Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy. Ischaemic heart disease (IHD) is the leading cause of morbidity and mortality in Western society, with an overrepresentation in the primary healthcare burden –3. In paThe myocardium is exquisitely sensitive to ischemia, with contractile dysfunction occurring shortly after an ischaemic stimulus. The degree of contractile impairment remains strongly under the influence of the severity and duration of the ischaemic event, with irreversible myocardial necrosis representing the end pathway of prolonged and significant coronary ischemia . Hence, Despite early intervention, patients with IHD have a predisposition to develop structural heart disease, with impairment of myocardial function leading to cardiac failure, a condition termed as “ischaemic cardiomyopathy” . Given tThe ability to distinguish whether dysfunctional myocardium is “viable” and thus able to recover following revascularisation, however, presents a clinical challenge in current practice.This review examines the concept of myocardial viability, with focus on imaging modalities and principal outcome trials.Viability of myocardial tissue is the central principal which underpins reperfusion therapies, whether in the acute phase following myocardial infarction or in chronic ischemia-mediated LV dysfunction. Should “viable” myocardial tissue be present, restoration of adequate coronary blood flow should in theory improve myocardial performance and LV ejection fraction (EF), with the hope of translating into improved long-term outcomes.Early work into CAD and myocardial flow limitation supported the hypothesis that myocardial ischemia results in significant myocyte injury . myocardial stunning, was defined as a prolonged and completely reversible dysfunction of the ischaemic myocardium that continued after restoration of coronary arterial flow [Heyndrickx and coinvestigators first demonstrated the impact of reversible ischemia on myocardial contractile reserve. Utilising animal models, they demonstrated that short (5- or 15-minute) induced episodes of ischemia to the myocardium, with a subsequent reperfusion period , resulted in regional deficits in contractile function that persisted despite reperfusion . This phial flow . Stunnedial flow .Myocardial stunning has also been found in clinical practice, particularly in the setting of increased myocardial demand or reduced coronary supply such as following coronary artery spasm, postmyocardial infarction, or postcardiopulmonary bypass secondary to “cardiac off-time.” Myocardial stunning is also prominent in patients following successful revascularisation postinfarct, wherein there is prolonged systolic dysfunction which takes several days to normalise after the incident event –15.Myocardial hibernation represents a condition of sustained depression of myocardial function in the setting of CAD, which is amenable to improvement in function postrevascularisation. This term was first coined by Diamond and colleagues in 1978 , and was repetitive stunning hypothesis. In this theory, multiple bouts of demand ischemia in context of flow limitation result in repetitive episodes of ischaemic myocardial dysfunction (or stunning), which eventually creates an environment of sustained depression of contractile function [An alternate hypothesis offered for the mechanism of sustained contractile depression is thefunction .Resting myocardial perfusion is normal or near normal in stunning but is reduced in hibernation. Stunning of the myocardium is frequently represented as transient regional LV wall motion abnormality persisting for hours to days following reperfusion after short-term but significant impairment of coronary blood flow. Hibernating myocardium, on the other hand, is a state of persistently impaired myocardial performance at rest due to a chronic reduction in coronary blood flow that can be restored by favorably altering the supply/demand relationship of the myocardium . AlthougIdentifying myocardial hibernation is of clinical relevance, as it represents potentially salvageable myocardial tissue. Coronary revascularisation in this context is likely to improve contractile performance, LV systolic function, and, in turn, overall morbidity and mortality. However, hibernating myocardium, if left untreated, has the potential to transform into clinically overt heart failure. Revascularisation, via either percutaneous angioplasty or coronary bypass surgery, is the primary avenue of restoring coronary blood flow, unless natural collaterals are formed from the primary diseased vessel.Pathologic Q waves, deep initial negative deflections of the QRS complex, were traditionally thought to be secondary to chronic transmural ischemia and representative of “dead myocardium.” On subsequent analysis, it has been demonstrated that presence of pathologic Q waves has a poor correlation with the lack of residual viable myocardial tissue, with a relatively low sensitivity (41–65%) and specificity (69–79%) relative to other imaging modalities , 20.Utility of exercise electrocardiography improves viability detection, with elevation of the ST segment during exercise in infarct-related leads being representative of viable myocardium (sensitivity 82% and specificity 100%) . A similUse of normalisation of abnormal T waves during exercise electrocardiography for viability assessment, on the other hand, has conflicting reports in the literature , 24, witAssessment of echocardiographic parameters at rest is important in assessment of viability. Severe dilatation of the LV is a marker of nonviable myocardium, with higher end-systolic volume indices associated with poor ventricular functional recovery . These f (i)μg/kg/min) can increase contractility in dysfunctional segments which are still viable. At higher doses (10–40 μg/kg/min), wall motion in these segments may further improve or paradoxically diminish, reflecting tachycardia-induced ischemia. This phenomenon is referred to as a biphasic response and has been shown to be highly predictable of functional recovery postrevascularisation. This finding is suggestive of limited, but present, myocardial reserve in the hibernating myocardium.Biphasic response: low-dose dobutamine (defined as 5–10  (ii)Worsening contractile function with lack of initial improvement with dobutamine: this response is suggestive of a hibernating myocardium which is supplied by a critically limited arterial supply, with no contractile reserve. (iii)Sustained improvement with increasing dobutamine dose: this response is traditionally seen in the setting of myocardial stunning. (iv)No response to dobutamine: this response is indicative of lack of functional reserve and, thus, lack of viable myocardial tissue.Dysfunctional areas with resting end-diastolic wall thickness of less than 6 mm are thought to reflect significant scar. They are not known to show functional improvement with DSE and do not improve postrevascularisation.Dobutamine stress echocardiography (DSE) is a valuable tool in the assessment of viability of the myocardium. Classically, four responses are noted in a dysfunctional myocardial response to dobutamine. These are as follows –33: (i)BDSE has been shown to have a sensitivity and specificity range for prediction of contractile recovery that is modestly high , with the biphasic response having the greatest predictive capability of the four responses .Myocardial contrast echocardiography (MCE) utilises acoustically reflective high molecular weight inert gases which form microbubbles and act as a contrast agent. These bubbles remain within the intravascular space and help attenuate the borders of the left ventricle. Tissue capillary blood flow, a determinant of myocardial perfusion, is the byproduct of capillary blood volume and myocardial blood velocity.Once the microbubbles reach a steady-state concentration, high-burst ultrasonography is used to displace the microbubbles, with subsequent replenishment within myocardial segments over the following cardiac cycles reflective of myocardial blood velocity. Segments are deemed viable if there is homogeneity of contrast intensity, which is in keeping with intact myocardial microvasculature. Nonviable segments, however, lack contrast enhancement and represent necrotic myocardial cells causing obstruction and collapse of the microcirculation –35.MCE has been shown to have a high sensitivity (78–90%), however, low specificity (51–72%), of myocardial contractile recovery postrevascularisation relative to DSE (which on average has a relatively high specificity but lower sensitivity) –39. A coMyocardial deformation indices, including tissue Doppler imaging (TDI) and strain assessment, are new echocardiographic modalities in the assessment of myocardial function, which allow for a more complete appraisal of myocardial motion and overcome traditional challenges of two-dimensional echocardiography with regard to regional myocardial assessment , 41. StrMyocardial deformation (strain) and deformation rate (strain rate) provide multidimensional evaluation of myocardial mechanics  and have the added advantage of being able to detect subtle wall motion abnormalities of regional function that do not decrease global LVEF , 43. ThiBoth TDI and speckle-tracking echocardiography have been shown to be facilitative in prediction of myocardial viability. This is of relevance given the limitations of subjective assessment of wall thickness as well as operator dependence with traditional two-dimensional stress echocardiographic methods. Bansal and colleagues (2010) revealed that longitudinal and circumferential strain and strain rate measurements at rest and low-dose dobutamine concentrations were predictive of functional recovery postrevascularisation using strain-based imaging. Furthermore, only tissue velocity imaging was found to have incremental value over wall motion analysis .18FDG [Based on a study by Hoffmann et al. (2002), an increase of peak systolic strain rate greater than or equal to 0.23/s had a sensitivity of 83% and specificity of 84% in discerning viable myocardium as determined by 18FDG . Additio18FDG . FurtherAdvantages of echocardiography include ease of procedure and widespread availability as well as its noninvasive qualities. Furthermore, with DSE, there is an ability to monitor functional response to accurate uptitration of inotropic therapy. Limitations of echocardiography include its high operator dependency with resultant inter- and intraobserver variability. Patients with comorbidities such as obesity, chronic obstructive airflow limitation, and thoracic chest wall abnormalities limit the acoustic window and thus impair LV views. Furthermore, with respect to DSE, assessment relies heavily on subjective visual interpretation of wall motion abnormalities.Single-photon emission CT (SPECT) is a modality which utilises radionuclide-labeled tracer compounds to measure myocardial uptake. Initial acquisition signifies delivery of the tracer throughout the circulation. The images acquired following this  reflect myocardial sarcolemmal integrity .99mTc-sestamibi, 99mTc-tetrofosmin, and 201Thallium. These molecules are lipophilic and permeate through myocardial cellular membranes via passive diffusion or active uptake from Na+/K+ ATPase systems. Intracellular retention, however, requires intact function of the mitochondrion with preservation of the action potential, and as such serves as a marker of viability. These tracer agents emit high-energy photons, which are captured via gated SPECT, and provide information of global LV function and viability of the myocardium [Primary tracers include ocardium , 48. late distribution imaging) [Viability assessment with SPECT can be performed at rest, following physical exercise or chemical coronary stress. With stress testing, physical exertion or chemical agents  are used. Imaging is performed immediately following the test, with delayed imaging repeated 3 to 4 hours later, allowing for adequate redistribution of the tracer agent. If warranted, imaging may be repeated at 24 hours after stress (termed asimaging) .Viability is seen with myocardial segments which reveal defective uptake immediately following stress, with subsequent replenishment of uptake at 3 to 4 hours. Critically hypoperfused