Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function. The identification of viable hibernating myocardium in patients with coronary artery disease and chronic left ventricular (LV) dysfunction is, up to today, the most common use of stress echocardiography in patients with heart failure. However, to search viable myocardium or the presence of contractile reserve is only one of plugs of the physiopathologic puzzle in a failing heart Figure  and 2. ITherefore, the present review will detail some important potential applications of stress echocardiography in patients with heart failure in the evaluation of the different clinical and physiopathologic aspects of heart failure syndrome.The most common cause of heart failure in the Western world is coronary artery disease, accounting for up to 60% of cases . In patiAfter brief episodes of coronary occlusion and reflow a reversible global LV dysfunction can occur. This phenomenon was called myocardial stunning . It is cHibernating myocardium" was first termed by Rahimtoola to indicate the state of reversible dysfunctional myocardium, which was considered to be the result of a state of persistently impaired myocardial function at rest, caused by reduced coronary blood flow, and which could be partially or completely restored to normal either by improving blood flow or reducing oxygen demand [The term "n demand .Echocardiography can detect viable myocardium during infusion of drugs which have ability to elicit an enhanced contractile response by recruiting contractile proteins. At least two drugs have these proprieties: the dobutamine, a synthetic β1 agonist with additional α1- and β2-stimulating properties and the enoximone that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase ,7. RoutiAn initial evaluation of end diastolic wall thickness of akinetic segments with resting echocardiography can be used as an initial screening technique for assessment of viability. Indeed, akinetic regions with an end diastolic wall thickness <6 mm do not contain viable myocardium and do not improve in function after revascularization . HoweverDuring stress echocardiography is possible to observe four response patterns based on regional wall function: normal, ischemic, viable and necrotic. In the normal response, a segment is normokinetic at rest and normal or hyperkinetic during stress. In the ischemic response, a segment worsens its function during stress from normokinesis to dyssynergy. In the necrotic response, a segment akinesia remains akinetic during stress. In the viability response, a segment with resting dysfunction improves during stress. During pharmacologic stress, a viable response at low dose can be followed by ischemic response at high dose (biphasic response). This biphasic response is suggestive of viability and ischemia, with jeopardized myocardium fed by a critically stenosed coronary artery . A restiregional function after revascularization was 84% and 81% respectively [The overall sensitivity and specificity of dobutamine echocardiography for predicting recovery of ectively . In a stectively . On the Sensitivity of dobutamine echocardiography may be affected by several factors such as the severe reduction of myocardial blood flow that can preclude the contractile response, the premature interruption of dobutamine infusion, resting tachycardia that may renders the myocardium ischemic and dobutamine can only augment ischemia . On the global myocardial function after revascularization. At this purpose there is a relation between improvement in left ventricular ejection fraction (LVEF) and the number of segments with contractile reserve, indicating that extent of jeopardized but viable myocardium determine the magnitude of improvement of LV function after revascularization. Usually a level of ≥ 4 viable segments, which corresponds an improvement in wall motion score index >0.25 (about 20% of left ventricle), is advised as a cutoff value to predict improvement of LVEF [The main clinical issue to search the myocardial viability is that patients with evidence of hibernating myocardium who do not undergo revascularization have poor prognosis with high incidence of cardiac events . In cont of LVEF . Thus, p of LVEF   to calculate the regugitant volume and the effective regurgitant orifice area (EROA), the LV volumes to assess the myocardial contractility and the tricuspid regurgitant jet velocity to measure the sPAP that is an useful index of the haemodynamic burden of MR.First, in symptomatic patients with LV dysfunction and a clinical picture suspicious for new or worsening MR, but not evident at resting echo examination, exercise echocardiography can demonstrate a worsening of MR which helps to correlate this scenario with the patient's symptoms  unmask patients at high risk of poor outcome. The cardiac mortality rate of medically treated patients with dynamic MR during exercise is 39% at 20 months which represents excess mortality in patients in functional class II or III . While in the ischemic cardiomyopathy the search of myocardial viability is focused to find the presence of reversible segmental myocardial dysfunction and its possible effect on global systolic LV recovery after revascularization, in DCM the primary end point is to evaluate the presence of residual global contractile reserve. Both dobutamine and exercise testing have been used in the study patients with DCM, but there is a clear predominance for the use of dobutamine test. The doses of dobutamine utilized vary from investigators, but safety in its use in this population has been documented in doses as high as 40 μg/kg per minute. In the interpretation of results both wall motion score index and the LV volume to derive LVEF must be calculated.LV systolic function at the time of diagnosis has been proposed to be the strongest predictor of survival in DCM, but now the presence of contractile reserve recognised by dobutamine echocardiography seems to be the best marker of good prognosis in patients with severe LV dysfunction at rest ,38. PatiStress echocardiography may also help in the identification of patients in the initial phase of cardiomyopathy overt normal resting echocardiographic parameters. Both dobutamine and exercise have to be used to screen for the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents .The prevalence of diastolic heart failure in the community is now to be at least as high as that reported in previous studies of hospitalised patients; almost half of all patients with heart failure have diastolic heart failure . The terResting echocardiography is most useful in the assessment of LV size, LVEF and the use of Doppler-derived indices of diastolic function has impact on the identification of diastolic dysfunction. However, to determine whether an abnormality of diastolic function is the cause of the patient's symptoms, we need to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Therefore, the stress echocardiography, in particular exercise echocardiography could be useful in dyspnoeic patients with apparently normal LV function to unmask the presence of diastolic dysfunction (signs of elevated LV filling pressure) during exercise as cause of symptoms.Patients with diastolic heart failure, as well as those with diastolic dysfunction and little or no congestion, exhibit exercise intolerance for several reasons. First, an elevated LV diastolic and pulmonary venous pressure during exercise causes reduction in lung compliance, which increases work of breathing and evokes the symptom of dyspnoea . Second,All these aspects can be assessed during exercise echocardiography Table . In partStress echocardiography with dobutamine infusion is particularly useful in clinical decision making in patients with aortic stenosis with LV dysfunction and low transvalvular gradients. In this group of patients, an important clinical question rises: is the low gradient a consequence of low cardiac output due to a severe aortic stenosis which has led to LV dysfunction or is the low gradient a consequence of LV dysfunction is unrelated to aortic stenosis and the aortic stenosis is an incidental finding?It is well known that the transvalvular gradients are flow-depentent parameters so that they are influenced by LV function. The aortic valve area can be accurately determined by Doppler echocardiography with continuity equation and that correlate well with Gorlin formula . HoweverTherefore, the assessment of valve area does not solve the diagnostic dilemma in these patients, because we cannot distinguish between severe fixed from flow-dependent (relative) aortic stenosis. Thus, it is important to perform pharmacological manoeuvres to increase cardiac output so that valve area can be calculated at higher flow rate. Dobutamine stress echocardiography until 20 γ/kg/min with concomitant evaluation of cardiac output, aortic valve area and gradients, is a useful and reliable test to distinguish between severe fixed from relative aortic stenosis in presence of low gradient and LV dysfunction. On the basis on test results, it is possible to distinguish 3 groups of patients  Figure : 1. Pati2 rather than an increase of ≥ 0.3 cm2 from baseline alone [When interpreting the results of a dobutamine study in these patients to rule out or confirm definitively the presence of a severe fixed aortic stenosis, it is advisable to use an absolute cut-off value of the aortic valve area at peak of dobutamine >1 cmne alone ,50.Beyond the identification of viable hibernating myocardium, stress echocardiography is particular useful in patients with systolic and diastolic heart failure to assess the different physiopathologic component of heart failure syndrome and can aid to an appropriate clinical decision making.LV: left ventricularMR: mitral regurgitationLVEF: left ventricular ejection fractionDCM: dilated cardiomyopathyTAPSE: Tricuspid annular plane systolic excursionsPAP: Systolic pulmonary artery pressureThe manuscript is not under consideration elsewhere and the data presented have not been previously published. All authors have read and approved the manuscript. No financial support was received for this study. The content of this manuscript is not associated with any financial interest or other relations that could lead to a conflict of interest.Concerning the authorship, the listed authors have contributed as follows to the manuscript:EA and MP: 1) conception, design, analysis and interpretation of data, 2) drafting of the manuscript and 3) final approval of the manuscriptMO and AM: 1) critical revision of the manuscript for important intellectual content, and 3) final approval of the manuscript.


