A number of myocardial Doppler-derived velocity, strain myocardial imaging parameters (DMI) and speckle tracking imaging (STI) have been proposed for the quantification of myocardial ischemia during stress echocardiography. The purpose of the study was to identify the best single ultrasound quantitative parameter for prediction of significant coronary stenosis and compare it with visual assessment during dobutamine stress echocardiography (DSE).Prospective analysis included data of 151 patients (age 61.8 ± 9.2) who underwent dobutamine stress echocardiography for known (n = 35) or suspected coronary artery disease (CAD) (n = 36) or symptomatic chest pain (n = 80), excluding patients with previous myocardial infarction. Systolic, post-systolic and diastolic velocities, strain and strain rate parameters were obtained at rest and at peak dobutamine challenge. Derivative markers as E'/A' ratio, post-systolic index and changes from rest to stress were calculated . Coronary angiography was chosen as reference method considering at least one stenosis ≥70% per patient as significant CAD. The predictive value of quantitative parameters and wall motion score index (WMSI) was obtained using logistic regression and ROC analysis.The value of single parameters discriminated as independent predictors of CAD appeared to be modest , comparing to AUC of WMSI 0.88. Sensitivity, specificity and accuracy of visual DSE evaluation was 82.4% , 92.6%  and 86.0% , respectively, Youden index 0.75. Sensitivity, specificity and accuracy of single predictors ranged from 40.0% to 93.3% , from 34.2% to 88.7%  and from 45.8% to 80.0%  respectively, Youden index ranged from 0.20 to 0.52.Multiple single quantitative parameters showed limited predictive ability to identify significant coronary artery stenosis. Visual assessment of DSE appears to be more accurate than single velocity and strain/strain rate markers in the diagnosis of CAD. Pharmacologic stress echocardiography is an established cost-effective technique for the detection and prognostication of coronary artery disease (CAD), howeverA number of myocardial velocity and strain parameters derived by DMI and STI are reported to be reliable quantitative markers of stress-induced ischemia. They include reduced response of systolic and diastolic velocities, prominent post-systolic velocities-8, reducThis case–control study aimed to discriminate the best single quantitative parameter for prediction of significant coronary stenosis from the wide range of velocity- and strain-based parameters, simultaneously applying pulsed wave DMI (PW-DMI), color coded DMI (CC-DMI) and STI during dobutamine stress echocardiography (DSE) test and compare them with conventional visual wall motion assessment.2), atrial or ventricular arrhythmias, bundle branch blocks or LV EF <45%. Mean wall motion score index (WMSI) at rest was equal to 1.02 ± 0.04 and mean left ventricular (LV) ejection fraction (EF) equal to 54.5 ± 1.8%. The study protocol was approved by the local ethics committee.Prospective analysis included data of 151 patients (age 61.8 ± 9.2) who underwent dobutamine stress echocardiography for known (n = 35) or suspected CAD (n = 36) or symptomatic chest pain (n = 80). Typical angina was found in 63 (41.7%) patients, while remaining patients presented atypical angina or other ischemic equivalents. Exercise ECG could not be performed or did not provide definite results in 105 (69.6%) patients. In order to shape homogenous study group in terms of baseline quantitative parameters patients with previous myocardial infarction were excluded. Previous myocardial infarction was identified either from medical history or from revealing the combination of resting wall motion abnormalities with silent corresponding coronary occlusion. Other exclusion criteria were previous cardiac surgery, permanent pacemaker, nonsinus rhythm, significant valvular heart disease, significant left ventricular hypertrophy  with 1,5 – 4,6 MHz transducer was used. A 12-lead electrocardiogram (ECG), blood pressure (BP), and standard two-dimensional echocardiograms were taken at baseline, low-dose, peak dobutamine levels and during recovery. The dobutamine infusion was terminated once 85% of the maximal predicted heart rate was achieved. Stress test was terminated prematurely in the presence of severe chest pain or other intolerable symptoms, severe arrhythmia, >2 mm ST-segment elevation or depression, systolic blood pressure >230 mm Hg, diastolic blood pressure >120 mm Hg, or a drop in systolic blood pressure >20 mm Hg.Each study patient underwent DSE. Betablocking medications were discontinued 48 hours prior to the study. Dobutamine was infused at 5, 10, 20, 30, and 40 The long and short axis of the left ventricle from parasternal window, 4- and 2-chamber views from apical window were acquired for comparison in four stages of stress test. Left ventricle was divided into 16 myocardial segments according to the recommendations of the American Society of Echocardiography for the assessment of local myocardial function by wall thickening and endocardial motion. Each myocardial segment was scored as 1 if normokinetic, 2 if hypokinetic, 3 if akinetic and 4 if dyskinetic, assessment was made using quad-screen display by experienced observers. It was considered that in some cases of normal variant basal inferior and basal inferoseptal segments could look and be scored as hypokinetic. The sum of all segmental scores divided by the number of assessed segments made wall motion score index.PW-DMI profiles, CC-DMI and STI images were recorded at baseline and peak dobutamine levels with breath-holding. Images were optimised for pulse repetition frequency, color saturation, sector size, and depth to allow high frame rates. The loops were stored digitally on hard disc and analysed off-line using customised software .Apical 2, 3 and 4-chamber views were used for the acquirement of longitudinal myocardial velocity profiles by pulsed-wave DMI. The frequency of transducer in pulsed-wave Doppler mode was 2.6 MHz. A sampling gate of 6.4 mm was placed at the centre of each evaluated segment. The spectral Doppler signal parameters were adjusted to obtain Nyquist limit 40 cm/s by using the lowest filter settings and the optimal gain to minimize noise. Special care was taken to align the ultrasound beam parallel to the direction of motion of each myocardial segment  and to avoid lateral displacement of the sample volume outside the segment.The frame rate of stored apical 2, 3 and 4-chamber cineloops was in the range of 140–150 frames/sec. A sample cursor was placed manually at the midpoint of each evaluated segment in the 3 apical views, and myocardial velocity, strain and strain rate curves were reconstituted off-line.The frame rate of stored apical 2, 3 and 4-chamber cineloops for speckle tracking analysis was in the range of 70–90 frames/sec. After manual tracing of endocardial borders in the end-systolic frame of the 2-D images, the software automatically tracked myocardial motion, creating 6 regions of interest in each apical image, with tracking quality labeled as verified or unacceptable. In segments with unacceptable tracking, the observer readjusted the endocardial trace line until a verified tracking was achieved. If this was not attainable, that segment was excluded from analysis. Graphical displays of deformation parameters  were then automatically generated for 6 segments in each view.Peak longitudinal systolic (S'), post-systolic (PS'), diastolic  velocities, peak systolic (SS) and post-systolic (PSS) strain, peak systolic (SSR) and post-systolic (PSSR) strain rate at rest and during peak stress were measured Figure. BesidesCardiac cycles associated with atrial or ventricular extrasystolic beats were excluded. Quantitative parameters were analyzed by investigators who were blinded to the coronary angiography findings. All the measurements were performed manually off-line. Five consecutive beats were averaged for each of these measurements to improve the signal to noise ratio of the derived curves.Event timing was performed using PW-DMI velocity profile of basal inferoseptal or basal inferior segment. The duration of positive systolic velocity wave was taken as systole. Post-systolic motion in PW-DMI mode was defined as positive wave, which appeared after the curve of systolic ejection had reached the zero line Figure, top. AtPost-systolic strain Figure, middle Peak longitudinal systolic strain rate was defined as maximal negative peak in strain rate curve during systole, post-systolic longitudinal systolic strain rate was measured as negative peak during IVRT up to 50–70 ms after the mitral valve opening Figure, bottom.All quantitative parameters were evaluated in 9 out of 16 myocardial segments, discriminated according to our previous DMI study as most The STENOSED group consisted of segments supplied by stenosed (≥70% narrowing) coronary arteries, while the NON-STENOSED group consisted of segments supplied by non-stenosed  coronary arteries .Ejection fraction was calculated using the modified biplane Simpson method. LV myocInterobserver agreement was determined by having two independent investigators measure representative parameters with three quantitative methods and assess WMSI in 15 randomly selected patients. Intraobserver agreement was determined by having 1 investigator repeat measurements and WMSI evaluation in other 15 randomly selected patients 1 month later, while being blinded to the previous measurements. Reproducibility is expressed as the mean percentage difference .Inova2100 . Clinical decision to perform coronary angiography was made independently of this study by consulting cardiologists, who frequently were aware of the results of DSE visual evaluation. Coronary angiographic data were analysed visually by 2 experts blinded to the clinical data and the results of DSE. Significant coronary stenosis has been defined as ≥70% artery lumen narrowing localized in the proximal or middle segments of the coronary arterial tree in 2 orthogonal angiograms.The coronary angiography was performed in all 151 patients referred to DSE within 6–8 weeks after dobutamine challenge in Vilnius University Hospital Santariskes Clinic using a standard technique with t-test (for independent samples) or Mann–Whitney test. As the amplitude of quantitative parameters depends on the location of the segment in the left ventricle, analysis was performed separately for each segment location. The level of significance was set to 0.05. All reported P values were two sided.Descriptives were presented as mean+/−standard deviation. Comparison of STENOSED versus NON-STENOSED segments with respect to different markers of interest was carried out with a help of The evaluation of predictive ability of different imaging methods was carried out using logistic regression and receiver operating curve (ROC) analysis. In each segment, markers which had predictive ability  were discriminated. To build logistic regression model SPSS 16.0 software was used. Sensitivity, specificity and accuracy were calculated using standard definitions; cut-offs were chosen as having the highest Youden index, which was calculated as [1- (1 - sensitivity) + (1 - specificity)].Clinical and echocardiographic