myocardial segments may still be viable if defective uptake is seen at this delayed time-point, warranting repeat imaging at 24 hours after stress to allow for redistribution of the tracer to significantly hypoperfused myocardial regions. Nonviable myocardium reveals fixed defective uptake throughout a 24-hour imaging cycle .SPECT has been shown to provide a higher sensitivity (64–72%) however lower specificity (45–88%) than modalities based on evaluation of residual contractile recovery , 50. Pri13N-labeled ammonia (13NH3) and 18F-fluorodeoxyglucose (18FDG), are utilised in standard practice.Positron emission tomography (PET) imaging is based on the shift of myocardial perfusion energetics, whereby chronically underperfused myocardial tissue shifts from utilization of free fatty acids (that require high oxygenation for use) to that of glucose metabolism, which uses a more anaerobic process at the expense of poor energetic efficiency. This translates into uptake of perfusion tracers in myocardial segments which are hypoperfused. Perfusion tracers, including 18FDG uptake. Regions of myocardium where there is a concordance between reduction of myocardial blood flow and 18FDG uptake (flow-metabolism match) reflect irreversible myocardial injury. In contrast, areas where FDG uptake (reflective of metabolism) is preserved or increased despite perfusion deficits reflect viable myocardium [Regions are classified according to the degree of “flow-metabolism” matching, which is reflected by concordance between myocardial blood flow and ocardium   . ReducedCine cardiovascular magnetic resonance (CMR) sequencing provides information on global left ventricular function and regional wall motion. It can be used in conjunction with dobutamine stress and gadolinium-chelated contrast. Gadolinium-chelated contrast agents have been utilised to detect perfusion deficits, microvascular obstruction, and myocardial scarring. Accumulation of contrast agents have a paramagnetic effect, which form bright signal intensities in areas of accumulation. These agents are unable to penetrate cardiac myocytes with intact membranes; however, they easily diffuse and accumulate into extracellular membranes with increased volume of distribution  or ruptured cellular membranes  during the “late” steady-state phase .The transmural extent of scarring is inversely correlated with functional recovery of the dysfunctional myocardium postrevascularisation, whereas the absence of late gadolinium enhancement in a hypokinetic myocardium is associated with functional recovery postrevascularisation , 53 Fig.Benefits of CMR over alternate imaging modalities include excellent spatial imaging, ability to discern transmural variations in viability, and provision of accurate quantification of nonviable or necrotic tissue. The ability of CMR for detection of scar (nonviable tissue) is robust, with a sensitivity of 83% and specificity of 88% , 54. PriA summary of trials evaluating the utility of different imaging modalities in viability assessment is shown in Numerous nonrandomized retrospective studies in the early 1990s evaluated the value of viability testing. A meta-analysis of these trials revealed a significant association between revascularisation and improvement in mortality utilising viability testing in patients with known ischaemic cardiomyopathy. This finding was shared irrespective of imaging modality chosen . PrimaryThere was significant clinical uncertainty with regard to the impact of viability on survival given the lack of large, heavily powered randomized trials. These questions were largely addressed in the Surgical Treatment for Ischaemic Heart Failure (STICH) trial (2011). The STICH trial was designed to evaluate the impact of coronary artery bypass grafting (CABG) in management of patients with CAD with reduced LVEF.n = 130), or SPECT (n = 321), or both (n = 150). Of the viability subgroup, 298 participants were randomly assigned to receive medical therapy plus surgical revascularisation (cardiac bypass) and 303 received solitary medical management. Participants were followed up at intervals  with a median length of follow-up of 56 months  [In this multicenter , nonblinded, randomized trial, 1212 participants were enrolled, with 601 undergoing myocardial viability assessments. Participants were enrolled on the basis of echocardiographic evidence of LV systolic dysfunction (defined as LVEF ≤ 35%) and coronary angiography revealing CAD amenable to surgical intervention. Myocardial viability assessment was provided via DSE (p = 0.21). Furthermore, assessment of myocardial viability did not provide a differential benefit for surgical intervention (p = 0.53). That is to say that viability assessment did not recognize participants who would benefit from CABG relative to medical therapy [Despite an association of viable myocardium to likelihood of survival in this cohort, multivariate analysis did not find a statistically significant mortality benefit with surgical intervention ( therapy .p = 0.05), composite death from any cause and hospitalization from cardiovascular causes . Long-term follow-up (>4 years) of both cohorts revealed a reduction in all-cause mortality in the surgical revascularisation cohort compared to solitary medical therapy; however, this finding was not statistically significant (p = 0.12). These positive secondary findings should be interpreted with caution given a negative primary outcome measure [Secondary endpoints were more forgiving towards revascularisation, with bypass surgery having a significant reduction in cardiovascular mortality  in the viability subgroup having single-vessel disease. Given the scope of the paper , this differential profile may have selected out participants for whom viability assessment may not have been required. Thirdly, analysis in this study was limited to DSE and SPECT modalities, with no analysis of PET or CMR on viability assessment. This creates difficulty with extrapolation of these results to other imaging modalities of viability assessment.Despite these limitations, this study represents the largest analysis of the influence of myocardial viability on clinical endpoints in persons with ischaemic cardiomyopathy to date,and was the first to assess the differential effect of viability on revascularisation versus medical management.The Heart Failure Revascularisation Trial (HEART) (2011) was a multicenter study comparing the efficacy of surgical revascularisation with optimal medical treatment in the management of persons with clinically diagnosed cardiac failure with reduced EF (LVEF < 35%) and evidence of CAD. Participants were screened for viable myocardium via DSE. An inclusionary prerequisite was the presence of at least 5 viable LV segments with reduced contractility using a 17-segment model .n = 65) and medical arms (n = 69) and followed up over a five-year period. The primary outcome revealed noninferiority of medical therapy. This study was, however, underpowered secondary to a relatively small sample size. Furthermore, the primary modality of viability assessment was DSE, which has a lower sensitivity for viability detection relative to other imaging modalities. Additionally, randomization had not occurred prior to viability assessment, therefore clouding the impact of viability assessment on treatment outcomes [138 participants were randomized to interventional (outcomes .The PET and Recovery Following Revascularisation-2 (PARR-2) trial (2007) evaluated the efficacy of perfusion FDG-mediated PET imaging in risk stratification and identification of patients who would most benefit from revascularisation .p = 0.15), with post hoc analysis showing a statistically significant reduction in adverse events in the FDG PET-assisted group  [The study enrolled 430 participants, with an inclusionary criterion of a LVEF <35% and suspected or confirmed CAD. Participants were randomly placed to receive FDG and perfusion PET imaging versus standard care . Effect of PET scanning on appropriate decision showed a nonsignificant trend towards a reduction in the predefined composite endpoint  at one year . The results of this substudy illustrated prognostic benefit with the utilization of FDG PET viability imaging in ischaemic cardiomyopathy when used in centers with experience in PET imaging [The Ottawa-FIVE substudy  (2010) evaluated 111 participants with LV systolic dysfunction  and suspected or confirmed CAD in a single center with experience with FDG PET imaging . A stati imaging .Despite the relatively disappointing results of the aforementioned trials, the 2013 American Heart Association/American College of Cardiology guidelines for management of heart failure remain unaltered in their Class IIa (Level of Evidence B) recommendation for viability testing in the work-up for revascularisation in patients with ischaemic cardiomyopathy. This is in keeping with the belief that there may still be diagnostic and prognostic benefit in the utility of viability studies which have not become apparent given the limitations of the aforementioned primary trials.Ischaemic LV dysfunction can arise from myocardial stunning, hibernation, or necrosis. In line with technological advances, noninvasive imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with each modality conferring a variable advantage in terms of sensitivity and specificity, culminating in the overriding goal of accurate stratification of patients into optimal treatment pathways.Despite determined research efforts, however, many questions remain unanswered with regard to myocardial viability. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. More recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy but have their own limitations. In lieu of these recent findings, however, assessment of myocardial viability therefore should not be the arbitrating factor for therapy choice. Optimization of medical therapy for all patients is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with CAD with reduced LVEF at present.It is clear that further trials are needed to better our understanding of the mechanistic underpinnings of the viable myocardium as well as the underlying pathos of ischaemic cardiomyopathy. Newer trials such as the AIMI-HF  study, the largest randomized trial to date evaluating the role of imaging in the treatment of ischaemic cardiomyopathy, are currently underway and will hopefully decipher some of these uncertainties .


Mitral annular (MA) kinetics during the cardiac cycle influences both systolic and diastolic function of the LV. Here we describe a novel cMRI approach to evaluate mitral annular kinetics and its relationship in mitral regurgitation post surgical repair.Population: Patients with degenerative mitral regurgitation (n = 35) with normal LV EF pre and 12 months post mitral valve repair. Normal volunteers (n = 51). Image Acquisition: All participants underwent MRI on a 1.5T scanner  optimized for cardiac application. An ECG-gated, breath-hold steady state free precision technique was used to obtain 2 chamber and 4 chamber views with 20 phase imaged in each cardiac cycle. Image Analysis: At end diastole (ED) and end systole (ES), anterior and inferior MA landmarks were manually marked on 2 chamber views. Septal, lateral and apex MA landmarks were marked on 4 chamber views. All landmarks were then automatically propagated to the remaining phases using custom software [1] and manually verified. In each phase, the MA was approximated by a flat plane fit to the 4 landmarks. The MA centroid and plane normal was computed in each plane. Differences in centroid position and plane normal angle were computed in each phase relative to ED.Centroid displacement and plane normal angle curves are shown in Figure MR mitral annulus transverse diameter and septolateral diameter were significantly dilated in both ED and ES at baseline vs. controls, but were returned to normal level after surgery. However, we found that mitral annular mechanics in MR patients were impaired at 1 year post-surgery, demonstrated by the significant decrease in peak mitral annulus anterior, inferior, lateral and septal displacements as well as the peak early diastolic mitral annulus velocities normalized to the LVED length vs. controls.NIH/NHLBI P50-HL077100, R01 HL104018.