Yet oxygen supplementation remains first line treatment in cardiovascular disease. We hypothesized that hypoxia improves and hyperoxia worsens myocardial performance.Low O2, 79% N2), 2) while inhaling a hypoxic gas mixture , and 3) while inhaling 100% O2. Tissue Doppler recordings were acquired in the apical 4-chamber, 2-chamber, and long-axis views. Strain rate and tissue tracking displacement analyses were carried out in each segment of the 16-segment left ventricular model and in the basal, middle and apical portions of the right ventricle.Seven male volunteers (mean age 38 ± 3 years) were examined with echocardiography at respiratory equilibrium during: 1) normoxia  and decreased with hyperoxia . Hypoxia increased strain rate in four left ventricular segments and global systolic contraction amplitude was increased . Tissue tracking displacement was reduced in the right ventricular segments and tricuspid regurgitation increased with hypoxia . The TEI index and E/E' did not change with hypoxia. Hyperoxia reduced strain rate in 10 left ventricular segments, global systolic contraction amplitude was decreased  while right ventricular function was unchanged. The spectral and tissue Doppler TEI indexes were significantly increased but E/E' did not change with hyperoxia.Hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. Tissue Doppler measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a consistent rational treatment. Low oxygen tension dilates coronary arteries and high oxygen tension is a coronary vasoconstrictor. Yet oxygen supplementation remains first line treatment in cardiovascular disease states such as myocardial infarction and pulmonary oedema.Endothelium-dependent vasodilation is reduced in patients with ischemic heart disease  and suchHyperoxia, a condition in which the total oxygen content of the body is increased above that normally existing at sea level, is associated with impairment of cardiac relaxation and increased left ventricular filling pressures in patients with and without congestive heart failure .Tissue Doppler imaging (TDI) objectively derives measurements of contraction and relaxation velocities directly from the myocardium and thus yields information not previously accessible by echocardiography . We usedSeven healthy men, (age 25–46 (mean 38) years) completed the study. All subjects were normotensive, non-smokers, on no medication, had a normal left ventricular function by 2-D echocardiography, and had no family history of ischemic heart disease. The local ethical committee approved the study.We used a system consisting of a ventilator, a gas analyser with pulse oximeter, and a computer. Computer programs control the experimental procedure and continuously collect data from the ventilator and gas analyser .Echocardiography was performed from the apical acoustic window. Tissue Doppler recordings were acquired as digital loops in the apical 4-chamber, 2-chamber, and long-axis views . To avoi2 97.9 ± 0.1 %), after 5 minutes of respiratory equilibrium during hypoxia (SpO2 77.6 ± 1.2 %), and after 5 minutes of respiratory equilibrium during hyperoxia (SpO2 99.0 ± 0.2 %). Heart rate was continuously recorded on computer by means of the pulse oximeter. Blood pressure was measured once during each of the three respiratory steady state situations by an automatic blood pressure measuring device based on the oscillometric method.TDI was performed when the subjects had rested for 15 minutes breathing room air  were made with a one-way repeated-measures analysis of variance. The Student-Newman-Keuls test was used post hoc to identify pairwise differences. Differences were considered statistically significant when P < 0.05.All data are presented as mean ± SEM. Comparisons of the responses to changes in F2 and FeO2 decreased with hypoxia and increased with 100% oxygen breathing (table 1). FeCO2 and tidal volume were unchanged in all three test situations, reflecting that the subjects were in respiratory steady state. There was a small, but statistically significant decrease in respiratory rate from normoxia to hypoxia, which might reflect that the subjects were more accustomed to the test situation at this stage.FiOThere was a significant increase in heart rate with hypoxia and a decrease with hyperoxia figure . NeitherA significant increase in strain rate was found in 4 segments figure . GSCA inHyperoxia worsened left ventricular function. Strain rate was reduced in 10 segments figure  with preThe main findings of the present study of healthy volunteers are: 1) hypoxia increased strain rate and tissue tracking displacement. 2) Hypoxia increased tricuspid regurgitation and reduced right ventricular tissue tracking displacement. 3) Hyperoxia reduced strain rate and tissue tracking displacement and increased the TEI index. The novelty of our findings, when compared to the literature, is the demonstration that longitudinal myocardial function, and thus the function of the subendocardium, is sensitive to moderate changes in inspired oxygen.Patients with ischemic heart disease and heart failure frequently encounter hypoxia but the consequences of hypoxia on left ventricular function remain a matter of controversy, in part because of differences in methodology and the measured parameters. In early studies using roentgenkymograms  and dye Hemoglobin saturation in healthy persons increase very little from breathing room air to breathing 100% oxygen. Nevertheless, profound cardiovascular effects were found. This is probably because of an anticipated increase in oxygen dissolved into plasma from 0.32% to 2.09% . HyperoxBecause of the finding of no change  or a disIn conclusion, hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. TDI measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a rational treatment that may sometimes be harmful or whether supplemental oxygen consistently results in an overall gain in delivered oxygen.


Since 3D structural data of the LV is now obtainable using standard transesophageal echocardiography (TEE) devices intraoperatively, the present study describes a method to transfer this data into a commercially available FEM analysis system: ABAQUS© Software was used for semi-automatic endocardial border detection, reconstruction, and volume-rendering of the clinical 3D echocardiographic data. A newly developed software program MVCP FemCoGen©, written in Delphi, reformats the TomTec file structures in five patients for use in ABAQUS and allows visualization of regional deformation of the LV.In this prospective study TomTec LV Analysis TEEThis study demonstrates that a fully automated importation of 3D TEE data into FEM modeling is feasible and can be efficiently accomplished in the operating room.For complete intraoperative 3D LV finite element analysis, three input elements are necessary: 1. time-gaited, reality-based structural information, 2. continuous LV pressure and 3. instantaneous tissue elastance. The first of these elements is now available using the methods presented herein. Intraoperative TEE is currently available in most cardiac surgical operating rooms. In some centers, intraoperative 3D echocardiography is used to evaluate geometry and to plan surgical interventions prior to LV remodeling surgery. However, quantitation of LV geometry is limited to rather imprecise measures such as ejection fraction. Thus the cardiac surgeon has no sophisticated, immediate, quantitative analysis of the preoperative 3D LV geometry. Intraoperative quantitative analysis of the dynamic behavior of the LV might provide optimal information upon which to base precise patient-specific planning of the surgical intervention, as well as to assess the adequacy of the completed surgical repair.Because the LV cannot be realistically described by a symmetric mathematical model, the modern approach consists of using a FEM mesh which approximates LV geometry  or wholeInitial attempts at FEM in the heart have been carried out with 3D segmentation and tracking using sophisticated and expensive cardiac MRI , but untFEM modeling of 3D intraoperative echo data provides an excellent tool for incorporating material properties, volumetric data and boundary pressures to more accurately record and then to simulate LV dynamic performance. Accurate simulation will be the foundation of surgical planning. The limitation until now in applying FEM intraoperatively has been the technical complexity of this technique. The purpose of this study is to take the first step towards introducing FEM into the operating room environment. The goal is to facilitate transfer of geometric data from 3D ultrasound data set into FEM.-6 m-3 kg-1 at a respiratory rate sufficient to maintain end-tidal CO2 levels between ~4.4*103 m kg-1 s-1 and ~5.1*103 m kg-1s-1.After obtaining institutional review board approval, LV images from clinical TEE data sets were obtained in five patients via the midesophageal window using a Philips 5500/7500 or and Acuson Sequoia ultrasound system. After induction of general anesthesia and airway protection, the esophagus was intubated using an omniplane TEE probe. 3D TEE data sets of the LV structures including mitral annulus and leaflets, chordae tendinae, papillary muscles and ventricular wall were obtained using the automated Philips/Acuson acquisition protocol at 10° increment. Images were gaited for both beat-to-beat variability and respiratory motion. In order to facilitate acquisition in the shortest possible timeframe, ventilation was modified to provide a tidal volume of 5*10© software module [All images were stripped of patient identifiers. For LV geometry reconstruction, the TomTec LV-Analysis TEEe module  was emple module . It alsoThe first landmark was set in the middle of the mitral valve at the level of its annulus. Care was taken to avoid having the mitral valve cusps cross this landmark. Two additional landmarks were placed in the middle of the aortic valve at the level of its annulus and at the endocardial level of the LV apex. With this landmarking procedure, a time-resolved LV geometric analysis with 18 models per heart cycle was obtained see Fig. .The rendered LV geometry resulting from the TomTec analysis tool was transferred to an ABAQUS input file using software written in Delphi. In this program, the TomTec file structure was reformatted to an ABAQUS system (version 6.3) input file based on standard ABAQUS FEM elements.© cardiac simulator [ABAQUS creates a time series of LV model files and requires continuous intraventricular pressure and tissue elastance parameters to process the model. For this analysis LV pressure was modeled using wave forms obtained from Columbia University's HeartSimimulator . A singlThe time required for each step in this process was recorded for each patient data set.