Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments. Viability means living, and myocardial viability refers to myocardium that is living, and contributes to, or has the potential to contribute to, systolic ejection of blood. The term is mostly used in relation to decisions on revascularization in patients with coronary artery disease. In patients with reduced left ventricular function it is important to determine whether myocardial tissue with reduced function and reduced blood supply will actually benefit from re-establishing blood supply. In this setting, the gold standard for viability is a retrospective one: the ability to improve function after revascularization. Accurate viability tests are important for diagnostic and prognostic purposes and, although retrospective studies suggest large benefits, there is a striking lack of prospective randomized controlled clinical trials determining the effect of viability testing on morbidity and mortality in patients with coronary artery disease.Before the introduction of gadolinium contrast agents, there were two main principles for viability testing: function and metabolism. The first is utilized in low-dose dobutamine stress, where an improvement in function from rest to 10 -20) microgram/kg/min of dobutamine is used as a marker of viability. This can be done with either echocardiography or magnetic resonance imaging 0 microgr.With the introduction of gadolinium contrast agents in cardiac MR, a new principle was established: late gadolinium enhancement imaging (LGE). The concept is based on the delayed wash in and wash out in tissue with an increased proportion of extracellular space. In the setting of an acute myocardial infarction, this is caused by cellular necrosis and lysis, and edema, while in the chronic infarcted tissue, the fibrous scar tissue with its increased extracellular space is the basis. The increased amount of gadolinium can be demonstrated by T1-weighted imaging, in the time period of 10-30 min after contrast administration.While late gadolinium enhancement was originally developed to image scar, it has also been found useful in other kinds of heart disease, mainly in the diagnosis of cardiomyopathies. Different kinds of cardiomyopathies exhibit different patterns of LGE, which opens up entirely new possibilities in the differential diagnosis in patients with reduced ventricular function. LGE is based on differences in extracellular space in different areas of myocardium and is therefore only useful if the disease is regional . In diseases that affect the whole myocardium the method runs into trouble. The most typical example is amyloidosis but general fibrosis also seems to be an important part, or common pathway, of the unfavorable remodelling and hypertrophy seen in, for instance, heart failure, aortic stenosis and hypertensive heart disease. Fibrosis is also a part of normal aging . In the following we will discuss the methodological aspects of gadolinium-based imaging, and also its applications and possible future developments.Gadolinium (Gd) is an element and is toxic in its unbound state. Therefore, the contrast agents (CA) consist of a large molecule with the sole task of keeping Gd bound during intravenous injection. There are three different groups of carrier molecules with different affinity to Gd , with the cyclic carriers considered safest (i.e. least likely to release Gd). The carrier molecules are relatively large and do not enter the intracellular space. Thus they are classified as extracellular contrast agents. The ones with the largest molecular size only extravasate to a limited degree and can be said to be vascular agents, like the gadolinium-based albumin-bound CA . An ideaMost of the CA are excreted by the kidneys, having a half-life of 2 hours and being almost completely cleared from the bloodstream after 24 hours. Although it has been considered a safe drug for years, we now know that Gd can cause a rare, albeit severely debilitating disease known as nephrogenic systemic sclerosis (NSF). This condition, which resembles scleroderma, is mainly seen in patients with reduced kidney function, especially those who are in dialysis and have undergone multiple angiographic exams with high doses of Gd. After the establishment of rigorous guidelines for the use of Gd-CA in patients with reduced renal function, there have been very few new cases. Some of the CA thought to have the lowest affinity to Gd have also largely been abandoned. This potential toxicity of current Gd CA has prompted the search for new MRI CA without this limitation. Gd is a paramagnetic element and reduces T1 time. Thus, T1 weighted sequences like fast low-angle shot (FLASH) can be used. The contrast to noise ratio was dramatically improved with the introduction of the inversion recovery principle (IR), which effectively nulls the signal from normal myocardium. The technique used for LGE consists of an injection of a 0.1-0.2 mmol/kg bolus of Gd-based contrast, and after 10-20 minutes the start of acquisition of T1-weighted images with an adequate inversion time (TI) to null the signal from normal myocardium. Choosing a correct TI is of crucial importance to obtain images with enough diagnostic quality. Optimal TI varies in each patient and in accordance with certain factors such as cardiac output or contrast dosage. The optimal TI is that which results in suppression of normal myocardium  along with a brighter signal from the myocardial cavity and a very bright signal in the scar tissue. An optimal TI should enable the examiner to differentiate endo-, mid- and epicardial LGE, and also to see possible intracavitary thrombi.The TI can be determined either by trial and error, which is effective for experienced examiners, or by using a Look-Locker sequence, that acquires a series of images with variable TI during one breath-hold, and lets the examiner pick the one with the most favorable contrast. It has also to be taken into account that the TI must be increased during the examination if LGE images are acquired over a period of more than 5 min. In order to overcome, at least partially, the disadvantages of TI selection, phase-sensitive inversion recovery (PSIR) techniques have been developed. Those techniques, available on some commercial scanners, permit the acquisition of DE images without having to pick a precise TI . Gadolinium contrast medium has a molecular size that allows it to distribute in the extracellular space without entering the myocardial cells in normal conditions. However, under certain pathologic circumstances, either the extracellular space may increase or the myocardial cell membrane may be disrupted, leading to an increase in the volume of distribution of gadolinium and, as a consequence, gadolinium enhancement. In acute myocardial infarction, for instance, cellular necrosis is associated with cell membrane rupture and increase in gadolinium distribution . On the The threshold that should be used to define hyperenhancement is not clear. In clinical practice, LGE is evaluated qualitatively by visual estimation, establishing a percentage of the thickness of infarcted myocardium in relation to the global wall, in order to define the transmural extent of LGE. A semiquantitative approach has also been described, using the American Heart Association 17 segment model and giving each segment a score from 0 to 4 depending on the extent of scar . A final score is given by the summation of all segments’ scores and division of the result by 17. , et al. [In addition to visual estimation, some commercially available softwares for quantification of scar have also been developed. However, the exact threshold to define scar is still not clear. Kim, et al.  used 2 SHyperenhancement on LGE has a close correlation to histopathology proven myocardial necrosis, as demonstrated by some studies. In an experimental study, Kim and colleagues  demonstrIn addition to the variability of TI between different subjects and conditions, a second drawback of LGE is that the scar size will be somewhat different depending on the time delay after contrast injection. This disadvantage, however, is probably less important in a clinical setting than in research, where quantification is essential.Perhaps the main drawback of the LGE technique is its limitation in evaluating diffuse fibrosis. Since the enhanced area is defined on the basis of the difference in signal intensity relative to that of the normal myocardium, if there is diffuse fibrosis no differences in signal intensity will be observed. In order to overcome this limitation, T1 mapping techniques have been developed that allow the quantification of the relaxation times of the myocardium, with or without administration of Gd agents. The most frequently used sequence is the modified Look Locker inversion recovery (MOLLI) sequence . AlthougCurrently LGE MRI is recommended by the scientific societies for scar detection  andis a LGE-MRI can also offer some important prognostic data. The extent of enhanced myocardium correlates with biomarkers of myocardial necrosis and left ventricle (LV) ejection fraction (EF) at late follow-up in patients with acute MI, as demonstrated in one work . Also, iLGE MRI is also a useful tool to detect microvascular obstruction (MVO). The visualization of MVO in LGE MRI is that of a subendocardial area of low signal intensity surrounded by enhancement. The detection of MVO has prognostic implications as well, since it has demonstrated correlations with adverse events , bigger infarct size, lower EF and LV remodelling , 20.Finally, in an acute MI setting, LGE MRI can be useful to detect the extent of the infarct peripheral zone. This peripheral zone, which possesses lower signal intensity than that of the infarct core, corresponds to an area with both viable and non-viable myocytes. A larger peripheral zone has been related to an adverse prognosis with higher mortality at follow-up due to arrhythmia .As has already been discussed, both acute and chronic scars from MI show LGE. In order to differentiate between the two, the presence of wall thinning as well as T2-weighted imaging may be useful; whereas wall thinning suggests chronic infarction, high-intensity on T2 is due to the edema of an acute MI.1). Kim and colleagues [In chronic ischemic heart disease (IHD), the major contribution of DE MRI is to predict recovery of function after revascularization. The presence and extent of LGE are strongly associated with the probability of improvement in contractility  imaging has emerged as an effective tool for the diagnosis of myocarditis, with high values of specificity . The patCMR has a good diagnostic performance (80%) in patients with chest pain, positive necrosis enzymes and absence of coronary artery disease, but its diagnostic capability improves when associated with endomyocardial biopsy (reaching 95%). There is a good diagnostic agreement between CMR and endomyocardial biopsy for the diagnosis of myocarditis (kappa=0.7) . AccordiApart from its diagnostic utility, the presence of LGE in patients with myocarditis seems also to have prognostic implications . In a reFinally, new emerging CMR techniques may also provide some new insights. The usefulness of CMR with magneto-fluorescent nanoparticles (MNP) for detecting myocarditis has been evaluated in a recent experimental study, in which it was demonstrated that MNP CMR allowed better visualization of myocardial inflammation than conventional CMR .2), as well as in the subepicardial and mid-wall in the LV [The presence of hyperenhancement in hypertrophic cardiomyopathy (HCM) is usually localized in the junction points of the right ventricle (RV) in the septum  with cardiac amyloidosis according to one study . The pat, et al., 13% of the patients with dilated cardiomyopathy and without significant coronary disease in the angiography showed a LGE pattern indistinguishable from that of the patients with IHD, suggesting a coronary recanalization after MI.Most patients will show no enhancement, whereas others may present with mid-wall hyperenhancement . In thisIn sarcoidosis the LGE pattern is usually midventricular or subepicardial, and affects specially the basal segments. Right ventricular cardiomyopathy may present with LGE affecting either the RV free wall or the septum. Chagas disease may show a pattern of LGE that is either transmural, subepicardial or subendocardial, with the inferolateral segments being the most frequently affected. Finally, the association of biventricular subendocardial enhancement with adjacent thrombus is typical for endomyocardial fibrosis.Several studies have assessed the role of DE-CMR in cardiac resynchronization therapy (CRT), showing an association between the presence of myocardial scar and lack of response to this therapy. It was demonstrated in one study  that a pHowever, given the relative contraindication of performing a CMR in the presence of a CRT device, the use of CMR in this subset of patients is limited to the pre-implant evaluation, using other imaging techniques for the patient follow-up.Recently, DE-MRI has also proved its utility in the field of atrial fibrillation (AF). Specifically, the group of Utah has applied this technique in the left atrium, allowing for the visualization of DE in this particular cardiac chamber . In a woIn order to detect inflammatory areas, contrast agents that infiltrate inmunocompetent cells have been used, allowing these cells to be tracked and, as a consequence, effectively delimiting inflammatory regions. Two possible approaches are used: one, using paramagnetic nanoparticles, and the second, using fluorine isotope. The latter has the advantage of lack of background signal and, thus, is highly specific. 19F atoms are used. PFCs are taken up by phagocytic cells and accumulate in inflammatory regions, offering the possibility of detecting inflammation and events to monitor treatment. However, it is still unresolved how to widely apply this technique in clinical routine [Perfluorocarbons (PFCs) which contain a high concentration of  routine .LGE MRI is a valuable tool for scar detection, as recommended by the principal scientific societies, based on the differences in volume distribution of gadolinium between normal tissue and that of fibrosis or necrosis. In ischemic cardiomyopathy its role in guiding revascularization is essential and it also offers prognostic information. Other myocardial diseases may also show different patterns of LGE, pointing out the usefulness of this technique in the diagnosis and even prognosis of some of these entities. Finally, new techniques are evolving that may generate novel applications of this technique in the future.


