More than 90% of heart murmurs in children are innocent. Frequently the skills of the first examiner are not adequate to differentiate between innocent and pathological murmurs. Our goal was to evaluate the value of a simple and low-cost phonocardiographic recording and analysis system in determining the characteristic features of heart murmurs in children and in distinguishing innocent systolic murmurs from pathological.The system consisting of an electronic stethoscope and a multimedia laptop computer was used for the recording, monitoring and analysis of auscultation findings. The recorded sounds were examined graphically and numerically using combined phono-spectrograms. The data consisted of heart sound recordings from 807 pediatric patients, including 88 normal cases without any murmur, 447 innocent murmurs and 272 pathological murmurs. The phono-spectrographic features of heart murmurs were examined visually and numerically. From this database, 50 innocent vibratory murmurs, 25 innocent ejection murmurs and 50 easily confusable, mildly pathological systolic murmurs were selected to test whether quantitative phono-spectrographic analysis could be used as an accurate screening tool for systolic heart murmurs in children.The phono-spectrograms of the most common innocent and pathological murmurs were presented as examples of the whole data set. Typically, innocent murmurs had lower frequencies (below 200 Hz) and a frequency spectrum with a more harmonic structure than pathological cases. Quantitative analysis revealed no significant differences in the duration of S1 and S2 or loudness of systolic murmurs between the pathological and physiological systolic murmurs. However, the pathological murmurs included both lower and higher frequencies than the physiological ones (p < 0.001 for both low and high frequency limits). If the systolic murmur contained intensive frequency components of over 200 Hz, or its length accounted for over 80 % of the whole systolic duration, it was considered pathological. Using these criteria, 90 % specificity and 91 % sensitivity in screening were achieved.Phono-spectrographic analysis improves the accuracy of primary heart murmur evaluation and educates inexperienced listener. Using simple quantitative criterias a level of pediatric cardiologist is easily achieved in screening heart murmurs in children. Although Dr. Laennec's invention, the stethoscope, has been in clinical use for more than 180 years, and electronic stethoscopes with variable amplification gain have been available for over 80 years, it is still difficult to understand auscultation findings . The phoThe first evaluation of children's heart murmur is one of the basic tasks of welfare clinic practitioners and school medical officers. However, based on their frequently limited auscultation experience, they might not be able to recognize the innocence of a heart murmur. Even the auscultation skills of pediatric residents have been found to be suboptimal -21. SevePrevious studies have shown that pediatric cardiologists, based on clinical examination, can differentiate innocent from pathological murmurs with high sensitivity (82...92 %) and specificity (76...99%) -33. EvenThe capability of a doctor or a computerized system to differentiate between pathological and innocent murmurs depends on the quality of the pathological murmurs. It is easy to recognize loud murmurs as pathological by means of clinical or digital analysis . SeriousThe purpose of this article was to demonstrate the capabilities of a modern digital system for phonocardiographic recording and analysis and to evaluate its potential for differentiating the characteristic features of heart murmurs in children. Another goal was to investigate how the numerical features measured from a phono-spectrogram can be used to distinguish innocent systolic murmurs from pathological murmurs, which are generally hard to identify in a routine clinical examination. This article additionally concludes more than ten years' experience of studying heart sounds.Heart sounds were collected at the outpatient pediatric cardiology clinics of the rural hospitals in the vicinity of Helsinki from 1995 to 1999. The Ethics Committees of Jorvi (4/95 number 17) and rural hospitals approved the study. The study series consisted of 807 children, whose ages ranged from newborn to 16 years. The recordings were done at random times, i.e. without pre-set dates. The patient roster was not available in advance and every patient with a positive attitude towards the study were included. From each patient, the auscultation finding at the point of maximal intensity was recorded. The patients were either children with murmurs referred for a cardiologic evaluation for the first time or patients with a known diagnosis. In all cases, the diagnosis was confirmed with echocardiography. The control series consisted of children without heart murmur, including children with paroxysmal supraventricular tachyarrhythmia, spontaneously closing