characteristics of the study population are reported in TableIschemia was visually assessed in 60 (39.7%) subjects: rest and peak WMSI was 1.02 ± 0.05 and 1.36 ± 0.21, respectively. A normal test was detected in 91 individuals (60.3%).A total of 53 (35.1%) patients had ≥70% coronary stenosis and 98 had normal coronary anatomy or <70% stenosis. Among the patients with significant coronary stenosis, 1-vessel disease was present in 32, 2-vessel disease in 11, and 3-vessel disease in other 11 patients. There was significant LAD stenosis in 34, LCX stenosis in 24, and RCA stenosis in 28 patients. The grade of stenosis ≥70% was found in 48 arteries, ≥90% – in 38 arteries. The majority of patients (122) had right dominance, 21 patients presented left dominance, and 8 patients had balanced type of coronary circulation.The stored images of 38 segments 2.8%) due to poor image quality were totally excluded from the analysis, therefore the data of 1321 (97.2%) segments were finally analysed. The prevalence of uninterpretable signals in the segments included in the final analysis for PW-DMI, CC-DMI and STI at rest was 1.8%, 0.6% and 2.1%, during stress 3.8%, 3.3% and 5% and in total 2.8%, 1.9% and 3.6%, respectively. One of the most frequently (15-20% of segments) unmeasurable marker was stress E' wave velocity due to the E' and A' waves fusion at higher heart rates, especially with CC-DMI and STI methods. The best inter- and intraobserver reproducibility is documented for strain rate, while strain parameters appeared to be more variable with both CC-DMI and STI. The mean percentage differences of inter- and intraobserver measurements of velocity, strain, strain rate by three quantitative methods and WMSI are summarized in Table.8% due tThe most informative single parameters for prediction of significant coronary stenosis discriminated by means of ROC analysis are presented in TableAccording to the size of AUC the strongest single predictors of stenosis appeared to be stress E' wave velocity  and stress systolic strain .Sensitivity, specificity and accuracy of single predictors ranged from 40.0% to 93.3% , from 34.2% to 88.7%  and from 45.8% to 80.0% , respectively, Youden index ranged from 0.20 to 0.52 . Thus, our results confirm the relation of substantial list of quantitative parameters of regional myocardial function to the obstruction of coronary arteries.We performed the search of the best predicting parameter of significant stenosis separately for each evaluated myocardial segment, taking into account known base-to-apex and wall-to-wall differencies of myocardial velocity and strain/strain rate,19-21. FIn agreement with previously published findings,11,22,23Also, in concordance with previous reports,24-26 alIn parallel to previous deformation studies-13 longiBy analogy with the prior clinical studies,13,27, lHowever, the predictive ability of discriminated single parameters appeared to be modest: AUC ranged from 0.63 to 0.72. Similar ability to predict significant CAD was reported for strain rate, strain parameters and post-systolic index  in the study of Hanekom et al.[None of the quantitative markers could compare with the visual assessment of DSE in terms of the accuracy of predicting stenosis, which was 86% in the present study (accuracy of single parameters ranged from from 45.8% to 80.0%). In MYDISE investigation similar limited sensitivity (67-69%) and specificity (60-67%) of myocardial systolic velocities before correction by logistic regression models were demonstrated. In the Limited value of distinguished indices largely could be attributed to known technical challenges of quantitative imaging: potentially inadequate spatial and temporal resolution, angle-dependency, less accurate tracking of ultrasound speckles at higher heart rates, noise and artefacts. Mutual Current lack of evidence on effective application of quantitative methods in routine practice is reflected in recommendation documents of EAE and ASE,31. ThesWe are aware that selected angiographic coronary stenosis does not always reflect the potential alteration in the regional myocardial perfusion. Although coronary angiography is widely accepted as the reference standard, the relationship between stenosis severity and physiological reduction of coronary flow is quite variable. Qualitative assessment of coronary stenosis, though reflects common clinical practice, constitutes another limitation of the study. Further research in creating user-friendly automated quantitative tool is warranted.Though stress echocardiography is a well established tool for the detection of coronary artery disease, visual analysis of regional myocardial function has a drawback of substantial subjectivity and inter-observer variability. Therefore, the implementation of an objective, operator-independent technique using novel quantitative methods seems to be an attractive clinical goal but still remains the Holy Grail in echocardiography.We failed to find single powerful quantitaive parameter applicable in each myocardial segment for prediction of coronary stenosis. Visual assessment appears to be more accurate than single velocity and strain/strain rate markers in the diagnosis of coronary artery disease. The need still remains to create more practical and less time-consuming quantitative tool for DSE interpretation.DMI: doppler myocardial imaging; STI: speckle tracking imaging; PW-DMI: pulsed wave doppler myocardial imaging; CC-DMI: color coded doppler myocardial imaging; DSE: dobutamine stress echocardiography; LV EF: left ventricular ejection fraction; ROC: receiver operating curve; AUC: area under the curve; ECG: electrocardiogram; BP: blood pressure; S': systolic velocity; PS': post-systolic velocity, systolic; E', early diastolic velocity; A', late diastolic velocity; SS, systolic strain; PSS: post-systolic strain; SSR: systolic strain rate; PSSR: post-systolic strain rate; RSSR: radial systolic strain rate; RPSSR: radial post-systolic strain rate; IVRT: isovolumic relaxation time; PSI: post-systolic index; RCA: right coronary artery; LAD: left anterior descending artery; LCX: left circumflex artery; MMI: myocardial mass index; CAD: coronary artery disease.The authors declare that they have no competing interests.JC participated in design creation, performed quantitative imaging during dobutamine stress tests, measured study parameters, participated in data analysis and drafting article. DZ participated in concept formulation and drafting article. VS performed statistical data analysis, helped to interpret the data and draft article. VZ participated in design creation and drafting article, performed critical revision of article. VG participated in data analysis, performed critical revision of article. JB collected and measured study parameters, participated in data analysis. LC collected and measured study parameters, participated in data analysis. AL participated in design creation and drafting article, performed critical revision of article. All authors read and approved the final manuscript.JC since 1999 works and since 2006 runs the unit of stress echocardiography tests, where about 1500 tests per year are performed.Celutkiene_ additional file 1.doc: Additional file 1. Full list of measured and calculated parameters.Click here for fileCelutkiene additional file 2 70.doc: Additional file 2. Mean values of significant predictors of stenosis in NON-STENOSED and STENOSED segments.Click here for file


Heart Failure (HF) is a common syndrome with multiple causes. Cardiovascular magnetic resonance (CMR) is a medical imaging technique with significant advantages, allowing the understanding of aetiology and pathophysiology of HF in the individual patient, permitting specific therapy to be administered and predicting prognosis. This paper discusses the diverse role of CMR in HF. Heart failure (HF) is a syndrome arising from any cardiac disease severe enough to impair the heart's ability to support the physiological circulation. Clinically, it is characterised by a number of symptoms and signs most of which relate to fluid accumulation; particularly fatigue, breathlessness, cough, and peripheral oedema. The incidence and mortality of HF is high with more than 24,000 deaths a year in the UK  and a 30The approach to the HF work-up is systematised. Diagnosis of the syndrome is based on history, clinical examination, electrocardiography, chest radiograph, and blood tests . Imaging in HF is challenging and requires a multimodality approach. Echocardiography is the first-line investigation for assessment of cardiac anatomy, function, and dynamics. It is cheap, widely available and can be done at the bedside. However, it is limited by poor image quality in some patients and gives very little information about tissue characteristics and coronary anatomy. Cardiovascular magnetic resonance (CMR) provides additional incremental data in patients with HF, providing accurate quantification of systolic dysfunction, determining aetiology and prognosis and predicting response to and selecting therapy. The excellent image quality obtained by CMR allows a detailed examination of cardiac structure and function, without the need for ionising radiation. There are also the key advantages of tissue characterisation (unique to CMR) and perfusion imaging. Evaluation of HF is therefore one of the major current roles of CMR in clinical medicine with the pilot EuroCMR registry of 11,000 patients finding that the most common reason for referral for CMR was to evaluate for potential myocarditis/cardiomyopathy . In thisAssessment of the coronary arteries is currently limited to assessment of origins and proximal courses using CMR. The small calibre of the vessels and movement during the cardiac cycle make flow limiting disease difficult to evaluate using this modality . CardiacThis paper provides an overview of the principles of CMR and then discusses its role in specific conditions that can cause HF.CMR is the use of MRI to image the heart. Any modern MRI scanner can be used, once ECG gating and specific sequences for cardiac work are installed. Scans are typically performed during multiple 7–15 second breath holds, with standardized protocols according to the referral indication , 7. The CMR is excellent for distinguishing different soft tissues based on their magnetic properties described by the relaxations times T1, T2, and T2*. Normal and abnormal myocardium may have different relaxation times, but the addition of a gadolinium contrast agent greatly magnifies these differences. Gadolinium is chelated and behaves as a passive, extravascular, extracellular contrast agent. After an intravenous bolus, three time phases are considered. The first pass can be used for perfusion imaging and is often given during vasodilator stress to detect ischaemia. Early after contrast, severely hypovascular regions will not enhance . In the late phase (5 minutes plus post bolus), contrast lingers in areas of infarction or focal fibrosis due to slower contrast kinetics and a greater volume of distribution in extracellular water associated with collagen. When imaged using a sensitive sequence (inversion recovery), focal fibrosis appears bright—a region of late gadolinium enhancement (LGE). This can be assessed either visually or