Conventional pulsed wave Doppler parameters are known to be preload dependent, whereas newly proposed Doppler indices may be less influenced by variations in loading conditions. The aim of the present study was to evaluate the effects of haemodialysis-induced preload reduction on both conventional and new Doppler parameters for the assessment of left ventricular (LV) diastolic function.This prospective observational study was conducted in a medical-surgical intensive care unit (ICU) and nephrology department of a teaching hospital. In total, 37 haemodialysis patients with end-stage renal disease (age [mean ± standard deviation]: 52 ± 13 years) and eight ventilated ICU patients with acute renal failure receiving vasopressor therapy  were studied. Echocardiography was performed before and after haemodialysis. Conventional pulsed wave Doppler indices of LV diastolic function as well as new Doppler indices, including Doppler tissue imaging early diastolic velocities (E' wave) of the septal and lateral portions of the mitral annulus, and propagation velocity of LV inflow at early diastole (Vp) were measured and compared before and after ultrafiltration.P = 0.005). All conventional pulsed wave Doppler parameters were altered by haemodialysis. In haemodialysis patients, E' velocity decreased after ultrafiltration when measured at the septal mitral annulus , but not at its lateral portion , whereas no significant variation was observed in ICU patients. Vp decreased uniformly after ultrafiltration, the difference being significant only in haemodialysis patients . Although of less magnitude, ultrafiltration-induced variations in Doppler parameters were also observed in haemodialysis patients with altered LV systolic function.The volume of ultrafiltration was greater in haemodialysis patients than in ICU patients (3.0 ± 1.1 l versus 1.9 ± 0.9 l; In contrast to other Doppler parameters, Doppler tissue imaging E' maximal velocity measured at the lateral mitral annulus represents an index of LV diastolic function that is relatively insensitive to abrupt and marked preload reduction. Left ventricular (LV) diastolic properties are a major determinant of LV filling and subsequent stroke volume. On clinical grounds, LV diastolic function is commonly assessed using echocardiography Doppler . UnfortuHaemodialysis provides a unique opportunity to evaluate the effect of a preload reduction on Doppler parameters currently used to assess LV diastolic properties. In this specific setting, recent clinical studies conducted in patients with chronic renal failure have yielded discrepant results -19. The The protocol was approved by the Ethics Committee of the Société de Réanimation de Langue Française, which waived the need of signed informed consent. All patients were informed about the study either at the time of echocardiography  or as early as possible after recovery (ventilated patients).2) were studied. All patients underwent long-term haemodialysis three times a week for 5.4 ± 5.2 years (range 1 month to 19 years). The aetiology of end-stage renal disease was diabetes in five patients, hypertension in three, lupus erythematosus in three, chronic glomerular disease in 12, chronic interstitial nephropathy in three, or miscellaneous in 11. Eleven patients had ischaemic heart disease and one patient had dilated cardiomyopathy.Thirty-seven ambulatory patients with end-stage renal disease  and had stable haemodynamics under vasopressor therapy. Patients received a constant dose of vasopressor during the study period . The reason for admission to the ICU was shock of septic origin (n = 3) or of other origin (n = 4), or a pulmonary oedema (n = 1). Only one ICU patient had a history of cardiac disease (ischaemic heart disease).Eight ventilated critically ill patients  admitted to the intensive care unit (ICU) with acute renal failure were also enrolled in the study. All patients were sedated so that they could receive volume-controlled ventilation  valvular insufficiency. In all patients, body weight, blood pressure and heart rate were measured before and after haemodialysis. Central venous pressure was also measured before and after the procedure in ICU patients.In ambulatory patients, haemodialysis was performed over four hours following a standard prescription that was unchanged for at least two months. In ICU patients, the haemodialysis regimen was adapted to both clinical status and metabolic perturbation. In all patients, the volume of ultrafiltration was determined by the attending physician.® catheters  were used in ICU patients.A Fresenius 4008 H system with biocompatible membranes  and bicarbonate-buffered dialysate  at 37°C was used for haemodialysis. Arteriovenous fistulae were used in ambulatory patients, whereas MahurkarPerdialytic hypotension was defined as a drop in systolic blood pressure of greater than 30% or to below 100 mmHg . When hyTransthoracic echocardiography (TTE) was performed in ambulatory patients, whereas transoesophageal echocardiography (TEE) was used in ventilated ICU patients. The echocardiographic study was performed before (baseline) and at least one hour after haemodialysis using a SONOS 5500 upper-end platform  equipped with a 2.5 to 4 MHz broadband transducer or a 5 MHz multiplane TEE probe. Respiratory tracing in spontaneously breathing patients or airway pressure curve in ventilated patients were displayed continuously. The same experienced operator performed all TTE and TEE studies and took offline measurements from digitally recorded images. All measurements were performed in triplicate at end-expiration identified on respiratory tracings, and were averaged. Measurements were performed in random order and not consecutively for the same patient, with the investigator being blinded to both body weight and study phase .Transmitral Doppler velocities were recorded in the four-chamber view with the sample volume located at the tip of mitral valve leaflets. In all patients, peak E and A wave velocities, and deceleration time of early transmitral flow velocity were measured. Isovolumic relaxation time was only measured in ambulatory patients. Pulsed wave Doppler velocity profile of pulmonary vein flow was obtained in the right upper pulmonary vein using TTE or in the left upper pulmonary vein using TEE. Peak S and D pulmonary vein forward flow velocities were measured. Both mitral early diastole/atrial contraction maximal velocity (E/A) and pulmonary vein systolic/diastolic maximal velocity (S/D) ratios were calculated. Finally, pulsed wave Doppler velocities of aortic flow were recorded at the level of the LV outflow tract in the apical five-chamber view using TTE or in the transgastric longitudinal view around 120°) with multiplane TEE. Cardiac index was obtained by measuring the velocity-time integral of aortic Doppler tracings and the diameter of the LV outflow tract [° with muA 5 mm DTI sample volume was placed at the septal and lateral portions of the mitral annulus to record early diastolic velocity (E' wave) in spectral pulsed mode. To obtain colour M-mode recordings, the width of field was reduced and centred on the mitral valve and LV inflow tract, and colour flow mapping was activated with a Nyquist limit set at around 45 cm/s . M-mode 2 or greater for men and 102 g/m2 for women [LV mass was measured using the method described by Reichek and coworkers  and LV hor women . LV voluor women . LV systP < 0.05 was considered statistically significant. In 20 randomly selected patients, the senior investigator repeated Doppler measurements after a two month interval and another investigator, who was experienced in echocardiography, performed the same measurements to determine their reproducibility. Inter-observed and intra-observer variabilities were calculated as the absolute difference between the two sets of measurements divided by the mean value of measurements, and expressed as a percentage of error. Agreement for the measurement of Doppler parameters was also assessed using the intraclass correlation coefficient.Two-dimensional echocardiographic findings and Doppler parameters were compared within the two study groups  before and after haemodialysis using a Wilcoxon matched pairs test. Haemodialysis patients were divided in two subsets, according to baseline LV systolic function (LV ejection fraction < 50% or ≥ 50%). The same comparison was performed within each subset of haemodialysis patients in order to assess the potential influence of LV systolic performance on ultrafiltration-related variations in Doppler parameters. Values are expressed as mean ± standard deviation. 2 versus 11 ± 4 ml/m2; P = 0.08). As a result, cardiac index significantly decreased after ultrafiltration in haemodialysis patients but not in ICU patients  and induced a comparable preload reduction, reflected by the close decrease in LV end-diastolic volume index . DTI E' velocity tended to be less affected by ultrafiltration when measured at the lateral than at the septal aspect of the mitral ring, and variations were less pronounced in the presence of LV systolic dysfunction. In contrast, Vp tended to decrease with preload reduction, regardless of LV systolic function (Table In haemodialysis patients, baseline LV systolic function apparently failed to alter the effect of ultrafiltration on Doppler parameters of LV diastolic function Table . The volInter-observer variability in measurement of Doppler parameters ranged from 1% to 13%, whereas intra-observer variability ranged from 2% to 7%. Notably, measurement of DTI E' velocity at the level of the mitral ring was more reproducible than that of Vp Table .Haemodialysis represents an unparalleled model of abrupt alteration in LV loading conditions. Ultrafiltration allows achievement of marked preload reduction, as reflected in our patients by a significant decrease in LV end-diastolic volume index, a commonly used surrogate of LV preload Table . ImportaThe high prevalence of LV diastolic dysfunction found at baseline in our patients with end-stage chronic renal failure using previously proposed diagnostic criteria based on DTI and colour M-mode  is relatIn the present study, certain recently proposed Doppler parameters of LV diastolic function appeared also to be sensitive to acute and marked variations in LV preload related to ultrafiltration. In haemodialysis patients, TDI E' velocity decreased with preload reduction when recorded at the septal portion of the mitral annulus, as previously reported , whereasIn our ventilated ICU patients, ultrafiltration-induced variations in pulsed wave Doppler parameters were similar to those observed in haemodialysis patients but were of lesser magnitude Table . Of noteAlthough of lesser magnitude, a substantial decrease in septal E' velocity and Vp induced by ultrafiltration was observed in the subset of haemodialysis patients with altered LV systolic function Table . In a siThe study has several limitations. Our results cannot be extrapolated to clinical settings in which variations in LV loading conditions are less abrupt than those obtained by intermittent haemodialysis. The group of ICU patients was fairly small, and observed results in this specific subset of patients remain to be confirmed. The hypothesis raised by the present data is that smaller changes in Doppler indices observed in ICU patients are presumably related to the lower volume of ultrafiltration withdrawn from these patients compared with haemodialysis patients, rather than a potential lusitropic effect of catecholamines. Finally, we did not assess the potential role of afterload variations and changes in cardiac contractility induced by haemodialysis on observed variations in Doppler indices .This study confirms the preload dependence of conventional pulsed wave Doppler parameters routinely used to evaluate LV diastolic function. Among the recently proposed Doppler indices for the evaluation of LV diastolic properties, TDI E' maximal velocity measured at the lateral portion of the mitral annulus appeared to be relatively preload independent and reproducible. In contrast, E' septal velocity and Vp appeared sensitive to a marked and abrupt preload reduction. The preload dependence of Doppler parameters was not significantly influenced by LV systolic function. Accordingly, Doppler parameters should be used cautiously to evaluate LV diastolic properties and to diagnose transient diastolic dysfunction in clinical settings characterized by abrupt and marked changes in cardiac loading conditions.• Abrupt variations in cardiac preload markedly alters conventional pulsed wave Doppler parameters routinely used to assess LV diastolic properties.• Marked preload reduction may also alter both DTI E' velocity when recorded at the septal mitral ring and Vp measured by colour M-mode.• DTI E' velocity recorded at the lateral aspect of the mitral ring appears to be relatively insensitive to variations in preload.• These variations were apparently unaffected by LV systolic function.DTI = Doppler tissue imaging; E/A = mitral early diastole/atrial contraction maximal velocity ratio; E' wave = DTI early diastolic velocity of the mitral annulus; ICU = intensive care unit; LV = left ventricular; S/D = pulmonary vein systolic/diastolic maximal velocity ratio; TEE = transoesophageal echocardiography; TTE = transthoracic echocardiography; Vp = propagation velocity of LV inflow at early diastole measured using color M-mode.The authors declare that they have no competing interests.PV, JCA and HG contributed to the design of the clinical study, data analysis and preparation of the manuscript. VA, JL, JFM and BF contributed to the recruitment and clinical evaluation of patients throughout the study period.