ventricular septal defect or ductus arteriosus. Healthy child volunteers were also recorded and included in the control series. Table A phonocardiographic system developed in Helsinki University of Technology was used to record heart sounds. The system consisted of an electronic stethoscope and a multimedia laptop computer. A parabolic-shaped cup combined with a high-quality electric microphone and variable-gain battery-powered amplifier in the electronic stethoscope gave a flat frequency response in the whole frequency range of usual heart sounds and murmurs (from 75 to 1500 Hz). The laptop computer had standard multimedia capabilities for audio input and output . Sound signals were recorded digitally using special software for the monitoring and analysis of auscultation. The software was specifically written for this project, and it had several end user  friendly capabilities, such as a database for recordings, basic patient information input dialog, real-time graphical monitoring during recording, selectable and changeable digital filters, tunable settings for the graphical display and analysis, free zooming and replaying of the interesting parts and tools for measuring intensity, duration and frequency range. The software was compatible with standard Microsoft Windows  environments.The examiner heard the sounds through earphones and monitored the signals on the computer screen. Thus, the recording was completed in almost the same time as traditional auscultation. Some additional effort was needed to enter the patient information. The new generation commercial electronic stethoscopes were also compatible with this recording program. During the recording it was possible to both to listen to the sound and to follow the phonospectrogram from the display screen, the process was completed often in less than ten minutes.In the post-analysis phase, the recorded sounds were re-played, and the fingerprints of innocent and pathological heart murmurs were simultaneously examined visually by using a phono-spectrogram. First the recorded sounds were digitally filtered using pass-band filtering (75–1500 Hz) (the 3rd order Butterworth type high-pass and low-pass filters). These filter settings were selected by a long term subjective trials where the objective was to trim the display to show the details of the murmurs as an experienced practitioner would understand them. For the traditional waveform display the signal was scaled by the signal's absolute maximum. The resulted waveform showed the relative intensities of the heart sounds as the ear recognizes them and thus absolute intensity scaling is not needed. Similarly in the spectrogram the intensities were scaled by finding the maximum intensity on the time-frequency distribution and calculating relative intensities in the decibel scale. Thus the value of 0 dB corresponded to the maximum intensity and value of -60 dB, which is almost unbearable to listen to. Short time Fast Fourier Transform (STFT) with Hanning windowing, 512 data samples (46 ms time resolution) and total of 1024 FFT points (10.7 Hz frequency resolution) were used for calculating the spectrogram.The three most common innocent murmurs, i.e. vibratory murmur, pulmonary ejection murmur and venous hum, and the five most common congenital heart defects, i.e. ventricular septal defect (VSD), aortic valve stenosis (AS), pulmonary valve stenosis (PS), patent ductus arteriosus (PDA) and atrial septal defect (ASD), are presented as examples of the whole data set.To differentiate between innocent and pathological murmurs, 50 vibratory innocent heart murmurs, 25 innocent pulmonary or aortic ejection murmurs and 50 mild pathological systolic murmurs with intensity equal to or less than grade 3/6 were selected from a larger heart sound database for more detailed analysis. 14 of the selected pathological cases were small VSD, 5 hemodynamically loading ASD secundum, 8 PS with a pressure gradient less than 30 mmHg, 8 AS with a pressure gradient less than 30 mmHg, 3 bicuspid aortic valves with velocity less than 2.0 m/s, 1 mild CoA with a measured 15 mmHg RR difference, 1 hypertrophic cardiomyopathy (HOCM) with a septum thickness of 12 mm but with laminar aortic flow, 5 mitral leakage with or without prolapse (MI) and 3 tricuspid valve leakage (TI).The timings, the intensities and the frequency contents of the sounds were manually extracted from the phono-spectrogram using the software's graphical measurement tools  and the occurrence of intensive high-frequency components were used as criteria for testing the pathology of the murmur.The system was able to display and reproduce cardiovascular sound events. The musical murmur caused by harmonic movements of the heart or the vasculature, of which vibratory innocent murmur is a good example, was usually visualized as a well-defined area or line in the spectrogram. Innocent systolic murmur appeared to have a lower peak frequency, below 200 Hz, and shorter duration than pathological murmurs, and it always faded before