quantitatively based on relative enhancement compared to the background . The extSternal wires and all cardiac prosthetic valves and cardiac stents in use in the UK are CMR safe at 1.5 and 3 T. Many intravascular clips are not safe. All ICDs and most pacemakers are not safe with the risk of malfunction and significant heating of the pacemaker leads. There are now CMR conditional pacemakers (generator and leads) available . In the The most common reason for the failure to complete a CMR examination is claustrophobia. In one study, this resulted in 4.2% of patients refusing to undergo CMR . HoweverCMR can be safely carried out in patients following acute infarction and primary angioplasty and aids risk stratification –15. T2-wFollowing the onset of coronary occlusion, irreversible myocardial injury/myocyte necrosis develops as a transmural wavefront which begins in the subendocardium and moves progressively towards the epicardium . LGE CMRThe excellent spatial resolution and wide field of view in CMR also allows for identification of the complications of acute infarction including thrombus, true or false aneurysm, papillary muscle involvement, and ventricular septal defect.The use of CMR in chronic myocardial infarction helps to guide therapeutic and revascularisation decisions. As well as looking at rest perfusion images, imaging can be performed during vasodilator stress to derive flow reserve. Perfusion defects can therefore be observed and the cause of these can be clarified by comparing the LGE images and regional wall motion abnormalities on cine imaging. Low dose dobutamine stress CMR can also be used to assess myocardial contractile reserve. Left ventricular dysfunction secondary to coronary artery disease typically is either reversible as in states of ischaemia, or potentially irreversible, as in transmural myocardial infarction. As ischaemic cardiomyopathy is potentially reversible, the assessment of myocardial viability is extremely valuable. CMR can assess multiple markers of myocardial viability in a single examination . Myocardial infarction has a characteristic LGE pattern due to the wavefront of myocardial necrosis. This always involves the subendocardium at the core of the infarct, although it may be transmural. Transmurality predicts potential functional recovery but with a grey-zone of 50% transmural infarction recovery with revascularisation it is more difficult to predict . Low dosThe identification of viable (dark on late gadolinium imaging) myocardium in a patient with regional or global left ventricular systolic dysfunction in the setting of ischaemic heart disease can represent hibernation, stunning, dilated cardiomyopathy, or dyssynchrony –30. SuchThis autosomal dominant disease resulting in otherwise unexplained left ventricular hypertrophy can present with a number of different clinical phenotypes and in some patients will result in the development of HF and sudden death . CMR is FDCM is characterised by left ventricular (LV) dilatation and impairment on the background of a family history . CMR proThis disease is characterised by fibrofatty infiltration of the right or both ventricles . It may This disease is characterised by the presence of a thick endocardium with prominent trabeculation and deep recesses communicating with the LV cavity . In someHeart failure is the final common pathway for many types of congenital heart disease. CMR can assist in the morphological diagnosis, functional assessment, angiography, flow and tissue characterisation, monitoring ventricular function, and tracking change over time. Flow analysis allows shunt detection—a ratio of >1.5 is considered significant and likely to result in patient symptoms (including those of heart failure) at some stage . Cine imPericardial disease, particularly pericardial restriction can cause HF in the presence of preserved ejection fraction but impairing cardiac filling . CMR canEchocardiography is the first-line test for valvular heart disease, providing excellent assessment of haemodynamics and anatomy in most patients. CMR has incremental value, particularly where echocardiographic windows are poor . Cine imaging will allow precise evaluation of ventricular size and function which can be important in deciding when to surgically intervene in valvular disease . It willFlow sequences will allow the calculation of the regurgitant fraction in regurgitant valve disease and the forward flow maximal velocity in stenotic disease , 53. In the thorax, sarcoidosis usually manifests with disease in the lungs, lymph nodes, or heart. Autopsy evidence has shown that cardiac involvement can occur in up to 30% of cases . CMR assThis condition is caused by inflammation of the myocardium, most commonly as result of infection . It can The most common cause of iron overload cardiomyopathy is repeated blood transfusions in patients with beta thalassemia major. This results in a 50% mortality in patients under the age of 35 years . CMR allCardiac involvement is common in patients with AL or TTR amyloidosis. The presence of amyloid protein results in accelerated removal of gadolinium from the blood and increased myocardial uptake, such that more of it is present in the myocardium than the blood pool . This chCardiac hypereosinophilia  causes endomyocardial fibrosis, valve disease and papillary muscle dysfunction, diastolic dysfunction, intracardiac thrombus formation, and heart failure. These are highly characteristic and well diagnosed and followed by CMR using T2-weighted imaging, early and late gadolinium techniques , 65.Endemic in South America, the chronic phase may result in heart failure  characteCardiac resynchronisation therapy (CRT) using biventricular pacing is a commonly used treatment for patients with HF and limiting symptom . Upto 1/The incidence of HF remains high throughout the world. CMR using the methods described above, is establishing itself as the gold standard non invasive method for phenotyping this condition, providing important insight into both the aetiology and pathophysiology of this syndrome in individual patients. In future years we expect that CMR will provide us with continuing improvements in image quality. Many new sequences are likely to become available which for example will improve LGE imaging  and allo


Right ventricular (RV) function has proven to be of importance for patient risk stratification in heart failure and is associated with sudden death and exercise limitation. RV dysfunction might play an important role in diabetic cardiomyopathy. We therefore assessed RV function and volumes using MRI in patients with otherwise uncomplicated type 2 diabetes mellitus (T2DM), and compared RV parameters with those of the left ventricle (LV).Steady-state free precession sequences were used to assess RV dimensions in 78 uncomplicated T2DM patients and 28 healthy subjects within the same range of age. Furthermore, flow velocity mappings across the pulmonary valve and tricuspid valve were used to assess RV outflow and diastolic filling patterns respectively.2 * 10-3 vs. 2.8 ± 0.8 mL/s2 * 10-3, P<0.01, respectively. All RV parameters strongly correlated with its corresponding LV parameter (P<0.001).RV end-diastolic volume was significantly decreased in patients compared to healthy subjects, also after adjustment for BMI and pulse pressure . RV systolic function was impaired: Peak ejection rate across the pulmonary valve was significantly lower . Indexes of RV diastolic function were impaired: E peak filling rate and E deceleration peak were 315 ± 63 ml/s vs. 356 ± 90 ml/s, P<0.01 and 2.3 ± 0.8 ml/sDiabetic cardiomyopathy affects the right ventricle, similar to changes in LV dimensions and function. These observations suggest that right ventricular impairment is a component of the diabetic cardiomyopathy phenotype.This research was performed within the framework of the Center for Translational Molecular Medicine (www.ctmm.nl), project PREDICCt (grant 01C-104), and supported by the Netherlands Heart Foundation, the Dutch Diabetes Research Foundation, the Dutch Kidney Foundation, and Eli Lilly, the Netherlands.


Duchene Muscular Dystrophy (DMD) is a lethal disease caused by ubiquitous lack of dystrophin, but the interaction with regional cardiac mechanical forces that may facilitate eventual expression of abnormal contractile function is unknown. Diffusion tensor MRI (DTI) was used to evaluate function in Langendorff perfused hearts in the mdx mouse model of DMD. Abnormal calcium kinetics  and sheet mechanics (by DTMRI) occurred more prominently at the mid-upper ventricle, suggesting that regional mechanics influence the development of heart failure.The relationship between abnormal sarcoplasmic Ca2+ handling and cardiac structural mechanics in mdx mice has not been defined. DTI has been used to quantify the contribution of myocardial sheet architecture in ventricular wall thickening mechanics. In this study, DTI was employed to assess altered sheet mechanics that might be influenced by impaired calcium homeostasis. Furthermore, optical mapping of AP and CaT were employed to characterize local difference in ex vivo beating hearts.Sixteen-month old mdx (n = 10) and age matched wildtype  mouse hearts were prepared for Langendorff perfusion by sequentially cardiac arrest in diastole and systole for DTI: The first group (WT-NC & mdx-NC) was perfused with regular St. Thomas’ cardioplegic solution containing normal [Ca2+] (1.2 mM) to arrest hearts in diastole. To assess the regulatory effect of [Ca2+] on diastolic sheet mechanics, the second group (WT-LC & mdx-LC) was perfused with modified cardioplegic solution containing low [Ca2+] (0.078 mM). All hearts were then reperfused with Krebs buffer to resume beating followed by 2.5mM barium-induced systolic arrest for DTI. Absolute values of sheet angles, |β|s, in each heart were calculated from the diffusion tensors. MANOVA was used for statistical analysis. Another set of Langendorff beating mouse hearts from WT (n=2) and mdx (n=3) mice were optically mapped. RH237 and Rhod-2 AM were used as membrane potential and calcium probes. Steady state restitution pacing protocol was applied to estimate the calcium dynamics at different heart rates.In diastole, mdx hearts exhibited lower |β| in mid-upper ventricle than WT did. Reducing Ca2+] in cardioplegic solution normalized the diastolic |β| in mdx hearts but had no detectable effect on WT hearts. No significant difference of systolic |β| was observed between mdx and WT hearts. Fig.  Optical + in cardThe observed lower diastolic |β| in mdx hearts indicates that mdx cardiomyocytes fail to fully relax in diastole. The regulatory effect of [Ca2+] on diastolic |β| of mdx hearts suggests that the myocardial sheet diastolic dysfunction is reversible despite the advance age of mdx mice. Optical mapping of CaT in beating hearts further confirmed the DTI-detected localized calcium-dependent abnormality, indicating that the ubiquitous dystrophin deficiency in mdx mice depends on regional cardiac features for its affection. In conclusion, the disturbed sheet mechanics may reflect functional consequences of abnormal Ca2+ handling in vivo, which likely correlates with membrane calcium channel dysfunction that precedes eventual cardiac failure.RO1 HL073646.