Reduced diastolic myocardial function is an early sign of diabetic cardiomyopathy. The aim of this study was to test the hypothesis that children and adolescents with type 1 diabetes mellitus (T1D), but without other known complications, have early reduced diastolic myocardial function diagnosed with echocardiographic color tissue Doppler imaging (cTDI).cTDI examination was carried out in 173 T1D patients and 62 age-matched controls. The T1D-patients were 8–18 years old with (mean (SD)) diabetes duration of 5.6 (3.4) years and HbA1c of 8.4 (1.3). All were treated with either insulin pumps or 4–6 daily insulin injections. cTDI early (E’) and late (A’) peak diastolic velocities and systolic peak velocity were measured from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus.p < 0001). The overall mitral E’/A’-ratio was negative associated with blood pressure (BP) and body mass index (BMI). Stratifying all participants into three groups according to BMI , the T1D had lower E’/A’-values in all stratified groups, except for in the highest BMI-group where both T1D and controls had the lowest E’/A’-ratio. Systolic function did not differ in any of the measurements. There were no associations with sex, diabetes duration, carotid artery intima-media-thickness, vessel elasticity or HbA1c.Myocardial diastolic function was reduced in the T1D-patients with higher peak A’-velocity and lower E’/A’-ratio in all registrations. Overall mean (SD) mitral E’/A’-ratio was 2.3 (0.5) in T1D and 2.7 (0.6) in the controls (Diabetic children and adolescents using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher BP and higher BMI. Clinical and experimental studies have demonstrated evidence of diabetic cardiomyopathy independent of coronary artery disease and hypertension , 2. DiabWe hypothesized that diastolic myocardial dysfunction is present at an early stage of T1D despite treatment with modern intensified insulin regimens and no signs of microvascular complications. The aim of this study was to explore the diastolic myocardial function in children and adolescents with type 1 diabetes compared to healthy controls.n = 800) were invited to participate in a study focusing on cardiovascular risk factors and early signs of atherosclerosis. Forty percent of the invited (n = 314) agreed to participate and were compared with 118 age-matched healthy control subjects. The diabetic cohort was found to be representative of the childhood T1D-population in Norway. None of the diabetic patients had signs of renal, retinal or neurological complications of the disease and all were using intensified insulin treatment (more than four daily insulin injections or insulin pumps). Results from the main study have been published earlier [All children and adolescents with T1D aged 8–18 years in Health Region South-East in Norway , weight and height were recorded, and body mass index (BMI) was calculated as the ratio of the individual’s body weight to the square of the height. Arterial BP was measured according to the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents .Glycated hemoglobin (HbA1c) was determined for all participants by liquid chromatography  at the Department of Clinical Chemistry at Oslo University Hospital, Aker. The normal reference range was 4.1–6.4 (±2 %), and the intra-assay coefficient of variation was <3 %. Annual HbA1c values were available from the Norwegian Childhood Diabetes Registry since 2001 or from the time of diagnosis for the majority of the patients. Mean HbA1c was calculated from all the HbA1c values available for each patient .Two experienced pediatric cardiologists (DF and LB) performed all echocardiographic examinations by use of a Vivid 7 scanner  with a standard phase-array multi-frequency transducer  transmitting at 2.4 MHz. The children were awake and relaxed in a left semi-lateral supine position. A structured sequential two-dimensional echocardiogram was made from subcostal, apical, parasternal long and short-axis and supra-costal views to rule out structural heart defects . Tissue From the apical 4-chamber view, the peak pulsed blood flow mitral valve annulus early diastolic (E) and late diastolic (A) velocities were measured with the sample volume positioned at the tip of the mitral leaflets and at an angle as parallel to mitral flow as possible.EchoPac software  was used for post processing of the TDI indices by color TDI (cTDI). cTDI early diastolic peak velocity (E’), atrial peak velocity (A’), E’/A’-ratio and systolic peak velocity were analyzed from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus. The region of interest (ROI) was set to 3x1 mm. Measurements were made with the ROI placed stationary in the ultrasound sector at the atrioventricular valve insertion. If artifacts occurred, the ROI was slightly repositioned in order to minimize background noise. If background noise could not be reduced, the recording was defined as poor quality and excluded from further analysis. Peak systolic velocity (cTDI S´) was measured at the maximum height of the systolic velocity curve.P = ((d + Δd)2-d2)/d2/Δp). Δp represents the change in pulse pressure, d the end-diastolic diameter (including the intima-media complex) and Δd the change in diameter from diastole to systole, assuming a circular lumen cross-section of the vessel [A standard ultrasonic protocol was used for measuring the common carotid artery intima-media thickness (cIMT) and the elasticity of the artery , as desce vessel .Demographic and clinical data are presented as percentages or means with their standard deviations. Means were compared with student’s t-test when the data was normally distributed, otherwise with Mann–Whitney U test. The participants were stratified with respect to BMI into three different groups; group I (levels <25 centile), group II (levels between 25–75 centile) and group III (levels >75 centile). The differences within the stratified groups were tested with student’s t- test or Mann–Whitney U test. Correlation was tested with Pearson’s linear regression method.The demographic data and baseline measurements of HbA1c, systolic and diastolic BP, cIMT as well as DC calculations are presented in Table p < 0001) .2 = 0.05, p = 0.003). Separated into those with diabetes or not, there was still an association in the T1D group , but not in the control group.There were no association between E’/A’-ratio and cIMT and no differences between the diabetic and non-diabetic population regarding cIMT. However, a small but significant positive correlation was found between DC and E’/A’-ratio for the whole group  had the lowest E’/A’-ratio of all, but there was no differences between the control and diabetic group Table . HoweverWe did not find any associations between E’/A’-ratio and diabetes duration or HbA1c as demonstrated by others . This maInterestingly we did not find any differences in E/E’-ratio. E/E’-ratio is a marker of elevated diastolic left ventricle and left atrium pressure . This miThere were no differences in measured S’ between children with and without diabetes. S’ reflects the systolic longitudinal function of the heart and our findings is in harmony with other papers. It support the hypothesis that diabetes cardiomyopathy debuts with a reduced diastolic function, while the systolic function is preserved until a more advanced stage of the disease.Children and adolescents with type 1 diabetes using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher blood pressure and higher body mass index both in the diabetic and in the non-diabetic groups.A, peak late mitral valve diastolic blood flow velocity; A’, peak late diastolic annulus tissue Doppler velocity; BMI, body mass index; BP, blood pressure; cIMT, carotid intima-media thickness; cTDI, color tissue Doppler imaging; DC, distensibility coefficient; E, peak early mitral valve diastolic blood flow velocity; E’, peak early diastolic annulus tissue Doppler velocity; MV, mitral valve; ROI, region of interest; S’, peak systolic annulus tissue Doppler velocity; T1D, type 1 diabetes mellitus; TDI, tissue Doppler imaging; TV, tricuspidal valve.


T2- and T1-mapping are novel CMR techniques allowing objective tissue characterization. These techniques have been shown to be superior to dark blood imaging in NSTEMI patients in detecting ischaemic area at risk and acute oedema. These methods have not been assessed in Tako-Tsubo cardiomyopathy (TC).The aim of the study was to assess myocardial involvement using T2- and T1-mapping in Tako-Tsubo cardiomyopathy (TC).Nine patients with TC and 15 controls were prospectively enrolled. Cardiovascular magnetic resonance (CMR) was performed a mean 2.8 days after the onset of symptoms and after a mean 4.6 month follow-up. CMR was applied using T2-mapping, pre and post contrast T1-mapping (MOLLI) and LGE sequences. Segmental and global T1 values have been measured before and after contrast administration. Wall motion abnormality (WMA) was assessed.All patients were female, had positive troponin (6±9µg/l) and medium and/or apical ballooning associated with moderate LV dysfunction (EF 44±7%). On admission, compared with controls, TC patients had significantly higher T2 values . Myocardial T2 was significantly higher in segments with WMA compared to normokinetic segments . Compared with controls, TC patients had significantly higher pre contrast T1 values  and significantly lower post contrast T1 values .Pre contrast T1 values were significantly higher in segments with WMA compared to normal segments . Post contrast T1 values were not significantly different in abnormal segments compared to normal segments . No patients had LGE . At follow-up: all had a complete LV recovery (EF: 67±4%) without significant WMA. Mean T2 and pre contrast T1 values decreased significantly at follow up . No differences were observed regarding post contrast global T1 values.In TC patients, T2-mapping and pre contrast T1-mapping allow identification of reversible myocardial injury. Post contrast T1 mapping does not provide additional information.No funding.