the second heart sound. The higher the velocity of flow in echogardiography, the more intensive the murmur and the wider the frequency scale. This phenomenon was clearly visible in the spectrogram.The attached illustrations . The physician needs to quickly confirm the benign nature of the heart murmur and thus to avoid misdiagnosis ,43. The 0, 41, 42It is not simple to estimate absolute volume of heart sound. The point of maximal intensity of the murmur and the thickness of the chest vary and affects on the intensities of the sound components. In our study, the sound volume of murmur was calculated as a percentage of the volume of murmur compared to the mean volumes of S1 and S2. This may be misleading, as we can see in case 4. The volume of the aortic closure sound is decreased because of valvular stenosis, and the volume of murmur is over estimated compared to auscultation findings.By analyzing the combined phono-spectrogram, it is possible to achieve the level of an experienced pediatric cardiologist in screening heart murmurs. In this study, by using special criteria, sensitivity of 90 % and specificity of 91% were attained. Both sensitivity and specificity were higher than using phonocradiographic or spectral analysis alone. The results were less good than those obtained in previous studies using the methods of advanced signal processing, pattern recognition and artificial networks ,13-15. ITypically, the screening method is allowed to include some false positive cases, but false negatives are unacceptable. In this study, ten (10) small muscular ventricular septal defects, three (3) cases of mild aortic stenosis, one (1) mild peripheral pulmonary stenosis, one (1) mitral valve prolapse with leakage and one tricuspid leakage fell below the 80 % duration criterion. However, each of these cases exceeded the 200 Hz frequency limit. Three (3) atrial septal defects and one (1) slight pulmonary valve stenosis included frequencies below 200 Hz, but each of them was sustained for over 80% of the systolic duration. Five (5) of the pathological murmurs were not caught with either of these two criteria. One (1) of them was a clinically insignificant tricuspid valve leakage, one (1) a very mild mitral valve leakage, one (1) a bicuspic aortic valve without stenosis and one (1) a bicuspic aortic valve with slight stenosis (pressure gradient 16 mmHg). The last and the worst missed pathological murmur was recorded from a three-year-old boy with hypertrophic cardiomyopathy (thickness of ventricular septum 12 mm). Seven out of 75 innocent murmurs exceeded one of the defined screening criteria. None of the ejection murmurs exceeded the 80 % duration limit, and 3 cases exceeded the frequency limit. All of these cases were aortic ejection murmurs with aortic velocity of 1.5–1.8 m/s. Of the vibratory murmurs, one (1) continued for over 80 % of the systolic duration, three (3) contained frequency components of over 200 Hz, but none of them exceeded both limits.Slight tricuspid leakage is a harmless finding. Mitral valve leakage and bicuspic aortic valve should be recognized because they require endocarditis prophylaxis. The patient with mitral leakage was a fearful retarded boy, and the recorded signal was weak in amplitude, which is why the highest frequencies were missed in the analysis, but the murmur was sustained until the beginning of the second heart sound, implying a pathological finding. The murmurs due to a bicuspic aortic valve without stenosis or with slight stenosis did not differ from the hyperkinetic aortic ejection murmur. The murmur of the patient with hypertrophic cardiomyopathy resembled vibratory innocent murmur . The difAs the examples show, the method did not recognize hypertrophic cardiomyopathy or mild aortic valve malformation and failed with the mitral leakage, because the recording was suboptimal. We recommend an echocardiography, when the vibratory or aortic ejection murmur is repeatedly found in adolescent age or when the recording is suboptimal. Naturally, young babies need always an echocardiography, because their pulmonary pressure may still be high and the results of heart sound analysis can be misleading.Modern electronic stethoscopes are suitable for heart sound recording. Visual presentation of the auscultation finding provides an opportunity to study more objectively and quantitatively the timing, quality (frequency contents) and intensity of different heart sound and murmur components and helps us to understand and learn about the hemodynamics of the heart and the origin of cardiac murmurs.Computer analysis is a powerful tool in teaching an unexperienced listener the art of auscultation ,11,46. FPhono-spectrographic analysis of heart murmur in children is a useful additional method for the clinical approach and an interesting educational tool as well. The 90 % sensitivity level of the tool may well be at the level of a trained paediatrician. However, it should be considered a single, suboptimal screening tool. As the case of HOCM