To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities , LV outflow tract obstruction and age.Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities , LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher’s exact test.804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion.In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease. Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic disorder with a prevalence of 0.2%. It is characterized by left ventricular (LV) hypertrophy in the absence of any other cardiac or systemic disease. HCM is heterogeneous in terms of various gene mutations, histopathology, presentation, clinical course and prognosis Myocardial perfusion abnormalities are common in HCM patients and seem important for pathophysiology and prognosis Local differences in myocardial blood flow (MBF) at rest and their relationship to tissue characteristics as evaluated by LGE and T2-weighted imaging have not yet been examined in detail. This is especially important as signal characteristics of a single sequence are not specific for certain pathologies in HCM: For example LGE in HCM patients may not only represent fibrosis, but also myocardial disarray, inflammation, and necrosis Therefore, the purpose of this study was to quantify resting LV MBF by MRI and to determine its relationship to important parameters of disease such as LV wall thickness, LGE, T2-signal changes, LV outflow tract obstruction and age.This prospective, Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Johns Hopkins Medicine institutional review board . Written informed consent was obtained from all participants.Seventy patients with HCM were recruited mostly during their initial visit at our tertiary referral center and underwent cardiac MRI between November 2007 and May 2011. Patients with MRI contra-indications such as cardiac pacemaker and implantable cardioverter defibrillator (ICD) were excluded. Diagnosis of HCM was based on the presence of LV hypertrophy  not originating from other causes All cardiovascular MRI examinations were performed on a 1.5 T MRI system  using a 6-channel array surface coil and a spine coil. Cine MRI was acquired in the short-axis view using a retrospective, electrocardiographically gated, balanced steady-state free precession (SSFP) sequence: Repetition time (TR)/ echo time (TE) 2.9/ 1.2 ms, flip angle 76°, matrix 256×154, slice thickness 8 mm, reconstructed cardiac phases 30. In order to assess myocardial T2-signal abnormalities a spectral attenuated inversion recovery (SPAIR) T2-weighted dark blood turbo spin echo sequence was applied in the short-axis view: 1400/ 76 ms TR/ TE, echo train length 13, matrix 256×186, slice thickness 8 mm. For perfusion imaging a bolus of gadopentetate dimeglumine  was injected at a dose of 0.04 mmol/kg bodyweight, which was followed by a 20 ml saline flush; both were injected at a rate of 5 ml/s. Images were obtained using a saturation preparation SSFP sequence: TR/ TE 2.4/ 1.0 ms, inversion delay 180 ms, flip angle 40°, parallel acquisition acceleration factor 2 , matrix 192×134, slice thickness 8 mm Imaging planes and positions of cine, T2-weighted and LGE MRI were matched to the slice location of the cardiac perfusion sequence to allow direct comparison of all parameters within the same myocardial region. Cine and LGE sequences covered the entire left ventricle, but only the matching slices were used for comparison with myocardial perfusion.Quantitative analysis of cine and perfusion MRI were performed by one reader (XX 2 years of cardiac MRI experience), who was blinded to clinical history and echocardiographic findings. In order to determine local differences of myocardial perfusion, LV wall thickness, LGE and T2-signal, the LV myocardium was divided into 6 segments per slice in each of the acquired short-axis slice according to the recommendation of the American Heart Association Using dedicated cardiac software  LV mass index, LV end-diastolic and end-systolic volume index and ejection fraction were determined from short-axis cine MRI. The end-diastolic LV wall thickness was measured in each segment, matching the cardiac perfusion segments.T2-signal changes and LGE were scored visually in corresponding slices and segments by consensus of two experienced readers (YY 9 years of cardiac MRI experience and XX). Edema, defined as focally increased T2-signal when compared to remote T2-signal, was scored as absent  =  0 or present  =  1 for each myocardial segment. Similarly, T2 dark signal (chronic fibrosis), defined as focally reduced T2-signal when compared to remote T2-signal, was recorded as absent  =  0 or present  =  1. The extent of LGE within each segment was scored visually from 0 to 4 based on the percentage area with hyperenhancement: 0  =  no LGE, 1  =  1–25%, 2 = 26–50%, 3 = 51–75% and 4 = 76–100% LGE .For absolute quantification of MBF, perfusion maps were generated on a pixel-by-pixel basis using the Fermi function model and dedicated perfusion software as previously described To further assess regional differences in MBF, relative perfusion values were calculated. In each patient, we first defined reference segments as non- or mildly affected segments with myocardial thickness <20 mm and LGE score 0–1 in the segment as well as the respective epi- and endocardial subsegments. These thresholds were chosen because some patients did not have segments without LGE and myocardial wall thickness <15 mm. The mean MBF of reference segments in one patient was calculated and relative perfusion for all segments in one patient was then calculated in relation to this mean value. In addition, mean relative MBF of all reference segments of all 70 patients (per definition 100%) and the standard deviation (SD) were determined and three categories of relative perfusion were defined: reduced perfusion <mean -1 SD (86.75%), elevated perfusion ≥mean+1 SD (113.25%) and perfusion within one SD of reference segments (86.75–113.25%), referred to as reference .Statistical analysis was performed using SAS 9.2 . Values are expressed as mean and 95% confidence interval [CI]. P <0.05 was considered to indicate significance.In order to characterize the association of LGE with T2 signal changes and LV wall thickness a logistic regression with repeated measures was performed. The presence of LGE (score 1–4) vs. no LGE (score 0) was defined as response variable; LV wall thickness, edema and T2 dark signal as independent factors. In a linear regression model with repeated measures the relationship of relative resting MBF with LV wall thickness, LGE score, edema score, T2 dark score, LV outflow gradient at rest (determined by Doppler echocardiography) and age was determined. All statistically significant parameters (p<0.05) were then evaluated together in a multiple linear regression model. Although the distribution of relative resting MBF was slightly skewed to the left, we regarded the data as approximately normally distributed owing to the rather large sample size.As relative resting MBF was heterogeneous even in segments with LGE (range 33.5–147.2%), a subgroup analysis including all segments with LGE (score 1–4) was performed. Within this subgroup segments with reduced or elevated perfusion in combination with LGE  were evaluated for the presence of LV wall thickness ≥20 mm, focally elevated and decreased T2-signal and the pattern of LGE. The frequency of those parameters in reduced and elevated perfusion segments of this subgroup was compared to the frequency of parameters in reference segments of the subgroup using Fisher’s exact test; odds ratios and relative risks were calculated. The respective extent of LGE in elevated and reduced perfusion segments in this subgroup was compared using an unpaired t-test. It should be noticed that the subgroup analysis was performed descriptively on a per segment basis, and only descriptive p-values are given.In 70 HCM patients  804/840 segments were included in the analysis. Patient characteristics are given in All morphological phenotypes of HCM were included: 45 septal, 9 mid-wall, 7 apical and 9 diffuse types. LGE was detected in 258 segments (32%) within 54 patients. In a logistic regression model the odds for the presence of LGE were 1.25  for each millimeter increase in end-diastolic LV wall thickness. The odds for the presence of LGE were 16.31  in segments with focal T2 bright signal and 14.02  in segments with focal T2 dark signal .Absolute resting MBF was not significantly different between segments with varying severities of myocardial wall thickening or LGE. Also there were no significant differences between absolute epi- and endocardial resting MBF.In a simple linear regression model for repeated measurements LV wall thickness (p<0.001), LGE score (p<0.001), edema (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) but not LV outflow gradient (p = 0.901) showed a significant effect when correlated with relative resting perfusion . For exaLGE (score 1–4) was present in 49.4% (78/158) of segments with reduced perfusion (<mean -1 SD) and in 22.2% (24/108) of segments with elevated perfusion (>mean +1 SD). In reduced perfusion segments LGE was more frequently accompanied by T2 bright signal (edema), T2 dark signal (chronic fibrosis) and increased LV wall thickness ≥20 mm compared to reference segments. In elevated perfusion segments LGE was only more frequently accompanied by increased LV wall thickness compared to reference segments . The extIn this study focal differences of relative resting MBF in HCM patients were observed using MRI. Relative perfusion correlated inversely with LV wall thickness (p<0.001), extent of LGE (p<0.001), edema (p<0.001), T2 dark signal changes (p<0.001) and age (p = 0.032). The LV outflow gradient did not affect resting myocardial perfusion, which is consistent with previous studies Myocardial perfusion is an important parameter in HCM, because perfusion abnormalities may lead to ischemia and myocardial scarring and thus, increase the risk for adverse cardiac events such as arrhythmias and LV dysfunction. For instance, a reduction of myocardial perfusion reserve at hyperemia or during exercise, indicating microvascular dysfunction, has frequently been described in HCM patients In comparison, in our study alterations of resting perfusion could only be appreciated as relative changes, because absolute MBF was highly variable between patients. This is in agreement with previous studies demonstrating that absolute resting MBF is not different among segments with differing severities of myocardial wall thickening or LGE and between epi- and endocardial myocardium It has been suggested that LGE in HCM is mainly attributed to macroscopic fibrosis and focal increase of collagen In contrast, regions of elevated perfusion  were ass15O-PET imaging, which is known to decrease with the extent of fibrosis in chronic myocardial infarction Furthermore, the fact that LGE was also accompanied by increased perfusion in some segments in our study supports the hypothesis of Knaapen et al., that LGE in HCM patients not only represents macroscopic fibrosis but is also related to myocardial disarray, microscopic fibrosis, abnormal intramural coronary arteries and inflammation A limitation of the present study is the calculation of relative perfusion values. In HCM, alterations of myocardial perfusion have been demonstrated even in segments without morphological changes In conclusion, quantitative mapping of MBF allows for visualization and quantification of focal changes of resting myocardial perfusion in patients with HCM. The extent of LGE and the presence edema and focal T2 dark signal changes were independent predictors of segments with reduced relative resting MBF. Different myocardial resting perfusion patterns have been defined, which may represent different stages of disease. Further research needs to determine if the described resting perfusion patterns are predictors for clinical outcome in HCM patients.