© [th image out of a set of 18 images per heart cycle) are displayed and can be visualized using ABAQUS viewer options. Each mesh element can be analyzed separately. This is shown in Fig. Both, the Philips Sonos 5500/7500 or the Acuson Sequoia ultrasound systems required less than 10 minutes acquistion time per patient. The application of the TomTec LV analysis algorithms with manual placement of the necessary landmarks took approximately 7 minutes per patient. In five patient data sets conversion from TomTec data to the FEM model was carried out in less than a minute for a heart cycle using the conversion tool MVCP FemCoGenThe general intention of this study was to demonstrate the feasibility of transporting individual patient's LV geometry data into a FEM model. Standard laptop computer technology was utilized to accomplish the transfer from common TEE-machines (Philips Sonos 5500/7500 and Acuson Sequoia).© package and ABAQUS FEM system, plus the recently developed MVCP FemCoGen©. Accomplishing this transfer will form the foundation for intraoperative surgical planning and quantitative outcome assessment of valvular and LV reconstructive surgery.The software running on the laptop was the commercially available TomTec LV Analysis TEEThe scope of this study was to produce a prototype in which the feasibility of the method could be assessed. In a fully operational system, we could postulate clinical applications such as enhanced/automated wall motion abnormality detection, assessment of regional relaxation which encompases the entire ventricle, assessment and guidance of ventricular remodeling operations, and serial assessment of recovery of regional wall function post myocardial stunning.FEM meshes have been used for approximately 30 years  in the aThe total time required for acquisition to a completed FEM model was approximately 24 minutes and can be accomplished during the time period when the patient is being prepared for cardiopulmonary bypass . Thus the feasilbility in terms of duration is clearly demonstrated.© Software is under review by the US FDA, but despite of lack of validation TEE is the only practical technology in the cardiac operating room for the forseeable future. Ultrasound tissue Doppler technologies may be developed in the future to allow automation of the registration process.In terms of procedure accuracy, reproducibility and duration, the primary limitation is the dependence of the TomTec software on manual entries of the three registration landmarks. This requirement is iterative. Manual entries must be done for multiple frames within the TEE data sets. Inter- and intraobserver variability is a general problem for ultrasonic imaging. The validation of the TomTec border detection has not been published. TomTec LV Analysis TEEA limitation of the present study is that it is focused on the deployment of the transfer method. The entire process will require extensive validation. The validation strategy will most likely involve comparision with preoperative cardiac MRI as well as comparison with bypass and post bypass tissue geometry in the same patients. Creating models from MRI based data sets analogous to the TomTec LV analysis and transfering these models to ABAQUS might lead to a new validation strategy which is not been possible up to now. The tool for modeling presented here facilitates vector-subtraction analysis for different points within the cardiac cycle. Quantification is therefore immediately available for both global and regional wall motion, shape and volume analysis. The future use of such instantaneous analysis has a number of potential applications for LV function assessment and surgical planning. This technology could enable a comprehensive automated regional wall motion analysis. A significant challenge in the evaluation and management of patients with coronary artery disease is determining the viability of myocardium. A biomechanical FEM of the LV myocardium can be imported to evaluate dynamic mechanical properties of regions of the myocardium. This approach could provide the basis for a new index of regional myocardial viability.For complete intraoperative 3D LV finite element analysis, three input elements are necessary: 1. time-gaited, reality-based structural information, 2. continuous LV pressure and 3. instantaneous tissue elastance. The first of these elements is now available using the methods presented herein. The later two parameters will be required for robust modeling and analysis. Pressure data will be easily available in the cardiac operating room. Strategies for computing elastance are presently under development. With all three parameters, it will be possible to begin to develop the computational strategies which will allow virtual procedures to be performed utilizing 3D display technology and a haptic-feedback robotic "instruments". Whether this new intraoperative information will be useful in assessing the effectiveness of surgical interventions such as LV remodeling remains to be studied.FEM analysis has not been feasible for LV in the intraoperative setting. The major roadblock was the complexity and the practicality of transfer of structural 3D data to a FEM analysis program. This study describes a method to rapidly transfer 3D structural data from the TEE device into a FEM analysis program. Once mesured pressure and calculated elastance are added to the model, near real-time dynamic stress-strain information in the operating room will be achievable.®, NSN did the data acquisition and the medical part. Both authors read and approved the final manuscript.JFV did the technical part implementing the FEM model in ABAQUS


In the present article we review the main published data on the application of Tissue Doppler Imaging (TDI) to stress echocardiography for the detection of myocardial ischemia. TDI has been applied to stress echocardiography in order to overcome the limitations of visual analysis for myocardial ischemia. The introduction of a new technology for clinical routine use should pass through the different phases of scientific assessment from feasibility studies to large multicenter studies, from efficacy to effectiveness studies. Nonetheless the pro-technology bias plays a major role in medicine and expensive and sophisticated techniques are accepted before their real usefulness and incremental value to the available ones is assessed. Apparently, TDI is not exempted by this approach : its applications are not substantiated by strong and sound results. Nonetheless, conventional stress echocardiography for myocardial ischemia detection is heavily criticized on the basis of its subjectivity. Stress echocardiography has a long lasting history and the evidence collected over 20 years positioned it as an established tool for the detection and prognostication of coronary artery disease. The quantitative assessment of myocardial ischemia remains a scientific challenge and a clinical goal but time has not come for these newer ultrasonographic techniques which should be restricted to research laboratories. Pharmacologic stress echocardiography is an established cost-effective technique for the detection of coronary artery disease . The widThe TDI modalities include myocardial velocity imaging, displacement imaging, strain rate imaging and strain imaging. TDI measures velocities by the Doppler shift of reflected ultrasound. Velocities are measured in the conventional imaging planes, from apical views as longitudinal velocities and from parasternal views as radial velocities. When we employ TDI, the velocities within a myocardial segment are the net result of motion caused by contractions in that segment, motion due to tethering to other segments, and overall motion of the heart. This tethering effect is the reason why longitudinal velocities increase progressively from the apex toward the base, when measured in an apical window. Therefore ischemia in the apical region reduces myocardial velocities not only in the apex, but also in the nonischemic basal segments . In pracFeasibility studies have been published demonstrating the applicability of TDI to stress echocardiography -27 but oCain et al  applied The main concerns refer to strict stress echocardiographic issues:1.the lack of a comparison between conventional visual assessment of regional wall motion and TDI analysis. In absolute terms the diagnostic accuracy is not striking: see Table 1  and Fig Voigt et al.  used a mIn a recent  article The quantitative interpretation of stress echocardiography is not superior to expert wall motion assessment. Open issues in the quantitative analysis remain at stake: which technique to be employed among systolic velocities, strain and strain rate, the assessment of normality criteria of myocardial velocities and how to interpret their values, the management of patients with regional and global left ventricular dysfunction, the analysis of the apical segments, the complexity of the analysis in a real clinical environment, the applicability to unselected populations, its unsuitability to exercise, the most widely used stressor in the clinical practice . What isTable 1.TDI vs visual assessment of myocardial ischemia during dobutamine stress echocardiography.Click here for file


By incorporating this concept in left ventricular (LV) models to simulate filling and systolic phases, we have obtained the time-varying expression for Ea and the LV-volume dependent expression for Ep.Description of the heart as a pump has been dominated by models based on elastance and compliance. Here, we are presenting a somewhat new concept of time-varying passive and active elastance. The mathematical basis of time-varying elastance of the ventricle is presented. We have defined elastance in terms of the relationship between ventricular pressure and volume, as: a is expressed as: ; Epis represented as: . Ea is deemed to represent a measure of LV contractility. Hence, Peak dP/dt and ejection fraction (EF) are computed from the monitored data and used as the traditional measures of LV contractility. When our computed peak active elastance  is compared against these traditional indices by linear regression, a high degree of correlation is obtained. As regards Ep, it constitutes a volume-dependent stiffness property of the LV, and is deemed to represent resistance-to-filling.Using the patient's catheterization-ventriculogram data, the values of passive and active elastance are computed. Ea) can be used to characterize the ventricle's contractile state, while passive elastance (Ep) can represent a measure of resistance-to-filling.Passive and active ventricular elastance formulae can be evaluated from a single-beat P-V data by means of a simple-to-apply LV model. The active elastance (E The heart may be conceived as a pump that receives blood from a low-pressure system and raises it to a high-pressure system. Although the mechanism responsible for generation of wall stress (and hence left ventricular (LV) pressure) is contraction of the myocardial fibers, an analytical formulation linking the myocardial and LV dynamics is still lacking. In the absence of this formulation, a popular way of linking LV pressure and volume dynamics is by means of LV compliance (or elastance) ,2. AlthoThe concept of compliance or elastance was first employed for blood vessels , by relaDefares  avoided Classically, ventricular