Diastolic dysfunction as demonstrated by tissue Doppler imaging (TDI), particularly E/e'  is common in critical illness. In septic shock, the prognostic value of TDI is undefined. This study sought to evaluate and compare the prognostic significance of TDI and cardiac biomarkers (B-type natriuretic peptide (BNP); N-terminal proBNP (NTproBNP); troponin T (TnT)) in septic shock. The contribution of fluid management and diastolic dysfunction to elevation of BNP was also evaluated.Twenty-one consecutive adult patients from a multidisciplinary intensive care unit underwent transthoracic echocardiography and blood collection within 72 hours of developing septic shock.P = 0.0002). Area under ROC curves were E/e' 0.94, TnT 0.86, BNP 0.78 and NTproBNP 0.67. An E/e' threshold of 14.5 offered 100% sensitivity and 83% specificity. Adjustment for APACHE III, cardiac disease, fluid balance and grade of diastolic function, demonstrated E/e' as an independent predictor of hospital mortality (P = 0.019). Multiple linear regression incorporating APACHE III, gender, cardiac disease, fluid balance, noradrenaline dose, C reactive protein, ejection fraction and diastolic dysfunction yielded APACHE III (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009) as independent predictors of BNP concentration.Mean ± SD APACHE III score was 80.1 ± 23.8. Hospital mortality was 29%. E/e' was significantly higher in hospital non-survivors (15.32 ± 2.74, survivors 9.05 ± 2.75; E/e' is an independent predictor of hospital survival in septic shock. It offers better discrimination between survivors and non-survivors than cardiac biomarkers. Fluid balance and diastolic dysfunction were independent predictors of BNP concentration in septic shock. Septic shock in adults refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes . AlthougTDI is an echocardiographic technique that measures myocardial velocities , which aPreviously, we demonstrated that evidence of diastolic dysfunction on TDI is common in critically ill patients . The sigCardiac biomarkers including BNP ,24, N-teThis study sought to evaluate and compare the prognostic significance of TDI variables and cardiac biomarkers in septic shock. An auxiliary aim was to evaluate the potential contribution of LV diastolic dysfunction and fluid management to elevation of plasma BNP concentrations in septic shock.This prospective observational study was approved by the Princess Alexandra Hospital Human Research Ethics Committee (project 2005/213), and the Guardianship and Administration Tribunal of Queensland (project 2006/07) and informed consent was obtained from the patient or legally authorized representative where appropriate.Twenty-one consecutive adult patients with septic shock were recruited from the ICU during an 11-month period (May 2005 to March 2006). Eligible patients were enrolled within 72 hours of admission to the ICU with septic shock or development of septic shock while in the ICU. Septic shock was defined as severe sepsis with persistent hypotension  < 60 mmHg or a reduction in systolic blood pressure (SBP) > 40 mmHg from baseline) despite adequate volume resuscitation in the absence of other causes for hypotension . Cardiac output was calculated as the product of stroke volume and HR. Stroke volume and cardiac output measurements were indexed to body surface area .Doppler interrogation of LV outflow tract velocity was guided by apical five-chamber view . Heart rMyocardial velocities were obtained using tissue Doppler settings, with the pulsed-wave Doppler sample volume at the septal mitral annulus in the apical four-chamber view. Peak systolic (s'), early diastolic (e') and late diastolic (a') myocardial velocities were measured. E/e' was calculated. When A and/or a' were indistinguishable due to sinus tachycardia, E and/or e' were measured as described by Nagueh and colleagues . In the As previously described , threshoGuidelines previously published by our group were used to grade LV diastolic function as normal, impaired relaxation, pseudonormal or restrictive . Age-dep® immunoassay , Plasma Troponin T  and NTProBNP concentration  were run on Roche Elecsys® analyzers . Plasma C reactive protein (CRP) concentration was measured using an immunotubidometric assay . Laboratory thresholds were used to determine elevation of biomarkers: BNP , NTproBNP , TnT (< 0.03 μg/L) and CRP (< 5.0 mg/L).Plasma BNP concentration was measured using a Biosite TriageCoded echocardiographic and Doppler recordings were analyzed at least one month after acquisition by a single observer blinded to clinical and biochemical data. Biochemical assay was performed on coded samples by technicians blinded to clinical and echocardiographic data.t-test for independent samples. BNP and NTproBNP concentrations were log-transformed to achieve normality before application of linear regression techniques. Discrimination between hospital survivors and non-survivors was evaluated by receiver operating characteristic (ROC) curve analysis.Analysis was performed by SPSS, version 14.0 for Windows . Descriptive measures were used to evaluate the distribution of variables. Differences between groups were assessed using Fisher's exact test for categorical data. Continuous data were assessed using Levene's test for equality of variance before applying Student's Cox proportional hazards regression was used for time to event outcomes  from the time of echocardiography. Adjustment was made for the potential influence of cardiac disease, fluid balance and grade of diastolic dysfunction upon E/e'.P < 0.1 in multiple regression models one by one until a final 'best' model was achieved.Multiple-linear regression analyses were undertaken to determine contributions to BNP concentration (lnBNP). Potential predictor variables included APACHE III score (first ICU day), gender, , cardiacP-value less than 0.05 was regarded as significant. Unless stated otherwise, results are reported as mean ± standard deviation (SD) (range).In final analyses, a Subgroup analysis of septic patients from data previously published by our group yielded a mean ± SD E/e' of 11.4 ± 5 (range: 3.59 to 23.15) and hospital mortality of 30% . It was Twenty-one consecutive septic shock patients were studied Table . FifteenP = 0.15). Of the mechanically ventilated patients, positive end-expiratory pressure (PEEP) requirements were not different between survivors and non-survivors .Sixteen patients (76%) were mechanically ventilated at the time of the initial assessment. The requirement for mechanical ventilation did not distinguish survivors from non-survivors (Eleven patients (52%) were in normal sinus rhythm and two (9.5%) were paced. Noradrenaline infusion was running at the time of initial assessment in seventeen patients . In addition to noradrenaline, one patient was receiving adrenaline and one was receiving dopamine. Mean ± SD fluid balance on the day of study was 1780 ± 1848 mL (range: -1734 to 5320).The diagnosis of cardiac disease Table  was baseSystolic dysfunction (EF < 55%) was evident in 14 patients (67%). Transthoracic measurement of e' and E/e' was feasible in 20 of 21 patients. Fusion of E and A waves was observed in four examinations (19%). Fusion of e'and a' waves was observed in three (15%). At initial assessment, e' was less than 9.6 cm/s in 11 (55%) patients. At this time, E/e' was more than 15 in three (15%), 8 to 15 in thirteen (65%) and less than 8 in four (20%) patients. TDI variables  were not significantly different between ventilated and non-ventilated patients. Diastolic function was graded as normal in nine (43%), impaired relaxation in three (14%), pseudonormal in seven (33%) and restrictive in two patients (10%). Thus, diastolic dysfunction was present in 57% of patients (n = 12).BNP was elevated in fifteen patients (71%), NTproBNP in six (28%) and TnT in fourteen (67%).P = 0.0002), e'  and s' . The area under the ROC curve (c statistic) for each of these variables was 0.94 for E/e', 0.86 for e'and 0.83 for s'. An E/e' threshold value of 14.5 offered sensitivity of 100% and specificity of 83% .Significant differences were observed between hospital survivors and non-survivors Table  with resP = 0.005), e' (P = 0.04), s' (P = 0.048) and TnT (P = 0.03). Adjustment for APACHE III score, history of cardiac disease, fluid balance and grade of diastolic function, revealed E/e' as an independent predictor of hospital mortality (P = 0.019). A Kaplan-Meier plot of the association between E/e' and survival to hospital discharge is shown in Figure Univariate Cox regression analysis Table  yielded P = 0.089), APACHE III score (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009). This final model accounted for 71.3% of variation in lnBNP concentration (adjusted R square 0.713).From an initial model containing APACHE III score, gender, cardiac disease, fluid balance, noradrenaline dose, CRP, EF and diastolic dysfunction, the backward elimination procedure yielded a 'best' model containing gender . We also observed that conventional measures of systolic function, such as EF and SVI Table  did not per se has not previously been reported.We have demonstrated an association between TDI indices of diastolic function and outcome in septic shock. The significance of this important new finding is highlighted by the superiority of these variables over the measures of cardiac systolic function and cardiac biomarkers incorporated into this study. Despite demonstrating value in a range of cardiovascular diseases , and morP = 0.07). Although no clear functional relation has been demonstrated, sepsis-induced diastolic dysfunction is likely to be associated with a range of histologic abnormalities such as inflammatory infiltrate, interstitial edema, apoptosis, and necrosis [Our demonstration of an association between diastolic function and mortality in septic shock complements previous data. In a radionuclide cineangiographic study, Parker and colleagues documented that non-survivors did not demonstrate LV dilation ('preload adaptation') and therefore were unable to maintain stroke volume and cardiac output ,44. Alsonecrosis ,47.The peak early diastolic mitral annular velocity (E)', as measured by TDI, reflects LV relaxation ,49. AlthP = 0.452). However, their study incorporated a number of patients with severe sepsis (lower severity of illness compared with the current study), and did not report