Heart transplantation is limited by a severe donor organ shortage. Potential donors with brain death (BD) and left ventricular dysfunction due to neurogenic stunning are currently excluded from donation – although such abnormalities can be reversible with aggressive treatment including Hormonal Treatment (HT) and deferred organ retrieval.To assess the recovery of left ventricular dysfunction in potential brain-dead donors with hemodynamic instability treated by aggressive treatment and HT.In a single-center, observational study design, we evaluated 15 consecutive brain-dead potential donors (DBD)  with hemodynamic instability. All underwent standard hemodynamic monitoring and transthoracic 2-dimensional echo (2-DE) with assessment of Ejection Fraction (EF). Measurements were obtained before BD and after BD within 6 h, at 24 h and within 48 h. HT  was started as soon as possible to treat hemodynamic instability and avoid administration of norepinephrine (NE). Eligible potential heart donors underwent coronary angiography.2 vs post 3.7 ± 1.2 L/min/m2, p < .05), EF  without administration of norepinephrine (NE) in 67% of cases. Five potential donors were excluded from donation . At pre-harvesting angiography, coronary artery stenosis was present in 2 of the 10 consented donors. Eight hearts were uneventfully transplanted. No early graft failure occurred and all eight recipients were alive at 6-month follow-up.After HT, we observed a normalization of hemodynamic conditions with improvement of mean arterial pressure , cardiac index , treat (with HT) and see (with 2D echo) strategy can help rescue organs suitable for heart donation. Heart transplantation is an established procedure in end-stage heart failure patients, with satisfying long-term results. However, this surgical therapy is continuously limited by a severe donor organ shortage in recent years. Therefore, adequate and optimal utilization of all suitable donor organs is mandatory for increasing graft availability . Evidenc2) > 90 mm Hg; and pH in the 7.35 to 7.45 range, dopamine < 10 μg/kg/min. Norepinephrine was not administered, or infusion was weaned as soon as possible. All potential heart donors underwent an echocardiogram for evaluation of global ventricular function according to American Society of Echocardiography (ASE) recommendations [From June 2010 through July 2011 we initially considered 27 consecutive brain-dead potential organ donors (DBD) with cerebral lesions of different etiology, mostly cerebral hemorrhage. Diagnosis of death was confirmed by strict adherence to standardized neurological criteria in accordance with Italian law and related guidelines. All donors were managed according to international guidelines . From thTM30 Gold Cardiovascular, Esaote, Italy) with a P4-2 MHz transducer. Two Neuro-ICU anesthesiologists trained in ultrasound performed the echocardiographic exams and eyeballing ejection fraction was assessed using apical 4- and 2-chamber views, adding a subcostal approach when useful to improve the examination quality [All potential donors underwent transthoracic echocardiography at baseline (within 6 h of brain death), and at the end of the first and the second day of hormonal treatment. We used commercially available equipment  were retrieved using standard technique and preserved with cold cardioplegic arrest and topical hypothermia Figure . All traSoftware  was used for statistical analysis. The statistical analyses included descriptive statistics . Pearson’s χ2 with Fisher’s exact test for categorical variables and the Mann–Whitney test for continuous variables for intergroup comparisons were performed to confirm significance .2 vs post 3.7 ± 1.2 L/min/m2, p < .05), peripheral arterial blood lactate . In 10/15 cases norepinephrine was never used after brain death; in 5/15 cases norepinephrine infusion was stopped within 12 h. Transthoracic echocardiography was feasible and interpretable in all brain-dead potential donors.Demographic, echocardiographic, laboratory and hormonal treatment data and outcome of individual potential donors with hemodynamic instability are shown in Table A typical pattern of recovery is shown in Figure , coronary artery stenosis was present in two of the ten consented donors, both with normal EF at study entry . Currently, brain-dead consented organ donors number around 1100 with less than 300 hearts transplanted per year . This severe shortage in transplantable heart status depends on eligibility criteria based on the donor age, which is continuously increasing, and functionality, which may be acutely affected by the consequences of brain coning and hemodynamic instability. Thus, new strategies enhancing functional recovery and reliable prediction of successful heart transplantation are needed. In brain-dead potential donors with hemodynamic instability, echocardiographic serial assessment of LV function is feasible and shows, in 40 % of patients, a moderate-to-severe alteration in global and regional LV function. These alterations may be fully reversible upon intensive care, in a couple of days. In this setting, regional wall motion abnormalities can occur in the absence of underlying coronary artery stenoses, and also coronary artery stenoses can be present with normal regional wall motion ,13. In tStandard rest echocardiography is a non-invasive, portable, and rapidly available investigation that is ideally suited to the accurate assessment of donor ventricular function. However, in the presence of left ventricular dysfunction, a “single spot” echocardiography does not predict reversibility or non-reversibility of ventricular function after heart transplant . If echoThe brainstem ischemia occurring in the terminal phase of the pathophysiological process which leads to brain death may cause an “autonomic storm” with intensive sympathetic nervous system activity, followed by vasoparesis and hypotension . Such inManagement of ‘marginal’ hearts should include donor graft ‘resuscitation’ and re-evaluation ,5, thus This is a single-center experience with a relatively low sample size. In addition, the observational, not randomized, study design does not allow us to separate the effects of HT (treat-wait-and-see) vs simple wait-and-see strategy on the observed benefit. In fact, neurogenic stunning can also spontaneously disappear with time, as clearly shown in patients with subarachnoid hemorrhage and Takotsubo cardiomyopathy . We usedThis study shows that it is possible to provide long maintenance periods based on high quality intensive care management without losing the possibility of organ retrieval. Consequently, the concept of “maintenance” of potential organ donors could be extended to “treatment” of a malfunctioning graft in the potential donor before organ retrieval. Larger, multicenter, prospective studies are needed to evaluate the effects of hormonal treatment and timing on potential organ donors under conditions of hemodynamic instability. This approach can be added to other strategies proposed to expand the heart donor pool, such as the ADONHERS project, with stress echo-driven selection of old donor hearts for heart transplantation -28. UsinDonor hearts with recovered LV function can be eligible for uneventful heart transplant. A strategy based on a) longer interval of maintenance of the brain-dead potential donor (wait), b) a circulatory targeted treatment including HT (treat) and c) heart function monitoring by 2D echo (see) can help to rescue organs suitable for heart donation.BD, brain death; BPS, biplane Simpsons; CVP, central venous pressure; DBD, brain-dead potential donors; EF, Ejection Fraction; HT, Hormonal Treatment; LV, left ventricular; MAP, mean arterial pressure; NE, norepinephrine; PaO2, partial pressure of oxygen; PGF, Primary graft failure; T3, triiodothyronine; 2-DE, 2-dimensional echo.The authors declare that they have no competing interests.MC and FP conceived this study, performed the data analysis, and drafted the manuscript; TB gave a contribution to the preparation of study design, data discussion, and critical revision of the manuscript; DS and MGG were responsible for data collection and revised the manuscript. All authors read and approved the final manuscript.MC, Transplant Coordinator, Neuro Intensive Care Unit, University City Hospital, Verona, Italy.TB, Scientific Coordinator of the CCM project n. 48 “ Aged Donor Heart Rescue by Stress Echo – ADONHERS” Institute of Clinical Physiology, National Research Council, Pisa, Italy. DS, Neuro Intensive Care Unit, University City Hospital, Verona, Italy.MGG, Echocardiography, Cardiology, University City Hospital, Verona, Italy.FP, Intensive Care Coordination, National Transplant Centre, Italian National Institute of Health, Roma, and Director, Neuro Intensive Care Unit, University City Hospital, Verona, Italy.Title of data. Serial four chamber cineloops of a potential heart donor with hemodynamic instability. Description of data: Left upper panel Normal LV function before brain death. Right upper panel. Takotsubo-like LV dysfunction immediately after subarachnoid hemorrhage and brain death: echocardiographically detected left ventricular systolic dysfunction excludes this heart from transplant according to standard criteria. Left lower panel Reduction of end-systolic volume and improved systolic thickening. One day after early and aggressive hormonal treatment, including triiodothyronine, vasopressin, insulin and methylprednisolone with improvement of heart function. Right lower panel. Two days after hormonal treatment the heart definitively normalized, was retrieved and was successfully transplanted.Click here for file