compliance is defined, at any point in time, as the change in ventricular volume concomitant with the change in ventricular pressure, such thatC = dV / dP, E = dP / dV     (1)If C is assumed constant, this equation becomes a linear relation, whose integration givesV = CP + Vc     (2)c is an integration constant. If the compliance varies with time, then all terms in equation (2) may vary with time, as:where VV (t) - Vc (t) = C(t)P(t)     (3)In this context, Suga  opted fod represents the unstressed LV volume corresponding to zero LV-pressure, obtained by drawing a tangent to P-V curves at end-ejection, as illustrated in Figure to represent the elastance of the contracting LV, where Vmax and of the volume-axis intercept (Vd) of the tangent to the P-V curve at end-ejection (as a measure contractility of the cardiac muscle) is not only unreliable  = ρh / 4πR2, for a spherical LV model (in mmHg/(ml/s2));E represents LV elastance (mmHg/ml).LV) is caused by both Ea variation as well as Ep decrease. The instantaneous time-varying ventricular elastance (E) is the sum of (i) volume-dependent passive elastance (Ep) and (ii) active elastance (Ea) due to the activation of the LV sarcomere. Hence,Likewise during ejection, the LV pressure variation (dPE = Ea + Ep     (6)p and Ea, and then their formulations. The passive (unactivated) myocardium exhibits properties of an elastic material, developing an increasing stress as strain increases, as occurs during ventricular filling. The passive stress-strain relation of myocardial muscle strip is nonlinear, and therefore cannot be described by Hooke's law. As an approximation, it follows an exponential relationship  = Vi = dPLV,i     (9)i and PLV,i are the monitored LV volume and pressure at this instant, and Eped is the passive elastance at the end-diastolic phase.where i is a time instant during the isovolumic contraction and relaxation, V and Ep is constant), the governing equation (5) becomes VdE = dPLV, which can be represented as:Also, during isovolumic relaxation  = Vi  = dPLV,i     (10)pes is the passive elastance at the end-systolic phasewhere ENow, applying equations (9 & 10) to the case shown in the Figure 1. For isovolumic contractionEa,1 = 0     (11-a)Ea,2 = (P2 - P1)/V2 + Ea,1 = 0.029477 mmHg/ml     (11-b)Ea,3 = (P3 - P2)/V3 + Ea,2 = 0.103771 mmHg/ml     (11-c)Ea,4 = (P4 - P3)/V4 + Ea,3 = 0.253584 mmHg/ml     (11-d)Ea,5 = (P5 - P4)/V5 + Ea,4 = 0.463599 mmHg/ml     (11-e)2. For isovolumic relaxationEa,18 = (P18 - P17)/V18 + Ea,17 = Ea,17 - 0.058954 mmHg/ml     (11-f)Ea,19 = (P19 - P18)/V19 + Ea,18 = Ea,17 - 0.177824 mmHg/ml     (11-g)Ea,20 = (P20 - P19)/V20 + Ea,19 = Ea,17 - 0.312656 mmHg/ml     (11-h)Ea,21 = (P21 - P20)/V21 + Ea,20 = Ea,17 - 0.463599 mmHg/ml     (11-i)a,17 at end-ejection is unknown. For different representative values of Ea,17, we can get different Ea curves. We need to determine the optimal value of Ea,17, such that Ea can be described by a smooth curve to fit both isovolumic contraction and ejection phases. In Figure a,17 = 1.1 mmHg/ml, and the polynomial expression for Ea(t) to fit its above calculated values during isovolumic contraction and relaxation. However, in order to (i) more suitably represent Ea to correspond with its role during the cardiac phases , and (ii) because of the sigmoidal shape of Ea curve and its variation resembling the LV pressure variation during systole  as:Now in the above expressions 11(f-i), ESo that its constituent parameters have physiological significance as indicated following equation (8).a(s) during isovolumic contraction, when u(t-d) = 0, we employ the expressionHence, to compute Ea0, τC and ZC to fit the monitored pressure-volume data. Then, to compute Ea(s) during isovolumic relaxation, we employ the total expressionand determine its parameters EτR and ZR to fit the measured pressure-volume data.and determine its remaining parameters d, a is depicted in Figure a can be employed as an index of contractility.For the sample data of Figure During the diastolic filling phase, equation (5) becomesp is constant at a particular volume Vi, equation (13) becomesNow because Ei and PLV,i are the monitored LV volume and pressure at this time, and M = ρh / 4πR2. For the patient data . Therefore, from equation (15), we can calculate the values of Ep at various instants during filling phase. We then plot Ep vs V, in Figure p, we obtain the values of the parameters Ep0 and zp, as:where i is a time-instant during diastolic filling, Vzp = 0.0395 ml-1, Ep0 = 4.375 × 10-3 mmHg / ml     (16)p function (corresponding to its expression given by equation 7) as follows:and the EEp = 4.375 × 10-3 eV 0.0395    (17)p as a measure of LV resistance-to-filling.We now propose to adopt Ea and Ep are varying. During ejection and filling phases, Ep can be calculated at any time using equation (17). Likewise, Ea can be calculated during ejection and filling phases using equation (8), once its parameters have been determined by employing equation (12-b & 12-b) during isovolumic contraction and relaxation phases. Their values during the cardiac cycle are listed in Table Hence during ejection, both Eequation 7. LikewiThe analyses, presented herewith, are now applied to clinically obtained data consisting of the subject's left ventricular (instant-to-instant) dimensions (obtained by cineangiocardiograph) and chamber pressure (obtained by cardiac catheterization). For each subject, passive and active elastances are determined from the left ventricular data. Table a vs incremental pressure (P-Ped) for this patient HEL. Note that the elastance is much higher at late-ejection than early ejection. This is because of a continuing sarcomere stress development and shortening. The active elastance reaches its maximum value at late-ejection (point 15), and thereafter decreases. However as shown in Figure The variations of model-derived nonlinear passive and active elastances for the subject HEL are shown in Figure p vs LV volume plots, in Figure p increases exponentially with increase LV volume; the parameters (EP0 and zp) characterize this relationship. The passive elastance curve is steeper for a stiffer myocardium, with a corresponding bigger value of the exponential coefficient Zp (subject ML). The Ea vs incremental pressure (P-Ped) plots, in Figure a during systole, which in turn governs the generation of LV pressure.Figures a variation is by means of the Ea vs normalized time (t/ts) plot, shown in Figure a,max could be regarded as an index of LV contractility. Hence, we decided to plot Ea,max vs the traditional contractility indices of EF and (dP/dt)max. These plots are displayed in Figures a,max has a high degree of correlation with both EF and (dP/dt)max. It is interesting to compare our correlation-coefficient value (0.8972) with the value of 0.89 obtained by Mehmel et al [d)]es.Yet another way to study Eel et al , althougThe active elastance curve can explain some critical LV physiological phenomena, namely LV pressure generation during isovolumic contraction and LV suction during early filling. The rapid decrease in elastance during isovolumic relaxation extends into the filling phase, and can explain the decrease in LV pressure (Vi - Vi-1) + Vi      (18)P term, based on the calculation of its value being of the order of 10-2 compared to (i) (Vi - Vi-1), which is of the order of 100 and (ii) Vi which is the order of 101.by neglecting the i can be less than Pi-1 (or that Pi - Pi-1 < 0) only if  is negative, i.e., active elastance is decreasing. Now for subject H.E.L  are:In equation 18), it is seen that P8, it is Ep,22 = 0.2768 mmHg/ml, Ea,22 = 0.0393 mmHg/ml, Ea,21 = 0.1140 mmHg/ml, V22 = 105 ml, V21 = 90.6 ml     (19)P22 - P21) = -3.22 mmHg, confirming decrease of pressure during early filling.Substituting these values into equation (18) gives .Hence, our novel concept of "decreasing E10 & t9), as follows:Similarly, both the active and passive elastances can explain LV pressure variation during ejection, using equation (18). Let us show how this happens by just taking two instants (V10 - V9) + V10     (20)PP10 - P9 = 1.92 mmHg, which is approximately equal to the actual value of 2 mmHg.Substituting these computed values (listed in Table P / (V - Vd) [max (given by ESPVR) as illustrated on Figure Previous works have described elastance as a derived parameter from LV pressure-volume data, based on the definition of (V - Vd) ,10,12-14p and Ea enable us to explain the phenomena of (i) LV suction during early filing, (ii) LV pressure rise during isovolumic contraction (iii) LV pressure variation during the ejection phase, and (iv) LV pressure drop during the relaxation phase. Both the concepts of Ea and Ep are made possible by our redefining elastance and compliance asOur definitions of EdP = d(EV) = d(V/C) = VdE + EdV     (21)a enables us to explain (i) the generation of pressure during isovolumic contraction and decrease of pressure during isovolumic relaxation, when the volume is constant, and (ii) the decrease of pressure during the rapid filling phase.Our concept of Ea along with increasing Ep during filling, which enables us to explain the LV suction effect during early filling, is indirectly supported by the work of Shoucri [Our concept of decreasing E Shoucri . He has a, as provided by us.However, the determination of this active fiber stress in his paper is empirical and not based on a well-defined concept and expression for Ea and Ep are invoked to explain the variations of pressure during the ejection and filling phases. From the viewpoint of intrinsic indices of LV assessment, Ep can represent LV myocardial stiffness property and resistance to LV filling. On the other hand, Ea has been shown to correspond to LV contractility, by means of Figures a,max and (dP/dt)max as well as EF.Finally, both Ep and Ea) with an arterial lumped-parameter model  in order to simulate and explain the mechanisms of chronic hypertensive states [a itself as a measure of LV adaptation to chronic hypertension induced in the circulation system.In future, we can also couple our LV model  = ρh, ρ is the myocardial density, and u is the radial displacement, dPel and dPLV are the incremental elastic-recoil and left ventricular pressures .where the myocardial element mass, Now since,r1 = r2 = RBy assuming we can write:ρs is the surface density, M = ρsh, and V is the LV volume. Now, referring to Figure A-1,where andRe is the resistance to LV filling , ρf is the blood density and v is the blood velocity at site 2.where LVdP) as:Let us now define incremental elastic recoil pressure , we haveIntroducing the term elastance (= 1/C), we can put downLiang Zhong carried out the elastance studies, participated in data acquisition, performed statistical analysis and drafted the manuscript. Dhanjoo N. Ghista conceived of the study, and participated in its design and coordination and helped to draft the manuscript. Eddie Y-K Ng participated in coordination and helped to draft the manuscript. Soo T Lim participated in its design and coordination. All authors read and approved the final manuscript.