fluid management, which is an important determinant of survival in sepsis [Two recent studies have utilized TDI in the evaluation of septic ICU patients. McLean and colleagues used E/e' as an estimate of LV filling pressure in their prognostic study of BNP in patients with severe sepsis and septic shock . They ren sepsis . Bouheman sepsis  used TDICardiac biomarkers including BNP ,24, NTprIn general, BNP is a peptide hormone secreted by the ventricular myocardial in response to wall stress . Its priOn the basis of previous laboratory data  and our In keeping with international guidelines for hemodynamic monitoring in shock, our unit does not routinely use pulmonary artery catheters , and LV We have reported TDI measurements taken at the septal mitral annulus. This technique was based on results reported by Ommen and colleagues demonstrating good prediction of LV end-diastolic pressure . AlthougIn clinical studies, it is challenging to standardize data collection at a fixed time from onset of sepsis. We studied patients within 72 hours of development of septic shock (admission to ICU or onset in ICU). The strength of this design is that it potentially optimizes the comparison of TDI with cardiac biomarkers, particularly BNP , as predThe findings of this study are of potential clinical importance. First, TDI might prove useful in risk stratification. This may help identify septic shock patients requiring more intensive therapy based upon their diastolic performance. Secondly, the association between diastolic dysfunction and mortality might offer a novel therapeutic target. Further research incorporating therapies targeted toward improved cardiac relaxation (lusitropy) must be pursued.In this preliminary study, we have found that after adjustment for severity of illness, cardiac disease, fluid management and grade of diastolic dysfunction, E/e' is an independent predictor of hospital survival in septic shock patients. In addition, E/e' offers better discrimination between hospital survivors and non-survivors than cardiac biomarkers . Fluid balance and diastolic dysfunction are independent predictors of BNP concentration in septic shock.• E/e' is an independent predictor of hospital survival in septic shock patients.• E/e' offers better discrimination between hospital survivors and non-survivors than cardiac biomarkers .• Fluid balance and diastolic dysfunction are independent predictors of BNP concentration in septic shock.A: peak active (late) diastolic transmitral flow velocity; a': peak active (late) diastolic septal mitral annulus velocity; APACHE III: Acute Physiology and Chronic Health Evaluation III; BNP: B-type natriuretic peptide; BSA: body surface area; CI: cardiac output indexed to body surface area; CRP: C reactive protein; CVP: central venous pressure; DBP: diastolic blood pressure; DT: E wave deceleration time; E: peak early diastolic transmitral flow velocity; e': Peak early diastolic septal mitral annulus velocity; E/A: ratio of E to A; E/e': patio of E to e'; EF: ejection fraction; HR: heart rate; lnBNP: multiple-linear regression analyses of BNP concentration; LV: left ventricle or ventricular; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; LVEDVI: LVEDV indexed to body surface area; LVESVI: LVESV indexed to body surface area; MAP: mean arterial pressure; NTproBNP: N-terminal proBNP; OTD: LV outflow tract diameter; PEEP: positive end expiratory pressure; ROC: receiver operating characteristic; s': peak systolic septal mitral annulus velocity; SBP: systolic blood pressure; SD: standard deviation; SOFA: Sequential Organ Failure Assessment score; SVI, left ventricular stroke volume indexed to body surface area; TDI: Tissue Doppler imaging; TnT: Troponin T; Vpeak: peak LV outflow tract velocity; VTI: LV outflow tract velocity time integral.The authors declare that they have no competing interests.D Sturgess conceived of the study, coordinated study design and implementation and drafted the manuscript. TM participated in study design and helped to draft the manuscript. C Joyce participated in study design and helped to draft the manuscript. C Jenkins participated in the design of the study, performed and coordinated echocardiography. MJ participated in the design of the study and provided statistical advise. PM participated in study design, provided laboratory equipment and advice regarding biochemical assays. D Stewart assisted in recruitment of participants and collection of data. BV participated in its design and helped to draft the manuscript. All authors read and approved the final manuscript.


Controversy still exists in the categorization of holes between the ventricles, although they are the most common congenital cardiac malformation. Advanced imaging techniques such as three-dimensional echocardiography and computed tomographic angiography offer superb anatomical details of these defects. In this review, we have sought to collate the features highlighted in different categorizations and identify their similarities, but also emphasize their differences. We hope that an analysis of this type, now achievable during life, using advanced imaging, might lead to the appearance of a unified system for diagnosis and description of holes between the ventricles. As holes between the ventricles are the most frequent congenital cardiac malformations, it is surprising that so many issues regarding their categorization remain contentious. To some extent, this reflects the understandable desire to relate the morphology of the defects to the anatomy of the normal ventricular septum. Those with knowledge of the normal anatomy, however, will appreciate that some of the holes, notably those opening directly beneath the conjoined leaflets of the arterial valves, cannot exist in an otherwise normally constructed heart. This is because, in the normal heart, the free-standing infundibular sleeve lifts the leaflets of the pulmonary valve away from the base of the ventricular mass. Recognition of such relatively subtle features is crucial, if appropriate genetic counseling is to be provided to those whose children have deficient ventricular septation, as the holes opening directly beneath the leaflets of the arterial valves are more closely related in developmental terms to the common arterial trunk than to the more frequent defect bordered directly by the atrioventricular component of the membranous septum. These latter defects, nonetheless, have also been contentious, as there has been a debate as to whether they should be considered perimembranous, albeit this term is now so widely used that it is unlikely to disappear from the pediatric cardiological lexicon. The term itself, however, is not always used in the fashion in which it was initially defined. In this Several popular, albeit disparate, approaches exist for the categorization of holes between the ventricles. A well-recognized approach is to plIn a second popular categorization, the defeThe third popular categorization emerged from Europe, underscoWhen this latter categorization is reinforced with information as to the direction of the opening of the holes into the right ventricle, and the presence or absence of septal malalignment, then it is our belief that the expanded classification contains all the information provided by the other systems. In an attempt to understand some of the reasons for disagreement, nonetheless, we should define with precision the plane of space we consider to represent the defect, and to establish whether a hole described as an interventricular communication is the same as a ventricular septal defect. As the hThe normal ventricular septum has extensive muscular and very small fibrous components. The fibrous part is usually known as the membranous septum. The extensive muscular septum is not related, as might be expected, to the components of the ventricles themselves. Goor andThe roof of the normal right ventricle is the so-called crista supraventricularis, or the supraventricular crest. Tomographic studies confirm dissections showing In all the systems for categorization summarized in our introduction, as far as we are aware, the morphological features of the holes themselves have been defined on the basis of their margins as seen from the morphologic right ventricle. This approach itself is not without its potential problems, should the hole described as the ventricular septal defect also be considered to represent the same plane in space as the interventricular communication. In the presence of overriding of an arterial valve, for example, the interventricular communication represents the plane of space subtended between the crest of the ventricular septum, relative to the circumference of the arterial valve . This plWhen seeking to distinguish the various types of defects, those developing the various systems discussed a little earlier used different features of the holes for categorization. The time-honored numerical system, for example, used as its primary defining feature, the positions taken by the different holes relative to the components of the normal ventricular septum. The systThere are four phenotypically discrete holes that open toward the right ventricular inlet. The most common type possesses, as part of its direct borders, fibrous continuity between the leaflets of the aortic, mitral, and tricuspid valves. This fibrous area incorporates the atrioventricular component of the membranous septum and, oftentimes, the interventricular component of the membranous septum can be recognized as a triangular fibrous flap that reinforces the posteroinferior margin . When th2The second type of defect that opens to the inlet of the right ventricle has exclusively muscular borders. All agree that such holes are well described as being muscular inlet defects. They are distinguished by recognition of the persisting musculature of the septum between the normally offset leaflets of the mitral and tricuspid valves . The preThe hole associated with straddling and overriding of the tricuspid valve also opens directly to the inlet of the right ventricle. Indeed, because of the overriding of the valvular orifice, the muscular ventricular septum in this setting extends across the full width of the right atrioventricular junction . This ty9It is possible, of course, to find the true atrioventricular canal defect in which shunting is confined to the ventricular level. In