In pulmonary arterial hypertension (PAH) increased pressure and resistance in the pulmonary vascular bed cause right ventricular (RV) hypertrophy with increased myocardial oxygen demand. Studies in animals with RV hypertrophy demonstrated maintained resting but reduced stress perfusion and coronary perfusion reserve, which may contribute to RV failure.The purpose of our study was to investigate myocardial perfusion by comparing coronary sinus flow reserve (CFR) between PAH patients and healthy controls and to correlate CFR with biventricular function and pulmonary hemodynamics using magnetic resonance imaging (MRI).norm = CSF/RPP). CFR was calculated by dividing stress CSF by resting CSFnorm (CFR = Stress CSF / Rest CSFnorm).Thirty-one patients with known or clinically suspected PAH underwent right heart catheterization (RHC) and 3T cardiac MRI on the same day. Twenty patients were found to have PAH, eleven patients did not have PAH. Seventeen age- and gender-matched healthy volunteers were also studied with MRI. Rest and adenosine-stress coronary sinus flow (CSF) were measured with phase contrast MRI Figure  and adju2 (area under the ROC curve 0.81 (95% CI: 0.55-1.00); sensitivity 83.3%, specificity of 85.7% for a threshold value of 1.67).CFR for PAH patients was significantly lower (2.22 1.40-3.22]) than for controls  (Table .40-3.22)PAH patients have a reduced CFR compared to healthy volunteers, which correlates with pulmonary hemodynamics and RV dysfunction. A decreased CFR is predicted by RV mass and may contribute to RV failure. Further studies are warranted to investigate the predictive value of CFR with regards to patient outcome.


Standard action potential duration restitution was obtained using the single extrastimulus method with measurement of the maximal restitution slope. Ventricular fibrillation threshold was measured as the minimal current inducing sustained ventricular fibrillation with burst pacing . Optical action potentials were recorded using the voltage-sensitive dye di-4-ANEPPS. Measurements were taken at baseline and after 60 min perfusion with BS (5 μm). Blebbistatin significantly prolonged left ventricular apical  and basal MAPD  and effective refractory period  whilst increasing the maximal slope of restitution  and ventricular fibrillation threshold . In other hearts, blebbistatin significantly prolonged optically recorded action potentials . In control experiments, the increase of MAPD with blebbistatin was present whether the hearts were perfused in constant-pressure mode (n= 5) or in unloaded conditions (n= 5). These data show that blebbistatin significantly affects cardiac electrophysiology. Its use in optical mapping studies should be treated with caution.Blebbistatin (BS) is a recently discovered inhibitor of the myosin II isoform and has been adopted as the mechanical uncoupler of choice for optical mapping, because previous studies suggest that BS has no significant cardiac electrophysiological effects in a number of species. The aim of this study was to determine whether BS affects cardiac electrophysiology in isolated New Zealand White rabbit hearts. Langendorff-perfused hearts ( What is the central question of this study?Does the mechanical uncoupler blebbistatin affect cardiac electrophysiology?What is the main finding and what is its importance?Blebbistatin significantly affects cardiac ventricular electrophysiology and induction of ventricular fibrillation. This is a new finding that has serious implications for optical mapping studies where blebbistatin is used to inhibit cardiac contraction.Optical mapping techniques for monitoring cardiac membrane potential are growing in popularity in cardiac electrophysiology research and are the technique of choice for elucidating the mechanisms that underlie cardiac arrhythmias. Optical mapping employs the use of a voltage-sensitive dye to allow the non-invasive, simultaneous recording of membrane voltage from multiple sites, and in the cardiac ventricle this can encompass the entire left ventricular (LV) epicardial surface, providing detailed spatial and temporal measurements of electrical activity. A major challenge in optical mapping is motion artefact generated from myocardial contraction, which results in a low signal-to-noise ratio (SNR) and poor quality action potential (AP) recordings. Several methods have been used to overcome this obstacle, ranging from mechanical techniques where the heart is contained within a glass chamber to reduce contractile movement (Blebbistatin (BS) is a recently discovered molecule that has been reported as an effective ECU in cardiac preparations  have not been adequately examined. The action potential duration (APD) restitution property of the myocardium is considered to be a key factor in arrhythmogenesis with increased wavebreak, oscillations and susceptibility to VF, and the importance of this property has been previously reviewed .All procedures were undertaken after local ethics approval at the University of Leicester and were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and the n= 39; Harlan, Shardlow, UK) were sedated with an intramuscular injection containing a mixture of medetomidine hydrochloride , ketamine  and butorphanol . Following 15–20 min of sedation, the animals were heparinized  and then killed with an overdose of pentobarbitone sodium  administered via the marginal ear vein. Hearts were rapidly excised and briefly immersed in ice-cold Tyrode solution before cannulation via the ascending aorta and perfusion in a retrograde Langendorff manner with Tyrode solution of the following composition (mm): Na+, 138.0; K+, 4.0; Ca2+, 1.8; Mg2+, 1.0; HCO3−, 24.0; H2PO4−, 0.4; Cl−, 121; glucose, 11; and acetate, 20.0. The solution was warmed to 37°C and was kept at a pH of 7.4 by continuous bubbling with a 95% O2–5% CO2 gas mixture. The time from death to cannulation was within 90 s. Hearts were perfused in a single-pass non-recirculating manner to avoid the confounding effects of byproducts that accumulate from perfusion effluent. A 3 French catheter  was inserted through the left ventricular apex to drain Thebesian venous effluent. Left ventricular pressure (LVP) was monitored with a fluid-filled latex balloon inserted into the left ventricle via the left atrium. The balloon was connected to a pressure transducer  using a 3 French cannula and the volume adjusted to keep end-diastolic pressure at 0–5 mmHg. Perfusion pressure (PP) was monitored with a second pressure transducer connected in series with the aortic cannula.Adult male New Zealand White rabbits  have been reported before  were used to record monophasic action potentials (MAP) at the apical and basal epidcardial surfaces of the left ventricle using a custom-made DC-coupled high-input-impedance differential amplifier  from the atrial stimulus spike to the time of activation of the ventricular MAP recorded at the apical region and the basal region.Hearts were paced at the right ventricular apex at the following three different cycle lengths: 300, 250 and 200 ms, for 5 min steady state at each cycle length. The MAPD was measured from the time of MAP activation to repolarization at 90% decay. The interval from the time of the ventricular stimulus spike to the activation of the MAP was also measured. Monophasic action potential duration and all measurements were made from MAPs at both apical and basal regions using NewMap software .90). Restitution was examined by analysis of the relationship between S2-MAPD90 and preceding diastolic intervals . An exponential curve [MAPD90= MAPD90max (1 – e−DI/τ)] was fitted using Microcal Origin Pro , where MAPD90max is the maximal MAPD90 and τ the time constant. The maximal slope of restitution was obtained by analysing the first derivative of the fitted curve.Standard APD restitution data were obtained with right ventricular pacing using a 20 beat drive train (S1) at 300 ms cycle length (CL) followed by an extrastimulus (S2), and repeated with progressively shorter S1–S2 intervals . Blebbistatin significantly increased the maximal restitution slope, as indicated by the dotted lines in The effects of blebbistatin on APD restitution and the maximal slope of restitution are illustrated in P < 0.05). Although the exact conduction path of the paced beats was not mapped, hence conduction velocity not measured directly, these data suggest that conduction velocity at short diastolic intervals is decreased with blebbistatin.During the extrastimulus protocol, the delay from S2 to the beginning of the S2 MAP signal (S2 delay) was measured and increased with progressively shorter S1–S2 intervals. An illustration of S2 delay is shown in n= 7) on changes in ECG recorded during perfusion with blebbistatin. There was no significant ST segment shift at baseline or during blebbistatin perfusion. Blebbistatin caused a significant increase in QT interval by 5 min perfusion, reaching a plateau between 10 and 15 min, mirroring the changes in MAPD ( in MAPD . Mean dan= 5 for each group). There was a trend for MAPD to be longer using the Tyrode solution of P= 0.05 and P= 0.06). However, irrespective of the Tyrode solution used, changing from constant-flow to constant-pressure mode did not significantly (P > 0.05) affect MAPD.The effects of changing from constant-flow to constant-pressure Langendorff mode using our modified Tyrode solution and that of n= 5 for each group). The MAPD was significantly (P < 0.001) increased during blebbistatin perfusion irrespective of the composition of the Tyrode solution.The effects of blebbistatin in hearts that did not have any intraventricular load  using our modified Tyrode solution and that of n= 5 for each group). The MAPD was significantly (P < 0.001) increased during blebbistatin perfusion irrespective of the Tyrode solution composition. Perfusion pressure was 59.4 ± 3.5 mmHg (our modified Tyrode) and 55.1 ± 4.3 mmHg (Fedorov Tyrode), whilst blebbistatin significantly (P < 0.05) reduced coronary flow irrespective of the composition of the Tyrode solution, from 47.5 ± 3.3 to 25.1 ± 5.3 ml min−1 (our modified Tyrode solution) and from 43.9 ± 1.6 to 31.2 ± 3.9 ml min−1 (Fedorov Tyrode solution).The effects of blebbistatin in hearts that were unloaded and perfused in constant-pressure Langendorff mode using our modified Tyrode solution and that of m, with a complete abolition of contraction at 5 μm. There was a significant increase in PP from doses of blebbistatin of 0.5 m and above . This equated to a mean increase of 36.5 ± 10.3 ms, or 27.6 ± 8.7%. In addition, baseline APD and APD measured during blebbistatin perfusion were remarkably similar when using either contact electrodes or optically recorded techniques, suggesting that regardless of the recording technique, blebbistatin significantly prolongs action potential duration.The effect of blebbistatin was investigated using optically recorded action potentials in four hearts and is illustrated in In this study, the effects of the ECU blebbistatin on LVP, PP, atrioventricular conduction, MAPD, QT interval, standard APD restitution and VF inducibility were measured. We have shown that blebbistatin resulted in an expected abolition of ventricular contractile force production and a biphasic effect on PP, with an initial vasodilatation followed by a secondary increase in PP with concomitant reduction in coronary flow. Blebbistatin did not affect heart rate, atrioventricular conduction or intraventricular conduction. However, we have shown, for the first time, that ventricular MAPD is prolonged, mirrored by QT interval prolongation, and the APD restitution slope and VF threshold are both significantly increased during perfusion with blebbistatin. Finally, we observed a consistent increase in MAPD in conditions of constant pressure and constant flow, in hearts that did not have any load in the left ventricle and in action potentials recorded with optical mapping. These findings are important with regard to their impact upon the field of optical mapping and suggest