Cardiac Resynchronization Therapy (CRT) has been shown to improve quality of life and decrease mortality in heart failure patients. However, up to 40% of patients fail to respond to this therapy. Validation of a response prediction model that incorporates both myocardial scar and dyssynchrony of the paced myocardial segments would allow for a targeted approach to CRT lead delivery.Patients planned for CRT under standard indications were prospectively enrolled. Serial short-axis tagged cine and delayed enhancement MRI was performed using standard imaging protocols. Echocardiography and gated CT Angiography (CTA) were performed at baseline and 3 months post-implantation. The repeat CTA was performed for accurate lead tip localization to a 16-segment model. Dyssynchrony was measured for each segment  from serial short-axis tagged MRI and expressed in milliseconds from onset of pulse trigger . A segmental scar score was then assigned using a blinded visual interpretation (score 0 to 4). The number of response prediction rules met was determined for each patient as follows: 1) LV lead tip placed on a dyssynchronous segment (Trs > 130msec), 2) LV lead tip placed on a viable segment (scar score <2), 3) RV lead tip placed on a viable segment (scar score <2). Clinical response to CRT, defined as a >=15% reduction in LVESV by echocardiography, was correlated to the number of prediction rules met.Forty consecutive patients were enrolled with a mean age and ejection fraction of 67.0 ± 8.6 years and 25.6 ± 6.6%, respectively. Twenty four patients (60%) met clinical response criteria with a mean reduction in LVESV of 20.5 ± 16.5% compared to a rise of 1.4 ± 6.3% in non-responders (p<0.001). A strong correlation was seen between the number of prediction rules met and clinical response to CRT. In patients with 3, 2, 1 and 0 prediction rules met, the response rates were 100%, 92%, 58% and 40%, respectively (p<0.001). A strong correlation was also seen between the number of prediction rules and the mean reduction in LVESV .Dyssynchrony and scar characteristics of the paced myocardial segments are strongly correlated with clinical response to CRT. A simple 3-point prediction model incorporating these variables appears to be highly predictive of response, and may be valuable for the selection of optimal pacing targets for CRT.


The aim of this study is to investigate if the use of individual, per segment reference values for cardiac strain allows for improved discrimination of pathological deformation. In a cohort of patients with a high likelihood of ischemic heart disease, preliminary results within the subgroup of patients without pathological findings on cardiac MRI suggest a spatial dependency of strain.In addition to perfusion and viability, systolic myocardial function constitutes one of the cornerstones in the evaluation of ischemic patients. Technical achievements have improved the accuracy of the quantitative assessment of myocardial function, allowing for better discrimination between healthy and diseased myocardium. These advances cannot be fully exploited without knowledge of the spatial dependency and individual variance of deformation in health and disease.In an ongoing study, a large cohort of patients with moderate chest pain and a high likelihood of coronary artery disease undergo cardiac MRI including cine loops for wall motion, perfusion at rest and during adenosine stress, acquisition of myocardial deformation with displacement encoding with stimulated echo (DENSE), and late gadolinium enhancement to demonstrate scar tissue.In this preliminary study, patient demonstrating maintained perfusion, normal wall motion, and no signs of scar at late gadolinium enhancement were selected for further evaluation.Regional deformation acquired with DENSE was evaluated in terms of radial and circumferential strains. All measurements were reported according to the seventeen segment model of the AHA. The apical cap was excluded from the quantification of regional deformation.Preliminary results for radial and circumferential strain for the 11 patients without pathological findings are presented in the Figure Preliminary results suggest a spatial dependency in deformation, larger than the fairly low standard deviation obtained using DENSE MRI. Hence, taking natural segmental variation of myocardial deformation into account might allow for better discrimination between normal and impaired myocardial deformation.County Council of Östergötland, Heart Foundation, Swedish Heart-Lung Foundation, and Swedish Research Council.


Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV) hypertrophy due to sarcomere dysfunction. In an important proportion of patients with HCM, the site and extent of cardiac hypertrophy results in severe obstruction to LV outflow tract (LVOT), contributing to disabling symptoms and increasing the risk of sudden cardiac death (SCD). In patients with progressive and/or refractory symptoms despite optimal pharmacological treatment, invasive therapies that diminish or abolish LVOT obstruction relieve heart failure-related symptoms, improve quality of life and could be associated with long-term survival similar to that observed in the general population. The gold standard in this respect is surgical septal myectomy, which might be supplementary associated with a reduction in SCD. Percutaneous techniques, particularly alcohol septal ablation (ASA) and more recently radiofrequency (RF) septal ablation, can achieve LVOT gradient reduction and symptomatic benefit in a large proportion of HOCM patients at the cost of a supposedly limited septal myocardial necrosis and a 10-20% risk of chronic atrioventricular block. After an initial period of enthusiasm, standard DDD pacing failed to show in randomized trials significant LVOT gradient reductions and objective improvement in exercise capacity. However, case reports and recent small pilot studies suggested that atrial synchronous LV or biventricular (biV) pacing significantly reduce LVOT obstruction and improve symptoms (acutely as well as long-term) in a large proportion of severely symptomatic HOCM patients not suitable to other gradient reduction therapies. Moreover, biV/LV pacing in HOCM seems to be associated with significant LV reverse remodelling. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited genetic disease characterized by compensatory LV hypertrophy mainly due to sarcomere dysfunction. Prevalence of the disorder in the general population is estimated to be 0.2% . A subseMedical therapy is at least partially effective in the majority of HOCM patients  and consIn severely symptomatic HOCM patients despite optimal medical treatment and with significant resting or provocable LVOT obstruction (with gradient ≥30 mm Hg at rest or ≥50 mm Hg during exercise) non-pharmacologic treatment is indicated  even in less symptomatic HOCM patients , with a  even in In the overwhelming majority of HOCM patients LV/biV pacing is acutely more effective for gradient reduction than standard RVA pacing: eight out of nine in one study  and all In contrast to studies with DDD RVA pacing, LV/biV pacing showed that the reduction in LVOT gradient induced a progressive and significant reduction in LV mass (reverse remodelling) . The thiDuring long term LV/biV pacing in HOCM there was no SCD/syncope in patients with CRT-P ,38. In tThe small number of patients included in studies with LV/biV pacing in HOCM as well as the fact that all of them are observational and uncontrolled  requires caution in interpreting the results. However, the differences observed in comparison with standard DDD RVA pacing warrants further research. Considering the relatively large number of HOCM patients submitted to cardioverter-defibrillator implantation for primary or secondary prevention, data for such analysis should be readily available.In selected patients with HOCM, LV/biV pacing is feasible and usually the best configuration for gradient reduction. Overall, LV/biV pacing in patients with HOCM significantly and progressively improves functional capacity and quality of life. It may also induce LV reverse remodelling.


Although a number of imaging modalities are available to non-invasively evaluate patients with suspected or known coronary artery disease (CAD), myocardial perfusion scintigraphy (MPS) with single photon emission computed tomography (SPECT) has been the workhorse for this purpose for over decades . NotwithBesides clinical risk factors, alternative imaging parameters may also aid in further risk stratification of a normal MPS. Transient ischaemic dilation (TID) has been linked to extensive CAD due to post-stress LV dysfunction, as a result of stunning and/or diffuse subendocardial hypoperfusion, which mimics LV enlargement by reduced subendocardial tracer uptake during stress. Abidov et al. explored the prognostic value of TID in patients with a completely normal MPS and identified TID  as an independent prognostic factor with a threefold increase in event rate . In rece−1∙g−1) and calculate coronary flow reserve (CFR) [Another powerful prognostic indicator is quantitative perfusion imaging. As already alluded to in Fig. ve (CFR) . A numbeve (CFR) . Moreoveve (CFR) .The study by Bom et al. reminds us that a normal MPS is not necessarily accompanied by a benign clinical course and may not always unveil potential serious coronary pathology. Fortunately, advances in imaging techniques enhance the diagnostic and prognostic evaluation of this category of patients. Nonetheless, a pivotal issue remains. These novel insights on the prognostic value of patient characteristics and imaging parameters have yet to be translated into improved patient outcome. At present, it is unclear whether a myocardial perfusion imaging guided treatment strategy in patients with overt ischaemia can improve outcome. This will prove to be even more difficult to ascertain in patients with a normal MPS and, on average, low event rate.


