perhaps the most essential requisite to ensure a successful PFO/ASD percutaneous closure procedure. The complication rates for both TEE and ICE imaging to guide this procedures appear to be low and acceptable, but ICE should be considered when suitable expertise is available. LAA percutaneous closure is an emerging approach and it, with appropriate patient selection, device iterations, and technical improvements, may become an important viable therapeutic alternative to chronic antithrombotic therapy. PVLs percutaneous closure is a new approach that can be useful for increasing PVLs because of increasing valve replacements. Appropriate designed devices for PVLs closure and improved imaging, particularly with ICE and with a wide use of 3D TEE, will help in this procedure. The echocardiography has an important and undeniable role. For the best result of percutaneous treatment, a close collaboration between sonographers and interventional cardiologists is required.Written informed consent was obtained from the patient for publication of this report and any accompanying images.AF: Atrial Fibrillation; AHA/ACC: American Heart Association/American College of Cardiology; AHA/ASA: American Heart Association/American Stroke Association; AR: Aortic Regurgitation; AS: Aortic Stenosis; ASA: Atrial Septal Aneurysm; ASD: Atrial Septal Defects; CDS: Clip Delivery System; CT: Computed Tomography; ESC: European Society of Cardiology; ESO: European Stroke Organisation; EuroSCORE: European System for Cardiac Operative Risk Evaluation; EVEREST: Endovascular Valve Edge-to-Edge Repair Study; ICE: Intracardiac Echocardiography; LA: Left Atrium; LAA: Left Atrial Appendage; LV: Left Ventricle; LVOT: Left Ventricular Outflow Tract; MR: Mitral Regurgitation; PFO: Patent Foramen Ovale; PVLs: Para-Valvular Leaks; Qp: Pulmonary Blood Flow; Qs: Systemic Blood Flow; STS score: Society of Thoracic Surgeons Cardiac Operative Risk Evaluation; TAVI: Transcatheter Aortic Valve Implantation; TCD: Transcranial Doppler; TEE: Transesophageal Echocardiography; TTE: Transthoracic Echocardiography; Valve in Valve procedure: percutaneous implantation of a second device inside the primary percutaneous aortic prosthesis.The authors declare that they have no competing interests.C Contaldi drafted the manuscript; MA Losi designed the paper; A Rapacciuolo, G Esposito, F Piscione, MA Losi and S Betocchi revised it critically; R Lombardi, V Parisi, M Prastaro, LS Parrella, A Giamundo, C Di Nardo and R Puglia analyzed data from literature. All authors have read and approved the manuscript.


Cine and DE-CMR performed in a cohort of patients revealed that the presence of LBBB was more frequently associated with increases in LV volumes and depression in LV function, whereas RBBB or nonspecific conduction delay were more strongly associated with septal replacement fibrosis.Ventricular conduction delay is thought to occur from a variety of differing mechanism including ischemia or infarction, left ventricular (LV) hypertrophy and/or dilation, and fibrotic degenerative disease of the conduction system. CMR is an ideal modality to evaluate for these mechanisms as cine-CMR is the “gold-standard” for assessment of cardiac morphology and function, and delayed enhancement (DE)-CMR has emerged as a robust modality for assessment of LV replacement fibrosis.To compare the prevalence of abnormalities on cine and DE-CMR in patients with various forms of ventricular conduction delay on 12 lead ECG.We prospectively enrolled 698 consecutive patients presenting to our center from July, 2009 to March, 2010 for CMR for a variety of clinical indications. Patients were categorized based on QRS morphology on concurrent 12-lead ECG tracings into the following 4 groups: 1) no conduction delay (QRS duration ≤ 100 msec); 2) nonspecific conduction delay (NSCD) [QRS duration more than 100 but less than 120 msec]; 3) LBBB (QRS duration ≥ 120 msec with LBBB morphology by Minnesota code); and 4) right bundle branch block (RBBB) [QRS duration ≥ 120 with RBBB morphology by Minnesota code]. Cine and DE-CMR images were analyzed for left atrial (LA) volumes, LV and right ventricular (RV) volumes and ejection fraction (EF), LV mass, and LV replacement fibrosis per standard methodologies for our laboratory.2 ± 0.27; heart rate was 75 bpm ± 14; and LVEF 57% ± 17. Imaging characteristics as segregated based on the QRS complex are shown in Table The baseline clinical characteristics of our cohort included cardiac risk factors of hypertension in 401 (57%); diabetes in 182 (25%); hyperlipidemia in 310 (44%); and tobacco abuse in 57 (8%). Symptoms of chest pain were present in 170 (25%) and dyspnea in 289 (41%). Prior history of myocardial infarction was present in 94 (13%). The systolic blood pressure was 127 mmHg ± 21; diastolic blood pressure was 72 mmHg ± 12; the body surface area was 1.94 kg/mRBBB or NSCD are more strongly associated with septal replacement fibrosis whereas LBBB is more frequently associated with increases in LV volumes and depression in LV function.None.