that further confirmatory study is required, as well as investigations into the mechanism of action.The changes observed in this study differ from those previously reported. m). We did not demonstrate similar spontaneous activity in our experiments; however, the dose required to abolish motion artefacts (5 μm) is lower than those reported by To our knowledge, the present study is the first to demonstrate that blebbistatin causes significant changes in the ventricular electrophysiology, although m.Currently, we have little explanation regarding the difference between our observations and previous reports, despite performing extensive control experiments to address differences in experimental approach, which includes replication of experimental conditions used in other studies. It is important to highlight that all hearts within our study were allowed to equilibrate for a period of 30 min prior to baseline measurement. Once a baseline was achieved, our measurements of MAPD, electrical restitution and VFT remain stable within an acceptable range over a period of up to 5 h, as indicated in the control stability data presented within this manuscript . We are In considering the differences between the findings of the present study in comparison to previous reports, we have performed control experiments to explore methodological differences between our study and others, which are discussed below, including the method of Langendorff perfusion, intraventricular load, composition of the perfusate, the method of measuring action potentials and recirculation of the perfusate.m), in keeping with its known vasodilatory properties (versus 5 μm), though PP was still significantly greater than control values. This trend was not found to be significant.The method of Langendorff perfusion is worthy of some discussion. Data published by In principle, this vasoconstriction could lead to a degree of mild global cardiac ischaemia, which may have secondary effects on cardiac electrophysiology, in addition to promoting tissue oedema. Such secondary ischaemia could cause a shortening of MAPD , also suggest altered intracellular calcium handling.The mechanism suggested by An interesting finding in our study was the dissociation of the electrical restitution property from ventricular fibrillation inducibility. Our previous data on restitution slope and VFT support an inverse relationship between the two parameters, especially in conditions of autonomic stimulation, which is in agreement with the restitution hypothesis, i.e. increase in restitution slope and increase in VF susceptibility (reduction in VFT). In the present study, we showed dissociation between the two parameters, with an increased VF threshold (reduced susceptibility to VF) coupled with an increase in restitution slope following blebbistatin perfusion, suggesting that other arrhythmogenic mechanisms may be relevant. The mechanism underlying these results would need further investigation. However, an increase in ERP was observed, which may be associated with the increased VF threshold despite an increase in restitution slope.Another noteworthy finding in our study was that blebbistatin prolonged S2 delay, suggesting a decrease in this surrogate marker of conduction velocity, although this could also represent delayed activation. We did not observe any change in pacing threshold during the experiment or during blebbistatin perfusion. An alternative hypothesis is that conduction slowing may reflect the encroachment of the S2 wavefront onto myocardium that is not fully repolarized, owing to the significant prolongation of MAPD, as opposed to a direct slowing of conduction. Nevertheless, it should be considered that the prolongation in S2 delay may represent an additional mechanism that causes the increase in VFT following blebbistatin perfusion.Monophasic action potentials were measured from only two sites of the left ventricular epicardial surface; therefore, the contribution of dispersion of repolarization  was not assessed, which may have an additional impact on arrhythmogenesis  between the recording and indifferent electrodes, and the intrinsicoid deflection represents the timing of local activation at the recording electrode, regarded as the beginning of the MAP signal relative to which duration is measured. In our study, MAPs could exhibit a phase 1-like morphology and ‘notch’ during the upstroke, representing an intrinsicoid deflection. This has been reproduced by others (m) caused significant changes in cardiac function, including an initial decrease and secondary increase of perfusion pressure, prolongation of action potential duration, increase of electrical restitution slope and shift of ventricular fibrillation threshold. Some of these changes were not completely reversed following a 2 h period of washout with blebbistatin-free Tyrode solution.In isolated, Langendorff-perfused rabbit hearts, blebbistatin (5 μ


Rheumatic fever is still a common cause of acquired heart disease in children and young adult in many developing countries. The aim was to investigate the role of myocardial involvement in the hemodynamic changes in patients with acute rheumatic fever using cardiac troponin assay and echocardiography. Design: A prospective cohort study was designed.Thirty-four children with acute rheumatic fever, 20 with carditis, and 14 without carditis. Level of cardiac troponin T (cTnT) and echocardiographic measurement of left ventricular function were the main outcome measure.The level of cardiac troponin in children with carditis was 0.051 ± 0.01 ng/dL, and it was 0.039 ± 0.02 ng/dL in those without carditis. The difference is not significant. In addition, there was no significant difference between the children with carditis and those without carditis regarding left ventricular ejection and shortening fractions.There are no significant echocardiographic measurements abnormalities or cTnT levels elevation suggesting clinically relevant hemodynamic abnormalities due to myocardial involvement during acute rheumatic fever. Streptococcal pharyngitis remain medical and public health problems in both industrialized and industrializing countries even at the beginning of the 21st century. The most devastating effects are on children and young adults in their most productive years.[Rheumatic fever is the most common cause of acquired heart disease in children and young adults all over the world. Despite ve years. Althoughve years. Cardiac ve years. Cardiac ve years.Acute valvular disease with heart failure or chronic valvular disease account for most of the morbidity and mortality associated with rheumatic fever. Revised The aim of this study was to investigate the role of myocardial involvement in the hemodynamic changes in patients with acute rheumatic fever using echocardiography and cTnT as a specific marker of myocardial damage.The study was a prospective cohort study conducted on the Suez Canal University Hospital.Children admitted with the diagnosis of acute rheumatic fever according to the modified Jones criteria.It includes the presence of associated congenital heart disease and recurrent or chronic rheumatic valvular lesions. For each patient, the following was done: complete history and physical examination to detect inclusion and exclusion criteria. A blood sample was collected from each patient to measure ESR, C-reactive proteins, ASOT, and cTnT. Electrocardiography and echocardiography were performed for each child. The patients received the regular treatment as per the hospital protocol for the cases of rheumatic fever. The patients were divided into two groups according to the presence or absence of carditis. Carditis was defined clinically as the prolongation of PR interval in the ECG, sleeping tachycardia out of proportion of fever, the presence of a new murmur of aortic or mitral regurgitation or the presence of heart failure. This was confirmed by echocardiography at the time of the diagnosis.A sample of blood was taken from each child. The blood was centrifuged, separated, and frozen at –20 °C until batch analysis was performed. Biochemical analysis was performed with an Elecsys Troponin T STAT Immunoassay . This electrochemiluminescent sandwich enzyme-linked immunosorbent assay has a lower limit of detection of 0.01 ng/mL, and the normal range for cTnT is 0.01–0.1 ng/mL.It was performed using the Hewlett-Packard sonos 1800 series equipped with 3.5–5 MHz transducer. All studies included parasternal long and short axis views, apical four, five chamber views, subxiphoid four chamber, and suprasternal view. Ejection fraction and fractional shortening were determined, and the severity of valvular regurgitation was graded qualitatively from 0 to 4 The data were analyzed using the statistical package SPSS. Descriptive statistics were used to present the characteristics of the study population. Continuous data were compared using Student’s t-test. Categorical data were compared with a two-tailed c2 test. Statistical significance was accepted as P < 0.05.A written consent was given from participants’ family with approval of ethics committee.The study group comprised 34 children with ARF, 19 (56%) were females and 15 (44%) were males. The mean age of the study group was 11.3 ± 2.65 years.Out of the study population, 20 children (59%) showed evidence of carditis, and 14 children (41%) had ARF without evidence of carditis.The distribution of valvular lesions in children with carditis is shown in P > 0.05).P > 0.05). In addition, there was no significant difference between the two groups regarding the fractional shortening which was 31.8 ± 6.2% in the group of children with carditis and 37.5 ± 6.4% in the children without carditis (P > 0.05).Despite pathologic evidence of myocardial inflammation, the significance of myocarditis in children with acute rheumatic carditis remains controversial. The guidIn this study, we could not find any biochemical alteration or echocardiographic measurements change suggestive of significant hemodynamic effects due to myocardial involvement. No statistically significant difference was found in the level of cTnT between patients with and without rheumatic carditis. Furthermore, all patients showed cTnT level within the normal range even in those with heart failure. Cardiac troponin T is considered as one of the new “gold markers” of ischemic myocardial injury and has been detected as a sensitive and specific marker of even subclinical myocardial injury. It is also used in the diagnosis and monitoring of nonischemic myocardial injury, like myocarditis.et al.,[et al.[et al.[et al.,[In addition, the echocardiographic study failed to show any significant difference in the left ventricular ejection and shortening fractions between children with and without rheumatic carditis whether or not they had congestive heart failure. Our results are in agreement with Tavli et al., who show.,[et al. also deml.[et al. examined.[et al., who demoThe low cTnT values, especially in the presence of active carditis, dispute significant ischemic myocyte injury. MyocardiWe can conclude that this study did not demonstrate an elevated cTnT level suggesting clinically relevant myocardial involvement during acute rheumatic fever even in patients with severe carditis and congestive heart failure. In addition, we failed to show significant difference in echocardiographic measurements between patients with and without carditis. These findings substantiate the view that myocardial involvement during acute rheumatic fever has no significant hemodynamic effects and does not play a role in the development of heart failure in patients with rheumatic carditis. Heart failure is related mainly to the extent of valvular lesions rather than the myocardial involvement.However, among study limitations are rather small number of studied population. Further studies are needed to confirm that myocardial involvement during acute rheumatic fever is not relevant in the development of heart failure in patients with rheumatic fever.