Detection of late gadolinium enhancement (LGE) is the method of choice for imaging myocardial scar. However, patients who suffer from cardiovascular disease often are afflicted with renal impairment. As a GFR <30 ml/min bears the risk of nephrogenic systemic fibrosis it would be beneficial to develop alternative cardiac imaging methods without contrast agent. De Jong et al have already used UTE (ultra short echo time) to detect myocardial scar with a fast T2* signal decay in a rat infarct model. The aim of the study was to validate UTE imaging to detect myocardial scar without contrast agent in patients with coronary artery disease.45 patients (75 +-10 years) with coronary artery disease and known myocardial scar were enrolled in the study. Cardiac MRI was conducted on a 1.5T Philips Archieva scanner with a standard cine balanced steady state free precession sequence for acquiring left and right ventricular volumes. Also, UTE was conducted with long (6 ms) and short TE (0.6 ms) for the imaging of fibrosis without contrast agent. LGE images were acquired for comparison of scar imaging with UTE-images. Measurements were compared with LGE images regarding fibrotic or scar tissue-area and signal intensity. Images were analyzed using Osirix 5.9 software.27 Patients of 45 were analyzed. 18 date sets were excluded due to poor image quality. There was a good correlation regarding fibrotic and scar tissue-area in UTE compared to conventional late gadolinium enhancement . There was good signal intensity of UTE-acquired images (t-test p<0.0001).In-vivo imaging of myocardial scar is feasible without contrast agent in patients with coronary artery disease. This is a great advantage for patients with renal impairment and contraindication for gadolinium contrast agent. In current status, UTE-images are only feasible with one slice imaging. Further work on the sequence need to be done, to image the whole left ventricle with UTE for scar imaging.Funded by the University of Duesseldorf.


Left ventricular (LV) enlargement has been linked to sudden cardiac death among young athletes. This study aimed to model the effect of long-term incessant endurance training on LV dimensions in female adolescent runners.n = 36, age: 15 years, height: 158.1 ± 4.6 cm, weight: 44.7 ± 6.1 kg, percent body fat: 17.0 ± 5.2%) underwent echocardiography and underwater weighing every 6 months for 3 years. Since the measurement occasions varied across subjects, multilevel analysis was used for curvilinear modeling of changes in running performance (velocities in 1500 m and 3000 m track race), maximal oxygen uptake (VO2max), body composition, and LV dimensions.Japanese female adolescent competitive distance runners  and LVEDd were similarly best described by quadratic polynomials. LVEDd did not change over time in the model including FFM as a covariate. Increases in LV wall thicknesses were minimal and independent of FFM. LV mass increased according to a quadratic polynomial trend even after adjusting for FFM.Initially, LV end-diastolic dimension (LVEDd) and LV mass were 47.0 ± 3.0 mm and 122.6 ± 15.7 g, respectively. Running performance and VO2max were improved by continued endurance training, further LV cavity enlargement hardly occurred beyond FFM gain in these adolescent female runners, who already demonstrated a large LVEDd.FFM was an important factor determining changes in LVEDd and LV mass. Although running performance and VO Many cross-sectional studies have indicated that young trained endurance athletes have larger left ventricles than sedentary controls –5. This The LV end-diastolic dimension (LVEDd) observed in highly trained endurance athletes is likely to exceed the normal limit , and dift tests or repeated-measure one-way analysis of variance (ANOVA) 25] [25] 15][ [25] 15]l growth , but the2). The LVEDd/BSA of our subjects was also larger than that of adolescent elite African male soccer players (33.3 ± 2.3 vs. 28.3 ± 2.3 mm/m2) [2) and cross-country skiers (LVEDd/BSA: 31.9 mm/m2) [2) [The left ventricles of our subjects were enlarged at baseline. Sharma et al.  reported9 mm/m2)  and even/m2) [2) . All our/m2) [2) 6]. The . The 2).measure), which indicated that the left ventricle was rapidly enlarged at the initial phase of the training career of subjects in the high school team Click here for additional data file.S2 Table(PDF)Click here for additional data file.


Estimation of heart and liver iron concentrations using T2* has become an essential diagnostic step in the management of iron overload. One of the limitations of more widespread use of these techniques has been calculating the T2* values from the original images due to need of special training and dedicated softwares. We sought to assess whether the use of an automated T2* in-line calculation protocol applied in a multicenter study in centers with different initial experience in this technique would be feasible and accurate.Seventy-six patients of the multicenter study All Iron Detected (AID) involving seven centers using different 1.5T scanners from a single vendor (Siemens AG) were included. Automated T2* maps were calculated in-line based on a prototype evaluation using original multi-echo images of the heart and liver with values obtained by drawing a region of interest in each organ directly in the originated map. Manual calculation of these values were also obtained by fitting the decay curves of the original images using the truncation method both locally as well as in a central core lab. Sixteen patients had repeated scans using a routine protocol with manual evaluation for comparison. Values of the automated pixel-wise fit T2* of the heart and liver were compared to the local manual ROI-fitting technique as well as the central core lab results values using Bland-Altman plots and intraclass correlation coefficients (ICC). Inter-scanner coefficients of variation among the repeated scans using the automated versus manual calculations was also assessed.The mean age of the patients was 32.1±23.1 years  with median automated T2* values of 31.1ms (range 4.2 to 61ms) for the heart and 5.5ms (range 0.7 to 32.4ms) for the liver. In the heart, the automatically calculated T2* values were significantly correlated to both local and core lab manual calculations, with a mean difference of -2.0ms (95%CI -2.9 to -1.1 ms) for the core lab comparison and ICC of 0.95 (95%CI 0.89 to 0.97). In the liver, the mean difference was 0.18ms (95%CI -0.03 to 0.39ms) with ICC of 0.99 (95%CI 0.991 to 0.996) comparing automated versus core lab manual measurements despite a lesser degree of agreement in patients with severe liver iron concentration (T2* < 1.8ms) with 0.5ms (95%CI 0.23 to 0.80ms) and ICC of 0.22 (-0.35 to 0.64). In the inter-scanner comparison, the coefficient of variation among the subgroup tested was 12.8% for the heart and 14.1% for the liver.The use of automated T2* maps for iron overload assessment of the heart and liver is feasible across different centers and results in accurate results compared to the traditional manual evaluation by a central core lab.N/A.


Focal myocardial injury is an important diagnostic feature of myocarditis and is typically assessed by cardiovascular magnetic resonance (CMR) on late gadolinium enhancement (LGE) images. T1 mapping, T2 mapping, and extracellular volume (ECV) imaging are novel techniques which potentially improve the diagnostic value of CMR in myocarditis. This study evaluated the potential of T1 and T2 mapping CMR to assess focal myocardial lesions in myocarditis.We included 20 patients with myocarditis who had typical focal myocardial lesions on LGE images as reference method. Native T1, T2, and ECV maps were acquired in addition to a conventional CMR protocol at 1.5 Tesla. Myocardial lesions were quantified on LGE images by a standard threshold technique using a region of interest in normal appearing myocardium as reference tissue. Furthermore, myocardial lesions were quantified using normal values for native myocardial T1, T2, and ECV obtained from a group of 20 matched healthy controls as reference tissue. Injured myocardium was defined by a signal-intensity, native myocardial T1, T2 and ECV ≥ 2 standard deviations above reference values and expressed in percent of LV myocardium.Median lesion size was 14% (9-20%) on LGE images. Areas with normal appearing myocardium on LGE images had significantly increased median native myocardial T1 and ECV values compared to myocardium of healthy volunteers (1085ms (1048-1120ms) vs. 1051ms (1021-1064ms); p<0.01 and 32% (30-35%) vs. 26% . Consequently, median lesion sizes were larger on native T1 maps (48% (32-56%); p<0.01) and ECV maps (58% (50-66%); p<0.01) compared to the median lesion size on LGE images. Median T2 values did not differ significantly between normal appearing myocardium of patients with myocarditis and myocardium of healthy volunteers (56 ms (54-60 ms) vs. 58 ms (53-62 ms); p=0.47). No significant difference in lesion size was found between T2 maps and LGE images (18% (9-38%); p=0.06).Native T1 and ECV maps reveal hidden myocardial injury in patients with myocarditis using myocardium of healthy controls as reference tissue.Dr. Marija Orlovic Foundation.


In this study we evaluate the diagnostic accuracy of myocardial perfusion pixel maps for detecting coronary artery disease (CAD). We also compare the performance of perfusion pixel maps with and without myocardial segmentation.Forty-seven patients had 1.5T steady state free precession, regadenoson stress perfusion CMR and either a ≤ 30% coronary narrowing by CT angiography (CTA) or a ≥70% stenosis by invasive coronary angiography (ICA). CMR perfusion pixel maps were generated by a model-constrained deconvolution with and without the myocardial segmentation. The two independent observers were blinded to clinical information.Significant coronary stenoses were present in 22 of 47 patients. The diagnostic accuracy of pixel-wise quantification of myocardial perfusion is summarized in Table Fully quantitative stress perfusion analysis at a pixel level has significant potential in clinical settings. As evidence of feasibility, diagnostic quality perfusion pixel maps could be generated without the spatial constraints of the epicardial and endocardial ROIs.ADT is supported by the Sarnoff Cardiovascular Research Foundation. CM is supported by the National Institutes of Health Research, UK. ADT, LH, HC, SW, KN, PK, SS, MC, PB, and AA are supported by the National Institutes of Health, USA.