these hearts, which possess all the phenotypic features of atrioventricular canal malformations, shunting is confined to the ventricular level because the bridging leaflets of the common atrioventricular valve are firmly attached to the superior margin of the atrioventricular septal defect . The scoOverall, most patients with holes between the ventricles have muscular defects. In patients requiring therapeutic closure, in contrast, the most common type of defect opens into the right ventricle, in the area usually filled by the interventricular component of the membranous septum. As we have discussed, the hole occupies an area appreciably larger than the space usually filled by the interventricular component of the membranous septum, and the As with the defects opening primarily to the inlet of the right ventricle, defects with markedly different phenotypes can open in direct relationship to the ventricular outflow tracts. The most common of these is the hole that possesses, as part of its border, fibrous continuity between the leaflets of the aortic and tricuspid valves . If the The second phenotypic defect opening beneath the ventricular outlets has exclusively muscular borders when viewed from its right ventricular aspect. The muscular border as seen from the right ventricle is the consequence of the fusion of the postero-caudal limb of the septomarginal trabeculation with the ventriculo-infundibular fold, the muscular bar thus formed interposing between the hinges of the leaflets of the aortic and tricuspid valves . DefectsThe third type of defect opening to the outlet of the right ventricle exhibits an entirely different phenotype. The defining feature of the holes of this type, is the fibrous continuity between the leaflets of the aortic and pulmonary valves . They exEchocardiography, and specifically three-dimensional echocardiography, can now be used accurately to describe and categorize each type of hole permitting shunting between the ventricles. There should be no debate that it serves as the diagnostic modality best utilized to accomplish these goals. While other imaging modalities can also exquisitely define the nature of holes between the ventricles and show their relationships to the surrounding structures, these techniques have drawbacks not associated with three-dimensional echocardiography. For instance, when performed appropriately, gated computed tomographic angiography provides superb anatomic details, can be acquired quickly, and rarely requires sedation of the patient. Acquisition of such images, nonetheless, requires exposure to radiation. Although minimal, this exposure courts the known associated, inherent, long-term risk of this technique. Three-dimensional echocardiography also offers other advantages over computed tomography, such as higher temporal resolution and the ability to analyze the characteristics of the flow of blood. Magnetic resonance imaging can also reveal intracardiac structures, including holes between the ventricles, but the extensive time and expertise required to acquire and analyze the necessary images limits its practicality in these patients.In the past, it had been the examination of an autopsied specimen that had usually been taken as the gold standard for the understanding of a cardiac structure. Surprisingly, however, there has been a failure between those using autopsied hearts to reach consensus as how best to catagorize the holes between the ventricles. In part this reflects the difficulty, in autopsied hearts, of recognizing such subtle features as the presence of the sleeve of free-standing muscular subpulmonary infundibulum that lifts the pulmonary valvular leaflets away from the base of the ventricular mass. It is also intuitive to presume that the ventricular septum, like the ventricles themselves, possesses discrete inlet, apical trabecular, and outlet components. The ability now to dissect the heart during life, using cross-sectional or three-dimensional echocardiography illustrates that this is not the case.Other reasons for the ongoing disagreements concerning the categorization of holes between the ventricles reflect the fact that different morphological features of malformed hearts have been chosen as the primary criterion for the developed heirarchy. On account of this, it has not thus far been possible to produce unity from mapped codes, as there is no certainty regarding equality between the phenotypes being mapped one to the other. In this review, therefore, we have sought to collate the features highlighted in different categorizations and identify their similarities, while also emphasizing their differences. We hope that an analysis of this type, now achievable during life, might lead to the appearance of a unified system for diagnosis and description of holes between the ventricles.


This entity presents a diagnostic challenge because many women in the last month of a normal pregnancy experience dyspnea, fatigue, and pedal edema, symptoms identical to early congestive heart failure. There are no specific criteria for differentiating subtle symptoms of heart failure from normal late pregnancy. Therefore, it is important that a high index of suspicion be maintained to identify the rare case of PPCM as general examination showing symptoms of heart failure with pulmonary edema. PPCM remains a diagnosis of exclusion. No additional specific criteria have been identified to allow distinction between a peripartum patient with new onset heart failure and left ventricular systolic dysfunction as PPCM and another form of dilated cardiomyopathy. Therefore, all other causes of dilated cardiomyopathy with heart failure must be systematically excluded before accepting the designation of PPCM. Recent observations from Haiti[Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. the symp PPCM is a rare and potentially fatal disease in pregnant, mortality rate of peripartum cardiomyopathy is 30%–60% and may be caused by severe pulmonary congestion and/or thrombo-embolic events. Survivors have a 50%–80% risk of developing cardiac failure during future pregnancies, with an associated mortality rate of 60%; so only timely diagnoses and prompt management can save two lives.rd hospital day). The patient was maintained on oral digoxin, ramipril, lasix, and potassium chloride. Oral atenolol was added on the 5th hospital day and she was transferred to a general obstetric ward on the 7th hospital day. On the 8th day after confinement, echocardiography showed improvement in ejection fraction to 35%. She was discharged with a healthy baby to home on the 12th day on digoxin, ramipril, potassium chloride, and a diet of salt restriction.A 37-year-old female (primigravida) G1P0L0 presented to the emergency department at night at 37 weeks gestation with chief complaint of progressively increasing breathlessness for 15 days and swelling in both lower limbs for 7 days. Routine general and obstetrical assessment showed on examination: general condition – poor, blood pressure – 180\110 mmHg, pulse – 136\min irregular, respiratory rate – 36\min, Pallor ++, JVP raised, pedal edema + cardiovascular exam showed S3 gallop rhythm present, P2 loud (pulmonary hypertension) and chest with bilateral crepitations (pulmonary edema). The patient's presenting complaints and examination indicated the presence of a cardiovascular system problem. Echocardiography performed demonstrated: EF 30% with mild generalized hypokinesia of left ventricle, mild to moderate TR and mild MR with signs of congestive heart failure (CHF). She was diagnosed with peripartum cardiomyopathy (PPCM) with left ventricular failure (EF 30%) with severe pre-eclampsia (PET). Immediate medical management was initiated with fruselac 50 mg, M-Dopa 200 mg QID, amlodipine 5 mg OD, deriphyllin 1 tab BID, and nebulization therapy every 8 h, Ensuing blood pressure was 170\106 mmHg at which time a nitroglycerine infusion was started. When the patient developed abdominal pain the next morning with thick meconium, she underwent an emergency Caesarean section. Echocardiography demonstrated an ejection fraction of 30% with mild generalized hypokinesia of left ventricle, mild to moderate TR and mild MR with signs of congestive heart failure (CHF). Her preoperative laboratory investigation showed hemoglobin of 10.2 gm%, B+ blood group, and unremarkable liver and kidney functions, coagulation profile, and normal blood sugar. A central venous pressure line was placed to manage the fluid overload. The initial CVP was 20 mmHg. The patient's congestive heart failure was managed with digoxin, dobutamine, and nitroglycerine infusion. Ranitidine and metoclopramide were given because the patient had not been on NPO status. Rapid sequence induction was performed utilizing etomidate: after delivery of the baby, oxytocin was started. In the post-operative state, pink frothy sputum was noted from the endotracheal tube. She was treated for pulmonary edema with fruselac(lasix) 40 mg, increased nitroglycerine, dobutamine, and ventilator support with controlled mode ventilation with positive end expiratory pressure (CMV+PEEP). The patient was managed with incremental lasix given up to 100 mg with hemodynamic monitoring drip of dobutamine and nitroglycerine, digoxin , and low molecular weight heparin . With aggressive management on the second hospital day, the patient's clinical status improved, and she was successfully extubated the next morning  after load reduction with angiotensin-converting-enzyme inhibitors (postpartum only) and beta-blockers after signs and symptoms of congestion have improved. ACE inhibitors should be considered a mainstay of treatment for PPCM after delivery. Treatment options during pregnancy include hydralazine and nitrates, and we started nitroglycerine from beginning when patient came. Calcium channel blockers can be used during pregnancy to control blood pressure (and decrease uterine contractility), but most have negative inotropic properties.Second-generation beta-adrenoreceptor antagonists have beneficial effects in selected patients with dilated cardiomyopathy in the postpartum period in patients who continue to have symptoms and echocardiographic evidence of left ventricular compromise despite more than 2 weeks of standard heart failure management.Patients with significantly depressed left ventricular function (ejection fraction ≤ 35%) may benefit from