indicates, ECG and echocardiography are advisable if the intensity of the murmur is fairly high and frequently audible. Patient history and careful physical examination remain the cornerstones in clinical practice.The author(s) declare that they have no competing interests.ALN carried out most of the clinical work, extracted the numerical data for the statistical analysis and wrote the clinical aspects of the manuscript. SL designed the recording system, performed the statistical analysis, wrote the technical description of the system, and reviewed the manuscript. AA participated in the system and study design and data acquisition. RS conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated . CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment  plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life. Complete atrioventricular canal (CAVC); Common atrioventricular canal; Complete atrioventricular septal defect.Reference of Complete atrioventricular canal is 06.06.09.CAVC is a complex cardiac malformation characterised by a variable deficiency of the atrioventricular area (crux cordis) in the developing heart. The malformation involves the atrial, ventricular and atrioventricular septa and both atrioventricular valves.Diagnosis of CAVC might be clinically suspected in patients presenting in the first few months of life with congestive heart failure, cardiomegaly on chest X-ray and left axis deviation, bi-atrial enlargement and bi-ventricular pressure and volume overload on electrocardiogram (ECG). Echocardiography is the key tool for the diagnosis and anatomic classification of this malformation. It shows the ostium primum atrial septal defect, with the underlying common atrioventricular valve, and the defect of the ventricular septal inflow Figure .The anatomic subgroups  can be classified on the basis of the chordal insertions and morphology of the superior bridging leaflet of the common atrioventricular valve Table . SimilarDifferential diagnosis of CAVC involves mainly the unrestrictive ventricular septal defect, associated or not to mitral valve insufficiency. The clinical picture of congestive heart failure, the bi-atrial and bi-ventricular overload on ECG, and cardiomegaly and pulmonary congestion on chest X-ray are common to the ventricular septal defect. However, on ECG the left axis deviation of QRS at -30°, usually combined with a various degree of right bundle branch block, appears to be suggestive of CAVC. Eventually, the echocardiographic examination is the cornerstone for diagnosis and is of help for that of any further associated cardiac malformation.CAVC accounts for about 3% of all cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected, with a slightly higher frequency in female  and a striking association with Down syndrome was found .The complete form of AVC shows an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the interventricular septum inlet ,3. This A "partial variant" of AVC exists . Nevertheless, some authors observed how "complete" and "partial" are inappropriate adjectives to describe these variants -11. IndeThe space between the left ventricular components of the superior and inferior bridging leaflets is traditionally called "cleft". Morphological studies suggested that this gap functions as a commissure, even though it is not supported by a papillary muscle . In RastSymptoms occur in infancy as a result of high pulmonary blood flow associated with pulmonary hypertension, and often complicated by insufficiency of the common atrioventricular valve. Failure to thrive, as well as congestive heart failure and frequent pulmonary infections, are invariably seen. Thus, patients with CAVC often have feeding problems and are virtually symptomatic in the first few months of life. Signs of congestive heart failure consist in feeding difficulties, excessive sweating, tachycardia, tachypnea, subcostal and intercostal retractions, mild wheezing, hepatic enlargement and poor peripheral blood perfusion . If a siHalf of children with untreated CAVC die in the first year of life ,13,14. Tμg/kg  in 3 doses over 24 h, continuing with a maintenance dose of 8–10 μg/kg/day in 2 doses. Diuretic therapy is mainly based on furosemide, at the dose of 1–6 mg/kg/day, and spironolactone, at the dose of 2–3.5 mg/kg/day. Vasodilator therapy consists chiefly in the angiotensin converting enzyme inhibitors, captopril  or enalapril . Increasing interest is raising regarding the utilisation and potential benefits of beta-blockers  in infants and children heart failure due to congenital heart defects with left to right shunt, although long-term results are needed. Finally, the new generation of pulmonary vasodilators dramatically improved the post-operative course and the overall prognosis of the patients 22][[22][21][[[22][21]Formation of atrioventricular canal results from complex interactions of components of the extracellular matrix. Septation of the atrioventricular junction is brought about by downgrowth of the primary atrial