In some cases, it may be necessary to combine distinct finite element meshes into a single system. The present work describes a scheme for coupling a finite element mesh, which may have curvilinear elements, to a voxel based finite element mesh.The method is described with reference to a sample problem that involves combining a heart, which is defined by a curvilinear mesh, with a voxel based torso mesh. The method involves the creation of a temporary (scaffolding) mesh that couples the outer surface of the heart mesh to a voxel based torso mesh. The inner surface of the scaffolding mesh is the outer heart surface, and the outer surface of the scaffolding mesh is defined by the nodes in the torso mesh that are nearest (but outside of) the heart. The finite element stiffness matrix for the scaffolding mesh is then computed. This stiffness matrix includes extraneous nodes that are then removed, leaving a coupling matrix that couples the original outer heart surface nodes to adjacent nodes in the torso voxel mesh. Finally, a complete system matrix is assembled from the pre-existing heart stiffness matrix, the heart/torso coupling matrix, and the torso stiffness matrix.Realistic body surface electrocardiograms were generated. In a test involving a dipole embedded in a spherical shell, relative error of the scheme rapidly converged to slightly over 4%, although convergence thereafter was relatively slow.The described method produces reasonably accurate results and may be best suited for problems where computational speed and convenience have a higher priority than very high levels of accuracy. In some cases, it may be necessary to combine distinct finite element meshes into a single system. For example, the task that motivated this work involved integrating a curvilinear mesh of the AMany types of volume meshing strategies exist. Meshes One approach for coupling a voxel mesh to a mesh with an irregular boundary (e.g. the outer heart surface) involves individual treatment of the voxel elements that intersect the boundary. This scheme, known as the Cartesian cut cell method, has theThe present work describes a technique that is a variant of the hybrid Cartesian/prism scheme, with a novel method for coupling the prism elements to the voxel elements. The scheme is easy to code, computes quickly, requires little or no user supervision, and has all the advantages associated with voxel meshes. The main drawbacks of the scheme are relatively uneven and slow convergence after a certain degree of accuracy has been reached. One additional limitation is that the scheme is most suitable for geometries which are reasonably well characterized by a spherical harmonic expansion.Ve) throughout the heart and the potential outside of the heart (Vo) in the elliptical equation[The present scheme will be described with reference to a particular problem that involves coupling a previously meshed heart to a tor equationDi + De)∇Ve = -∇•(Di)∇Vt; within heart muscle∇•(σo)Vo = 0; in the torso and blood pools     (1)∇•, the normal component of the extracellular current is continuous with the normal component of the current through the torso/blood pools , and there is no flow of intracellular current into the torso/blood pools (nT DiVi = 0).where Figure p = . It will be assumed that the voxels are isotropic (side length = s) and chosen to be defined with respect to some convenient origin. The preliminary voxel mesh should extend for a distance of at least 1s in the x, y and z directions beyond any point on the outer heart surface. The voxel size s is preferably the desired voxel size for the entire torso mesh.Given the heart surface, a preliminary voxel mesh is generated that is slightly larger than the heart. In the two dimensional example illustrated in Figure b ⊆ Xp that are outside of the heart but closest to it, as illustrated in Figures b, which are defined as those voxels that have at least one node within the heart and at least one node outside of the heart. The boundary nodes Xb ⊆ Xp are defined as all of the nodes within these voxels Vb that are outside of the heart.The next step involves locating boundary nodes XThere are a number of methods for locating the boundary voxels. One convenient method, which was used in the present example, is applicable to any surface (e.g. the heart surface) that may be characterized by spherical harmonics. In thish is approximated by Rh = F, where Rh is the radius of the approximate outer heart surface, F is a spherical harmonic polynomial as will be further described below, and θ and Φ are azimuthal and polar angles, respectively. Figure h. Rh, θ, and Φ are defined with respect to a convenient origin which is at the point . This origin is preferably chosen such that it results in a good spherical harmonic expansion. The grid points Xp are translated so their origin is , which results in a set of translated node points X'p = . The azimuthal and polar angles θp and Φp  origin) are computed for X'p, and then the value F is computed, which is the radius of the outer heart surface at the angles θp and Φp. If this radius is greater than the radius h ⊆ Xp.More particularly, the outer heart surface Sh ⊆ Xp within the heart. The boundary voxels Vb are then defined as those voxels that have at least one node within the heart (Xh) and at least one node outside of the heart. The boundary points Xb are those nodes that are within the boundary voxels but outside of the heart.The above procedure locates the nodes Xb) is generated by fitting a spherical harmonic expansion to the points Xb about the origin . The radii (Rb) and azimuthal and polar angles θb and Φb are computed for the boundary points, as indicated in Figure b may be expressed asA surface , P and C are matrix and vector representations of the Legendre function values and coefficients, respectively, and Rb is a vector representation of the radii Rb. A least squares fit (C = P\Rb in Matlab notation) results in a set of coefficients Cbs that define the boundary surface Sb characterized by Rbs = F, where F is the spherical harmonic expansion of order N with coefficients Cbs, and Rbs is the radius of a point on the surface Sb at a given pair of azimuthal and polar angles .where N is the number of terms in the spherical harmonic expansion, PThe appropriate value of N will depend on the geometry of the problem and may be determined empirically. For the heart shown in Figure h to the boundary nodes Xb. The scaffolding mesh, which is indicated by the purple region in Figure h to the boundary surface Sb. With reference to Figure h, shown as black filled circles) and the boundary nodes . The scaffolding mesh is only an estimate of this electrical coupling because the mesh does not include the actual Xb nodes, but approximations (dotted red circles) of the locations of the boundary nodes (Xb).The next step involves forming a scaffolding mesh that couples the original heart nodes Xh and one on the boundary surface Sb, whose corresponding vertices are joined to one another. The triangles, in turn, are formed from combinations of the original heart nodes Xh and boundary nodes Xb, and projections of these nodes.In three dimensions, the scaffolding mesh comprises prismatic elements. Each prismatic element consists of two similar triangles, one on the heart surface Sh are projected onto the surface Sb by a line that passes through the heart nodes and the heart origin , as illustrated in Figure b are projected onto both the surface Sb and the surface Sh by a line that passes through these nodes and the heart origin . The projection of the boundary nodes on to Sb will be referred to as Xb'. From an implementation standpoint, the projections may be accomplished by calculating the  pair for any point  origin), and then computing the radius R = F for either the heart surface Sh or boundary surface Sb from its corresponding spherical harmonic expansion F.More particularly, the heart nodes Xh and the other on Sb, such that each point at a given  on a surface has a corresponding point on the other surface at the same . Thus, a triangular tessellation of one surface may be used to generate an identical triangular tessellation of the other surface.The result of the mutual projections is two sets of points, one on Sh. These nodes formed a regular grid in the  coordinates by choice; it is easy to form a such a regular grid when the surface at issue (Sb) is characterized by spherical harmonics. Because of the cyclicity of the azimuthal angle θ, the original  grid (-π<=θ<=π) points were augmented such that those points  with θa<=-4π/5 were identified, and new points with  added to the grid. This "wrapped around" grid was triangulated, and the triangles characterized by all three points having θ>2*π were removed. This type of tessellation is generally acceptable only in cases when there are points at both poles (Φ = +/-pi) and there is a reasonably smooth gradation in the Φ values of the points. This condition was satisfied in the present case because the original heart points Xh were generated via a spherical harmonic expansion with an even division in the Φ direction.There are many ways to tessellate a surface. The approach that was adopted took advantage of the regularity of the  coordinates of the heart nodes Xb (red) triangulated in the manner described above. The boundary surface  has shape very similar to that of the heart surface and the triangulation is identical to that shown for the heart surface.The left panel in Figure Because each triangle on the heart surface has a corresponding triangle on the boundary surface, connecting the corresponding triangle nodes by radial line segments defines a prismatic element. All of the prismatic elements define the scaffolding mesh.Ak) for the prismatic element (scaffolding) mesh describes the electrical coupling between the heart surface and the boundary surface. However, this matrix contains extraneous elements, i.e. the projected heart nodes on the boundary surface (Xhp), and the projected boundary nodes on the heart surface (Xbp). These extraneous nodes must be removed, resulting in a transfer matrix between the heart nodes and the boundary nodes.The finite element stiffness matrix (h) shown as filled black circles and the boundary nodes (Xb) shown as filled red circles. The positions of the boundary nodes (Xb) are approximated by the dotted red circles (Xb'), so in actuality the final desired stiffness matrix will reflect the coupling between the filled black circles and the dotted red circles. However, the scaffolding matrix also contains electrical coupling between the desired nodes (filled black and dotted red circles) and extraneous nodes , which are the projected heart nodes on the boundary surface (Xhp), and the projected boundary nodes on the heart surface (Xbp). These extraneous nodes must not exist in the desired final system matrix.The concept of extraneous nodes will be further described with reference to Figure Ak) for the prismatic element mesh, the local stiffness matrix for each prism element is constructed. This may be done in a number of ways. For a Galerkin type FEM, a closed form local matrix based on the prismatic geometry may be used. Alternatively, each prism may be decomposed into tetrahedrons, and the stiffness matrix, based on linear basis functions, may be computed for each tetrahedron.First, to assemble the finite element stiffness matrix  to be removed, and the subscript b' denotes the projected boundary nodes Xb'. The desired coupling matrix (Ac) between Xh and Xb' is found by solving for the extraneous nodes in the set of equations Ak = 0:where the subscript h denotes the heart surface nodes XwhereAk = 0 is somewhat of an oversimplification of the process of eliminating extraneous nodes. More precisely, the right hand side corresponding to each extraneous node is set to 0. To take a simple example, assume it is desired to eliminate a variable x2. If the row in the matrix Ak corresponding to x2 is equal to -3x1 + 4x2 - 2x3, then setting this row equal to 0 and solving for x2 yields x2 = 1/4(3x1 + 2x3). 