Endotoxin adsorption therapy by direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been widely used in patients with septic shock in Japan. Many Japanese doctors use each PMX cartridge only for 2 hours; however, the mechanisms and optimal duration of PMX treatment remain unclear. We have performed PMX-DHP for longer than 2 hours to confirm that an extended duration of PMX-DHP for patients with septic shock would give significant improvements of hemodynamics.We performed an extended PMX-DHP on 13 patients whose hemodynamics did not achieved the target of mean arterial pressure (MAP) >65 mmHg and inotropic score <5.0 at the time point of 2 hours after PMX-DHP. Hemodynamic parameters such as MAP, heart rate and the dose of vasoactive agents were assessed before treatment, 2 hours after the start of PMX-DHP, immediately and 24 hours after completion of PMX-DHP. The following were also recorded during the study: microbiological data, the APACHE II score, the Sequential Organ Failure Assessment (SOFA) score and 28-day mortality.P < 0.01).APACHE II and SOFA scores were 26.0 ± 9.0 and 10.4 ± 3.0, respectively. The 28-day mortality rate was 15.4%. The average duration of PMX-DHP was 14.9 ± 7.5 hours. PMX-DHP was well tolerated and showed no side effect over extended duration in treatment. MAP was increased: 64.2 ± 8.8 mmHg (baseline), 79.7 ± 10.5 mmHg (2 hours after the start of PMX-DHP), 88.4 ± 13.8 mmHg (immediately after completion) and 89.8 ± 12.8 mmHg (24 hours after completion). The inotropic score was also decreased: 16.4 ± 9.2 (baseline), 13.5 ± 7.2 (2 hours after the start of PMX-DHP), 5.7 ± 6.8 (immediately after completion) and 2.8 ± 3.6 (24 hours after completion). These improvements for 2 hours were statistically significant (The hemodynamics kept improving during extended duration of DHP with one PMX cartridge. And we could use these cartridges safely. Thus we suggest that an extended duration of PMX treatment affords beneficial effects and may contribute to improve the mortality of patients with septic shock.


Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique.A large cohort of healthy volunteers  from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate.Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent “midwall myocardial” T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intra-individual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average.Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of “myocardial midwall” T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping. In magnetic resonance imaging, T1, also known as the spin–lattice relaxation time, is an intrinsic magnetic property of a tissue , and devIn order to use native myocardial T1-mapping to accurately identify disease states, a stable normal range and factors that influence it need to be established. These include common physiologic variation in the normal population as well as technical factors inherent to the measurement technique and image analysis.In this study, we aimed to establish the normal range, potential sources of error and confounds of native myocardial T1 relaxation times in a large cohort of healthy human volunteers. T1-mapping was performed at 1.5T using the Shortened Modified Look-Locker Inversion Recovery (ShMOLLI) technique . We examMyocardial T1-mapping was performed in 342 subjects representative of a general healthy population  over 374 separate scans in three clinical MR centres: Oxford Centre for Clinical Magnetic Resonance, UK (OXF 297 scans), London Heart Hospital, UK (LON 64 scans) and VU University Medical Center, Amsterdam, The Netherlands (AMS 13 scans). All subjects were recruited through advertising as control cases for research studies. None had evidence of cardiovascular disease or cardiac risk factors including hypertension or diabetes, based on medical history. None were referred as patients for a clinical cardiovascular MR (CMR) scan which then turned out to be normal. In majority of cases the 12 lead ECG, blood pressure or selected blood tests were confirmed normal on the day of scan. There were no pathological findings identified in the available cine images. All study procedures were approved by the respective local ethics committees in each centre and all subjects gave written informed consent.All T1 measurements were performed without the administration of any invasive agents using ShMOLLI  using thAll images were analysed using in-house software written in IDL by SKP . Myocardial contours were drawn directly on the T1 maps with full control over image windowing in order to separate consistent myocardial tissue with minimal partial volume of the neighbouring tissues. All contours were reviewed for consistency with further adjustment as deemed necessary by a single observer (SKP). Each MR scan typically provided 3 myocardial slices per subject  for analysis, representing an average myocardial volume sample of 25 ± 11 ml (~3000 ± 1400 interpolated pixels) per subject. The T1 ± SD per subject for each measurement was calculated as an average using all the slices available for that subject in areas of the left ventricular myocardium, left and right ventricular blood pools . To study the impact of partial volume on T1 values, the areas marked as myocardium were systematically inflated  and eroded (by 1–5 pixels) at both epi- and endo-myocardial outlines and the average T1 ± SD for each measurement re-calculated as above. The tissue sample outlined by myocardial contours following a 1-pixel erosion was defined as the “myocardial midwall”.Thirty-two additional scans in 21 individuals  were used to test the reproducibility of T1-mapping. Eighteen subjects were scanned more than once within the Oxford centre over a period of 3 years. For inter-centre comparisons, 9 subjects were scanned in both the Oxford and London centres within 24 hours, while 2 of these subjects were also scanned in both the Oxford and Amsterdam centres within a separate 24-hour period. Overall, the repeated measurements represented ~10% of the datasets from each centre and spanned 435 ± 303 days . T1 values from these measurements were compared for intra- and inter-centre reproducibility.Primary physiological factors with potential effects on T1 variability were the age and gender of each subject. For the analysis of the primary physiological factors and general population characteristics , hematocrit, myocardial wall thickness averaged between slices, and average heart rates from sequence timing.Given that virtually all the studied variables have known primary age and/or gender dependencies, and that male variables generally demonstrated less age-dependency, we chose to equalise the secondary physiological factors to average male values by removing the gender difference and any identified linear trend with age before any subsequent analysis:Slope and Offset describe linear regression between variable “X” and age for either gender. “X” may be any T1 or physiological factor. Correction is applied independently of statistical significance of respective regressions. AGC stands for “age- and gender-corrected”.where All data are presented as mean ± SD for individuals or measurements as indicated. All differences were assessed using unpaired student t-tests to simulate independent group comparisons. Significance is quoted when probability is less than 0.05 divided by number of simultaneous comparisons in the relevant analysis (Bonferroni correction). Repeated measurements were analysed using the Bland-Altman method .The overall population statistics are summarised in Table Partial volume effect on myocardial T1 was assessed by changing the average distance between epi- and endo-myocardial outlines from 0.5 to 12 mm  and smaller areas of pericardial fat, liver and other tissues. While the average T1 value increased by 1.6, 3.8 and 6.9% in successive steps of contour inflation Figure A, there Conversely, erosion of myocardial contours produced an opposite but more limited effect. Only the initial 1-pixel erosion towards the myocardial midwall resulted in a significant 1% reduction in T1 values (p < 0.005). The partial volume effect on T1 reduction was less prominent in men than in women (-0.76% vs. -1.05%) due to the significant difference in the original myocardial wall thickness Table A. There We had therefore applied a 1-pixel erosion to the original, manually-drawn myocardial contours to outline the “midwall myocardial” tissue to minimise partial volume effects whilst still preserving the sampled tissue volume .Differences in midwall myocardial T1 values on repeated measurements are shown in Figure The average myocardial and blood T1 values are presented in Figure In males, there was no age-dependency of either myocardial or blood T1 values on either individual or age-group regression analysis (p > 0.3).In females, on the contrary, myocardial T1 was consistently higher than males up to the age of 45 years, after which there was convergence with no significant difference from male T1. This resulted in a significant overall trend towards female myocardial T1 decreasing with age (p < 0.01), with the slope ranging from -0.7 ms/year  to -0.8 ms/year . Blood T1 in the LV and RV showed similar age- and gender-dependency  removed any inherent relationships of a variable to age and gender, and most interdependencies amongst the physiological factors studied. Specifically, after AGC, heart rate did not correlate with any other physiological factor; only myocardial thickness correlated with height and BMI, but not weight. Here, we present the effects of secondary physiologic factors on myocardial and blood T1, both before and after AGC, the latter of which is summarised in Figure T1 is related to the water content in any tissue , which wBefore AGC, myocardial T1 increased with increasing heart rate . After AGC, this relationship strengthened to r = 0.27 with a slope of 0.56 ms/bpm. On the contrary, blood T1 decreased with increasing heart rate , but this did not achieve Bonferroni-corrected significance after AGC Figure C. IntereBefore AGC, there were significant negative correlations between midwall myocardial T1 and height (r = -0.28), weight (r = -0.32) and BMI , but all were either rejected (height) or reduced to trend level (weight and BMI) after AGC Figure D.For blood T1, there were significant negative correlations between body height, weight and BMI for LV blood T1 r < -0.25) and RV blood T1 (r < -0.31), both before and after AGC  is consistent with the resting partition of blood volume in myocardial tissue  [Blood T1 of LV and RV are strongly correlated with each other independent of AGC . There were significant correlations between blood and myocardial T1 in males, females, overall, before and after AGC. After AGC, the slopes of the relationship between myocardial and blood T1 (0.11 for T1 0.0001) .In this work, we have presented the largest database to-date on normal myocardial T1 relaxation times measured using the ShMOLLI method in three clinical centres. We demonstrated that native myocardial T1 is a robust and reproducible biological parameter with a narrow normal range. The primary technical factor that may influence myocardial T1 analysis is the partial volume effect when there is gross over-inclusion of neighbouring tissue at the image post-processing stage. Hierarchical analysis of physiologic influences showed that females have higher myocardial T1 values compared to males up to the age of 45 years, after which there is no difference from male T1. Following compensation for age and gender, only heart-rate remained as a secondary physiologic factor with a small effect on myocardial T1 values.The results of this study affirmed the reproducibility and robustness of T1-mapping by comparing data amongst three clinical MR centres. The stability of the method is based on data that withstood the tests of time, various software upgrades, MR scanners in different