septum, fusion of the endocardial cushions and forward expansion of the vestibular spine between atrial septum and cushions . Thus, aEpidemiological studies ,33 showeIn the presence of a single affected family member, the risk of siblings of inheriting the defect is about 2%, with a higher percentage for the offspring of an affected parent. Concordance for atrioventricular malformations among siblings is higher than for other types of congenital heart defects .Due to the strict association with Down syndrome and other chromosomal anomalies, genetic antenatal counselling after the foetal echocardiographic diagnosis of CAVC is mandatory. At present, prenatal diagnosis of CAVC has been associated with a 58% risk of aneuploidy, mainly trisomy 21 . Again,


Several strategies for mapping ventricular outflow tract tachycardia have been reported as useful indices for differentiating between those originating from the right and the left side. Recently, tissue tracking imaging (TTI) has been demonstrated as a novel non-invasive modality for identifying the origin of outflow tract tachycardias. Tissue tracking imaging is an ultrasonographic technique that measures the myocardial motion amplitude towards the transducer in each region during systole, identifying regional myocardial displacement on the basis of myocardial velocities using color Doppler myocardial imaging principles. In this technique, the origin of the arrhythmia could be recognized as the site where the earliest color-coded signal (ECCS) appeared on the myocardium at the onset of the systole. In preliminary studies this modality was found to be useful in differentiating outflow tract ventricular tachycardias. ECCS was always found below or at the level of the pulmonary valve in all arrhythmias which could be ablated from the right ventricular outflow tract, while in those where the ECCS was above and close to the pulmonary valve it could be ablated from the left sinus of valsalva. These results indicate that TTI can provide detailed and accurate information on the arrhythmia origin of outflow tract tachycardia and may be useful for differentiating between an outflow tract tachycardia originating from the LV epicardium remote from the LSV and that from the LSV. Newer advances in echocardiographic technologies like high resolution, high frame rate real time three dimensional echocardiography with speckle tracking may further improve the precise localization of arrhythmias in the future. Radiofrequency (RF) catheter ablation has been established as an effective and curative therapy for ventricular tachycardias (VTs) or symptomatic premature ventricular contractions (PVCs) originating from the outflow tract (OT-VT/PVCs) in structurally normal hearts . Most ofSeveral strategies for mapping RVOT VT have been used including activation mapping, pace mapping, use of basket catheter , and nonAlgorithm based on surface ECG has overall sensitivity of 88 % and specificity of 95% for localization of OT-VT/PVCs. Body surRecently, tissue tracking imaging (TTI) has been demonstrated as a novel non-invasive modality for identifying the origin of OT-VT/PVCs . TTI is Tissue tracking imaging visualizes the velocity-time integrals (VTI) of different regions in a color, 2D mode online, together with the systolic wall motion. Tissue tracking displays the integral of the tissue velocity during systole, which equals the distance motion along the Doppler axis during systole. There are seven colour bands that indicate different distances of motion with a stepwise increase in the distance of the motion . The sitIn the article by Tada H et al , TTI wasHowever some questions remains to be answered before it can be considered as the modality of choice. Tissue tracking imaging has limitations inherent to tissue Doppler imaging technique . In the Myocardial deformation can be assessed from the B mode images by automated point wise tracking of speckle patterns. It has the advantage of angle independence and may be superior to tissue Doppler based techniques for strain estimation . WhetherElectrical phenomena and its surrogate, the propagation of myocardial contraction, are three-dimensional events with variable sites of origin and distribution patterns. Next generation maps must be able to map the full thickness of the atrial and ventricular wall. One major challenge in clinical electrophysiology is to precisely visualize target cardiac structures and simultaneously depict electrical events. Using intracardiac ultrasound with high TDI frame rates, TDI is suitable for displaying more rapid changes in tissue motion related to the onset and propagation of electrical excitation in the myocardium at a very early stage with high temporal resolution. This ultrasound imaging technique should have an important impact on the diagnosis and management of cardiac arrhythmias. Such technology will foster simultaneous single modality visualization of anatomy, function and electrical events for the purpose of refining the proper intervention.