The contribution of fibrogenesis to impaired cardiac function is increasingly recognized. Molli sequence is a new tool in clinical practice allowing cardiac interstitial fibrosis quantification using MRI and might bring new information comparing to delayed myocardial enhancement. The goal of this work was to assess the potential value of segmental quantification of myocardial fibrosis using T1 mapping in dilated cardiomyopathy (DCM) in comparison to late contrast enhancement imaging and circumferential strainThis study was performed after approval of the institution's review board. Informed consent was obtained from all patients who were enrolled in this study. Seventeen patients with DCM, and 11 controls subjects were prospectively included. All patients underwent cardiac MR  with the following sequences (parameters set according to recommendation of the SCMR): 1) cine sequence, 2) tagging sequence CSPAMM TR/TE=37.1ms/1.4ms; matrix 256, FOV 340, temporal resolution 37.1 ms, distance between tag: 6mm in mid LV slice. 3) Molli sequence  acquired before and 5, 7, 9 min after gadolinium injection . 4) Late gadolinium enhanced sequence 10min after injection. T1 values were assessed in blood and in the 6 segments of the mid LV slice. Were calculated: R1, ΔR1, ΔR1 ratio . Statistical analyses were performed for patients and for segments with (+) and without (-) enhancement on LGE. Mixed linear model was used to estimate the effect of the imaging parameters of interest, allowing us to take into account the dependency between myocardial segments.In all DCM, λ was significantly higher compared with the value obtained in control subject p<0.0001). In DCM, λ was higher in segments showing enhancement on LGE (0.56±0.05) compared with segments showing no enhancement . On the other hand λ was not significantly different between patients without  and with at least one segment showing enhancement on LGE  (figure . In DCM,In DCM fibrosis was a diffuse process involving all the myocardium. There was a correlation between the quantity of fibrosis and circumferential strain.This study was supported by a national research grant: PHRC_CMD_IRM # 2011-A00887-34


Chronic heart disease contributes to the mortality of patients with AIDS. Although studies of left ventricular function in patients with acquired immune deficiency syndrome (AIDS) have been conducted, studies of right ventricular function are rare. The present study aimed to characterize the tricuspid annulus movement and evaluate the right ventricular function of patients with AIDS by tissue Doppler imaging. Tissue Doppler echocardiography was performed on 106 patients with AIDS and 64 controls. Tricuspid annulus movements were detected from the apical four-chamber view and the apical right heart two-chamber view. The peak diastolic early period velocity (Ve), peak diastolic later period velocity (Va) and peak systolic velocity (Vs) were measured at the anterior, posterior and lateral walls and also at the interventricular septum. Mean values were calculated, as well as the Tei index of the lateral site. Compared with the values in the control group, the Vs and Va of the AIDS group decreased at all sites with the exception of the lateral wall, whereas the Ve decreased at all sites of the tricuspid annulus (P<0.05). The Tei index was higher in the AIDS group than in the control (P<0.05). The results obtained in the present study show that the function of the right ventricle decreases in patients with AIDS, which is indicative of susceptibility to right ventricular dysfunction. Acquired immune deficiency syndrome (AIDS) is a serious disease that spread rapidly in the world since 1984. AIDS has spread rapidly in China as well as numerous other developing countries. During the end of the last decade, AIDS spread rapidly through serum sampling in Henan Province, China. Chronic heart disease contributes to the mortality of individuals with AIDS . AlthougIn total, 106 patients with AIDS were enrolled in the study, comprising 46 males (43.40%) and 60 females (56.60%), aged 20–59 years, with a mean age of 41.26±7.47 years. The CD4 counts ranged between 1 and 390 cells/μl, with a mean of 185.09±118.12/μl. All cases were infected by serum sample and were confirmed to be infected with the testing of plasma samples  . The infection period was between 4 and 27 years, with a mean of 11.69±4.04 years. The AIDS group was compared with an age- and gender-matched population of 64 normal subjects. No abnormal observations in the control group were observed by physical