anticoagulation therapy to prevent thrombosis and emboli. Arrhythmias should be treated according to standard protocols. Atrial arrhythmias may be treated with digoxin, which may also be used for its positive inotropic effect. Salt and water restriction are important, particularly in women with symptoms and signs of heart failure. If this treatment is ineffective, more aggressive ventricular support such as intra-aortic balloon counter pulsation, and left ventricular assist device or heart transplantation may be considered.When cardiomyopathy occurs during pregnancy, delivery of the fetus reduces the hemodynamic stresses on the heart. As cardiomyopathy manifests in the final trimester, the fetus is usually mature and can be delivered safely before or at the time of commencement of medical therapy. The mode of delivery for patients with peripartum cardiomyopathy is generally based on obstetric indications. The advantages of vaginal delivery are minimal blood loss, greater hemodynamic stability, avoidance of surgical stress, and less chance of postoperative infection and pulmonary complications. Effective pain management is a necessity to avoid further increases in cardiac output from pain and anxiety. The use of local infiltration anesthesia in combination with bilateral ilio-inguinal nerve block has been described. However, regional anesthesia has the additional advantages of reducing preload and after load and minimizes the fluctuations in cardiac output associated with labor. Regional anesthesia is contraindicated in anticoagulated patients. Caesarean delivery is reserved for indications such as fetal distress or failure to progress as in our case.There is scant information in the literature regarding the anesthetic management of peripartum cardiomyopathy, although several anesthetic options for CS have been reported.4 In patiThe incidence of peripartum cardiomyopathy ranges from 1 in 1300 to 1 in 15,000 pregnanccies. There isAlthough it seems likely that women of reproductive age all over the world have some risk of developing PPCM, good data about incidence are unavailable because so few population-based registries exist. Recent reports suggest an estimated incidence of one case per 299 live births in Haiti13 one ca14nd stage of labor and the increase in venous blood returning to the heart from the contracting uterus. Cardiovascular stresses do not return to pre-pregnancy levels until several weeks after delivery. The cause and mechanism of pathogenesis of PPCM remain unknown, and many hypotheses have been proposed. Early suggestions that nutritional disorders, such as deficiencies in selenium and other micronutrients, might contribute could not be confirmed in studies of Haitian patients with PPCM, although unidentified nutritional factors might exist.Pregnancy stresses the cardiovascular system, often worsening known heart disorders or unmasking occult heart disorders. Stresses include decreased hemoglobin and increased blood volume, stroke volume, and eventually, heart rate. Cardiac output increases by 30% to 50%. These changes become maximal between 28 and 34 weeks gestation. During labor, cardiac output increases approximately 20% with each uterine contraction; other stresses include straining during the 2Because of immune system changes related to pregnancy, associations with autoimmune mechanisms and inflammation have been studied since the 1970s. Melvin and colleagues proposedThe most common presentation of PPCM is with symptoms and signs of systolic heart failure.22 ClinicEarly signs and symptoms of heart failure can be obscured by pregnancy, because often the patient considers them to be a normal part of pregnancy. New York Heart Association (NYHA) cardiac functional classification varies from NYHA I to IV, although most frequently the initial presentation is with NYHA III and IV. Sudden cardiac arrest might occur in a situation where cardiopulmonary resuscitation is neither available nor successful. Delayed Left ventricular thrombus is common in PPCM patients with a left ventricular ejection fraction of less than 0·35. With progression of disease, four-chamber dilation may be seen, with thrombus formation in the left atrium and right ventricle. Peripheral embolisation then becomes possible to any part of the body, including arterial occlusion of the lower extremities with compromised circulation,25 cerebr27The medical management of patients with PPCM is similar to that for other forms of heart failure, and has been reviewed in detail. Treatmen30Subsequent monitoring depends on response to treatment, and includes a follow-up echocardiogram in the first several weeks to confirm improvement of left ventricular systolic function. After that, an echocardiogram is indicated approximately every 6 months until recovery is confirmed or a plateau is reached. The best time to discontinue ACE-inhibitors or β blockers is unknown; however, one or both of these medications should be continued for at least 1 year. Where resources exist, left ventricular assist devices and heart transplantation may be utilized if necessary.33 LimitePeripartum cardiomyopathy (PPCM) is a rare cardiomyopathy of unknown cause which is a serious threat to life. PPCM remains a diagnosis of exclusion and Echocardiography provides clues to Diagnosis in a symptomatic patient. Decompensated PPCM needs a multidisciplinary approach and hence is a serious challenge in the Emergency Department as well as in the hospital.


Becker-Kiener muscular dystrophy (BMD) represents an X-linked genetic disease associated with myocardial involvement potentially resulting in dilated cardiomyopathy (DCM). Early diagnosis of cardiac involvement may permit earlier institution of heart failure treatment and extend life span in these patients. Both echocardiography and nuclear imaging methods are capable of detecting later stages of cardiac involvement characterised by wall motion abnormalities. Cardiovascular magnetic resonance (CMR) has the potential to detect cardiac involvement by depicting early scar formation that may appear before onset of wall motion abnormalities.In a prospective two-center-study, 15 male patients with BMD  underwent comprehensive neurological and cardiac evaluations including physical examination, echocardiography and CMR. A 16-segment model was applied for evaluation of regional wall motion abnormalities (rWMA). The CMR study included late gadolinium enhancement (LGE) imaging with quantification of myocardial damage.Abnormal echocardiographic results were found in eight of 15 (53.3%) patients with all of them demonstrating reduced left ventricular ejection fraction (LVEF) and rWMA. CMR revealed abnormal findings in 12 of 15 (80.0%) patients (p = 0.04) with 10 (66.6%) having reduced LVEF (p = 0.16) and 9 (64.3%) demonstrating rWMA (p = 0.38). Myocardial damage as assessed by LGE-imaging was detected in 11 of 15 (73.3%) patients with a median myocardial damage extent of 13.0% (range 0 to 38.0%), an age-related increase and a typical subepicardial distribution pattern in the inferolateral wall. Ten patients (66.7%) were in need of medical heart failure therapy based on CMR results. However, only 4 patients (26.7%) were already taking medication based on clinical criteria (p = 0.009).Cardiac involvement in patients with BMD is underdiagnosed by echocardiographic methods resulting in undertreatment of heart failure. The degree and severity of cardiac involvement in this population is best characterised when state-of-the-art CMR methods are applied. Further studies need to demonstrate whether earlier diagnosis and institution of heart failure therapy will extend the life span of these patients. Muscular dystrophy type Becker-Kiener (BMD) and type Duchenne (DMD) represent X-linked genetic diseases related to mutations in the dystrophin gene which is located on chromosome Xp21.1 .Myocardial involvement with the development of dilated cardiomyopathy (DCM) has been described in up to 72% of BMD patients, mainly based on echocardiographic studies . It is bEarly diagnosis of cardiac involvement in patients with BMD may be useful, since an early institution of heart failure medication may lead to beneficial ventricular remodelling with improvement in LV systolic function or at least to decelerating progressive dysfunction ,7. HowevWith this study, we aimed at 1) comprehensively characterising cardiac disease manifestation in patients with BMD, 2) demonstrating the superiority of CMR compared to conventional echocardiography in cardiac evaluation of patients with BMD and 3) elucidating the in vivo cardiac damage pattern of patients with BMD.In a prospective two-center-study, 15 patients with BMD were consecutively ascertained and studied with respect to their neurological disorder at the neuromuscular outpatient clinic of the Department of Neurology, University of Ulm, Germany, followed by a comprehensive cardiological work-up at the Division of Cardiology of the Robert-Bosch-Krankenhaus Stuttgart, Germany. The diagnosis of BMD was confirmed by skeletal muscle biopsy evaluation with immunohistochemical analysis of the dystrophin protein and/or a genetic work-up with screening for dystrophin gene deletion and duplication. Cardiological work-up included physical examination, 12-lead ECG, echocardiography and CMR. Blood samples were obtained for laboratory studies including measurement of total creatine kinase (CK), cardiac troponin-I (TnI), brain-natriuretic-peptide (BNP) and C-reactive-protein (CRP) apart from others. This study was approved by the local ethical committee. Written informed consent was obtained from each patient or his legal guardian before inclusion to this study.Two-dimensional echocardiography was performed on a commercially available system  using a 3.5-MHz transducer with the patient in the left lateral decubitus position. Standard two-dimensional long and short axis views were recorded with the transducer in the apical and parasternal position. Measurements included left ventricular (LV) endsystolic and enddiastolic volumes. Biplane LV ejection fraction (LVEF) was calculated using the Simpson's rule. A semiquantitative global wall motion score index (GWMS) was calculated based on a 16-segment model as recommended by the American Society of Echocardiography : two exp®, Bayer-Schering, Germany) was 0.15 mmol/kg. In addition, fat-saturated and T2-weighted images were obtained