centres, multiple operators, choice of available 16 and 32 channel coils, positioning, shimming strategies and other study-dependent factors that are beyond practical control. Despite this, the consistency observed was not far from the initial intra-scan repeatability of our method of about 1.6% at 1.5 T .Given that T1-mapping serves as an objective method for myocardial characterisation that is less prone to observer bias, we examined how operator placement of myocardial contours and partial volume may affect T1 values. Our analysis suggested that the human operator places endo- and epi-cardial contours just on the edge of the myocardial interface with neighbouring tissue, with a relatively small 1% overestimation from the midwall myocardial T1. In other words, tightening or loosening of endo-and epi-cardial boundaries around human-drawn contours produces only a ±2% variation in myocardial T1. Thus, intra-centre post-processing of T1-maps with consistent analysis protocols using midwall myocardial T1 values should not suffer from any major impact from partial volume effects. However, for inter-centre or inter-study comparisons, it may be helpful to quote myocardial thickness when reporting myocardial T1 values. This is due to the fact that 1-pixel erosion indicated in this study may not be appropriate to myocardial contours drawn according to different guidelines, in which case the reference point in Figure The primary physiologic determinants of myocardial T1 examined were age and gender, with the largest effect seen in younger females, showing an average T1 prolonged by 24 ms compared to males. While changes in myocardial and blood T1 in women appeared to show a sharp transition at around 45 years of age, a possible link to menopause needs to be confirmed. Given that the residuals of simple regression were within the range of variability according to age groups, modelling the age-dependence of T1 with higher order non-linear models is unwarranted without a clear hypothesis to test.Since the largest age-related effect corresponded to a T1 change of only 7–8 ms/decade of age , ShMOLLI T1 mapping may be used without age- and gender-correction for the detection of major myocardial events such as acute infarction, edema or myocarditis in which myocardial T1 increases substantially ,5,15,23 Overall, we found that blood T1 was more sensitive than myocardial T1 to the secondary physiological factors. While there are biologically plausible reasons for the observed dependencies of blood T1 on the hematocrit (water content), weight and BMI (lipids in blood), we do not see a clear reason for heart-rate dependency. It remains to be established whether this dependency is related to any aspect of blood physiology or arises from inflow or other technical issues not yet identified from phantom studies. The relationship between myocardial T1 and heart-rate is relatively flat at 5.6 ms/10 bpm (±1.5% variation within the range of 50–100 bpm).The results of this study showed that the potential influence of any single factor tested was within 2% of the average myocardial T1 values. While errors can be additive, it is foreseeable that primary physiological factors such as age and gender can be matched. Similarly, differences in groups can be compensated for using the correction factors summarised in Table From the technical standpoint, all numeric results presented in this study are estimates subject to measurement bias and variability related to the choice of method. In particular, T1-mapping using ShMOLLI was introduced as a clinically-applicable method that improved on the longer breath-hold duration and known heart rate sensitivity of conventional MOLLI and its variants ,24,25. Oincreases with a slope of 2.7 ms/BPM [Such comparisons do not include high T1 values of blood and in significant tachycardia where MOLLI variants exhibit an increasing heart-rate dependence ,25. Also7 ms/BPM . Counter7 ms/BPM  is thus 7 ms/BPM ,25. Rece7 ms/BPM  describe7 ms/BPM . It is u7 ms/BPM . Surpris7 ms/BPM , even th7 ms/BPM .The lack of full detail, applicability criteria and validation of such attempts to improve accuracy makes myocardial T1 data hard to compare across the literature. Furthermore, the recent experiments on the residual sensitivity to tissue T2  and the The multicentre data in this study was reviewed and analysis performed by a single observer (SKP). While re-analysis of the whole material by another observer would be impractical given its quantity, our prior analysis showed intra- and interobserver differences to be small at ±0.5% , which iMOLLI methods are SSFP-based and thus are sensitive to certain imaging artefacts, which were primarily assessed by visual inspection and rejection. In this study, we aimed to establish a normal range for native myocardial T1 without artefact influence and thus removed about 10% of the myocardial tissue sample volume; however, it was reassuring that re-inclusion of rejected data did not significantly influence the population myocardial T1 average. Thus artefacts are unlikely to affect the clinical applicability of the method when the trained operator is able to identify problematic measurements and to repeat scans with frequency offset or improved shimming, as is frequently done for other common CMR methods.In this study we are aware of small dependencies that arise from predictable changes in imaging parameters, such as the length of the acquisition, number of k-space lines and MOLLI timings that are automatically adjusted with image planning. These contribute to the presented relationships, but given the complicated dependencies between numerous MR physics factors, the dedicated analysis of underlying mechanisms has been delegated to future research. From the insight offered by the variation in the imaging parameters presented in the MR acquisition section, we estimate that technical factors do not substantially affect the presented relations as to have a significant effect on ShMOLLI T1 performance in the detection of large acute T1 changes. In the future, the application of additional corrections, or keeping all image acquisition parameters as constant as possible, may increase sensitivity to small differences between clinical groups.Native T1-mapping using ShMOLLI at 1.5 T appears to be a highly reproducible, robust and stable biomarker for characterising the human myocardium. Native myocardial T1 exhibit a narrow normal range with limited variability related to common technical and physiologic factors, rendering it a potential method for quantitative disease detection without the need for exogenous contrast agents. The main technical factor affecting myocardial T1 analysis was partial volume effect which is more pronounced in thinner myocardium, but can be alleviated by careful placement and/or erosion of myocardial contours. The primary physiological factors affecting native myocardial T1 are female gender, female age and heart rate. The study of cardiac conditions with more subtle changes, such as diffuse fibrosis or small focal changes, may benefit from age and gender matching between patients and controls. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping.SYSTEMS AND METHODS FOR SHORTENED LOOK LOCKER INVERSION RECOVERY (Sh-MOLLI) CARDIAC GATED MAPPING OF T1. September 29, 2010. All rights transferred to Siemens Medical.US patent pending 61/387,591: SKP, MDR and AG. SKP provided the concepts, performed data analysis and drafted the manuscript. VMF contributed data, processed images and contributed significantly to the drafting of the manuscript. AJL, NABN, contributed data, processed images. RB, CH, MBMH, DMS, VM, SW, ML contributed data. MBMH, TK, JCM, SN, PL, MDR supervised projects contributing data and acted in last author capacity. All authors read, commented or edited the manuscript, and approved the final version.Typical ShMOLLI parameter list.Click here for file


Patients with anterior MI experience worse LV remodeling and dysfunction than non-anterior MI patients. It remains unclear whether this difference is due to larger MI size or whether infarct location plays a role beyond MI size.To assess the relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodeling.A cohort of 260 reperfused ST-segment elevation MI patients was studied with cardiovascular magnetic resonance (CMR) at 1-week (baseline) and 4-month (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late gadolinium enhancement imaging, respectively. Adverse LV remodeling was defined as increase in LV end-systolic volume ≥15% at follow-up.One-hundred twenty-seven(49%) patients had anterior MI and 133(51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (p=0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodeling (p=0.017) and lower LV ejection-fraction at follow-up (p=0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis baseline MI size but not its location was an independent predictor of adverse LV remodeling  and ejection-fraction at follow-up .Anterior MI patients experience more pronounced post-infarction LV remodeling and dysfunction than non-anterior MI patients due to greater magnitude of irreversible ischemic LV damage without any independent contribution of MI location.


We present the results of transmural perfusion gradient (TPG) analysis  versus fractional flow reserve (FFR) for the detection of hemodynamically significant coronary artery disease (CAD).The subendocardial layer of the left ventricle is affected earlier and more severely by ischemia as a consequence of the interaction between coronary microvasculature and cardiac contraction. The identification of subendocardial ischemia is thus considered a sensitive and specific endpoint for the diagnosis of CAD. TPG due to subendocardial ischemia can be visualised on high resolution perfusion cardiovascular magnetic resonance (CMR) images and their presence can be specifically assessed by the gradientogram plot. This study tests the hypothesis that transmural perfusion gradients by adenosine stress CMR predict hemodynamically significant CAD as assessed by FFR and compares TPG with perfusion quantitative analysis.63 patients  with known or suspected CAD underwent high-resolution (1.2 x 1.2 mm in plane) adenosine stress perfusion CMR at 3.0T. FFR was measured in all vessels with >50% severity stenosis. FFR<0.80 was considered hemodynamically significant. TPG were measured by the gradientogram plot and data analysed based on different thresholds of transmural perfusion redistribution . Myocardial perfusion reserve (MPR) was assessed by Fermi deconvolution.In the first group of 28 patients, who served as a training group, a 15% TPG was identified as the best diagnostic threshold for FFR<0.80. Lower (5% and 10%) and higher thresholds (20%) resulted in less accurate results . When the same MPR cut-off was applied to the quantitative analysis of Group 2, it resulted in a sensitivity of 0.70 and a specificity of 0.91. On ROC analysis, the AUC was 0.82. Gradient analysis was more accurate than myocardial perfusion reserve (p=0.001).The detection of transmural perfusion gradients by high-resolution CMR allows an accurate diagnosis of hemodynamically significant CAD as compared to FFR and in this study was more accurate than myocardial perfusion reserve.The Centre of Excellence in Medical Engineering funded by the Wellcome Trust and the Engineering and Physical Sciences Research Council (EPSRC) under grant number WT 088641/Z/09/Z. Andreas Schuster received grant support from the British Heart Foundation (BHF) (RE/08/003 and FS/10/029/28253) and the Biomedical Research Centre (BRC-CTF 196). Sven Plein was funded by a Wellcome Trust Research Fellowship during the early phase of this study (WT078288).and is currently funded by a British Heart Foundation Senior Research fellowship (FS/10/62/28409). Timothy Lockie was funded by a British Heart Foundation Clinical Research Training Fellowship (FS/08/058/25305).


Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as coronary artery disease (CAD) and heart failure (HF). In these conditions, myocardial mitral annular systolic (S’) and early diastolic (E’) velocities have been shown to predict mortality or cardiovascular events. In heart failure non invasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E’) is a strong prognosticator, especially when E/E’ is > or =15. Moreover, other parameters derived by TDI, as cardiac time intervals and Myocardial Performance Index, might play a role in the prognostic stratification in CAD and HF. Recently, a three-dimensional (3-D) TDI imaging modality, triplane TDI, has become available, and this allows calculation of 3-Dvolumes and LV ejection fraction. We present a brief update of TDI. Tissue Doppler imaging (TDI) is an echocardiographic technique that uses Doppler principles to measure myocardial motion velocity.Doppler echocardiography relies on detection of the shift in frequency of ultrasound signals reflected from moving objects. With this principle, conventional Doppler techniques assess the velocity of blood flow by measuring high-frequency, low amplitude signals from small, fast-moving blood cells. In TDI the same Doppler principles are used to quantify the higher amplitude, lower-velocity signals of myocardial tissue motion .TDI can be performed in three modalities: pulsed wave, color mode and 3D mode.Pulsed-wave TDI is used to measure peak myocardial velocities and is particularly well suited to the measurement of long-axis ventricular motion due to the longitudinally oriented endocardial fibers, which are more parallel to the ultrasound beam in the apical views. Since the apex remains relatively stationary throughout the cardiac cycle, mitral annular motion is a good surrogate measure of overall longitudinal left ventricular (LV) contraction and relaxation . To measWith color TDI, a color-coded representation of myocardial velocities is superimposed on gray-scale 2-dimensional or M-mode images to indicate the direction and velocity of myocardial motion. Color TDI mode has the advantage of increased spatial resolution and the ability to evaluate multiple structures and segments in a single view .Recently, a three-dimensional (3-D) TDI imaging modality, triplane TDI, became available, which allows calculation of 3-Dvolumes and LV ejection fraction. With 3D-TDI, a color-coded TDI is applied to the triplane view, obtained from the apical window in triplane modus, acquiring simultaneously the apical four-, two- and three-chamber views. At least two consecutive beats are recorded from each view, and the images are digitally stored for off-line analysis. To assess 3D volumes, the triplane dataset is frozen in end-diastole and the endocardial border is manually traced in the apical four-, two- and three-chamber, views respectively. Then, using the same heartbeat, the triplane dataset is frozen in end-systole and again the endocardial border is manually traced in the apical four-, two- and three-chamber views. A 3D LV end-diastolic and end-systolic volume is generated automatically by the software and LV volumes and ejection fraction are reported accordingly.The triplane technique also permits to assess LV dyssynchrony, through the simultaneous acquisition of TDI from all LV segments during the same heartbeat. In this case, during post-processing analysis, the triplane TDI dataset is used to analyze myocardial velocity curves and then to calculate the time from the beginning of the QRS complex to peak systolic velocity (Ts), using the same heart beat. Subsequently, the standard deviation of Ts (Ts-SD) of the 12 myocardial segments is calculated and used as a parameter of LV dyssynchrony .The PW Tissue Doppler Imaging allows to obtain several indices, which have clinical and prognostic implications. three waveforms: The cardiac cycle is represented by Sa: systolic myocardial velocity above the baseline as the annulus descends toward the apex; Ea: early diastolic myocardial relaxation velocity below the baseline as the annulus ascends away from the apex;Aa: myocardial velocity associated with atrial contraction. The lower-case “a” for annulus or “m” for myocardial (Ea or Em) and the superscripted prime symbol (E’) are used to differentiate tissue Doppler velocities from conventional mitral inflow. dP/dt.Systolic myocardial velocity (Sa) at the lateral mitral annulus is a measure of longitudinal systolic function and is correlated with measurements of LV ejection fraction and peak Traditional echocardiographic assessment of LV diastolic function relied on Doppler patterns of mitral inflow. Because mitral inflow patterns are highly sensitive to preload and can change dramatically as diastolic dysfunction progresses, the use of mitral valve inflow patterns to assess diastolic function remains limited. TDI assessment of diastolic function is less load dependent than that provided by standard Doppler techniques. Validated against invasive hemodynamic measures, TDI can be correlated with τ, the time constant of isovolumic relaxation. In adults > 30 years old, a lateral Ea velocity> 12 cm/s is associated with normal LV diastolic function. Reductions in lateral Ea velocity to ≤ 8 cm/s in middle-aged to older adults indicate impaired LV relaxation and can assist in differentiating a normal from a pseudonormal mitral inflow pattern. Unlike conventional mitral inflow patterns, Ea is resistant to changes in filling pressure, although preload dependence is more pronounced in structurally normal hearts.3Simultaneous cardiac catheterization and echocardiographic studies have shown that LV filling pressures are correlated with the ratio of the mitral inflow E wave to the tissue Doppler Ea wave (E/Ea). The E/Ea ratio can be used to estimate LV filling pressures as follows: E/lateral Ea > 10 or E/septal Ea > 15 is correlated with an elevated LV end-diastolic pressure, and E/Ea < 8 is correlated with a normal LV end diastolicpressure.time intervals, measured from the sites  at mitral annulus, are: Although most studies refer to TDI’s focus on the measurement of velocities, some investigators have used TDI to obtain systolic and diastolic time intervals. TDI IVCT - isovolumic contraction time (from the end of the wave A’ to the beginning of the wave S’), ET - ejection time (from the beginning to the end of the wave S’), IVRT - isovolumic relaxation time (from the end of the wave S’ to the beginning of the wave E’), St – systolic time (from the end of the wave A’ to the end of the wave S’), Dt – diastolic time (from the end of the wave S’ to the end of the wave A’) .Combining systolic and diastolic time intervals, we obtain the Myocardial Performance Index (MPI), defined as the sum of isovolumic contraction (IVCT) and relaxation time (IVRT) divided by the ejection time (ET).This index, derived by conventional Doppler or Tissue Doppler, was reported to be simple and reproducible. One important limitation of conventional MPI is that the IVCT, IVRT and ejection time are measured sequentially and not on the same cycle. Consequently, the accuracy of the results may be compromised by heart rate fluctuations. Tissue Doppler echocardiography enables us to simultaneously measure both the diastolic and systolic intervals from the myocardium .et al [dp/dt, suggesting a relationship between MPI and preload. Thus, even when contractility is constant, significant changes in preload may cause significant alterations in conventional MPI. A possible disadvantage of conventional MPI is the effect of loading conditions on conventional MPI. Tei et al . found aTDI, conversely, is relatively independent from the volume loading condition  and enabSeveral studies have demonstrated that the Tei index obtained by TDI correlates well with the Tei index determined by pulsed Doppler .The agreement between the methods in healthy subjects and in patients with dilated cardiomyopathy is high, while is slightly lower in patients with previous myocardial infarction (MI). Other studies have shown that the agreement between TDI and conventional method is not good, because systolic intervals are longer and diastolic intervals are shorter when measured with TDI. The disagreement exists on healthy people and it is increased on patients with prior myocardial infarction .A study of healthy adults and patients with congestive heart failure has investigated the clinical agreement between MPI measured conventionally and by PW-TD of the mitral annulus. The results confirmed mild agreement between MPI measured by the conventional method and by PW-TDI. Both methods had similarly high diagnostic accuracy for cardiac heart failure; however, this study supports the use of a higher MPI cut-off point for best diagnostic accuracy when using the new PW-TDI method .isovolumic indices. In the normal ventricle, there is segmental shortening before onset of left ventricular ejection, which contributes to changes in global left ventricular geometry and may mobilize blood that allows the mitral leaflets to bulge into the left atrium during systole. This pre-ejection shortening represents active contraction and most likely contributes to isovolumic velocities as measured by TDI. During isovolumic contraction (IVC) phase, tissue Doppler imaging studies suggest dynamic myocardial motions with biphasic longitudinal tissue velocities in left ventricular long-axis views. PW-TDI has also proved useful in the evaluation of the 2). Peak IVA by TDI is calculated in different ways: We can assess two indices: IVV - peak myocardial velocity during isovolumic contraction (cm/s) and IVA - myocardial acceleration during isovolumic contraction  .as the difference between the 2sequential IVC velocities, with the largest velocity increment divided by the frame-by-frame time interval .from the derivative of the velocity curve .et al. used a computerized method to measure acceleration and this approach might improve the accuracy of such measurements [Hashimoto urements .et al. showed that IVC acceleration (IVA) is a reliable measurement of right ventricular contractility and is relatively load independent [et al have assessed the usefulness of IVA to measure left ventricular contractile function and force-frequency relationships in an experimental preparation. They have demonstrated that IVA is a measurement of left ventricular contractile function; furthermore it is unaffected by preload and afterload changes within a physiological range and can be used noninvasively to measure left ventricular force-frequency relationships [A study has assessed that peak positive myocardial velocity (IVV) of the left ventricular free walls, measured by PW-TDI during the IVC phase, correlates well with left ventricular global contractility. These observations have the potential to be of clinical value since disturbances of myocardial motion occur predominantly during the isovolumic phases, (i.e. during contraction and/or relaxation), and such non-invasive recordings might therefore be a sensitive marker of myocardial dysfunction . In an aependent . These aionships .Then IVV (isovolumic velocity) and IVA (isovolumic acceleration) are an additional non-invasive tool to be taken into consideration for complete assessment of left ventricular contractility. However, the usefulness of IVV and IVA in the early detection of myocardial dysfunction needs to be clarified .The