examination, X-ray, electrocardiography (ECG) and echocardiography. None of the enrollees had a medical history of cardiovascular abnormalities and none of the patients with AIDS had undergone highly active antiretroviral therapy. The study was conducted in accordance with the Declaration of Helsinki and with approval from the Ethics Committee of the People’s Hospital of Zhengzhou University . Written informed consent was obtained from all participants.Echocardiography was performed in all enrollees using American GE Vivid 3 or 7 ultrasound systems , with transducer frequencies of 1.7–3.5 and 1.5–4.0 MHz, respectively. Enrollees were positioned in the left-lateral position and had normal respiration. Doppler tissue velocity mode was used and focused at the tricuspid annulus level, with a sample volume between 4 and 5 mm. Care was taken in directing the transducer beam as close as possible to the DTI beam at <20° in selected planes. Tricuspid annulus movements in all subjects were detected from the apical four-chamber view and the apical right heart two-chamber view. The peak diastolic early period velocity (Ve), peak diastolic later period velocity (Va) and peak systolic velocity (Vs) were measured at four sites  and the mean value of these variables, including ‘s’, ‘e’ and ‘a’, were calculated. The DTI spectrum of tricuspid annulus movements includes three waves: ‘s’, movement towards the apical during systole; ‘e’, quick movement towards the roof of the atrium during early diastole; and ‘a’, movement caused by atrium systole during late diastole. At the lateral site of the tricuspid annulus, the interval from the end of the ‘a’ wave to the beginning of the next ‘e’ wave, was recorded as line A and the interval from the beginning to the end of the ‘s’ wave was recorded as line B. The Tei index was calculated using the following formula: (A – B)/B. All parameters were measured three times and mean values were obtained.Data were analyzed using SPSS version 11.5  and are expressed as mean ± SD. A Student’s t-test was used to compare the mean values between the two groups. P<0.05 was considered to indicate a statistically significant difference.Recently, the improved control of opportunistic infection has resulted in a greater awareness of cardiovascular complications in individuals who are HIV positive or have AIDS –9. GenerThe Tei index is a parameter that reflects the systolic and diastolic function of the heart . The res


Dobutamine and adenosine stress are the two methods most often used in CMR for the diagnosis of ischemia. Both methods have demonstrated good results in patients after coronary artery bypass graft (CABG). However, a direct comparison has not been examined.Comparison of the diagnostic accuracy of dobutamine wall motion analysis (DSMR) and perfusion (DSPERF) with adenosine perfusion (APERF)One hundred nine patients  after CABG underwent CMR imaging on two appointments. 1) LV-function, DSMR (10-40µg/kg/min + 2mg atropine if needed until target heart rate) imaging (SSFP) of 3 short axis  and 3 long axis views at each stress level. Perfusion imaging of 3 short axis  were acquired every second heart beat during dobutamine stress at maximal stress level with a contrast bolus of 0.1mmol/kg Gd-DTPA. Late gadolinium enhancement (LGE) imaging  10min after additional 0.1mmol/kg Gd-DTPA. 2) Adenosine and rest perfusion (140 µg/min/kg body weight)  using a 0.05mmol/kg contrast bolus of Gd-DTPA. Images were analyzed visually using the standard 16 segment model. A developing wall motion abnormality or stress induced perfusion defect  in >1 segment was defined as pathological. Invasive coronary angiography served as the reverence. Significant stenosis was defined as >50% in a bypass graft or a native vessel > 2mm diameter in areas without >75% transmural LGE.Prevalence of angiographically significant stenosis was in 63% of patients. Surgery was performed 9.5±6.6 years before CMR. Stent placement after CABG was performed in 68 patients. Ejection fraction was 48±8%. LGE was present in 68% of patients. Sensitivity, specificity and diagnostic accuracy are shown in table DSMR was the best test for the detection of ischemia in patients after bypass surgery and outperforms adenosine stress perfusion. The addition of DSMR perfusion increases sensitivity, but decreases diagnostic accuracy.Caption for image: Angiographically ischemia in the inferior and lateral wall. Wall motion abnormalities in the lateral wall. Perfusion defect (dobutamine and adenosine) is larger extending to the inferior wall and apical anterior. No LGE present.