to allow differentiation among subepicardial LGE, epicardial fat, and pericardial effusion.Electrocardiographic-gated CMR was performed in breath-hold using a 1.5-T system . Both cine and late gadolinium enhancement (LGE) short-axis CMR images were prescribed every 10 mm (slice thickness 6 mm) from base to apex. In-plane resolution was typically 1.2 × 1.8 mm. In addition to cine CMR, LGE images were acquired on average five to ten minutes after contrast administration with the use of a segmented inversion recovery gradient echo technique with constant adjustment of inversion time . The conCine and contrast images were evaluated by two blinded observers as described elsewhere . In brieData for continuous variables are expressed as median values in addition to minimal and maximal values, whereas data for categorical variables are expressed as the number and the percentage of patients. Comparisons between groups were done using a two-sided unpaired Student's t-test for normally distributed, and Mann-Whitney U test for non-normally distributed continuous variables. For categorical variables we used the chi-square test and Fisher's exact test, where appropriate. Agreement between methods was measured with Kappa statistics. Simple linear regression analyses were performed in order to identify possible determinants of reduced LVEF. The difference between two groups was defined to be statistically significant if the two-sided p-value was < 0.05.The patient characteristics are shown in Table As expected, all patients had elevated serum CK enzymes, however, all but one patient were TnI-negative suggesting a skeletal muscle origin of these enzymes Table . InteresAbnormal echocardiographic results defined as LVEF<60% and/or visual observation of rWMA were present in eight of 15 (53.3%) patients with all eight patients demonstrating reduced LVEF as well as some rWMA . Interestingly, CMR revealed abnormal findings (defined as LVEF<60% and/or rWMA and/or presence of LGE) in 12 of 15 (80.0%) patients (p = 0.040 compared to echocardiography) with 10 (66.6%) of them having reduced LVEF  as well as 9 (64.3%) demonstrating rWMA . Both techniques revealed rWMA in the same eight patients. However, using echocardiography rWMA was mostly observed in septal wall segments (n = 4) followed by lateral segments (n = 2) while CMR revealed rWMA primarily in the (infero-)lateral segments (n = 6). The kappa-test showed good agreement in the assessment of rWMA with echocardiography compared to CMR when studies without any rWMA were included to the analysis (kappa = 0.86). However, there was only a modest agreement in the assessment of rWMA when studies without rWMA were excluded (kappa = 0.37).2 = 0.770; p < 0.001). The youngest patient demonstrating at least some LGE was found to be 26 years of age and all patients older than 26 years had some myocardial damage. LV systolic function was depressed in the absence of LGE only in one patient aged 23 years.Myocardial damage as indicated by LGE imaging was detected in 11 of 15 (73.3%) patients with a median myocardial damage extent of 13.0%  were compared to those with reduced LVEF , significant differences were detected for age, BMI, LV-EDV, LV-mass, LVEDD, GWMS and LGE extent Table . Right vClinical examination revealed skeletal muscle involvement in 12 patients (80.0%), however, at least minor degrees of skeletal muscle weakness and pathology were detected by EMG in all patients limiting their effort and exercise capacity, thereby potentially masking cardiac exercise-dependent symptoms. Only four patients (26.7%) were already taking heart failure medication  and rWMA was found suggesting that a progressive reduction in LVEF is primarily due to the extent of myocardial damage.To the best of our knowledge, this is the first study subjecting a group of 15 patients with BMD (aged 11 years to 56 years) to comprehensive cardiological work-up including LGE imaging with CMR. Our results indicate that cardiac evaluation with CMR is more sensitive in detecting abnormal findings compared to ECG and conventional echocardiogpraphy, respectively. The findings of this study suggest that progressive myocardial damage is causing regionally accentuated loss in contractility, thereby resulting in progressive decrease in global LV systolic function. Furthermore, cardiac involvement in terms of myocardial damage in patients with BMD is predominantly beginning at the subepicardium of the inferolateral wall in the 3Cardiac involvement has been described in patients with MD for decades by post-mortem analyses ,16. In pBlood sample analysis for total CK revealed increased CK levels in all patients included to this study. Interestingly, higher CK-values were found in those with still preserved LV function. This finding is in accordance with previous studies suggesting that there is no correlation between cardiac disease severity and the degree of skeletal myopathy ,17. SurpIn the past, ECG changes attracted great interest as sensitive signs of cardiac involvement in BMD patients. The typical ECG changes described in the literature were felt to reflect a reduction in electromotive forces in the posterobasal and contiguous lateral wall ,21. HoweThe comparison of patients with normal and reduced LVEF confirmed previous results: patients with reduced LVEF were older, had larger and heavier hearts and demonstrated more rWMA. Left ventricular characteristics such as LV-EDV, LV mass and LVEDD were significantly associated with LVEF as shown by simple linear regression analysis. Interestingly, we found a substantial agreement between the presence of myocardial damage as demonstrated by LGE imaging and rWMA (kappa = 0.69). Since the highest coefficient of determination of LVEF was calculated for the parameter GWMS which depends on the extent and severity of rWMA which in turn is related to regionally pronounced myocardial damage, we conclude that the progressive reduction in LVEF is primarily due to the extent of myocardial damage.In post mortem hearts, it has already been demonstrated that myocardial damage is starting from the epicardial third of the inferolateral wall with possible transmural extension in contiguous segments ,22 and aThe detailed cellular and molecular mechanisms leading to myocardial contractile dysfunction in patients with MD are still to be elucidated. Preliminary animal studies suggest early alterations in cell metabolism and signal transduction in dystrophin-deficient hearts with a possible defect in the NO/cGMP pathway  and exceInterestingly, our group as well as other research groups have shown previously that this subepicardial pattern of myocardial damage which was detected predominantly in the posterolateral myocardial wall of patients with BMD is also a characteristic finding in biopsy-proven myocarditis ,26,27. TAs we did not perform endomyocardial biopsies in our patients with BMD, we could not rule out that myocarditis was the ultimate cause of the observed posterolateral pattern of myocardial damage. However, due to the fact that almost all patients aged ≥23 years showed this pattern, and all patients had proof of genetically determined abnormalities of dystrophin protein, an additional infectious cause seems highly unlikely.not diffusely distributed but accentuated in the posterolateral wall [How can one explain that a presumably diffusely distributed dystrophin abnormality in the human heart results in a pattern of myocardial damage which is preferentially located in the subepicardial portions of the posterolateral wall? One possibility is that the genetically determined dystrophin damage is ral wall . The othral wall ,25 leadiral wall  or arrhyral wall  demonstrEarly cardiac evaluation including state-of-the-art non-invasive imaging of young patients with MD is required in order to identify those who will most likely benefit from early heart failure therapy. Timely onset of heart failure medication has been shown to result in beneficial ventricular remodelling with improvement in LV systolic function or at least in retardation of progressive cardiac dysfunction ,7,36. InThe study size was small (with only 15 BMD patients) preventing further statistical analyses. However, considering the prevalence rate of this rare disease, it still constitutes a substantial number and no comparable CMR-based comprehensive studies focusing on LGE-imaging have been performed on a cohort of BMD patients previously, although there is a prior case report . We acknCardiac evaluation with CMR is more sensitive in detecting abnormal findings in BMD patients compared to conventional echocardiogpraphy. Myocardial damage is predominantly beginning at the subepicardium of the inferolateral wall – similar to cardiomyopathy in viral myocarditis – with an age-dependent increase in its extent and a progressive reduction of LVEF. Based on the results of this study, regular CMR examinations in BMD patients older than 20 years may be useful in order to prevent the underdiagnosis of cardiac involvement and the delay in onset of beneficial heart failure medication.BMD: Becker-Kiener muscular dystrophy; BNP: brain-natriuretic-peptide; CMR: cardiovascular magnetic resonance; CK: creatine kinase; CRP: C-reactive-protein; DCM: dilated cardiomyopathy; DMD: Duchenne muscular dystrophy; GWMS: global wall motion score index; LGE: late gadolinium enhancement; LV: left ventricular; LVEF: left ventricular ejection fraction; MD: muscular dystrophy; rWMA: regional wall motion abnormalities; TnI: troponin-I.The authors declare that they have no competing interests.AY designed the study, participated in the CMR exams, carried out the data and statistical analysis, and wrote the manuscript. HJG participated in the study design and carried out the neurological examinations. HB participated in the study design and the CMR exams and carried out the data analysis. HM participated in the analysis of the CMR data and reviewed the manuscript. GM participated in the analysis of the CMR data and reviewed the manuscript. CB participated in the evaluation of the study results and reviewed the manuscript. GT participated in the evaluation of the study results and reviewed the manuscript. ADS carried out the neurological examinations and reviewed the manuscript. ACL supervised the neurological examinations and reviewed the manuscript. US supervised the study and critically reviewed the manuscript.