Left ventricular (LV) longitudinal systolic dysfunction has been identified even in asymptomatic patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF). However, its relevant clinical features have not been fully evaluated.We studied 144 asymptomatic DM patients without coronary artery disease. Their mean age was 57 ± 15 years, 79 (55%) were female, and mean LVEF was 66 ± 4% . Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. With the pre-defined cutoff for subclinical LV systolic dysfunction in DM patients with preserved LVEF set at GLS < 18%, this dysfunction was detected in 53 patients (37%).χ2 = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia , and further improved by addition of nephropathy and neuropathy  as variables. Furthermore, albuminuria significantly correlated with GLS , and a multivariate regression model showed it to be the factor most closely associated with GLS .Multivariate logistic regression analysis revealed that type 2 DM, hypertriglyceridemia, overweight/obesity, nephropathy and neuropathy were independently associated with GLS < 18%, with nephropathy being the highest risk factor . For sequential logistic regression models, a model based on clinical variables including gender, type 2 DM and DM duration (Diabetic complications, hypertriglyceridemia and overweight/obesity were closely associated with early stage of LV systolic longitudinal myocardial dysfunction in asymptomatic DM patients with preserved LVEF. Our findings can be clinically noticeable for the management of DM patients. Diabetes mellitus (DM) is considered a major contributor of the development of heart failure (HF) despite absence of coronary artery disease and hypertension even in patients with preserved left ventricular (LV) ejection fraction (EF). This condition is known as diabetic cardiomyopathy -3. Altho2; (5) hypertension >180/100 mmHg uncontrollable despite medical therapy; (6) significant valvular heart disease; (7) atrial fibrillation; and (8) left or right bundle branch block. All patients underwent exercise stress testing such as treadmill exercise or stress myocardial perfusion scintigraphy within at least 2 weeks after admission, and none of the patients showed an ischemic response. Six initially eligible patients (4%) were excluded from all subsequent analyses because of suboptimal images from poor echocardiographic windows. As a result, the final study group consisted of 144 patients. The study protocol was approved by the ethics committee of our institution and all patients gave informed consent before participation.A series of 150 consecutive DM patients including type 1 and type 2 DM who were admitted to Kobe University Hospital between July 2013 and November 2014 were prospectively recruited for this study. The diagnosis of DM and its type were established according to the World Health Organization criteria . We excl2.7, considering influence of obesity. LV stroke volume was determined in terms of the velocity-time integral and assessed by means of pulsed-wave Doppler positioned at the LV outflow tract. The early diastolic (E) and atrial wave velocities and the E-wave deceleration time were measured using pulsed-wave Doppler recording from the apical four-chamber view. Spectral pulsed-wave Doppler-derived early diastolic velocity (E’) was obtained from the septal mitral annulus, and the E/E’ ratio was calculated to obtain an estimate of LV filling pressure [All echocardiographic studies were performed using a commercially available echocardiographic system within at least 2 weeks after admission . Digital routine grayscale two-dimensional cine loops from three consecutive heartbeats were obtained at end-expiratory apnea from the standard parasternal long-axis view and three apical views at depths of 12–14 cm and mean frame rates of 67 ± 8 frames/sec. Sector width was optimized to allow for complete myocardial visualization while maximizing the frame rate. Digital data were transferred to dedicated software  for subsequent offline analysis. Standard LV measurements were obtained in accordance with the current guidelines of the American Society of Echocardiography/European Association of Cardiovascular Imaging . LV volupressure .Speckle-tracking strain analysis was performed for each patient with the aid of a single dedicated software . GLS was assessed by means of two-dimensional speckle-tracking strain from the three standard apical views as previously described in detail. Briefly, a region of interest was traced on the endocardium at end-systole with a point-and-click approach for each of the three apical views. A second larger region of interest was then generated and manually adjusted near the epicardium. Apical images were divided into six standard segments and six corresponding time-strain curves were generated. GLS was determined as the averaged peak strain of 18 segments from the three standard apical views , and was2 according to World Health Organization’s definition. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, or currently use of medication for hypertension [2) [Overweight/Obesity was defined as body mass index (BMI) ≥25 kg/mrtension . Dyslipirtension . Similarrtension . Fastingsion [2) . Experiesion [2) .t test or Mann- Whitney U test as appropriate. Proportional differences were evaluated with Fisher’s exact test. Relationships between two variables were analyzed by means of linear regression and were expressed as Pearson correlation coefficients. The associations of baseline clinical parameters with reduced GLS were identified by logistic regression in univariate and multivariate analyses. Variables with p-values <0.10 were incorporated into the multivariate model by means of stepwise selection. There was not multicollinearity between variables in the multivariate model. A sequential logistic model for GLS < 18% was created to determine the incremental enhancement of the prognostic value of the patient’s characteristics including obesity, nephropathy, and neuropathy compared to that of clinical variables including age, gender and DM duration. A statistically significant increase in the global log-likelihood χ2 of the model was used to determine the incremental enhancement of the prognostic value. The confounding factors for logistic regression analysis and sequential logistic regression models were based on the associated factors with subclinical LV dysfunctions in DM patients which were previously reported. The inter-observer and intra-observer variability of GLS was expressed as the absolute difference between the measurements divided by their mean value from 20 randomly selected patients. Albuminuria was converted into a logarithmic scale according to its distribution for each analysis. For all steps, a p value of < 0.05 was regarded as statistically significant. All analyses were performed with SPSS version 16.0  and MedCalc version 14.10.2 .Continuous variables were expressed as mean values and standard deviation for normally distributed data and median and interquartile range for non-normally distributed data, while categorical variables were expressed as frequencies and percentages. The parameters of the two subgroups were compared by using Student The baseline clinical and echocardiographic characteristics of the 144 DM patients are summarized in Table Subclinical LV systolic dysfunction, defined as GLS < 18%, was observed in 53 patients (37%), and the remaining 91 patients (63%) were classified as having preserved LV systolic function  for patients with GLS < 18% tended to be larger, but the difference was not statistically significant.χ2 = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia  and further improved by addition of nephropathy and neuropathy .Univariate analysis using the logistic regression model showed that type 2 DM and presence of overweight/obesity, hypertriglyceridemia, nephropathy, neuropathy, and retinopathy were associated with GLS < 18%. The odds ratio (OR) and 95% confidence interval (CI) for each of these variables are given in Table The findings obtained with the multiple linear regression analysis for association of clinical features with LV geometry and function is shown in Table This study confirms previous reports describing the subclinical LV longitudinal systolic dysfunction in DM patients. Nakai et al. reported that GLS in DM patients was significantly lower than that in age-matched normal subjects despite of similar LVEF, and 43% (26/60) of DM patients showed LV longitudinal systolic dysfunction determined as GLS < 17.2%. In addiPathophysiological causes of LV longitudinal dysfunction in DM patients are microvasculopathy, myocardial hypertrophy and cardiac fibrosis . The traOur study established that diabetic nephropathy and neuropathy were factors independently associated with LV longitudinal systolic myocardial dysfunction in asymptomatic DM patients with preserved LVEF. In addition, nephropathy had stronger influence on reduced GLS than neuropathy in multivariate logistic regression. Close cardio-renal connection can make us understood the dominance of nephropathy . TherefoOverweight/obesity and hypertriglyceridemia were also identified as two of the contributing factors of GLS in our study, while other studies reported that obesity and metabolic syndrome were harmful factors for LV subclinical systolic and diastolic functioning -44. MoreThe pathogenesis of diabetic cardiomyopathy is considered to be multifactorial but the exact cause remains unknown. As previously stated, LV longitudinal systolic myocardial function could be a key parameter for the development of HF or LV remodeling in asymptomatic DM patients with preserved LVEF. However, what clinical features of DM patients are associated with impaired LV longitudinal systolic myocardial function has not been fully investigated. Our findings indicate that the highest risk factor of reduced GLS is diabetic nephropathy, and that albuminuria is the most closely associated with GLS. The detection of diabetic cardiomyopathy in the early stages is important for the prevention of HF that will develop in the future in asymptomatic DM patients with preserved LVEF. The new insights attained by our study therefore suggest that early detection of diabetic complications including diabetic nephropathy and neuropathy is important for the maintenance of LV longitudinal systolic function as well as the prevention of overweight for asymptomatic DM patients, even though their LVEF or LV diastolic function are preserved. It is therefore advisable for medical specialists, especially diabetologists, to jointly plan assessment for better management of DM patients.This cross-sectional study covered a relatively small number of patients in a single center study, so that future studies of larger patient populations with longitudinal cohort design are necessary to assess our findings. Our study populations included both type 1 (28%) and type 2 (72%) DM patients. However, when we performed the analyses for type 2 DM patients only, the overall results were similar. Finally, the confounding factors for logistic regression analysis and sequential logistic regression models were based on previously reported findings, so that a more complete description for this analysis may necessary.The assessment of diabetic complications, hypertriglyceridemia overweight/obesity could prove to be important for detecting of early stage of LV myocardial dysfunction in asymptomatic DM patients despite preserved LVEF. Our findings thus may well have clinical implications for better management of DM patients.


TDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function.To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI and MPIConv measured.In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI was significantly associated with invasive (dP/dt max) and echocardiographic measures of systolic  and diastolic function , whereas MPIConv was significantly associated with LVEF, e’ and global strainrate e .IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders . IVCT, ET, IVRT/ET, and MPI differed significantly between males and females, displaying that women, in general exhibit better cardiac function. MPITDI (but not MPIConv) is associated with most invasive and established echocardiographic measures of systolic and diastolic function.Normal values of cardiac time intervals differed between genders and deteriorated with increasing age. The MPI Conv)[Regional), has in recent years been an attractive method in the obtainment of cardiac time intervals[Cardiac time intervals are sensitive markers of cardiac dysfunction, even when it goes unrecognized by conventional echocardiography–4. TheseConv),11. AddiConv) and MPI intervals–15. The intervals,8,16–19.intervals,18, reflTDI) and established echocardiographic and invasive measures of systolic and diastolic function has to be evaluated. The aim of this study was, therefore, to define normal values of cardiac time intervals obtained by TDI M-mode through the MV in a large sample obtained from the general population without known cardiovascular disease and cardiovascular risk factors. A further aim of this study was to evaluate the association of MPITDI (the novel method of obtaining MPI) and MPIconv  as described by Tei and colleagues[Nevertheless, clear definitions of normal and pathological cardiac time intervals, including their normal values, have to be established before we can use these in a clinical setting in order to be able to identify miniscule levels of impaired cardiac function. In addition, the association between this novel method of obtaining MPI , heart failure (CHF) or atrial fibrillation who are included in the echocardiographic sub study of the fourth Copenhagen City Heart Study (Study group A),8,18,20,This population includes all participants from the fourth Copenhagen City Heart Study examination 2001–2003, who had an echocardiographic examination, including TDI, performed and who were free from any cardiovascular disease and cardiovascular risk factor (n = 974) at Department of Cardiology, Gentofte Hospital, University of Copenhagen between April 2009 and February 2011. JSJ and SG were the treating physicians performing coronary angiography in group B.All participants gave written informed consent, and the study was performed in accordance with the second Helsinki Declaration and approved by the regional ethics committee for the region of Copenhagen and the Danish data protection agency.In group B, left heart catheterization was performed. Left ventricular (LV) pressures were measured, and an echocardiogram was performed according to a standardized protocol. Invasively measured pressure curves were obtained using 5 French pigtail catheters placed in the LV chamber and the pressure set and transducer were calibrated. Measurements were obtained over at least three cardiac cycles and saved as hard copies and digitalized in relation to this study. The LV pressure curves were digitalized using Dagra Version 2.0.12.35924. In all cardiac cycles the rate of LV pressure rise in early systole (dP/dt max) and the rate of LV pressure decline in early diastole (dP/dt min) were measured and averaged over all the cardiac cycles. In addition to dP/dt max and dP/dt min, the time constant of LV isovolumic pressure decline (tau) was measured.All echocardiograms were obtained using Vivid ultrasound systems  with a 2.5-MHz transducer. All participants were examined with conventional two-dimensional echocardiography and color TDI. All echocardiograms were stored and analyzed offline with commercially available software .<50 years > 2.5, E/A50–70 years > 2, or E/A>70 years > 1.5, respectively[In group A ,18, regipectively,8. In grpectively.2 or above.The myocardial thickness and the dimensions of the LV in end-diastole (LVIDd) and the left atrium in end-systole (LAD) were measured. LV mass index (LVMI) was calculated as the anatomic mass divided Conv was calculated as: (A to E time–ET)/ET[Additionally, in group B time intervals were measured using the method described by Tei and colleagues,11. The me–ET)/ET,11.In group B, Two-dimensional strain echocardiography (2DSE) was performed from the apical 4-chamber, 2-chamber and apical long-axis view . By speckle tracking, the endocardial border was traced in end systole. The integrity of speckle tracking was automatically detected and visually ascertained. In case of poor tracking, the region of interest tracing was readjusted. Global longitudinal strain (GLS) was measured in all three apical views and averaged to provide GLS. Furthermore, in each three apical views, global longitudinal systolic strain rate (GL SR s) and global longitudinal early diastolic strain rate (GL SR e) were measured, and averaged to provide global estimates.In group A ,18, coloIn both group A ,18 and g2-test, continuous Gaussian distributed variables with Student’s t-test or Mann-Whitney test if non-Gaussian distributed. The association between cardiac time intervals, age and gender was tested by univariable and multivariable regression analyses including significant confounders detected from the baseline differences between genders  which is visualized in Conv and dP/dt max .The clinical characteristics of the validation cohort undergoing left heart catheterization are displayed in Conv nor MPITDI were significantly associated with dP/dt min , reflecting improved diastolic function , R2 = 0.00, p = 0.71, per 100 mmHg/sec decrease; E/e’: β = -0.006 (-0.532 to 0.520), R2 = 0.00, p = 0.98, per 100 mmHg/sec decrease).Neither MPIP/dt min . With rel values), reflectl values). In contfunction . In compTDI nor MPIConv were significantly associated with tau  has been proven to be an independent predictor of mortality in the general population[TDI (but not MPIConv) is significantly correlated with the invasive measure of contractility and systolic function dP/dt max  were significantly associated with changes in dP/dt min. The lack in correlation between our invasive measure of diastolic function (dP/dt min) and the echocardiographic measures of diastolic function may, therefore, display an inherent limitation in the invasive dP/dt min parameter than in the echocardiographic measures investigated in this study.Neither MPITDI increased significantly with worsening systolic function determined by all the echocardiographic measures of systolic function , whereas MPIConv only increased significantly with worsening LVEF (TDI and MPIConv increased with worsening diastolic function determined by the measures of diastolic function (e’ or GL SR e) [TDI, but not MPIConv, displays an ailing systolic and diastolic function, as determined by the comparison with 2D-speckle tracking echocardiographic measures . Our and previous results illustrate that an ailing systolic or diastolic performance can be detected by an increasing value of MPI when assessed by TDI. We found when the MPITDI was increased in our validation population (group B) above the reference limit obtained from the healthy general population (group A), the probability of identifying an impaired echocardiographic examination, defined by either an impaired systolic and/or diastolic function, was 100%, illustrated by a positive predictive value of 100%  . Neitherith E/e’ . This maF and e'). In addi of 100% . Additio of 100% . FurtherThe inhabitants of Denmark and the study population contributing to the normal values are primarily Caucasian, which limits the generalizability of our findings to other general populations with another race composition.Our invasive validation population was small, comprised only 44 individuals, which limits our study. Nevertheless, this was a larger study group than can be found in previous studies which evaluate the association of cardiac time intervals with invasive measures of systolic and diastolic function,31.TDI and MPIconv with established invasive measures of systolic and diastolic function.The echocardiograms in group A and B were obtained and analyzed with almost a decade apart why the methods of assessing systolic and diastolic function differ between the two cohorts. These differences, together with the fact that group B consists of patients suspected of ischemic heart disease who underwent coronary angiography and group A consist of healthy participants from the general population, limits the comparability between the two groups. However, the aim of the present study was not to compare the two groups but rather to define normal values of cardiac time intervals obtained by TDI M-mode from the general population without known cardiovascular disease and to evaluate the association of MPITDI (but not MPIConv) is significantly associated with most invasive and established echocardiographic measures of systolic and diastolic function.The normal values of cardiac time intervals deteriorated with increasing age and differed between genders, displaying that woman, in general, exhibit better cardiac function. MPI


CMR is the imaging modality of choice to quantify myocardial injury in studies of cardioprotection. Remote ischemic conditioning (RIC), using transient limb ischemia and reperfusion, is a novel therapeutic intervention, which can protect the heart against acute ischemia-reperfusion injury (IRI). Whether RIC can reduce myocardial infarct (MI) size, and improve myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI), is unknown, and was investigated in this randomized control clinical trial using CMR.323 consecutive patients with suspected STEMI were screened and randomized to receive either RIC (four-5 minute cycles of upper-arm cuff inflation/deflation) or control (un-inflated cuff) prior to PPCI. 197 met study inclusion criteria of confirmed STEMI with TIMI 0 flow. The primary study endpoint was MI size, measured by late gadolinium enhancement (LGE) on day 3-6. Myocardial edema was quantified for the first time in a clinical trial by T2 mapping, the extent of edema representing the area-at-risk (AAR). T2 values were assessed in remote myocardium and the area-at-risk, providing an additional surrogate marker for the amount of edema present. The Otsu thresholding technique was pre-validated as the most reproducible technique for quantification of both MI and T2 edema compared to 8 other techniques .RIC reduced MI size by 27% . However, RIC also reduced the extent of myocardial edema measured by T2-mapping CMR , and lowered mean T2 values , precluding the use of CMR edema imaging to correctly estimate the area-at-risk (AAR). Using CMR-independent coronary angiography jeopardy scores to estimate the AAR, RIC was found to significantly improve the myocardial salvage index (MSI) when compared with control .In STEMI patients treated by PPCI, remote ischemic conditioning, initiated prior to PPCI, reduced myocardial infarct size and increased myocardial salvage. Unexpectedly, RIC also reduced the extent of myocardial edema and lowered T2 values. This supports the cardioprotective efficacy of RIC, but importantly, adds to current controversy questioning the use of T2-CMR to estimate the AAR.Dr White is supported by a Clinical Research Training Fellowship from the British Heart Foundation (grant FS/10/72/28568).This work was also supported by the British Heart Foundation , the RoseTree Trust, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr Frohlich is supported by a research grant from the Swiss National Foundation.