feasibility, reproducibility and variation of IVA between segments have not been studied in detail, and thus its utility in clinical practice has not been established.Recently, a study has confirmed that IVA may be used as a research tool if it is measured at the medial mitral annulus, but its clinical applicability is hampered by low reproducibility, especially in patients with impaired left ventricular function in whom it would otherwise be most useful .mechanical dyssynchrony and to determine the response in left ventricular structure and function after cardiac resynchronization therapy. An index of dyssynchrony, originally described by Yu and co-workers [TDI is also used to assess global left ventricular -workers , 21, is In our experience, we found that there is a learning curve associated with the understanding and utilization of TD imaging. Differences in obtaining and interpreting TD data were observed between experienced and non-experienced TD operators. All operators could in fact easily evaluate systolic velocity (S’), early (E’) and late (A’) diastolic velocities, the ratio of early to late diastolic velocity (E’/A’) and the transmitral to mitral annular early diastolic velocity ratio (E/E’), but the different time intervals calculated by Tissue Imaging  and tissue Myocardial Performance Indexwere achieved only by experts in TD echocardiography .TDI has been introduced as a method to quantify myocardial function in terms of tissue velocities and the results so far are promising.myocardial velocities during isovolumic contraction phase and isovolumic relaxation phase in addition to ejection velocities. As demonstrated in animal models and in patients with coronary artery disease, myocardial ischemia is characterized by a decrease in peak systolic myocardial velocity (S’), indicating impairment of regional contractile function. There are important limitations in the ability of peak systolic velocity to serve as a quantitative marker of regional function. Furthermore, a more comprehensive analysis of the myocardial Doppler velocity signal may improve the ability of TDI to identify ischemic myocardium. This analysis includes measurement of non ischemic ventricle the isovolumic contraction period (IVCT) is dominated by a positive velocity spike of short duration, which represented slight longitudinal shortening before LV ejection. During isovolumic relaxation time (IVRT), there is a pattern opposite to that during isovolumic contraction period, with a negative velocity spike of short duration, representing slight elongation before onset of filling. Possibly, twist in gand untwisting effects may have contributed to the IVC and IVR velocities.In the there is a decrease in systolic shortening and then a decrease in peak early ejection and mid-ejection velocities.early-ejection Doppler velocities remain positive and therefore don’t reflect the marked impairment of myocardial function. The mechanism of the positive early-ejection velocity in dyskinetic myocardium is not clear, but it might represent cardiac translational motion or tethering effects resulting from contractions in other myocardial segments.severe ischemia is a large negative velocity spike during isovolumic contraction period. During severe ischemia, IVR velocities reverse and a large positive velocity component (post systolic shortening of ischemic myocardium) persists throughout the entire IVR period, and in some cases continues after the early-diastolic LA/LV pressure crossover.The dominant systolic velocity component during Then, in severely ischemicand dyskinetic myocardium, IVC and IVR velocities arethe strongest markers of myocardial dysfunction. Myocardial ejection velocities have very low amplitudes and appear to be influenced by tethering effects and/or translational motion .time intervals in the assessment of coronary artery disease.Some studies have investigated the useful of the conventional Tei index was found to be significantly more greater than in healthy controls [In patients with acute myocardial infarction the controls .A study, in patients with prior myocardial infarction, has assessed the degree of agreement between PWD and a method based on tissue Doppler imaging. TDI intervals may be influenced by intraventricular conduction disturbs, asynchrony and the differences in the contraction and relaxation times between the different myocardial segments. Mitral annulus velocity intervals, in particular, could be highly influenced by the contractility of basal segments. In these patients, the differences between conventional MPI and TDI-MPI were similar in patients with good contractility of basal segments and even in patients without segmentary contractility alterations. Furthermore, similar observations could be found in healthy subjects. Therefore the disagreement between methods does not seem to depend on contractility alterations. The values of IVCT and ET intervals measured with TDI were larger than the ones obtained with conventional Doppler; this could increase TDI-MPI values. On the other hand, IVRT interval was usually shorter with TDI, and this could decrease TDI-MPI values. The results of both the influences were values of MPI and TDI-MPI of similar range, but not accurate ones. Of the intervals needed to calculate TDI-MPI, ET showed lower differences with the conventional method, while IVCT and IVRT correlated poorly with classic intervals. Therefore, isovolumic times are in most part the responsible components of MPI which explain the differences between conventional MPI and TDI-MPI .TDI-MPI has proved useful in the assessment of left ventricular thrombosis risk after acute myocardial infarction (AMI). Particularly when an MPI > 0.6 was used as the cutoff, LV thrombus formation could be predicted with a sensitivity rate of 81%, a specificity rate of 73%, a positive predictive value of 62%, and a negative predictive value of 88% .et al have evaluated the systolic and diastolic function of left ventricle by PW-TDI in patients with or without preinfarction angina in acute myocardial infarction. The patients with preinfaction angina showed values of E' and E'/A' higher than patients without preinfarction angina, while the ratio E/E' and the MPI were significantly lower in the first group of patients. So the diastolic function was better in patients with preinfarction angina than patients without [Baykan  without .A variety of indices derived from Doppler-echocardiography have been used to predict outcome in patients with heart failure. Recently, tissue Doppler imaging (TDI) has been used to assess systolic and diastolic function . Severalet al. examined whether TDI derived parameters added incremental value to clinical and other standard Doppler-echocardiographic measurements to predict cardiac mortality in patients with a variety of cardiac diseases and ventricular function. They showed that the TDI derived parameters Sm, Em, and Am are powerful predictors of cardiac mortality. In particular an Em<3 cm/s, Sm<3 cm/s, Am <4 cm/s, and E/Em>20 can identify patients at very high risk of cardiac death in the subsequent two years [Wang wo years .et al have tested the hypothesis that, when measured in the long axis, left ventricular systolic function is abnormal in patients with diastolic heart failure. The mitral annular peak mean velocity and amplitude in systole were lower in the patients with diastolic heart failure (mean (SEM), 4.8 (0.2) cm/s) than in the age matched normal controls (6.1 (0.14) cm/s), but higher than those with systolic heart failure (2.8 (0.13) cm/s) . Similar changes were seen the mitral annular amplitude during systole. Peak early diastolic velocity and amplitude were also significantly reduced in the group with diastolic heart failure. This study has showed that in patients with diastolic heart failure and evidence of left ventricular hypertrophy, there is systolic left ventricular impairment as measured by myocardial Doppler imaging of the longitudinal axis. Thus subtle abnormalities of systolic function are present in patients with heart failure and a normal left ventricular ejection fraction, and there appears to be a continuum of systolic function between those with truly normal, mildly impaired (labelled diastolic heart failure), and obviously abnormal left ventricular systolic function [Yip function .Recently, the ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E') has been shown to be useful to assess LV filling pressure. A persistent elevation of E/E’ ratio may be an indicator of patients with or at risk of DHF among subjects with preserved systolic function independent of LV hypertrophy .In diastolic heart failure patients persistent E/e’>15 is an index of higher clinical events. Then elevated E/E' after optimized medical therapy may be useful in predicting cardiac events in patients with HFPSF (heart failure with preserved systolic function) .et al have hypothesized that an E/e' ratio >15 would predict poorer survival after acute MI. An E/e' >15 was associated with excess mortality and was the most powerful independent predictor of survival . The addition of E/e' >15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001). Noninvasive estimation of left ventricular filling pressure by E/e' is a powerful predictor of survival after acute myocardial infarction [Hills farction .time intervals and Myocardial Performance Index might play an important role in the diagnosis and prognosis of heart failure. TDI conventional MPI is found to reflect the severity of LV dysfunction and was proved to be an independent prognostic factor for mortality, similar to the EF. The higher Tei index values in these patients than in healthy individuals are attributable to prolongation of the isovolumic intervals and shortening of ET. The Tei index is significantly correlated with NYHA class, EF and ventricular volumes, while values > 0.77 are associated with higher 1-, 3- and 5-year mortality [et al. investigated the prognostic value of the Tei index in 60 patients with severe, symptomatic heart failure (EF < 30%) of ischemic aetiology or not. A Tei index >1.4 was an independent prognostic factor for death or emergency heart transplant during two years’ follow up and had more predictive power than EF or NYHA class [In patients with dilated cardiomyopathy, the ortality . The useortality . Harjai HA class .Tissue Doppler echocardiography enables us to evaluate new parameters and allows greater prognostic stratification of patients with heart failure.The length of time intervals, derived from TDI, varies by type of heart failure, systolic or diastolic. In fact, the duration of the systolic contraction time was statistically shorter in diastolic heart failure patients compared with controls and still shorter in the systolic heart failure group.Instead, the isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT) tend to increase in diastolic heart failure and even more in the systolic. Consequently, the MPI will tend to increase in diastolic and systolic heart failure .In a study conducted on a population of 112 patients  value of MPI ≥ 0.55 was associated with a relative risk of adverse cardiovascular events of 18,7 .In another study, conducted on a population of patients with predominant diastolic heart failure, an MPI > 0.59 might be useful in identifying subjects with concomitant systolic impairment and neurohormonal activation .Therefore the MPI correlates