Asymptomatic aortic stenosis (AS) remains a challenging clinical entity characterised by adverse left ventricular remodelling, microvascular dysfunction and sudden cardiac death. Previous studies have shown reduced myocardial strain in patients with asymptomatic aortic stenosis, however the relationship between impaired myocardial strain, ischaemia and major adverse cardiac events (MACE) remains poorly understood. We therefore assessed myocardial strain and myocardial perfusion reserve index (MPRI) in these patients and followed patients prospectively.96 consecutive patients  underwent CMR scanning on a 1.5T scanner with a 32-channel coil. Of these, 45 underwent adenosine stress perfusion scanning. The remaining 51 patients had medical contraindications for perfusion imaging or refused consent. LV mass and MPRI were analysed and late gadolinium enhancement imaging (LGE) was performed using standard protocols, and scored by two independent operators blinded to other CMR results. Patients were then followed prospectively for a mean of 1.5 ±0.8 years and the predictors of MACE determined.19 of 96 patients suffered a MACE: 1 death, 12 valve replacements, 1 atrial fibrillation, 1 pacemaker insertion, and 4 unplanned hospitalisations with cardiac symptoms. Patients with MACE had significantly impaired mid ventricular peak systolic circumferential strain compared to those without MACE  was not related to strain or to MACE.British Heart Foundation, Heart Research UK, Oxford Biomedical Research Centre, National Institute for Health Research.


Takotsubo cardiomyopathy (TCM), otherwise cardiomyopathy,apical ballooning syndrome or broken heartsyndrome is a reversible cardiomyopathy, predominantly occurs in post-menopausal women and commonly due toemotional or physical stress. Typically, patients present with chest pain and ST elevation or T wave inversion on theirelectrocardiogram mimicking acute coronary syndrome, but with normal or non-flow limiting coronary artery disease.Acute dyspnoea, hypotension and even cardiogenic shock may be the presenting feature of this condition. The wall motionabnormalities typically involve akinesia of the apex of the left ventricle with hyperkinesia of the base of the heart.Atypical forms of TCM have also recently been described. An urgent left ventriculogram or echocardiogram is the key investigationto identify this syndrome. Characteristically, there is only a limited release of cardiac enzymes disproportionateto the extent of regional wall motion abnormality. Transient right ventricular dysfunction may occur and is associatedwith more complications, longer hospitalisation and worse left ventricular systolic dysfunction. Recently, cardiac MRI hasbeen increasingly used to diagnose this condition and to differentiate from acute coronary syndrome in those who haveabnormal coronary arteries. Treatment is often supportive, however beta-blocker and angiotensin-converting enzyme inhibitoror angiotensin II receptor blocking agent are being used in routine clinical practice. The syndrome is usually spontaneouslyreversible and cardiovascular function returns to normal after a few weeks. This review article will elaborate onthe pathophysiology, clinical features including the variant forms, latest diagnostic tools, management and prognosis ofthis condition. The cardinal feature of TCM is transient and reversible left ventricular (LV) dysfunction triggered by severe emotional or physical stress, in the presence of unobstructed coronary arteries. The exact stressors and pathogenesis remains unclear. Variant forms of left ventricular dysfunction have been reported, including wall-motion abnormalities, such as mid-ventricular ballooning with sparing of the basal and apical segments, or inverted Takotsubo. Right ventricular involvement is also reported in TCM . VentricTo date, there have been little more than 1200 Pubmed published reports on TCM. The prevalence among patients with symptoms suggestive of acute coronary syndrome is 1.0–2.5%, with almost 90% of cases being in post-menopausal women , 5. OverIn those patients who were included in the large multi-centre randomised Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study comparing bivalirudin with abciximab and heparin in STEMI, the prevalence of TCM was reported as 0.45% . HoweverThe exact mechanism of TCM is unknown. The trigger is frequently, but not always, an intense emotional or physical stress eg, catastrophic news, death of a relative, particularly if unexpected, arguments, natural disasters (including Tsunamis), war, or even surgery. The pathogenesis is not well understood but a number of theories exist:et al have reported the development of all variants of TCM in nine patients following intravenous epinephrine and dobutamine infusion, supporting the concept that catecholamines have a role in the genesis of TCM [et al. also noted an increased beta-2 concentration gradient from apex to base commonly found in TCM [Catecholamine activation of alpha-adrenoceptors and beta-adrenoceptors is the primary trigger of TCM changes. Catecholamine concentrates such as epinephrine and norepinephrine levels have been noted to be high during the acute phase of TCM . Wittstes of TCM . Rona res of TCM . Later ss of TCM . Studiess of TCM . Predomid in TCM . These od in TCM .Oxidative stress can lead to myocardial necrosis, remodelling, and contractility disturbances -15. The 2.-) hydrogen peroxide (H 2 O 2) and hydroxyl radical (OH)) may cause sarcoplasmic reticulum dysfunction, and these processes may lead to calcium overload, which in turn could exacerbate the damage initiated by oxygen species. ROS generation can also alter the function of cardiac sodium channels, potassium channels, and ion exchangers, such as the Na/Ca exchanger [Bolli proposed three main mechanisms for myocardial stunning: 1) generation of oxygen radicals, 2) calcium overload, and 3) excitation-contraction uncoupling due to inadequate release of calcium by the sarcoplasmic reticulum . The thrxchanger .There is now evidence to suggest that LV dysfunction in TCM may be related to oxidative stress in response to excess catecholamine in animal model . It was et al. showed that when ovariectomised rats without oestradiol supplementation were exposed to immobilisation stress they demonstrated significantly greater increases in the heart rate and reduction in LV function in comparison to rats that had oestradiol supplementation [About 90% of patients presenting with TCM are postmenopausal women. Animal models have demonstrated the cardioprotective properties of oestrogen. Ueyama entation . Furtherentation . This evet al. in 1990 [Transient coronary artery spasm leading to transient myocardial stunning without long lasting myocardial damage was proposed as aetiology of TCM by Sato  in 1990 , 23. How in 1990 , and theet al. investigated functional polymorphisms of β1 and α2c adrenergic receptors, but found no significant differences in polymorphism frequencies between TCM patients and controls [Sharkey controls . It has controls . Viral illness has been considered in particular because of the infiltration by mononuclear lymphocytes and macrophages observed in histological examination of most cases. However, so far no viral agents were isolated from patients with TCM.The clinical features of TCM are important to recognize as they mimic those of acute coronary syndrome (ACS) in the absence of significant coronary artery disease. Symptoms include acute chest pain (70%) and dyspnoea (20%) , 26 accoThe Mayo Clinic published diagnostic criteria for TCM (2008)is given below: Transient hypokinesis, akinesis, or dyskinesis of the left ventricularmid segments with or without apical involvement; the regional wallmotion abnormalities extend beyond a single epicardial vasculardistribution; a stressful trigger is often, but not always, presentAbsence of obstructive coronary artery disease or angiographicevidence of acute plaque ruptureNew ECG abnormalities (either ST elevation and/or T wave inversion)or modest elevation in cardiac troponinAbsence of other precipitants eg phaeochromocytoma, myocarditisElectrocardiographic abnormalities are the most common finding in TCM. ST segment elevation was present in up to 56% of patients particularly in anterior leads, 39% had T wave inversion and the remaining had QT prolongation or pathological Q waves . ArrhythCardiac enzymes such as CK and Troponin assays are typically only mildly elevated. This is disproportionate to the extent of regional wall motion abnormalities noted on imaging tests such as echocardiogram, left ventriculogram or cardiac MRI. The levels of brain natriuretic peptide (BNP), however, tend to be higher in TCM compared with acute coronary syndrome.Echocardiography usually shows characteristic apical wall changes including hypokinesia, akinesia and dyskinesia. The overall systolic function is reduced, with the reported ejection fraction ranging from 20 to 49%. However, more recently, variations of TCM have been reported such as inverted (23%), and mid cavity (10%) wall motion abnormalities . Left ventricular outflow tract (LVOT) obstruction can occur in patients with TCM  and in oet al. in 2006, the RV involvement was noted in 26% of the patients with TCM.[There have also been reports of right ventricular dysfunction in TCM. In a series by Haghi with TCM. The most2). Almost all have unobstructed coronary arteries but a substantial proportion have incidental findings of coronary artery disease. This could merely be an innocent finding reflecting the general population. Left ventriculogram is very useful to identify TCM in acute situation when the coronary arteries are normal with ST elevation on ECG. The typical left ventriculogram in diastole (Panel A) and systole (Panel B) of TCM is shown in Fig.  is usually absent, in contrast to other causes of myocardial damage such as myocardial infarction or severe LV dysfunction due to myocarditis. Apical myocardial oedema is commonly seen in TCM on CMR correlating with LV systolic dysfunction. On T2 weighted imaging of CMR, ventricular oedema appears as high intensity signal with a diffuse or transmural distribution in this condition. Moreover, the location of the oedema is not related to a vascular territory of coronary arteries, and oedema is distributed in both the apical and mid planes of the LV, which is also helpful to differentiate from acute MI . CMR can 123I-MIBG scintigraphy has been used to evaluate Takotsubo cardiomyopathy. There is decreased uptake of 123I-MIBG in areas of myocardial stunning. Villarroel et al. demonstrated a case of typical TCM and performed 123I-MIBG for the patient [123I-MIBG in the distal anterior and inferior wall and apex, corresponding to the akinetic segments on left ventriculography. Rest 99mTc-sestamibi images performed the following day for comparison show normal uptake in areas of decreased 123I-MIBG, therefore 123I-MIBG can be seen, notably from the inferior wall and apex [ patient . These wand apex . These aThe most common presentation is chest pain with ST segment elevation in anterior leads