Diabetes is one of the major risk factors for cardiomyopathy and heart failure with reduced ejection fraction (EF) and highly associated with left ventricular (LV) dysfunction in human. This study aimed 1) to noninvasively assess cardiac function using echocardiography; 2) to test the hypothesis that like diabetic human, cardiac function may also be compromised; in spontaneously developed obese, dysmetabolic and diabetic nonhuman primates (NHPs).Cardiovascular functions were measured by noninvasive echocardiography in 28 control, 20 dysmetabolic/pre-diabetic and 41 diabetic cynomolgus monkeys based on fasting blood glucose and other metabolic status.The LV end-systolic volume (ESV) was higher while end-diastolic volume  and EF (63 ± 12.8 %) significantly lower in the diabetic compared to control (14 ± 7 mL and 68 ± 9.8 %) group, respectively. The E/A ratio of LV trans-mitral peak flow rate during early (E) over late (A) diastole was significantly lower in the diabetic (1.19 ± 0.45) than control (1.44 ± 0.48) group. E-wave deceleration time (E DT) was prolonged in the diabetic (89 ± 41 ms) compared to control (78 ± 26 ms) group. Left atrial (LA) maximal dimension (LADmax) was significantly greater in the diabetic (1.3 ± 0.17 cm) than control (1.1 ± 0.16 cm) group. Biochemical tests showed that total cholesterol and LDL were significant higher in the diabetic (167 ± 63 and 69 ± 37 mg/dL) than both pre-diabetic (113 ± 37 and 41 ± 23 mg/dL) and control (120 ± 28 and 41 ± 17 mg/dL) groups, respectively. Multivariable logistic regression analysis demonstrated that LV systolic (reduced EF) and diastolic  dysfunctions are significantly correlated with aging and hyperglycemia. Histopathology examination of the necropsy heart revealed inflammatory infiltration, cardiomyocyte hypertrophy and fragmentation, indicating the myocardial ischemia and remodeling which is consistent with the LV dysfunction phenotype.Using noninvasive echocardiography, the present study demonstrated for the first time that dysmetabolic and diabetic NHPs are associated with LV systolic  and diastolic  dysfunctions, accompanied by LA hypertrophic remodeling (increased LADmax), the phenotypes similarly to those found in diabetic patients. Thus, spontaneously developed dysmetabolic and diabetic NHPs is a highly translatable model to human diseases not only in the pathogenic mechanisms but also can be used for testing novel therapies for cardiometabolic disorders. Cardiovascular disease remains one of the leading causes of death in the United States, accounting 52 % type 2 diabetic (T2D) patients who have a higher risk of mortality at comparable levels of coronary artery disease to those without T2D –3. On thEchocardiography has been widely used as an essential diagnostic tool in clinic to noninvasively examine cardiac structure, ventricular function, non-perfused myocardium, etc. because of convenient, rapid, economical, and none radiation , 17. AmoTherefore, the aims of this study are to test the hypothesis that like diabetic human, cardiac functions may also be compromised in spontaneously developed obese, dysmetabolic and diabetic NHPs, by 1) To establish an echocardiography method for noninvasive measurements of cardiac functions in NHPs; 2) to determine if these NHPs also have a compromised LV diastolic dysfunction; and 3) to examine the relationship between the LV diastolic dysfunction and the accompanying cardiovascular risk factors.Experiments were carried out in the entire colony of 89 cynomolgus monkeys of either genders then existed onsite, individually housed under ∼ 21 °C room temperature and a 12 h. light/dark (6 pm–6 am) cycle with continuous access to water ad libitum and controlled access to food with a complete nutritionally balanced diet  enriched with seasonal fruits and vegetables. These monkeys had no history of pharmaceutical treatment in the past 2 months whose pathophysiological conditions were stable.n = 28, FBG < 85 mg/dL), pre-diabetic/dysmetabolic  and diabetic . The diagnosis of diabetes and dysmetabolism is not just based on a single FBG measurement, it is based on multiple measurements over the progressive history for at least 3 months, along with other metabolic parameters such as intravenous glucose tolerance test (ivGTT), body fat composition measured by dual-energy X-ray absorptiometry (DEX); HbA1c, insulin and lipids levels, etc.The revised guidelines on diagnosis and classification of T2D in clinic from Diabetes Mellitus Expert Committee is fasting blood glucose (FBG) ≥126 mg/dL. There is currently no consensus in research community for the exactly criteria to define dysmetabolic and diabetic standard for NHP model. However, the FBG in normal young adult lean NHP population is typically ~20 mg/dL lower than that in healthy humans. Therefore, we pre-divided the 3 experimental groups using the below arbiter standard: control  at an initial dose of 10 mg/kg followed by maintenance doses of 5 mg/kg as needed. Body temperature was maintained at ∼ 37 °C by a thermostatically controlled warm water-circulating pad placed underneath the animal. Throughout the experimental period, animals were monitored on the vital signs which may trigger intervention (supportive and/or emergent care) and/or study termination including: oxygen saturations <90 %; body temperature <35 °C; heart rate (HR) <100 or >200 beats/min; respiratory rate < 20 or > 60/min, serious arrhythmia and respiratory artifacts, etc.Each monkey underwent a comprehensive transthoracic scanning with 2-dimensional, M-mode, and pulsed-wave Doppler echocardiography using an ultrasound system . Qualified echocardiographic images were captured and stored for offline analysis with each parameter being taken from 3 to 5 consecutive cardiac cycles to obtain an average value. The LV inner dimensions at end-systolic (LVIDs) and end-diastolic (LVIDd), and septal dimension (LVSD) along with heart rate (HR) were measured using M-mode tracing from the parasternal long axis (PLAX) view. From these parameters, fractional shortening (FS), ejection fraction (EF), cardiac output (CO), end-diastolic (EDV), end-systolic (ESV) and stroke (SV) volumes were calculated. The LV diastolic filling function was assessed by trans-mitral flow velocities with pulsed-wave Doppler under the apical four-chamber view . The peaAfter completion of the echocardiographic scanning, animals were returned to their home cage and closely monitored by a trained personnel until completely recovery from anesthesia when the animals were in the upright position and food and water were then provided.In 1 male and 1 female diabetic monkeys with LV diastolic dysfunction and LA remodeling who died naturally due to unknown reasons , necropsy was performed and the hearts were collected and placed in 4 % paraformaldehyde, and then imbedded with paraffin. Tissues were cut into 5 μm sections and stained with hematoxylin and eosin (H&E). Histopathological changes were examined via light microscopy by a histopathologist.The experimental protocol and procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Crown Bioscience, Inc. and in accordance with the guidelines of Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).t-test was used to compare the mean values between 2 experimental groups. One-way analysis of variance (ANOVA) was used for comparison of the mean values among 3 experimental groups.All the data were expressed as mean ± standard error (SE). Statistical analysis was conducted using SPSS 17.0 software . Student P-values were 2-sided and considered statistically significant when < 0.05.Univariate logistic regression analysis was conducted to examine the relationships between the prevalence of LV dysfunction with other parameters such as age, fasting blood glucose, HbA1c, insulin treatment, gender, etc. To simplify the analysis, the below arbiter cut-off values were used. LV systolic dysfunction defined as EF <55 % and diastolic dysfunction as E/A ratio <1 or >2 were used to associate with aging (>10 years old), hyperglycemia (FBG > 85 mg/mL), HbA1c (>7 %), insulin treatment, gender, etc. Currently, there is no consensus in the research community for the exact definition of the above abnormality for NHP model. First, a multiple logistic regression analysis using a step-wise backward method was conducted with the prevalence of LV dysfunction as dependent and all other factors as independent variables, which were significantly associated with myopia prevalence in the univariate analysis. Multivariable logistic regression analysis with odds ratios and 95 % confidence intervals (CI) were then used to examine the associations between animals with certain risk factors and those without. Certain risk factors identified by univariate analyses were subjected to multivariable logistic regression analysis as independent variables. All The diabetic group was older than the other 2 groups. The fasting blood glucose (FBG) was significantly higher in the pre-diabetic, and the highest in diabetic compared to control group. The blood lipid concentrations, including TG, CHO and LDL were significantly higher and HDL lower, thus, LDL/HDL ratio higher in the diabetic than control or pre-diabetic groups. There were no significant differences in age, body weight, HbA1c and blood lipid levels between the control and pre-diabetic NHPs.There were no significant differences in LV dimensions  and mitral valve parameters (MVAmax and VMVmax) among 3 experimental groups although the trans-mitral valve pressure gradient (MV ∆P) significantly elevated in the diabetic NHPs Table .Table 2EThe LV ejection fraction (EF), fraction shortening (FS), stroke volume (SV) and cardiac output (CO) were significantly lower in the diabetic compared to both control and pre-diabetic groups. Both the SV and CO, but not EF and FS were significantly lower in the pre-diabetic than control group. The LV end-systolic volume (ESV) and heart rate (HR) were not significantly different among 3 groups. The original M mode images obtained from the representative animals showed expended LV inter dimension at both end-diastolic (LVIDd) and end-systolic (LVIDs) phases in the diabetic compared to control one.The peak mitral flow rate during early (E-wave) but not late (A-wave) diastole was significantly lower in both the pre-diabetic and diabetic compared to control group. As a result, E/A ratio was significantly lower only in the diabetic compared with control group. The original pulsed-wave echocardiographic images obtained from the representative animals showed that the E/A ratio was reversed in the diabetic compared to control animal. The LV end-diastolic volume (EDV) was significantly lower and E-wave deceleration time (E DT) prolonged only in the diabetic, but not pre-diabetic compared to control group. The maximum LA dimension (LADmax) was significantly higher in the pre-diabetic and the highest in diabetic compared to control group, indicating LA remodeling resulted from LV dysfunction.P < 0.05. The incidence of abnormal E/A ratio, but not low EF was significantly higher in overly diabetic NHPs with insulin treatment for more than 6 months than those without insulin treatment (Right). In contrast, the gender seemed not an independent predictor of LV dysfunctions (data not shown).The incidences of low EF and abnormal E/A ratio in old and hyperglycemic NHPs were significantly higher than those in young (Left) and normal glycemic (Middle) ones. Consistently, in 32 NHPs with HbA1c >7 %, there were 30 (94 %) with low EF, while in 57 NHPs with HbA1c ≤7 %, there were only 18 (32 %) with low EF, the difference in the incidence of LV dysfunctions between the normal and high HbA1c group being statistically significant with OR = 32.5, CI 95 % 29.0–36.0, In 2 representative diabetic monkeys with significant LV diastolic dysfunction and LA remodeling revealed by echocardiography, histopathological examination of the necropsy heart was performed postmortem. In a 23 year old female animal with sever hyperglycemia and significantly reduced E/A ratio, there were focal myocardial inflammation with inflammatory cell infiltrated around the small vascular and myocardial edema (A), as well as some signs of myocardial ischemia such as of myocardial muscle fiber fragmentation and increased eosinophils (B). In another 21 year old male animal with diabetes and reduced E/A ratio, the H&E staining showed signs of myocardial ischemia and cardiac muscle atrophy with accumulation of brown granules at the nuclear poles of the cardiac muscle fiber cytoplasm (C).Using noninvasive echocardiography, the present study detected left ventricular dysfunction for the first time in spontaneously developed obese, dysmetabolic and diabetic NHPs and its interaction between the LV dysfunctions and metabolic disorders, which is consistent with human disease.The optimal performance of LV depends on its converting ability between systolic ejection and diastolic filling. Strong systolic contractility causes quick rise of LV pressure that enables blood to be effectively ejected into the aorta under high pressure gradient between the LV and aorta, while good diastolic compliance enables blood quickly and effectively to fill the LV from LA under low pressure condition that prompts the next contraction phase. Either systolic or diastolic dysfunction would compromise cardiac function to effectively pump blood for supplying the body needs.Rubler et al. first described the existence of ‘diabetic cardiomyopathy’ in 1972 based on some adult diabetic patients with chronic heart failure that could not be explained by coronary artery disease, hypertension, valvular heart disease, or alcoholism . In prosElevation of LV ESV also indicates reduced systolic function. Multivariate analysis identified ESV as an independent predictor of cardiac death after adjustment for perfusion and EF data. Tali et al. reported that if ESV = 70 mL is defined as a threshold, patients with severe perfusion abnormalities but ESV ≤ 70 mL had very low cardiac death rates (0.4 %/year), whereas patients only with mild/moderate perfusion defects but ESV > 70 mL had high cardiac death rates 8.2 %/year) [.2 %/yearDiastole is the portion of the cardiac cycle that begins with aortic closure and ends with mitral closure. Increased LV stiffness or decreased LV compliance would cause abnormality in LV relaxation, alter the onset, rate, and extent of LV pressure decline, thus, building resistance to LV filling, which are important pathophysiologic mechanisms in LV diastolic dysfunction . These cLA remodeling is a continuous process under chronic diastolic burden or as long as cardiovascular risk factors or diseases still persist. Thus, LA enlargement becomes a reliable indicator of advanced diastolic dysfunction, regardless of LV systolic function, underlying cardiovascular disease or LV hypertrophic remodeling . PatientThere is evidence supporting the existence of diabetes-induced direct structural and functional alterations in the myocardium . GlycosyDiabetes has such an important influence on the development of congestive heart failure that it has been incorporated as a risk factor in the guidelines by American College of Cardiology/American Heart Association . HyperglUsing noninvasive echocardiography, the present study demonstrated for the first time that obese, dysmetabolic and diabetic NHPs are associated with LV systolic  and diastolic  dysfunctions similarly to that in diabetic patients. In addition, similar pathogenic characteristics and accompanying risk factors are observed in both humans and NHPs. This makes the current NHP model of spontaneously developed obese, dysmetabolism and diabetes a unique translational tool not only for studying early development and environmental factors that affect the pathogenesis of obesity, dysmetabolism and diabetes, but also can be used for testing novel pharmacological interventions for cardiometabolic disorders.