1/4(3x1 + 2x3) is then substituted for x2 wherever it appears in any other equation, effectively eliminating x2 from the system of equations.The set of equations Ao), the FEM heart to torso coupling matrix Ac, and the FEM torso matrix At.The total system matrix comprises a combination of the preexisting FEM heart matrix  for the entire system is:The FEM matrix  that connect interior heart nodes to other interior heart nodes (Ac and At have been partitioned into portions: (i) that connect "internal nodes" (i.e. nodes that are not a part of any other matrix) to other "internal nodes"; (ii) that connect "internal nodes" to "overlapping nodes" (i.e. nodes that appear in two matrices); and (iii) that that connect "overlapping nodes" to "overlapping nodes."where the subscript g denotes the set of torso mesh nodes excluding the boundary nodes, and the subscript i denotes the set of original heart nodes excluding the outer surface heart nodes XAo. Similarly, Ac. The matrix entry in As for the coupling of the outer heart nodes to themselves is thus the combined entry For example, AsVe = Ao, rhsVt, where Ve and Vt are the vectors corresponding to the continuous variables in equation (1), and Ao, rhs is the original, pre-computed stiffness matrix corresponding to the right hand side of equation (1). Ao, rhs and Vt must be appropriately augmented with 0's to match the size of AsVe. The boundary conditions at the heart/torso boundary, that Ve is continuous and the normal component of the current is continuous[As.The discretized version of equation (1) is ontinuous, are necThe above described scheme was tested as follows. A spherical shell, analogous to the outer heart surface, was coupled to a surrounding spherical "torso". The potentials on the inner spherical shell were set equal to those which would have occurred had there been an ideal current dipole, normalized to unit strength, located at the sphere's origin and oriented along the z axis. Given this potential distribution, the potentials throughout the spherical "torso" were computed and compared with the analytic solution:where Φ is the polar angle (as before), R is the radius of the outer spherical torso surface, and r is the radius to an observation point. For the test problem, R was set at 50. The radius of the spherical shell/heart surface was set at 40, roughly the same size as the heart shown in Figure At was computed. Next, a coupling matrix Ac to link the torso to the nodes on the spherical shell/heart surface was created. The system of equations As *Vc = 0 was constructed, where As is the total system FEM matrix and Vc is the solution. The spherical shell/heart surface nodes were set equal to their corresponding potential V, resulting in an augmented system A'*V' = b, where V(i)' = 1 where i represents the spherical shell/heart surface nodes. This system was solved using the biconjugate gradient stable method, after preconditioning by scaling each row in the matrix so that its diagonal element was equal to 1.A voxel mesh, akin to the torso mesh shown in Figure Relative error was defined as:c is the computed solution  and Va is the analytical solution. Both the number of nodes on the spherical shell/heart surface and the number of nodes in the "torso" were varied.where VVt. Maximum Vt was 100 mV, with the resting potential set at 0 mV. Initial left ventricular and right ventricular activation sites were chosen roughly in accord with Selvester et al.[The heart in Figure er et al. but wereA propagation sequence was generated by a simple eikonal like scheme, according to which propagation velocity (v) was assumed to be proportional to the square root of bulk cardiac tissue conductivity. The eikRepolarization was initiated from the right ventricular breakthrough area and alloWithin the heart muscle: (i) intracellular conductivity along and transverse to fiber direction was set equal to 1 and 1/6, respectively; (ii). extracellular conductivity along and transverse to fiber direction was set equal to 1 and 1/3, respectively. Ventricular blood and torso conductivity were set at 5 and 2.5, respectively.The heart mesh had approximately 270000 nodes and the torso mesh had approximately 120000 nodes. The system of equations was solved with Matlab's preconditioned conjugate gradient routine. The preconditioner was an incomplete Cholesky (0 fill in) factorization of the system matrix.For the sphere test, Figure Figure The top panel in Figure This work describes a convenient scheme for coupling a pre-existing, possibly curvilinear, finite element mesh to a voxel mesh. The scheme is easy to code and generates a complete system matrix  fairly quickly, on the order of 10's of seconds for the heart/torso coupling example problem on a 2.80 GHz Xeon processor running Microsoft Windows XP with 3 GB of DRAM. The relatively good speed is helpful in cases, such as in the example problem, where some experimentation is required to fix the orientation of the preexisting and voxel meshes.In this problem, the only user supervision involved orienting the heart within the torso. The rest of the process, namely the generation of coupling and torso matrices and assembly of the final matrix, was automatic.The disadvantages of the scheme are that it appears to converge relatively slowly after a given degree of accuracy has been reached. It also may converge non-monotonically if only the number of nodes in the voxel mesh is increased. Given the weight of advantages and disadvantages, the scheme may be most useful for prototyping, where high accuracy is not required at the outset and experimentation is required to align the preexisting and voxel meshes.b can not perfectly fit the boundary nodes because this surface can not follow the sharp corners between some of the adjacent boundary nodes. Indeed, for this reason, the error of the fit between Sb and the boundary nodes decreases slowly as the number of torso nodes is increased, which mirrors the overall slow convergence of the scheme.One possible reason for the slow convergence is that the boundary surface SThere are a few possibilities for improving the scheme. First, instead of trying to fit the boundary surface to all of the boundary nodes Figure , the corAnother possible improvement would be to generate the coupling matrix with a very high spatial resolution mesh, and then couple this to a lower spatial resolution voxel mesh by removing extraneous nodes from the higher resolution mesh in the same manner that extraneous nodes were removed from the scaffolding matrix in the scheme described above. The coupling between higher and lower resolution meshes would be easy because both are voxel based meshes, so that it is easy to generate a low resolution mesh whose nodes are all within the set of the high resolution mesh nodes. For example, the high resolution mesh could be generated by creating nodes at the midpoints of the low resolution mesh, as shown in Figure Yet another alternative would be to couple the outer heart surface and the boundary surface with the boundary element method, which would avoid the requirement of eliminating extraneous nodes.The present scheme may be applied to problems in bioengineering other than the heart/torso coupling problem. Further, the present scheme could be used in areas outside of bioengineering. However, extensions of the scheme to problems in which the preexisting mesh (e.g. the heart mesh) is not reasonably smooth may prove difficult because prismatic elements in the scaffolding matrix could be very irregularly shaped. Similarly, irregular node spacing on the preexisting mesh might also cause problems. If there are too few nodes on the outer surface of the preexisting mesh, then the scaffolding mesh might not have sufficient resolution for an accurate solution. If the physics of a problem require a very accurate representation of the geometry in the area of the boundary between the scaffolding mesh and voxel mesh, the present scheme will likely not prove suitable.In summary, a scheme has been advanced that may be useful in situations where rapid computational speed and ease of use is a higher priority than great accuracy. Further, it may be possible to improve the convergence of the present scheme.Ac – the desired coupling matrix between Xh and Xb'Ak – the FEM scaffolding mesh matrixAo – the preexisting FEM heart matrixAs – the total system matrix, assembled from Ao, Ac, and AtAt – the FEM torso matrixBoundary nodes – the nodes within the preliminary voxel mesh that are closest to, but outside of, the outer heart surfaceBoundary surface – a surface that is fitted to the boundary nodesOuter heart surface – the outer surface of the preexisting heart meshPreliminary voxel mesh – a voxel mesh that is slightly larger than the heart mesh, which is embedded within the preliminary voxel meshScaffolding mesh – a mesh that is constructed that fills in the volume between the outer heart surface and the boundary surfaceh – outer heart surfaceSb – boundary surfaceSp – nodes in the preliminary voxel meshXb – boundary nodesXh – radius of spherical harmonic surface that approximates ShRp – Xp points translated to the origin of the heart coordinate systemX'h – the subset of Xp that lies within the heartXb' – nodes derived by projecting boundary nodes on to SbXhp – the heart nodes as projected on the boundary surface; part of scaffolding mesh nodesXbp – the boundary nodes as projected on the heart surface; part of scaffolding mesh nodesX


Although echocardiography is a useful and cost-effective technique for the detection of morphological and functional cardiac abnormalities, it has a main limitation in its subjectivity. Therefore the aim of the present study was to assess the intra-observer reproducibility and validity of 2-dimensional guided M-mode echo measurements at a Nigerian metropolitan HospitalStandard echocardiographic examination was performed on twenty randomly selected patients (11 men and 9 women) aged 59.8 ± 12.6 years in two different sessions seven days apart.A good degree of intraobserver agreement was observed between test 1 and test 2. The correlation coefficient between the first and second studies ranged between 0.60 and 0.96; measurement errors between 0.050 and 0.205.We would conclude that 2-dimensional guided M-mode measurements at echocardiography performed at our centre are reproducible with low intra-observer variability. Echocardiography came into use in Nigeria in the mid 70's, however, in very few centres mostly concentrated in urban areas. Accessibility to echocardiography in Nigeria is still very low due to the high costs of the technique and to the lack of highly specialized personnel performing it. In fact, the country has less than fifty cardiologists serving a population of over 120 million inhabitants. Training in echocardiography is part of the postgraduate residency training requirements in cardiology in Nigeria.The country, like most developing nations does not have an accreditation process as those designed in Europe and the United States. Separate proficiency examinations in echocardiography such as the British Society of echocardiography examination or similar examination recently introduced by the European Society of Echocardiography are not available. Nevertheless, some of the cardiologists had part or all of their clinical training in advanced countries.Echocardiography is a highly subjective technique that requires a standardized approach due to its proven clinical usefulness.Therefore, the aim of our study was to assess the intra-observer variability in M-mode echocardiographic measurements in an urban hospital and to provide a picture of the main indications to an echo exam in Nigeria. This type of survey was never addressed before. We therefore, assessed the intraobserver variability in echocardiographic measurement in our centre.The study was carried out at the Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria between September and November 2005. The centre is a relatively young tertiary institution, established in 1993 by the Federal Government of Nigeria to cater for the health need of the people of Ogun State in South-western Nigeria. The state has a population of about 3.2 million and a land area of about 16,409.26 square kilometres.Echocardiography is performed at our centre on a weekly basis except in emergency situations. An average of ten echocardiograms is performed per week.During the period of the study, a total of one hundred and four subjects had echocardiogram. The main indications for echocardiography were hypertensive heart disease, congestive cardiac failure, heart murmur and pre-operative evaluation of cardiac function. Twenty-three of the subjects were randomly selected for the study. (with the use of computer generated random numbers) Two of the subjects had poor 'echo' window and one had regional wall motion abnormality due to left bundle branch block and were therefore excluded. All the other twenty subjects had symmetrically contracting left ventricles.Informed consent was obtained from the subjects and