Echocardiography has shown to be an essential diagnostic tool in the critically ill patient's assessment. In this scenario the initial fluid therapy, such as it is recommended in the actual clinical guidelines, not always provides the desired results and maintains a considerable incidence of cardiorrespiratory insufficiency. Echocardiography can council us on these patients' clinical handling, not only the initial fluid therapy but also on the best-suited election of the vasoactive/inotropic treatment and the early detection of complications. It contributes as well to improving the etiological diagnosis, allowing one to know the heart performance with more precision. The objective of this manuscript is to review the more important parameters that can assist the intensivist in theragnosis of hemodynamically unstable patients. The critically ill patient is under an intense threat for his life. Therefore, the diagnostic methods used in the Critical Care and Emergency departments must be fast, reliable and reproducible to assure a successful therapeutic strategy., avoiding patients' displacements, and can provide transcendental information on real time for making vital decisions in a noninvasive or semiinvasive form, such as fluid therapy continuity, early vasoactive or inotropic treatment, realization of a pericardiocentesis in a cardiac tamponade (Image 1), systemic fibrinolysis in severe pulmonary embolism (Image 2), or the indication of cardiac surgery for the existence of mechanical complications in context of acute coronary syndrome, between others. In spite of this, it continues being an underused diagnostic method, even in the coronary units .The cardiac output (CO) is the most important hemodynamic parameter in critically ill patients and can be easily estimated by echocardiography. To calculate it, we need to get the diameter of the LVOT in proto-midsystole, in parasternal long axis, and calculate the VTI in apical 5-chamber view with pulsed Doppler (Image 12). We must not forget that all these calculations are altered in aortic valve disease or significant subaortic obstruction.If the quality of the image obtained for calculating the diameter of the LVOT in parasternal long-axis view is not optimal, it is possible to determinate it in apical 3-chamber view and, alternatively, a measurement of 2 cm in adult can also be used empirically. If the patient is in atrial fibrillation, an average of at least 6 determinations should be performed . The detTei index  is an ecIn certain clinical cases, a right ventricular (RV) dysfunction may be responsible for the continuing situation of shock. The right ventricle can also be studied with echocardiography with ability to provide information on RV function similar to that provided by the PAC. Size, wall thickness, contractility, ejection fraction (RVEF) and abnormal movements of the interventricular septum (IVS) can be studied. The RVEF is usually estimated qualitatively, because the shape of the RV is not cylindrical, unless there is 3D echocardiography or radionuclide angiography available, although there are currently various parameters that can estimate the RVEF with a strong correlation.The abnormal movements of the IVS and the flattening or paradoxical motion may suggest the existence of elevated right ventricular end-diastolic pressures. The leftward shift of IVS during systole is a sign of pressure overload and during diastole is a sign of volume overload, both reflecting an abnormal RV hemodynamics .Tricuspid annulus Plane Systolic Excursion) is measured in 4-chamber view with M-mode on the lateral wall of the tricuspid annulus. A value of less than 1.6 cm is suggestive of RV systolic dysfunction. This parameter has shown a high correlation with RVEF calculated by radionuclide angiography [13A-13B).Tricuspid Annular Plane Systolic Excursion (TAPSE), the RV Tei index, tricuspid DTI and Cardiac Magnetic Resonance Imaging have gained value. The longitudinal displacement of the tricuspid annular plane toward the apex of the RV , which can lead to a decrease in right ventricular cardiac output. In addition, the RV does not usually compensate acute elevations in afterload, since it is perfused in diastole and systole as well and may develop cardiogenic shock because it is unable to expand quickly, which occurs in massive pulmonary thromboembolism. The two main causes of acute pulmonary hypertension in the ICUs are massive pulmonary embolism and ARDS (up to 25% of cases). In both, there is RV dilatation, leading to diastolic overload, and dyskinesia of the IVS, producing systolic overload. In these patients it is essential to reduce RV afterload to ensure coronary perfusion pressure.sine