To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis.Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization.In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI , and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization .Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted. Left ventricular (LV) wall motion abnormalities (WMA) induced during intravenous dobutamine are associated with flow limiting epicardial coronary artery stenoses, and predict future cardiac events including myocardial infarction (MI) and cardiac death -4. TypicThis study was performed to determine if the absence of inducible WMA during intravenous dobutamine would be associated with a favorable cardiac prognosis regardless of resting LV EDWT. To address this question, we measured LV EDWT and performed extensive follow-up on individuals undergoing dobutamine stress cardiovascular magnetic resonance (DCMR) examinations with cine white blood fast-gradient echo techniques.The study complies with the Declaration of Helsinki, and was approved by the Institutional Review Board at the Wake Forest University School of Medicine. All patients gave both verbal (for performing follow-up questionnaire) and written  informed consent. Between 1997 and 2001, 175 consecutive participants with a LV ejection fraction >55%, and no inducible LV WMA indicative of ischemia in any of 17 myocardial segments during DCMR were enrolled in the study. After DCMR, participants blinded to DCMR test results performed the outcomes analysis.As previously described ,5, imageAt rest and during graded doses of dobutamine/atropine stress, LV wall motion was confirmed as normal across all 17 myocardial segments . The resWithin 7 years of the DCMR exam, each participant was contacted to determine the post-procedure occurrence of cardiac events. All persons were contacted initially by phone or personal interview. If deceased, the next of kin was contacted. Questions were administered to identify the possibility of myocardial infarction (MI), unstable angina (USA) or congestive heart failure (CHF). Any change in physical state, medical condition, or medicationwas confirmed in all cases by review of the participant's medical records. If an event was suspected or identified during contact with the participant, medical records from the site of the event were obtained and confirmation of the event was determined according to data collected from the medical record. Established, published criteria were utilized to define events. Hard events were defined as cardiac death  for Windows. Based on previously published criteria, participants were dichotomized into those with a LV EDWT < or ≥12 mm . In thisTo determine the intra observer variability for measuring LV EDWT, a randomly selected sample of 20 participants was analyzed twice separated by 1 year. To determine inter observer agreement in measures of LV EDWT, this same sample from 20 participants was analyzed by a separate individual. In both the intra and inter observer comparisons, repeat assessments were performed in an unpaired fashion blinded to the results of prior analyses.The authors had full access to the data and take responsibility for its integrity.Contact was made with all 175 patients; their clinical data are displayed in Table Over the 5.5 average years of follow-up, the rate of hard events was 8.4% Table . The 5.5The proportion of participants free of both hard and any cardiac events is shown in Figure The intra observer correlation of LV EDWT was 0.73, and the inter observer assessment of LV EDWT was 0.77.Prior studies have found that increased LV EDWT during a dobutamine stress test is associated with a decreased sensitivity for detecting flow limiting coronary arterial luminal narrowings detected with contrast coronary angiography . Other sFour possibilities could explain our results. First, with dobutamine stress echocardiography, previous investigators have noted an inability to visualize all myocardial wall segments during cardiac stress testing procedures ,5, and tSecond, as shown in Table Third, Smart, et al , have shFourth, the presence of increased LV EDWT may portend a poor prognosis independent of the presence of coronary arteriosclerosis. Increases in LV EDWT can result from one or more of several factors including: increased LV afterload , or preexisting genetic abnormalities ,22. AlsoThe findings of the current study have several important clinical implications for the management of patients with chest pain syndromes. First, the absence of dobutamine induced WMA in individuals with a resting left ventricular EDWT of ≥12 mm does not forecast the same cardiac prognosis as for individuals with a LV EDWT <12 mm. In fact, in the participants in this study with a LVEF >55% and no inducible LV WMA, the 2-year hard event free survival was 89%. In a previous study from our group that included patients referred for dobutamine stress that exhibited inducible ischemia and a LVEF >40%, the 2-year event free survival was 84% , but alsSecond, further investigation should be considered to risk stratify patients with a LV EDWT >12 mm but without inducible WMA during intravenous dobutamine. Recently, Paetsch, et al , has demThird, it is important to recognize that we did not measure left ventricular mass in the current study. Thus, those individuals with eccentric left ventricular hypertrophy, who may have normal wall thickness, or those with concentric remodeling, who may or may not have an absolute increase in wall thickness depending upon their left ventricular cavity size, are not included in the current analyses. For this reason, these data are somewhat preliminary and further studies that would understand the relationship between left ventricular hypertrophy and the patterns of hypertrophy and adverse cardiovascular events are warranted.Fourth, the study was performed using measures of LV EDWT derived from cine, gradient-echo white blood imaging techniques. At 1.5 T, this image acquisition strategy often exhibits flow artifacts along the LV endocardial surface, particularly in apical views when LV systolic function is reduced. Though this technique has been used in large 6000 person population studies such as the Multi-Ethnic Study of Atherosclerosis , newer sOur study has the following limitations. First, according to previously published criteria from transthoracic echocardiography, we selected a dichotomous variable of < or ≥12 mm in LV EDWT as our primary outcome variable . AbnormaSecond, measures of LV mass using a multi-slice short axis Simpson's Rule acquisition strategy were not acquired in the current study. Importantly however, our measures of LV EDWT are easily acquired and can be reported during echocardiographic as well as CMR techniques; hence the clinical applicability of this finding is high. Finally, we are unable to identify whether there is a threshold of LV EDWT that confers information regarding cardiac prognosis among individuals with different race . The preThese data indicate that in those with a LV ejection fraction >55% at rest and no inducible WMA during intravenous dobutamine, a LV EDWT measurement of ≥12 mm using cine white blood gradient-echo imaging techniques is associated with adverse cardiac events. Increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.CAD: coronary heart disease; CHF: congestive heart failure; DCMR: dobutamine cardiovascular magnetic resonance; EDWT: end-diastolic wall thickness; HR: hazard ratio; LV: left ventricular; MI: myocardial infarction; USA: unstable angina; WMA: wall motion abnormalities.The authors declare that funding for MRI image acquistions were in part supported by NIH R01HL074330 and NIH General Clinical Research Center M01RR07122 grants and through a small ownership in Prova, Inc., a company that produces and sells software for cardiac MRI image display.TFW performed follow-up, designed study and wrote manuscript; EDA performed follow-up, designed study, and wrote manuscript; TMM designed study, provided statistical analysis and edited manuscript; WN designed study and edited manuscript; KML performed MRI studies and image analysis, and edited manuscript; CAH enabled image acquisition and analysis, and edited manuscript; DWK designed study and edited manuscript; WGH designed study, performed MRI studies and image analysis, and edited manuscript.


Recent studies have shown that real-time three-dimensional (3D) echocardiography (RT3DE) gives more accurate and reproducible left ventricular (LV) volume and ejection fraction (EF) measurements than traditional two-dimensional methods. A new semi-automated tool (4DLVQ) for volume measurements in RT3DE has been developed. We sought to evaluate the accuracy and repeatability of this method compared to a 3D echo standard.LV end-diastolic volumes (EDV), end-systolic volumes (ESV), and EF measured using 4DLVQ were compared with a commercially available semi-automated analysis tool  in 35 patients. Repeated measurements were performed to investigate inter- and intra-observer variability.p < 0.001). Bland Altman analysis revealed high agreement of measured EDV, ESV, and EF compared to TomTec (p = NS), with bias and 95% limits of agreement of 2.1 ± 21 ml, -0.88 ± 17 ml, and 1.6 ± 11% for EDV, ESV, and EF respectively. Intra-observer variability of 4DLVQ vs. TomTec was 7.5 ± 6.2 ml vs. 7.7 ± 7.3 ml for EDV, 5.5 ± 5.6 ml vs. 5.0 ± 5.9 ml for ESV, and 3.0 ± 2.7% vs. 2.1 ± 2.0% for EF (p = NS). The inter-observer variability of 4DLVQ vs. TomTec was 9.0 ± 5.9 ml vs. 17 ± 6.3 ml for EDV (p < 0.05), 5.0 ± 3.6 ml vs. 12 ± 7.7 ml for ESV (p < 0.05), and 2.7 ± 2.8% vs. 3.0 ± 2.1% for EF (p = NS).Average analysis time of the new tool was 141s, significantly shorter than 261s using TomTec (In conclusion, the new analysis tool gives rapid and reproducible measurements of LV volumes and EF, with good agreement compared to another RT3DE volume quantification tool. Left ventricular (LV) volumes and ejection fraction (EF) are important parameters for diagnosis and prognosis of patients with heart disease -3. TradiReal-time three-dimensional (3D) echocardiography (RT3DE)  echocardiography) is gaining popularity as a routine clinical tool , and hasCurrently, two commercially available volume measurement tools for RT3DE exist on the market; QLAB , and TomTec 4D LV-Analysis . Different versions of the TomTec tool have been verified against cardiac magnetic resonance imaging (cMRI) in several studies ,14-16, sGE has introduced a new semi-automated tool for 4D LV volume quantification (4DLVQ) in RT3DE . 