ethical approval was obtained from our institution's ethical review committee.Baseline clinical and demographic characteristics were obtained from the subjects. These included date of birth, age, gender and indication for echocardiogram.Blood pressure measurements were obtained according to standard guidelines  with a m2(m2). Body surface area (BSA) was calculated using the formula of Dubois [Body mass index (BMI) was calculated using the formula: BMI = Weight (kg)/HeightTwo-dimensional guided M-mode echocardiography with the use of commercially available echo-machine  and a 3.5 MHz linear array transducer was performed on each subject in the partial decubitus position. All measurements were made according to the American Society of Echocardiography (ASE) leading edge to leading edge convention [LV mass was calculated from the ASE measurements using the cubed formula :3 - (LVIDd)3]} + 0.6LV mass (g) = 0.8 × {1.04 × [(IVSTd + LVIDd + PWTd)All the measurements were taken at baseline and one week after. Measurements were taken online and in three cardiac cycles and average of the three values calculated. Off-line measurements were not possible because of the lack of the software in our centre. Image storage was with the use of videotapes. One experienced cardiologist performed all the echocardiography.Data management and analysis were performed with SPSS software version 11.0. . Continuous variables were expressed as mean ± SD (standard deviation) and categorical variables expressed as percentages. The paired student t-tests was used to compare the means of baseline and repeated measures. Differences between the repeated measures (measurement 1 minus measurement 2) were plotted against the mean of repeated measures (measurement 1 plus measurement 2 divided by 2) according to the method of Bland and AltmanA 2-tailed p value <0.05 was considered to be significant.Table1 shows the baseline clinical and demographic characteristics of the subjects. The study subjects were made up of eleven men and nine women constituting 55% and 45% respectively. The mean age was 59.8± 12.6 years (range 39–76 years).2 while mean body surface area was 1.77 ± 0.25 m2. Mean systolic blood pressure, diastolic blood pressure and pulse rate were 139.4 ± 26.6 mmHg, 84.7 ±16.5 mmHg and 85.6 ± 12.9 beats/min respectively.The mean body mass index was 28.2 ± 6.9 kg/mThe indications for echocardiography were hypertensive heart disease (sixteen subjects), rheumatic heart disease (two subjects) and dilated cardiomyopathy (two subjects).Echocardiographic diagnosis made were hypertensive heart disease (left ventricular hypertrophy and/or diastolic dysfunction) in ten of the sixteen hypertensives, and normal study in the remaining six subjects. Mixed mitral valve disease  was diagnosed in the two female subjects with rheumatic heart disease.The dilated cardiomyopathy cases were pregnancy related  which is a common disorder in Nigeria especially in northern Nigeria, which is reported to have the highest incidence in the world.Scatter plots of LV measurements were performed for measurements 1 and 2 (plots not shown) Bland – Altman plots were also performed to determine the 95% confidence limits of agreement between the two measurements. Two of such plots are shown in figures The plots provided visual information on the degree of disagreement, as well as the relationship of the differences and size of the measurements. Most of the plots were near the zero- difference line and showed uniform distribution pattern.Table Table Large standard deviations of the difference were found for end diastolic LV diameter, right ventricular outflow tract diameter, aortic root diameter, aortic valve opening and LVM.Echocardiography is becoming a common practice in Nigeria especially in the major cities. Conventional echocardiographs are commoner. Portable echo-machine is probably available in only one centre. Transoesophageal echocardiography is yet to be introduced into the country. Measurements are obtained on-line in all the centres due to the high cost of off-line software and machines. Recording is mainly by videotapes.The common indications for echocardiography in Nigeria are hypertensive heart disease, cardiomyopathies, and valvular heart disease.In a report by Balogun et al, hyperteThe potential of echocardiography as a research tool in Nigeria cannot be overemphasized. Studies emanating from the country have focused on the common cardiovascular diseases in the country such as hypertensive heart disease -15, hearThis quality assessment study addressed the intraobserver variation of 2-dimensional guided M-mode echocardiographic measurements in our centre. The study demonstrated that echocardiographic measurements by a single cardiologist is consistent and has acceptable intraobserver variation. Interobserver variation was not evaluated in this study because only one cardiologist performs the procedure in our hospital.Results from other studies on intraobserver variations of echocardiographic measurements vary in study design and method of analyses.Schieken et al  studied In the study by Ladipo et al , intraobThe main limitation of echocardiography is its subjectivity in the face of a proven clinical usefulness. Training and accreditation procedures are key factors to obtain a reliable and standard examination. The results of our study demonstrate that when the same person with an appropriate training performs echocardiography, the intra-observer variability is low. This assessment is important in order to have an internal control for our laboratory since this technology might represent the only possible procedure for any given clinical condition. Our data are consistent with previous reports.Workers have highlighted the sources of variation in echocardiographic measurements-32. ThesInterobserver variability was not analyzed in the present study since echocardiography is performed at our center by only one cardiologist. In Nigeria as previously stated, the number of cardiologists is very small. Nonetheless this analysis and results were aimed at providing an objective assessment of the quality of our laboratory. Furthermore, Doppler measurements were not evaluated. We also did not obtain measurement using the 2D technique, which has been shown to have better reliability than the M-mode techniqueWe would conclude that quantitative 2-dimensional guided M-mode echocardiography performed in our centre is reproducible and has good validity. It therefore provides a valuable tool for cardiac structure and function studies.The authors declare that they have no competing interests.OSO conceived of the study, carried out the echocardiograms, analysed the data and drafted the manuscript.AAT, OAS and JJT participated in the recruitment of subjects and in data management. All authors read and approved the final manuscript


Real-time myocardial contrast echocardiography (MCE) is a novel method for assessing myocardial perfusion. The aim of this study was to evaluate the feasibility of a very low-power real-time MCE for quantification of regional resting myocardial blood flow (MBF) velocity in normal human myocardium.®. Following transient microbubble destruction, the contrast replenishment rate (β), reflecting MBF velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function; y (t) =A (1-e-β(t-t0)) + C.Twenty study subjects with normal left ventricular (LV) wall motion and normal coronary arteries, underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during constant IV. infusion of SonoVue were 0.21–0.69 s-1, with higher values in medial than lateral, and in basal compared to apical regions of scan plane (p = 0.03 and p < 0.01). Higher β-values were obtained from end-diastole than end-systole (p < 0.001), values from all-frames analysis lying between.Quantification was feasible in 82%, 49% and 63% of four-chamber, two-chamber and apical long-axis view segments, respectively. The LAD (left anterior descending artery) and RCA (right coronary artery) territories could potentially be evaluated in most, but contrast detection in the LCx (left circumflex artery) bed was poor. Depending on localisation and which frames to be analysed, mean values of Low-power real-time MCE did have the potential to give contrast enhancement for quantification of resting regional MBF velocity. However, the technique is difficult and subjected to several limitations. Significant variability in β suggests that this parameter is best suited for with-in patient changes, comparing values of stress studies to baseline. MCE is an emerging technique for non-invasive evaluation of myocardial perfusion and coronary heart disease (CAD) -11. ReceThe majority of MCE studies have reported data relying on visual assessment somewhat limited by its subjective approach . Wei andThe quantification of replenishment rates is often limited to selected myocardial regions due to imaging problems ,22. To oTwenty study subjects were enrolled; ten healthy male volunteers (age 24 ± 3) and ten patients (age 55 ± 5), five of them female. The study subjects were not screened for echocardiographic image quality, the only inclusion criteria being an age above 18 and confirmed normal left ventricular regional and global systolic function by conventional echocardiography. The ten patients had undergone coronary angiography due to chest pain, with the findings of open and normal coronary arteries and normal left ventricular end-diastolic pressures. The healthy volunteers were assumed to have normal coronary anatomy and myocardial perfusion, due to the abscence of CAD risk factors and symptoms, and normal findings on standard echocardiography. All the subjects were in sinus rhythm. Exclusion criteria were pregnancy or lactation, known allergy to the contrast agent, significant valve diseases or shunts, severe pulmonary hypertension, and severe extra-cardiac disease. All the subjects gave their written informed consent to the participation. The study conformed to the declaration of Helsinki, and the Regional Commitee of Medical Ethics approved the protocol.®  was used, consisting of microspheres of sulphur hexafluoride gas (SF6) stabilised by a phospholipid monolayer in an aqueous solution. SonoVue® was infused continuously by a manually rotated volume pump through a 20G vial in a proximal forearm vein. There were slight individual changes of the infusion rate (70–100 ml/ hour) to optimize the myocardial opacification and minimize the far-field attenuation. Once steady state was reached and the recording started, the infusion rate was held constant in every individual study.The ultrasound contrast agent SonoVueImaging was performed with Vivid 7™  with a M3S matrix array transducer. The contrast-specific application, Coded Harmonic Angio™, is a very low power, real-time technique based on pulse inversion combined with power Doppler, operating at a frame rate of 20 Hz. With this choice of application and contrast agent, the optimal agent-tissue-ratio was achieved with a mechanical index (MI) as low as 0.04–0.05. The signal amplitudes were color-coded by the Angio mode and displayed as overlays on fundamental tissue grey-scale images. The focus was set basally, close to the mitral valve plane. The depth was set to let the left ventricle fill the image sector, and color gain was adjusted to reduce the signal-to-noise ratio to the point that hardly any noise was observed within tissue and cavity. The time gain compensation was adjusted to obtain homogenous SI and to reduce the noise from the myocardium, the epi-/ pericardium and the mitral valves. After the initial adjustments all settings were held constant in every individual study.Baseline imaging was acquired in tissue harmonic mode for confirmation of normal anatomy and wall motion. MCE was performed in the apical four-chamber, two-chamber and long-axis views. Standard views were at times slightly modified, i.e. by centralising the lateral or anterior walls in the scan sector, to optimize the contrast detection and avoid attenuation and shadowing. When the myocardial contrast opacification reached a steady state, a 'flash' of 15 frames of high MI (1.0), timed to cover at least the entire systole, was applied for transient microbubble destruction. This was followed by immediate, automatic return to low MI continuous imaging of microbubble replenishment in end-expiration . Measurement of mean signal intensity (dB) was done in manually placed, equally sized and shaped regions of interest (ROI) in the 16 standard myocardial segments , plus th-β(t-t0)) + Cy (t) =A  