qua non, thus obtaining the pressure gradient between RV and right atria (Image 14). In the absence of pulmonary stenosis or other obstruction in the RV outflow tract, right ventricular systolic pressure is equal to that of the pulmonary artery, therefore, the SPAP is calculated by adding, to the pressure gradient, the mean right atrial pressure (MRAP). A transpulmonar flow in “W”, determined with pulsed Doppler in paraesternal short axis view, in suggestive of severe pulmonary hypertension.Doppler echocardiography can estimate systolic pulmonary artery pressure (SPAP) with good correlation with invasive methods. For its calculation, the Bernoulli equation is applied (4 x velocity ²) on a jet of tricuspid insufficiency, a condition 2) analyzing the changes in the ICV respiratory diameters. Pulmonary hypertension is considered when SPAP is greater than 35 mmHg and when it is greater than 60 mmHg is it considered severe. Mean and diastolic pulmonary artery pressures can also be calculated with echocardiography (Image 15).All patients with hemodynamic instability usually have a central venous access, hence the determination of the CVP may be possible to determine the MRAP. But everyone knows that the CVP has its limitations, thus in most studies the MRAP is considered a continuous variable between 5 and 20 mmHg. Other studies have shown that the MRAP can be estimated more accurately , can also be determined by echocardiography if we had previously the MRAP, with the following formula: SVR =  x 79.9 . AnotherIn a hemodynamically unstable patient, echocardiography can quickly provide enough information to get a successful theragnosis. Its use in critically ill patients is unquestionable; however, no clinical trials that endorse an increase in survival with echocardiography-guided therapy have been performed.In pursuit of "excellence" in the treatment of critically ill patients, intensivists were trained and successfully performed percutaneous tracheostomy, thoracocentesis, pericardiocentesis, continuous renal replacement therapies, fibrobronchoscopies, transitory and permanent pacemakers, among others. Now is the time that hemodynamic monitoring guided by echocardiography be generalized in all ICUs.


Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms.We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model.The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability.In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention. Ischaemic heart disease (IHD) is a common cause of left ventricular (LV) systolic dysfunction leading to chronic heart failure (CHF) . PatientThe proportion of patients who have a substantial volume of myocardium that is dysfunctional but viable is uncertain . The incRevascularisation might lead to improvement in LV systolic function and improve the clinical state of patients with CHF. However, the potential for revascularisation is dependent upon the extent of reversible ischaemia as opposed to scar in the areas to be revascularised. In addition, the extent and distribution of transmural scar may also affect the response to cardiac resynchronisation therapy (CRT) ,14. We tWe prospectively enrolled patients with stable clinical signs and symptoms of CHF (New York Heart Association (NYHA) functional class I to III) due to LV ventricular systolic dysfunction and IHD attending a community-based heart failure clinic serving a population of just over 0.5 million. The diagnosis of heart failure was based on symptoms and signs assessed by a cardiologist. Patients with a baseline echocardiogram showing a LVEF < 50% were considered to have systolic dysfunction. The diagnosis of IHD was confirmed by a history of myocardial infarction, coronary revascularisation or > 50% of luminal diameter coronary stenoses on angiography .Exclusion criteria were significant primary valvular or congenital heart disease, a myocardial infarction or revascularisation during the 12 months prior to recruitment, and conventional contraindications to CMR . Patients who reported anginal symptoms were also excluded from the study since these patients would be expected to have substantial amounts of viable myocardium subtended by diseased coronary arteries. Patients with severe co-morbidities or who were considered too frail for revascularisation were also excluded.Patients were first treated with appropriate pharmacological treatment including diuretics, renin-angiotensin-aldosterone system (RAAS) inhibitors, β-blockers and aldosterone antagonists unless contra-indicated or not tolerated and were seen regularly in a heart failure clinic to ensure continued optimisation of treatment and were then referred for CMR. Typically there was a delay (mean ± standard deviation: 4 ± 5.5 months) between initial assessment and CMR during which ventricular function may have improved with therapy. Written informed consent was obtained in all study patients. The study complies with the Declaration of Helsinki and was approved by the local research ethics committee.Patients underwent CMR on a 1.5 Tesla scanner  using ECG-triggered breath-hold gradient-echo in steady-state acquisition (FIESTA) imaging. After initial localizing scans, cine LV horizontal long-axis, vertical long-axis and contiguous short-axis images covering the LV from apex to base (slice thickness 10 mm) were obtained. The multi-slice short-axis cine data sets were analyzed by an expert observer whose reliability and reproducibility has already been tested .The reproducibility and reliability of the observer who visually evaluated the presence of wall thickening abnormalities was examined in 30 randomly selected CMR scans. The observer reviewed the data twice within 2 months blind to the results of the first scan. A second observer reviewed the same scans once. Intra- and interobserver agreement was high with Cohen's th segment (apex).A commercially available gadolinium-based contrast agent, gadodiamide , was injected intravenously at a dose of 0.1 mmol/kg of body weight, and 10-15 min after the injection CMR was performed using a segmented inversion-recovery fast gradient echo sequence that has been described in detail previously . LGE imaPotentially viable but dysfunctional myocardial segments were defined as those with impaired thickening but with ≤50% LGE . A patieP value < 0.05 was considered significant.Results are presented as median and interquartile range (IQR) for continuous variables or as numbers (percentages) for categorical variables. Comparisons between sub-groups were made using the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables. Linear regression analysis and the Pearson correlation coefficient was apply to examine the association between LVEF and the number of dysfunctional segments. A Clinical characteristics of the study population are shown in Table On CMR, 186 patients had at least one dysfunctional segment while seven patients had normal systolic function. LGE was observed in 169 (88%) patients. Substantial myocardial viability, that is ≥5 dysfunctional segments with ≤50% LGE, was found in 107 (55%) patients of whom 49 (25%) had ≥5 dysfunctional segments with no scar and 25 (13%) patients also had ≥5 dysfunctional segments with > 50% LGE. 64 (33%) patients had ≥5 dysfunctional segments with ≤25% scar thickness. Dysfunctional segments without LGE were not uncommon, with 104 patients (53%) having at least one such segment . Consequently, they had more severe LV systolic dysfunction and dilation and were less likely to tolerate treatment with a RAAS inhibitor and a β-blocker. In other words, patients with more severe LV dysfunction were more likely to have substantial viability , P < 0.0001) and increased LVEDV index (131 ml/m2 (112 ml/m2-173 ml/m2) v 114 ml/m2 (92 ml/m2-145 ml/m2), P = 0.001) and LVESV index (94 ml/m2 (75 ml/m2-126 ml/m2) v 72 ml/m2 (51 ml/m2-100 ml/m2), P< 0.0001) but there were no differences in the LVMM index (82 g/m2 (70 g/m2-97 g/m2) v 82 g/m2 (74 g/m2-101 g/m2), P = 0.507).57 patients (29%) had ≥ 5 segments with scar thickness > 50% but 2 out of 5 of them (24 patients) also had ≥ 5 dysfunctional segments with no or ≤ 50% partial thickness scars. Compared to the other patients they had lower LVEF (29% (22%-34%) The prevalence of LGE on a per segment basis is shown in Figure v 25%, P = 0.002). These gradients in distribution were true for partial thickness (≤50% scar thickness) and extensive (> 50%) scars, but more extreme for the latter group .Figure There is still uncertainty as to the proportion of patients with CHF due to IHD who have a substantial volume of viable but dysfunctional myocardium and who might, therefore have recoverable myocardial function. It is difficult to compare studies because they used different imaging methods, different segmental models and different definitions for the number of affected segments required to declare a substantial problem. In previous echocardiographic or radionuclide studies which specified that a substantial (e.g. 4/16 or 5/19 segments) number of such segments had to be present, the proportion of patients with a substantial amount of viable but dysfunctional myocardium ranged from 27% to 61% .The inability of these techniques to distinguish the relative amounts of scar and viable tissue may limit their use in predicting the recovery of dysfunctional myocardium in response to therapy. Nuclear imaging methods detect viability by