Heart failure (HF) and atrial fibrillation (AF) are two growing epidemics associated with significant morbidity and mortality. They often coexist due to common risk factors and shared pathophysiological mechanisms. Patients presenting with both HF and AF have a worse prognosis and present a particular therapeutic challenge to clinicians. This review aims to appraise the common pathophysiological background, as well as the prognostic and therapeutic implications of coexistent HF and AF. In developed countries, heart failure (HF) affects 2% to 3% of the population and is a major cause of morbidity and mortality . DespiteThis review aims to appraise the common pathophysiological background, as well as the prognostic and therapeutic implications of coexistent HF and AF.Among HF trials and registries, the prevalence of AF ranged from 13% to 41%, depending in part upon age and the severity of HF ,6, with The prognostic importance of the presence of AF in HF patients is well established in different settings. Both observational studies  and randTogether, these data show that HF and AF often coexist and when together they are associated with worse prognosis.An increased left ventricular filling pressure (LVFP) is a hallmark feature of the HF hemodynamic profile, which can be caused by either a systolic or diastolic dysfunction . This inOn the other side, AF can interfere with the ability of the heart to pump or accommodate blood. An increased resting heart rate and an exaggerated hear. rate response to exercise shorten the LV filling time. Together with the concomitant loss of an effective atrial contraction, AF can significantly compromise diastolic function. In addition, a sustained rapid heart rate can impair systolic function by reducing myocardial contractility  Table 1.Atrial stretch results in an increased neurohormonal activation. The renin-angiotensin-aldosterone system (RAAS) activation enhances signal transduction of downstream pathways such as mitogen-activated protein kinase (MAPK) ,14,15, JIn the interstitial compartment, fibroblasts modify the extracellular matrix with effects on ventricular size, structure, and stiffness. If AF persists, further structural changes occur, promoting volume increase of atrial myocytes, sarcomeres misalignment, accumulation of glycogen, and gap-junctional remodeling . In the l-type calcium current, leading to atrial refractory period shortening in order to compensate for the calcium overload and consequently promoting multiple re-entry [l-type calcium currents and action potential durations [Calcium overload of atrial myocytes occurs early in the development of AF and causes changes in gene expression that down-regulate the re-entry . After dre-entry . Atrial re-entry ,41,42. Ire-entry . These furations . These rFibroblast growth factor-23 (FGF-23) is a bone-derived hormone that plays a central role in phosphate homeostasis. FGF-23 acts on the kidney to promote urinary phosphate excretion and to inhibit the production of 1,25-dihydroxyvitamin D, thereby reducing gastrointestinal absorption of dietary phosphate . CirculaUnderstanding the association between atrial structure and function with thromboembolic and HF risk is very important to improve preventive and therapeutic strategies. The Effective aNticoagulation with factor xA next GEneration in AF-Thrombolysis In Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study  evaluateObesity increases the risk of developing HF, ischemic heart disease, and AF ,53. ChamIn contrast to AF, patients with HF were found to have less epicardial fat mass and smaller adipocytes than controls , possiblThe mechanisms underlying susceptibility to most forms of AF remain unknown . Some foIn general, the evidence on HF or AF treatments is generalizable to patients presenting with both diseases because it is unlikely that the proven benefit to one disease disappears when the other is simultaneously present. In addition, most of the trials testing specific treatments to AF or HF included a subset of patients who had both diseases, which further strengthens their external validity to this specific group of patients. Nevertheless, there are some specific therapeutic implications when managing patients with coexistent HF and AF that clinicians should be aware.versus rate control decision is the presence of symptoms attributed to AF despite controlled heart rate. Despite some dissent results regarding quality of life (QoL) impact of these treatment strategies [As previously discussed, AF is a robust and independent prognostic marker in HF populations. However, the conjectural benefit of rhythm control has never been empirically proved. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)  and the rategies ,81, the rategies .Several clinical trials have consistently shown the benefits of anticoagulation in AF, which is a powerful risk factor for stroke and thromboembolism. The decision to initiate anticoagulation therapy is adequately informed by thromboembolic risk stratification scores as CHADS2  and CHA2DS2-Vasc  . These sThe efficacy of conventional HF drugs in primary prevention of AF remind us how interconnected these diseases are. Angiotensin-converting enzyme inhibitors , angioteCardiac resynchronization therapy (CRT) consists of a biventricular pacing in order to restore synchronicity of left and right ventricles activation. Several trials demonstrated a mortality benefit in HF populations, however the presence of AF has been significantly associated with a non-response to CRT . This maAF and HF are two growing epidemics that often coexist due to common risk factors and shared pathophysiological mechanisms. The translation into the clinical practice of the significant advances in the comprehension of the underlying AF pathophysiology has been poor, as there is a lack of specific targeted treatments. Despite the numerous clinical trials that had addressed different aspects of treatment of patients with isolated HF or AF, few have focused on the management of patients with the combination of both diseases. Nevertheless, when managing a patient with HF and AF, the clinician should be aware of the prognostic significance and some therapeutic implications of this increasingly common disease combination.


The cine steady-state free-precession (SSFP) is the standard sequence for left ventricular (LV) function evaluation. However, SSFP mandates uninterrupted RF excitations to maintain steady-state (SS) during suspended respiration. In patients who cannot perform breath-holds (BH), a respiratory triggered (RT) free breathing (FB) retrospectively cardiac gated cine SSFP sequence that drives the magnetization to SS before commencing cine acquisition may be an alternative [1]. In this work, we validate the RT FB SSFP sequence by comparing it to the BH SSFP sequence for LV function evaluation.This prospective study included 21 consecutive patients  undergoing clinically indicated CMR. MR Acquisition: Images covering the LV in short-axis (SA) were acquired on a 1.5 T MR scanner  using identical parameters for both BH and FB RT cine SSFP sequences - TR/TE/flip angle: 2.6/1.32/70 degrees; acquired voxel size: 1.7-2.0 × 1.6-2.0 × 8 mm3; SENSE acceleration factor: 1.3-1.9; 12-14 slices to cover the LV; temporal resolution: 30 - 40 ms. Data Analyses: Image sets were randomized and anonymized. Two fellowship-trained cardiac imagers blinded to the study design independently scored image quality for myocardium-to-blood pool contrast, endocardial edge definition and inter-slice alignment on a 3-point scale . Readers also performed independent quantitative volumetric analyses on both image sets by manually drawing the LV endocardial and epicardial contours.There was no statistically significant difference in the quantitative metrics of global LV function, EDV, ESV, and EF estimated from images acquired with FB and BH MR techniques Table . Image qThe FB RT-SSFP sequence generates diagnostic image sets with contrast and spatio-temporal resolution that is comparable to BH SSFP sequence at the expense of a modest time penalty. Given that the LV functional parameters obtained from the two sequences were in good agreement, the FB RT sequence offers a robust alternative method for LV function evaluation in patients with impaired breath-holding capacity.NA.