and end-diastolic (close to peak R-wave) frames.The myocardial SI was plotted against time (t) and fitted to the exponential function: ty level . The intThe myocardial segments were assigned to the coronary artery perfusion territories Figure , and theContinuous variables are presented as mean ± 1SD. Comparison between groups was performed with linear regression analysis (ANOVA), a posthoc analysis was done using Bonferroni's correction. Differences were considered statistically significant at p less than 0.05 (two-sided) with a power of 0.80.Some visible myocardial contrast enhancement was obtained in all views of all the study subjects. Precontrast myocardial tissue SI was negligible, but in spite of careful adjustment of the time-gain compensation we noticed relatively strong precontrast signals from the mitral valve and basal epi-and pericardium. On average 6 minutes of infusion time was spent to aquire repeated replenishment cineloops in the apical views. Myocardial contrast first appeared around one minute after the infusion was started, and steady-state SI was reached after a mean period of 2.5 minutes. After the 'flash' an almost complete disappearance of myocardial color signals was observed, leaving the myocardium dark. Real-time visual grading of myocardial SI during post-destruction wash-in was difficult due to cardiac contraction, translation and cyclic changes of myocardial SI, both between systole and diastole and from beat to beat. By reviewing selected end-systolic frames, refilling was first observed in the mid-septum progressing to full opacification in 3 to 5 heartbeats. However, when observed in end-diastole the refilling clearly appeared faster, yet variable. Selected end-systolic images of destruction-refill sequences of the apical LV views are presented in Figure All 360 myocardial segments were evaluated regardless of baseline image quality. Since the LV wall motion was normal, any contrast defect was considered to be due to attenuation or inadequate detection, and the current segment was thus excluded from the quantitative analysis. Following this, the myocardial opacification was regarded as sufficient for quantification in 98 of 120 (82%) of the four-chamber view segments , and at greater depths . The A parameter similarly was found to be higher in medial (9.89 ± 2.7 dB) than lateral regions , while it was significantly lower in basal than apical segments .Beta-values were derived by curve fitting in the 233 feasible segments . The β-values from all-frames analysis were lying between (0.43 ± 0.17 s-1), significantly different from both end-systolic and end-diastolic values . Approximately the same level of differences was found between cardiac phases for A-values.By using the software's capability to perform an off-line ECG triggering, we did separate analysis from end-systolic and end-diastolic images Figure . Signifi-1, respectively) nor between healthy volunteers and patients (0.36 ± 0.14 vs. 0.35 ± 0.13 s-1).There were no significant differences in mean end-systolic β between four-chamber, two-chamber and long-axis views , resulting in a thinner scan plane with myocardial contrast destruction, and thereby faster replenishment of contrast from adjacent areas not affected by destruction.The contrast refilling measurements were also influenced by the selection of frames from the cardiac cycle. We assessed significantly higher β-values from end-diastolic compared to end-systolic measurements. Corresponding values from all-frames analysis were lying in-between. Even the first diastolic frames after the 'flash' displayed some contrast signals, while the earliest systolic frame did not. This might be due to early bubble refilling through larger intramyocardial arterioles that are patent in diastole, but collapsed during systolic contraction ,28. By aThese findings are in accordance with results from experimental studies ,16. LeonInsufficient contrast detection with too low agent-to-tissue signal ratio still remains a basic problem in quantifying the perfusion by pulse inversion Doppler. One disadvantage of the low-power real-time mode compared to destructive intermittent imaging, is the weaker backscatter from the non-destructive microbubble behaviour. A larger amount of contrast agent is required, which must be balanced against the degree of far field attenuation. Furthemore, some tissue harmonics are always present, and the movement artefacts will probably not be completely removed by the addition of power Doppler.Relatively low temporal resolution was another anticipated problem. However, in our experience the applied frame rate of 20 Hz gave sufficient image quality to allow anatomical orientation and wall motion assessment.An advantage of real-time MCE is the very short data aquisition time. Information that would require approximately a minute with intermittent imaging was recorded during seconds, making it possible to obtain all refill frames during one breathhold. The mean contrast infusion time of 6 minutes allowed us to aquire several replenishment loops from each scan view in every subject. But despite short data acquisition time, the procedure is still demanding. Given a beam elevation of only 3–4 mm at focus, it is mandatory to maintain a stable probe position during the entire destruction-replenishment period. Of the same reson, it is important to put an effort in avoiding off-axis views, particularly whenever tilting the scanplane to centralize a wall for improving contrast detection. Out-of plane imaging would possibly contribute to increased variability of the segmental quantitative parameters. Furtermore, the patients must be cooperative and able to hold their breath for up to ten seconds, preferably in end-expiration, to avoid lung interference and cardiac translation. Even some of our young, healthy study subjects experienced difficulties in this regard.The sample size of this study was small, and the patients were selected from baseline image quality. The coronary anatomy was not known in all study subjects, and we did not use other methods to ensure normal perfusion in our patients. However, due to the selection criteria it is highly unlikely that subclinical CAD could explain our results.The main limitation of this study is that we did not apply any manipulations to change blood flow, i.e. adding of vasodilator to obtain maximal hyperaemia. Regional resting perfusion is normally variable, both between segments and study subjects, and this variability is further reinforced by imaging and technical problems with the applied destruction-replenishment approach. In the presence of a non-critical coronary stenosis, normal resting blood flow is maintained by arteriolar vasodilation. And patients with critical lesions often have collateral circulation, making assessment of resting perfusion complex. Hence, the interpretation of replenishment kinetics is particularly difficult at rest. Since normal perfusion is expected to increase at least 3-fold during hyperaemia, giving faster contrast replenishment after transient destruction, the evaluation of stress-to-rest ratios (the MBF velocity reserve) would be a more appropriate quantitative approach to assess normal or abnormal perfusion.Interestingly, a simplified algorithm using qualitative evaluation of MBF velocity  from a single stress MCE perfusion study, was recently shown to detect CAD in patients with normal left ventricular function at rest, avoiding the need for resting MCE studies . HoweverOur study indicated that a very low-power real-time MCE could provide contrast opacification in multiple myocardial segments of the LV apical views. However, the acquistion of flash-replenishment loops adequate for quantification is limited by imaging and technical problems. The interpretation of regional resting replenishment curves is in addition complicated by great variability in normal perfusion. Our data support previous findings in experimental studies, which established that the absolute values of MBF velocity are highly influenced by ultrasound field geometry and which cardiac phase to be analyzed. The MBF velocity need to be interpreted with regard to the imaging technique used and the segments from which they are obtained, and due to the great variability is is probably best applied by analysis of relative changes, that is comparing values during stress with baseline.The author(s) declare that they have no competing interests.Movie demonstrating a real-time destruction-replenishment loop of the LV apical long-axis viewClick here for file


Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately. Congestive heart failure (HF) has become a highly prevalent medical syndrome in developed countries, which primarily affects older patients with a history of hypertension, coronary artery disease and diabetes mellitus . There iDuring exercise, pulmonary capillary pressure remains unchanged, decreases or slightly increases in healthy subjects ,16, thouAccording to the Starling's principles regarding fluid exchanges through the capillary wall, the fluid movement across the pulmonary capillary membrane is governed by the integrity of the capillary membrane and a balance between opposing filtrative and absorbing forces:Fluid movement = k(CHP - IHP) + k(πif - πc)Where k = filtration coefficient defining the fluid conductance across the capillary membrane, CHP = intra-capillary hydrostatic pressure, IHP = interstitial hydrostatic pressure, πif = colloid osmotic pressure of interstitial fluid and πc = plasma colloid osmotic pressure.Landmark studies have demonstrated experimentally that pulmonary capillary hypertension is the straightforward hemodynamic condition of cardiac pulmonary edema -23, alonGiven the limitations inherent to invasive recordings, Doppler echocardiography has become an invaluable tool for non-invasively determining LV diastolic pressures routinely. Currently, the American Society of Echocardiography recommends the use of color M-mode and spectral tissue Doppler-derived indexes, E/Vp and E/E' respectively, for assessing left atrial pressure in clinical trials . This isThe peak early diastolic mitral E velocity is primarily influenced by left atrial pressure, LV relaxation and LV systolic pressure in order of decreasing significance -43. The Numerous clinical studies using spectral tissue Doppler for recording mitral annular velocities have produced convincing evidence of a positive, linear relation of E/E' with invasively determined mean LV diastolic pressure regardless of LV ejection fraction, rhythm and heart rate ,48-60. SSymptoms of dyspnea and fatigue usually characterize exercise intolerance in chronic congestive HF (stage C of the ACC/AHA classification for chronic HF) , regardlExercise-induced changes in the E/E' ratio are adequately recorded in most patients. In healthy subjects, E/E' remains unchanged during exercise because of a proportional increase in E and E' velocities . It has The clinical application of diastolic stress echocardiography  in the setting of exertional dyspnea is relevant for establishing the cardiac contribution to symptoms. In the study by Skaluba et al in which most patients presented with a normal LV ejection fraction, septal E/E' > 10 at rest was a strong, independent predictor of reduced exercise performance beyond LV systolic and diastolic function, as defined by the LV ejection fraction and the mitral filling pattern respectively . In the Acute, transient exacerbation of symptoms is a common clinical presentation of HFPSF, particularly among elderly patients . The cliAn echocardiographic LV ejection fraction of < 40–45% has been reported to be a powerful predictor of cardiac origin in patients presenting with acute dyspnea ,94. In tNoninvasive assessment of LV diastolic pressures at presentation, before tailored therapy, is clinically relevant particularly for patients with severe symptoms, inconclusive clinical, radiographic and biochemical data and preserved LV ejection fraction at echocardiography (see Table According to the ACC/AHA recommendations, the diagnosis of congestive HF is defined by the association of structural heart disease with symptoms compatible with the diagnosis. In the light of the present review, we can state that tissue Doppler evidence of pulmonary capillary hypertension at rest and unmasked during exercise is likely to become a hallmark for the diagnosis of congestive HF in the setting of preserved LV systolic function, regardless of the clinical presentation.financial competing interestsNoneNon-financial competing interestsNone