assessing perfusion, cell membrane integrity and metabolism but have limited spatial resolution and do not image scar directly . Two smaOur study highlights the complexity of the myocardial substrate in patients with CHF and IHD. Moderate to severe contractile dysfunction was most commonly associated with partial thickness scar, with slightly more than half of the patients having five or more segments affected. Contractile dysfunction in the absence of underlying scar was also commonly observed, a disturbance of myocardial metabolism most likely induced by ischaemia, hibernation or stunning. Finally, extensive (> 50%) scar was also frequent and affected one third (32%) of the dysfunctional segments. There is likely to be an added complexity in segments with partial thickness scar, where contractile dysfunction will reflect not only the extent of the scar but also the contractility of the remaining myocardium. Ischaemia, hibernation and stunning of the residual myocardium is likely to be common in these segments.Some meta-analyses have shown that revascularisation in patients with viable myocardium improves outcome . On the Ultimately, assessing the extent to which LV dysfunction is due to myocardial scar may be more important than trying to assess the potential for functional recovery when assessing a patient for revascularisation. With existing therapies, myocardial scar reflects irreversible damage. Successful revascularisation might not only eliminate myocardial ischaemia and stunning and resuscitate hibernating myocardium but also reduce the risk to viable myocardium, whether or not it is dysfunctional, from further coronary occlusions. The potential of attempted revascularisation to cause irreversible myocardial damage, to which hibernating myocardial may be more prone, should also be considered .Our results may also be important for the selection of patients for CRT. Extensive myocardial scar, perhaps especially when it affects the postero-lateral wall of the LV predicts a lower chance of recovery of ventricular function with CRT ,14. ThisThere was a delay between the initial echocardiographic assessment of cardiac function and CMR. During that period, treatment with RAAS inhibitors and β-blockers were initiated or increased, which may have led to recovery of function in viable myocardial segments. Accordingly, this report will underestimate the prevalence of viable but dysfunctional myocardial segments in a treatment naïve population, although it is still a good estimate of the proportion of segments with extensive scar.Although the evaluation of the contractile function of the myocardial segments was based on wall thickness it is possible that tethering or reciprocal changes caused by neighboring dyssynchronous segments could lead to inaccurate estimations. By convention, a myocardial segment was considered viable if ≤50% of the segment showed LGE. However, a strict definition of "viability" requires that the segment's contractility improves after revascularisation. As our patients are not routinely revascularised in the absence of angina, we cannot be certain that the segments we have labeled "viable" meet this definition. Although available, the end-diastolic wall thickness of the studied segments was not included in our analysis as the conventional cut-off value of < 5.5 mm is not accurate in excluding functional recovery after revascularisation ,35. A siWe used the cut-off of 5 segments to define "substantial" myocardial viability since observational studies show that functional improvement following revascularisation is more likely if a third of LV segments show contractile dysfunction with viability . HoweverViable but dysfunctional myocardial segments in patients with CHF due to LV systolic dysfunction and IHD remain common despite contemporary medical therapy and frequently reflect two different pathologies, partial thickness scar and contractile dysfunction, that may have different prognostic and therapeutic implications. The extent of myocardial scar, which currently reflects irreversible damage, may be a useful guide to the likely extent of recovery of ventricular function with pharmacological interventions and revascularisation.The authors declare that they have no competing interests.CVB involved in data analysis and drafting the manuscript; NPN designed the study and involved in drafting the manuscript; HPL RdeS and NS contributed in data collection and interpretation, EIL analyzed the CMR images, ACT, MFA and SG revised the manuscript for important intellectual content while KW interpreted the study findings and ALC and JGFC were the general supervisors of this study. All authors have read and approved the manuscript.