mimicking anterior STEMI. Therefore the initial treatment is most likely to be based on suspicion of anterior STEMI. In places where there is no primary angioplasty facility, there is a risk of these patients getting thrombolysed. Therefore initial history such as emotional stress is important and TCM should be suspected in all post-menopausal women who presents with anterior STEMI. The advantage of primary angioplasty is acute STEMI can be ruled out with angiography and the left ventriculogram may clinch the diagnosis of TCM at an early stage. The main stay of management in patients with TCM is supportive. There is no consensus on pharmacological management of TCM and due to the rarity of this condition; no RCTs have been conducted so far. Conservative treatment frequently leads to rapid resolution. However, in the initial stages, patients are treated with Aspirin and other anti-platelet agents, their role of which will be difficult to interpret. et al. in 2009 demonstrated that α and β adrenoceptor blockers may have a role in prevention of stress induced cardiac dysfunction [et al., in 2010, however reported in their series from a single institution that 20% of patients were already on beta-blockers while they developed TCM, either first or recurrent episode [The use of b-blockers has been specifically advocated due to the possible abnormal response to excessive catecholamines . This isfunction . Sharkey episode . They arThe LV function starts to recover from few days and recovers completely in 3-4 weeks. Though TCM is not benign during the acute episode, there is an excellent survival outcome if managed appropriately during the acute phase. The in-hospital mortality rate varies from 1.1% to 2%. .TCM is a reversible cardiomyopathy with a generally favourable outcome. It is a relatively recently described phenomenon which needs to be considered early in any patient that presents with acute dyspnoea, chest pain or collapse after an acute episode of grief, shock or stress. Multiple mechanisms potentially contribute to the pathogenesis of myocardial stunning but the exact mechanism is still not known. Catecholaminergic storm and β-adrenergic receptor-stimulated apoptosis in cardiac myocytes, mediated by reactive oxygen species/kinase-dependent activation of the mitochondrial pathway are two of the main theories. Irrespective of the cause, patients with the classic stress-induced cardiomyopathy morphology deserve special attention because this extensive distribution of wall motion abnormalities has implications for potential associated complications. CMR can be crucial in differentiating from acute MI. The management of TCM is usually conservative. The high prevalence of TCM in post-menopausal women suggests a role for oestrogen therapy. This review should provide not only a conceptual framework for further investigation of the pathophysiology of reversible cardiomyopathy but also a rationale for developing clinically applicable interventions. There is a need for national or international registry for TCM patients to understand more about this condition and manage appropriately.


There have been significant advancements in the ability of echocardiography to provide both morphological and functional information in children with congenitally malformed hearts. This progress has come through the development of improved technology such as matrix array probes and software which allows for the off line analysis of images to a high standard. This article focuses on these developments and discusses some newer concepts in advanced echocardiography such is multi-planar reformatting [MPR] and tissue motion annular displacement [TMAD].Our aim is to discuss important aspects related to the quality and reproducibility of data, to review the most recent published data regarding advanced echocardiography in the malformed heart and to guide the reader to appropriate text for overcoming the technical challenges of using these methods. Many of the technical aspects of image acquisition and post processing have been discussed in recent reviews by the authors and we would urge readers to study these texts to gain a greater understanding . The quawww.3dechocardiography.com] is the only way of visualising the advantages of this technology in real time.Three dimensional echocardiography (3DE) is an attempt to visualise the dynamic morphology of the heart. Although published media is the basis for theoretical knowledge of how to practically acquire images, electronic media [eg.It is important to be aware of the limitations of this technology and that much of the data gleaned from using these methods is at a research stage and not yet in regular clinical practice. They found that 3D volume assessment was feasible using both systems with good correlation of LV volume measurements   following the Percutaenous Left Atrial Appendage Transcatheter Occlusion (PLAATO) trial which demonstrated the feasibility and the safety of this process .The orifice of the left atrial appendage should be measured in two orthogonal views to select the most appropriate device size. RT3D TOE will improve the accuracy of the measurements by providing views where the left atrial appendage orifice could be visualized and measured without geometric assumptions. There have been two studies comparing 3D TTE with 2D TOE in identifying LAA thrombus. No LAA thrombus was missed with 3D TTE and it also offered the advantage of better distinguishing pectinate muscles from thrombi , 29.3D Echocardiography continues to develop and will play a more significant role in a number of clinical areas in the future. There are a number of current reviews discussing 3D echocardiography in detail .Strain and strain rate give us measures of cardiac deformation and contractility respectively. Strain and strain rate have also been determined using tissue Doppler but for the purposes of this review we will be focussing on speckle tracking echocardiography.Congenital heart disease faces a number of challenges when attempting to assess ventricular function due to complex anatomy, variable loading conditions and the fact that the right ventricle with all its complexity is as important as the left ventricle. Speckle tracking echocardiography has the potential to advance the understanding of cardiac function in congenital heart disease overcoming these obstacles.The introduction of new technology comes with a number of difficulties. Different vendors will have different solutions for the same problem, and in the context of this one needs to ensure the standardisation of acquisition and analysis of data. It is then important to acquire data on feasibility, reliability and accuracy of the method and to establish a set of normal values as a point of reference.Speckle tracking echocardiography is in the early stages of this process. Although a number of studies have been published on its application in various aspects of congenital heart disease it is not yet used for regular clinical decision making. The limitations of speckle tracking echocardiography have been outlined by a number of experts in this field -33. It iet al. compared results obtained from strain analysis using Echopac, SPEQLE and QLAB Phillips  in the context of combined pressure and volume loading . In this4).This pathophysiology has also been noted in other conditions such as aortic stenosis where there is an increase in deformation initially in response to increased after load and with chronicity and severity both strain and strain rate become reduced , 47 .This is a simple and accurate method available through QLAB (Phillips) for assessing cardiac function in normal children. This uses 2DSTE to track the displacement of the mitral or tricuspid valve annulus through the cardiac cycle. During off line analysis of an apical four chamber view three points of interest are placed on the lateral aspect of the valve annulus, the medial aspect and the ventricular apex. The value obtained gives a measure of the displacement of the valve towards the ventricular apex. This value is similar to TAPSE but is obtained with 2DSTE and is angle independent. No data has been published using TMAD in congenital heart disease. Unpublished data from our institution has shown TMAD to be an easy, reproducible method for assessing LV function in normal children. TMAD of the mitral valve annulus correlated with MRI derived LVEF [r=0.69] and was superior to M-Mode derived EF [r=0.33]. This is a method that once validated will have a significant impact on bed side assessment of cardiac function .Real time 3D has become available due to advances in transducer and beam forming technology. With current 3D technology there is a trade off for spatial and temporal resolution which will affect the data acquired. The benefit of 3D is simplicity of acquisition within one heart beat, it is useful for volumetric assessment, complex shapes and in arrhythmias. Future developments in 3D technology allowing acquisition with higher spatial and temporal resolution are needed. This is currently a research tool but with advancing technology holds promise for evaluation of ventricular function in malformed hearts (Fig. et al. have compared three-dimensional speckle tracking echocardiography with cardiac magnetic resonance and found that three-dimensional speckle tracking echocardiography measurements were in close agreement with the cardiac magnetic resonance reference values, in the presence of an adequate transthoracic two-dimensional acoustic window. To achieve automated assessment of left ventricular volumes and function with three-dimensional speckle tracking ultrasound, shortcomings have to be overcome such as low temporal resolution and random noise affecting the ability to track speckles during the cardiac cycle.Data has been published in which 3D speckle tracking has been used to quantify left ventricular volumes . Nesser 3D STE has also been used in assessing left ventricular mechanical dyssynchrony during CRT in heart failure patients .New developments and new technology will continue to emerge in the field of echocardiography. Strain analysis during stress echocardiography and three-dimensional imaging with shape analysis will advance our understanding of ventricular function in the malformed heart. It remains important, however, to have a good understanding of traditional methods of echocardiographic assessment of ventricular morphology and function. Although current developments hold exciting prospects for the future they are not yet at the stage where relevant clinical decisions can be made using them. When introducing new technology into your clinical environment it is important to be aware of the learning curve you will need to face. Image quality and validation of data obtained is essential before application in a clinical setting. Using this review and other similar articles to glean as much information as possible about image optimisation would be a good place to start. And, as stated previously, electronic media will play a large role in demonstrating the dynamic images produced using this technology.