with the occurrence of adverse events in the follow up of patients with chronic heart failure. In fact, a poor outcome in subjects with heart failure and with an MPI > 0.90 was demonstrated .In our study we found that TDI time intervals may be able in stratifying the risk of recurrent hospitalization for acute HF in subjects with chronic HF. Re-hospitalizations for acute HF were predicted by lower values of ET, ST and FT, and higher values of MPI, and ICT/ET. ET and ST values ability to predict future adverse events remained significant even after correction for LVEF and several other traditional prognostic factors in chronic HF; their assessment in subjects with preserved LVEF may be therefore useful in identifying patients with a higher risk of hospitalization, regardless of LVEF. In particular, ET ≤236 ms identified subjects with occurrence of re-hospitalization for acute HF with a specificity of 78% and a negative predictive power of 93%, FT≤317 ms with a specificity of 69% and a negative predictive power of 94%, ST≤306 ms with a specificity of 90% and a negative predictive power of 91%, ICT/ET values below 0.72 with a specificity of 94% and a negative predictive power of 91% .i. These data might therefore suggest possible mechanisms by which statins exert part of their positive action on dysfunctional ventricles of patients with chronic HF [Exact mechanisms by which TDI intervals are related with prognosis in chronic HF are not completely known. Recently we showed as, in ischemic chronic HF patients, therapy with statins is related with a better TDI performance  and prognosis ronic HF .isovolumic indices in heart failure. Recently was explored the incremental value of quantification of tissue Doppler velocity during the brief isovolumic contraction phase of the cardiac cycle for the prediction of exercise performance in patients with reduced left ventricular ejection fraction (LVEF), referred for cardiopulmonary exercise testing (CPET). Patients with reduced EF had lower IVV, Sa and Aa velocities. Similarly, % predicted peak VO2was lower in patients with reduced EF and correlated with the variations in IVV. Then assessment of TD-derived IVC and atrial stretch velocities provide independent prediction of exercise capacity in patients with reduced LVEF. Assessment of LV pre-ejectional stretch and shortening mechanics at rest may be useful for determining the myocardial functional reserve of patients with reduced EF [Few studies have evaluated the useful of duced EF .Despite recent advances in management, chronic heart failure (CHF) is still associated with a high morbidity and mortality. Cardiac resynchronization therapy (CRT) has been established as an adjunctive treatment for patients with left ventricular systolic dysfunction and medically refractory heart failure with a wide QRS interval. The CRT, reducing ventricular asynchrony, improves cardiac performance, reduces mitral regurgitation, reduced filling pressures and induces reverse remodeling of the left ventricle.However up to 40% of patients who receive a CRT device for established indications do not respond to CRT. In the search for better selection criteria for CRT, it has been shown that patients with LV dyssynchrony have a higher likelihood of a positive response to CRT .The most frequently used technique is TDI, which can be used to determine the response in left ventricular structure and function after device implantation and emerging evidence as a method for selection of patients who may derive clinical benefit from CRT. Several indices of LV dyssynchrony have been proposed as predictors of response to CRT, but the recently published PROSPECT trial failed to identify an ideal echocardiographic parameter of dyssynchrony .The assessment of intraventricular dyssynchrony can be done through various indices, including one proposed by Yu and co-workers , 21. ThiTo calculate this parameter of LV dyssynchrony, three apical views need to be acquired separately. A 3-dimensional (3D) TDI imaging modality (tri-plane TDI) has become available to overcome this limitation. Tri-plane TDI allows simultaneous acquisition of all LV segments during the same heartbeat rendering the technique more precise than the 2-dimensional (2D) TDI equivalent. Then a 3-D probe has become available and useful to identify responders to cardiac resynchronisation therapy (CRT).A study has evaluated the value of triplane TDI to predict reverse left ventricular (LV) remodelling after CRT. Sixty patients with heart failure, scheduled for CRT, underwent triplane echocardiography with simultaneous TDI acquisition before and 6 months after implantation. Intraventricular dyssynchrony was quantitatively analysed by evaluating time from onset of the QRS complex to peak myocardial systolic velocity in 12 LV segments from the triplane dataset and calculation of the standard deviation (Ts-SD-12). Clinical response was defined as an improvement of at least one New York Heart Association class. Reverse LV remodelling was defined as ≥ 15% decrease of LV end-systolic volume at 6 months' follow-up. This study has demonstrated that triplane TDI echocardiography predicts clinical response and reverse LV remodelling 6 months after CRT implantation .As stated above, to obtain myocardial velocity curves for 12 LV segments with 2D-TDI, multiple acquisitions are essentially required. Thus, TDI analysis of dyssynchrony has been applicable only to patients with sinus rhythm fitting into the setting of regular RR intervals for three apical images. Assessment of SD in patients with atrial fibrillation (AF), characterized by randomly irregular cycle lengths, theoretically requires simultaneous image acquisition in three planes. Although AF is associated in large portions of patients with heart failure, many studies evaluating LV asynchrony or response to the cardiac resynchronization therapy (CRT) have excluded patients with AF because of the lack of standard method by conventional echocardiography. In this regard a study has demonstrated the feasibility of the new triplane TDI method for measuring the SD in patients with AF. The authors have proved that the eight-cycle average SD for 12 LV segments showed significant correlation with echocardiographic parameters of systolic function. This method should be further validated, and the mechanism and clinical impact of dyssynchrony in patients with AF should be investigated in further studies .nuclear imaging. In particular, a recent development is the use of gated myocardial perfusion single photon emission computed tomography (GMPS) for assessment of LV dyssynchrony. Recently, Chen et al. [four quantitative indices that can be used as markers of LV dyssynchrony. Recently, these four GMPS indices have been compared with LV dyssynchrony assessment by TDI in 75 patients with severe heart failure. It was shown that among the four quantitative indices of phase analysis, the variables histogram bandwidth and phase SD correlated best with LV dyssynchrony as assessed by TDI [Information on cardiac dyssynchrony can also be derived from n et al.  developed by TDI . The curet al. performed a direct comparison with tri-plane TDI in a cohort of heart failure patients. The results of this study confirm the feasibility to evaluate LV dyssynchrony with phase analysis by GMPS and its applicability in the clinical setting. In particular, histogram bandwidth and phase SD showed a good correlation with LV dyssynchrony measured with Ts-SD as assessed with tri-plane TDI. Future prospective studies in larger patient populations with follow-up after CRT implantation are needed to elucidate the potential role of GMPS with phase analysis for prediction of response to CRT [To further validate the use of GMPS with phase analysis for the assessment of LV dyssynchrony, Marsan e to CRT .An other method to assess global left ventricular mechanical dyssynchronyis the real-time 3D echocardiography (RT3DE) .A study has assessed the comparability of left ventricular mechanical dyssynchrony assessment by TDI and RT3DE in patients with a wide range of LV ejection fractions and different causes of cardiomyopathy. In addition, this study has evaluated the ability of both techniques to predict response to cardiac resynchronization therapy (CRT). Mechanical dyssynchrony was measured with TDI using the standard deviation of time to peak systolic tissue velocity of 12 LV myocardial segments. With RT3DE, the standard deviation of time from QRS onset to minimal volume of 16 LV subvolumes was assessed. The results have confirmed that marked differences between techniques are found for the presence of mechanical dyssynchrony when current cutoff values are applied, making interchangeability of these techniques uncertain. Furthermore assessment of mechanical dyssynchrony by RT3DE might be an appropriate alternative to TDI for accurate prediction of response to CRT .Other parameters, useful to identify the responders to CRT, are the TDI time intervals. In a previous study, the baseline LV Tei index was significantly higher in responders and exhibited an acute and sustained improvement after CRT. The baseline RV Tei index was similar in responders and non responders but improved significantly only in responders .The results of another study indicate that the Tei index and E/E’ ratio are independent predictors of poor response and cardiac events after CRT .et al have evaluated the predictive value of echo/Doppler derived indices, which reflect the duration of the isovolumic phases of the cardiac cycle, in identifying CRT responders. In 105 patients, before and 6 months after CRT, the following echo/Doppler parameters were evaluated: myocardial performance index (MPI) and total isovolumic time (t-IVT) as the sum of IVCT and IVRT divided by the RR interval ; standard deviation of the time to systolic peak velocity (Ts-SD) (obtained by TDI) as asynchrony index. At baseline, responders had higher t-IVT and MPI than non responders. Receiving operating characteristic curve analysis showed that both t-IVT and MPI could predict CRT response. Then Echo/Doppler derived indices, describing physiologic abnormalities of the isovolumic contraction and relaxation phase, are able to predict CRT-induced reverse remodeling [Recently, Porciani modeling .et al. [P< 0.001) and was clearly superior to rest LV dyssynchrony in predicting functional improvement at 6 min walking test. Exercise TDI ECHO showed also an overall predictive value for CRT response of 92%. It could therefore be used to improve selection criteria for patients who are candidates for CRT, thus reducing the frequent inappropriate implantation of biventricular pacemakers. Rocchi et al.  have demPW-TDI is a useful complement to standard echo-Doppler examination and a helpful tool in the diagnosis and prognosis of CAD and HF. TDI-MPI is considered a reliable parameter for evaluation of global left ventricular function. PW-TDI has proved useful in the evaluation of the isovolumic indices, which correlate well with left ventricular global contractility. TDI is used to assess global left ventricular mechanical dyssynchrony and to determine the response in left ventricular structure and function after cardiac resynchronization therapy.Part of information included in this article has been previously published in INTERNAL AND EMERGENCY MEDICINE Volume 6, Number 5, 393-402, DOI: 10.1007/ s11739-010-0469-3.