4DLVQ provides a simple user interface and an efficient workflow by eliminating the need for manual tracing, making the tool simple to use for non-expert users.The objective of this study was to evaluate the agreement of LV volumes and EF measured by 4DLVQ compared to TomTec, to evaluate the repeatability of these parameters, and to determine the potential of 4DLVQ as a clinical tool.4DLVQ is a volume quantification tool for rapid semi-automated detection of the LV endocardial border in RT3DE. When entering the tool, the user is presented with a quad-screen, showing cine loops of three apical views with 60° inter-plane spacing, and one short axis (SAX) view. If required, the apical views can be manually corrected to show the standard apical four-chamber (A4CH), apical two-chamber (A2CH), and apical long axis (ALAX) views, thereby eliminating foreshortening. When this anatomical alignment step is complete, the ED frame is automatically detected from the EGG, but can be manually corrected if necessary.While displaying the ED frame, surface detection is initialized by manually selecting two points identifying the mitral annulus and one point identifying the LV apex in each of the three apical views shown in figure The above procedure is repeated for ES. The frame corresponding best to end systole is estimated automatically from the R-R interval of the EGG ,19 and cWhen surface detection is complete for both ED and ES, preliminary measurements of EDV, ESV, and EF are presented to the user. However, better measurements can be achieved by manually triggering temporal 4D surface detection to detect LV surfaces for each frame in the entire cardiac cycle. This typically requires less than 10 seconds, depending on the frame- and heart rate, and gives a full time-volume curve  and end-systole (ES).User input is facilitated by generating spring-like forces that pull the deformable model towards the spatial location of user-defined landmarks .The relative weights of the image and model forces were tuned on more than 100 training data sets to obtain a good trade-off between accuracy and robustness in different imaging situations and for various pathologies.After completed surface detection, LV volumes were derived from the triangulated surfaces by summation of all triangular patches using the divergence theorem .n = 20, exclusion criteria: atrial fibrillation, severe non-cardiac diseases), and Rikshospitalet University Hospital, Oslo, Norway, . Of note is that the original studies did not use 3D data. 3D echocardiograms were therefore only recorded in randomized sub-groups of the total study populations, as an addition to the primary protocols.Evaluation was done in 3D echocardiograms recorded in conjunction with two previous studies, giving data from a total of 56 patients  referred for echocardiography at St. Olavs Hospital, Trondheim, Norway,  and a 3D transducer (3V). Electrocardiogram (EGG) gated sub-volumes were acquired at 20–30 frames per second from four consecutive cardiac cycles during breath-hold, with the participants in the left lateral recumbent position. The sub-volumes were automatically stitched to a sequence of full 3D volumes covering the entire LV, and stored digitally for analysis.In 20 (36%) of the 56 patients, less than 70% of the myocardium was visualized, caused by a too narrow imaging sector, shadows, or dropouts. Stitching artefacts were found in one additional patient (2%). These factors would prohibit reliable volume measurements , and theA customized EchoPAC workstation  with the 4DLVQ software integrated was used by an expert operator according to the described tool workflow. Accurate anatomical alignment to the standard A4CH, A2CH, and ALAX views, were applied in all cases. If necessary, the ED frame was corrected to agree with the maximum cavity area, while the ES frame was adjusted primarily to agree with aortic valve closing, secondarily by visually determining the minimal cavity area. We always applied 4D segmentation to compute the full time-volume curve, as our experience was that this gave the most accurate EDV and ESV estimates. Manual editing of the detected surfaces was done as necessary at ED, ES, and after performing 4D segmentation. When a satisfactory result was obtained, EDV, ESV, and EF, were recorded for analysis.Repeated measurements were done in a randomized order using an EchoPAC workstation with a TomTec 4D LV-Analysis plug-in ver. 2.2. by the same expert operator after a minimum of 14 days. The operator was equally experienced with both 4DLVQ and TomTec, and was blinded to previous measurements. An overview of the TomTec workflow is given in figure Initialization of the TomTec surface detection algorithm was done by manually tracing the endocardial border using a spline-based annotation tool in the three apical views. Contrary to 4DLVQ, manual tracing was completed at both ED and ES in each apical view before continuing to the next view. Manual editing of the LV surface after surface detection could be avoided by tracing the endocardial border as accurately as possible during initialization . While tFor both methods, the analysis time was measured from the start of analysis of volumetric data until the volume and EF measurements were displayed on the screen. The analysis time was reported as average time ± standard deviation (SD).Intra-observer variability for 4DLVQ and TomTec was assessed in all 35 patients by the primary operator in a randomized order. The second expert operator assessed inter-observer variability in 10 randomly selected patients. Both operators were equally experienced with both 4DLVQ and TomTec, and were blinded to previous measurements. The minimum time interval between repeated measurements was 14 days.To compare repeatability with other studies, we adopted the method of Jacobs et al.  and Sugep < 0.05 regarded as significant). The agreement between the two methods was reported as the mean difference (bias) and the corresponding 95% limits of agreement. For comparison with other studies, Pearson's correlation coefficient between the two methods was also reported.The relationship between 4DLVQ and the TomTec reference values was analyzed by linear regression and Bland Altman analysis . The latp < 0.05 regarded as a significant).Agreement between inter- and intra-observer variability of the two methods was computed from the absolute differences between repeated measurements , which required 261 ± 63 s. The maximum time required for the two tools was 266 and 392 seconds respectively. The 4DLVQ tool required on average three additional manually defined landmarks to correct the initially detected surfaces.Semi-automated analysis was feasible in all 35 data sets. A full 4D analysis using 4DLVQ required 141 ± 37 s including image alignment, initialization, and manual correction of the detected surfaces. This was significantly quicker than for Tom Tec  in 35 patients.3D echocardiography makes it possible to capture the shape and function of the entire LV in a single data set. Compared to 2D echocardiography, this is an advantage for LV quantification, since geometric assumptions of LV shape can be completely eliminated. Further, 3D echocardiograms allowed for manually aligning the displayed views to the true anatomical LV main axis to avoid foreshortening and to ensure precise identification of the LV apex. These factors make automated 3D quantification better suited for accurate and reproducible measurements of ventricular volumes and EF than manual 2D methods. Also, an automated method can provide time-volume curves from a full cardiac cycle, giving more accurate EF estimates. The time-volume curve can potentially also be used to improve echocardiographic diagnosis, by providing information about timing of cardiac events, and filling rates in diastolic function analysis.Analysis time was significantly shorter with 4DLVQ than with TomTec. This difference was mainly due to the simplified 4DLVQ initialization procedure, requiring only nine easily located landmarks at ED and ES, instead of triplane tracing used for the TomTec analysis. Because of this simplified initialization, a few additional manually defined landmarks were often required to include papillary muscles in the LV volume, but since this was done interactively with immediate visual feedback, the overhead was minimal. One might argue that the TomTec analysis time could be reduced by a less accurate initialization, but it has been shown that accurate initialization is required to avoid time-consuming manual editing of the detected LV surface when using TomTec . SolimanWe have shown that EDV, ESV, and EF assessed by 4DLVQ compare well to measurements performed by TomTec, with small bias, narrow 95% limits of agreement, and high repeatability. A limitation of this study is the lack of an independent reference, and it is therefore not possible to determine which of the two methods is more accurate. However, since the agreement between the two methods was high for EDV, ESV, and EF, we conclude that 4DLVQ performs at least as well as TomTec in clinically realistic data, even with a lower analysis time.Several studies have presented repeatability assessment for various versions of TomTec. Soliman et al.  reportedDifferences between the workflows provided by TomTec and 4DLVQ are illustrated in figure The clinical feasibility of RT3DE relies on simple and efficient analysis tools, ideally integrated as a part of the scanner software to facilitate on-line analysis during examinations. This puts strong constraints on the performance and ease of use of the tool, also with respect to manual correction of automatically detected surfaces. The presented volume quantification tool was implemented as an off-line analysis tool for use on the EchoPAC workstation. We have shown that a full 4D analysis can be done in less than 3 minutes, also in patients where manual correction was needed. This indicates that the tool is well suited for on-line analysis.4DLVQ seems to be a reliable clinical tool, which provides rapid and reproducible measurements of LV volumes and EF with good agreement compared to TomTec. It has a simple workflow that makes it easy to use for non-expert users. Recent development within the field of automated landmark detection in RT3DE  may be uIt has been shown that the accuracy of LV volumes and EF is highly correlated to the amount of myocardium that is visualized in the RT3DE recording . We defiIn this study, both TomTec and 4DLVQ were evaluated on the same data sets, to rule out differences in measured volumes and EF caused by differences during acquisition related to frame rate, probe position, and differences in image quality. This study design also ruled out comparison with Philips QLAB, due to file format limitations. Analysis of inter-examination variability, and comparison with analysis packages from multiple vendors should be addressed in a future study.Cardiac MRI is currently accepted as the gold standard for LV quantification, and several studies have shown that TomTec compares well with cMRI, giving good agreement in measured EF, but with slightly under estimated volumes ,12,14-16We have evaluated a new volume quantification tool for automated EDV, ESV, and EF measurements in volumetric echocardiograms. The tool compared well to a commercially available analysis tool , with higher repeatability, and a significantly shorter analysis time. This is an important step towards wide spread use of RT3DE in clinical routine.JH worked as consultant for GE Vingmed Ultrasound. SIR is employed by GE Vingmed Ultrasound. SU, KL, and SM received research grants from GE Vingmed Ultrasound.JH contributed to development of the analysis tool, was the primary observer, drafted the manuscript, and performed the statistical analysis. SIR designed and developed the analysis tool, was the secondary observer, supervised the project, and participated in drafting the manuscript. SU collected data, supervised the clinical aspects of the project, and participated in drafting the manuscript. KL collected parts of the data, and revised the manuscript critically for important intellectual content. SM collected parts of the data, and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.Temporal 4D (3D + time) analysis results from a normal left ventricle with normal function. The movie shows four anatomically aligned cut planes through a 4D recording of a normal left ventricle, where left ventricular (LV) surfaces (green contours) have been detected for each frame in the entire cardiac cycle. Manually added landmark points are shown as green circles. The time-volume curve (right) shows the volumes computed from the detected surfaces in each frame of the cardiac cycle, along with the end diastolic (ED) and end systolic (ES) frames computed from the maximum and minimum volumes respectively.Click here for fileTemporal 4D (3D + time) analysis results from a dilated left ventricle. The movie shows four anatomically aligned cut planes through a 4D recording of a dilated left ventricle, where left ventricular (LV) surfaces (green contours) have been detected for each frame in the entire cardiac cycle. Manually added landmark points are shown as green circles. The time-volume curve (right) shows the volumes computed from the detected surfaces in each frame of the cardiac cycle, along with the end diastolic (ED) and end systolic (ES) frames computed from the maximum and minimum volumes respectively.Click here for file