Ashrafian and colleagues describe the use of myocardial contrast echocardiography to assess a 63-year-old man with ischemic heart disease. A 63-year-old man presented to our accident and emergency department with a 2-hour history of crushing central chest pain, excessive sweating, and difficulty in breathing. Past history included non-insulin-dependent diabetes mellitus controlled by oral hypoglycaemic agents.On examination, he appeared unwell, with pulse of 94 beats per minute, blood pressure of 124/68 mm Hg, and respiratory rate of 20 breaths per minute. Jugular venous pressure was not elevated, but chest auscultation revealed bilateral basal crackles. Cardiovascular system examination was unremarkable. His electrocardiogram on admission showed >2 mm ST segment elevation in chest leads V1–V4 .The combination of typical chest pain and electrocardiographic changes were characteristic of acute anteroseptal myocardial infarction. A presumptive diagnosis of probable left anterior descending (LAD) coronary artery occlusion was made. Our patient was promptly thrombolysed with recombinant plasminogen activator and managed as per our hospital's acute myocardial infarction (AMI) protocol. This involved administration of diamorphine, aspirin, intravenous nitrates, heparin, a beta-blocker, an angiotensin converting enzyme inhibitor, and a statin.Within 30 minutes of thrombolytic therapy, there was complete cessation of pain and subsidence of elevated ST segments . His peaOur patient presented with electrocardiogram changes of a myocardial infarction (MI). Although this is most likely due to coronary occlusion, the ST elevation may occur for reasons other than infarction . MoreoveRadionuclide imaging  showed aMCE is shown inThe patient underwent coronary angiography, which showed flow-limiting coronary stenosis in the mid-LAD . This waMajor advances have been made in reperfusion therapy for AMI. Pharmacological developments have led to the introduction of recombinant thrombolytic therapies, which are increasingly safe and effective . MoreoveHowever, pharmacological or mechanical reperfusions are not without risk and financial burden, and should be preferentially directed to a viable myocardium . EffectiEven if thrombolysis appears to be clinically successful, as in our patient, before more elective interventional therapy is considered it is prudent to quantify what proportion of dysfunctional myocardium may be viable and hence salvageable. This proportion is a marker of a patient's prognosis. Moreover, even if angioplasty—a therapy that is fast becoming the standard of care worldwide—rather than thrombolysis is the primary therapy for the AMI, assessing myocardial perfusion or lack thereof still informs prognosis.  How would these patients be stratified? Although clinical features such as the relief of pain and the absence of electrocardiographic Q waves have widely been regarded to imply a good response to thrombolysis and hence a residual mass of viable myocardium, they have been shown to be imprecise . More reMCE has emerged as one of the most effective of these modalities and has the added benefit of being available immediately at the patient's bedside; broadly, this technique relies on the application of echocardiographic ultrasound waves to intravascular microbubble contrast media that reflect these signals (echoes) ,9. MicrHow does MCE compare with other imaging modalities? Technetium-99m Sestamibi single-photon emission computed tomography is the most commonly used clinical imaging modality assessing myocardial perfusion; it has been successful in predicting coronary stenosis. A number of studies have compared these two modalities in the context of coronary artery disease and have broadly shown that MCE was equal or superior to single-photon emission computed tomography during dipyridamole stress for the diagnosis of coronary artery disease ; MCE doeIn the specific setting of MI, by demonstrating an area of impaired perfusion (through microbubble paucity) MCE can define the vulnerable myocyte territory and make the diagnosis of MI efficiently . In doinIndicating the value of MCE, in a recent study of >1,000 patients with chest pain presenting to an emergency department, MCE was found to be the best predictor of both short-term (48 hours) and long-term (up to 2 years) outcome . Unlike data collected from other modalities, MCE data were available immediately at the bedside after hospital presentation, and they remained superior even after all clinical, electrocardiographic, and serum biomarker information were taken into account .While the literature strongly advocates the use of perfusion imaging to assess the presence of coronary artery disease and to direct further therapy, perfusion imaging in general and MCE in particular do have some limitations. The first and most important limitation is that of training; clearly, the application of this novel technique relies on specialist expertise. In order for “real-world” studies to reflect existing studies, a significant learning curve will have to be traversed. Secondly, while readily available, at present no microbubble contrast agents have been licensed for clinical practice. Although it is likely that they will be licensed, it is important to complete large-scale studies for regulatory bodies to be satisfied that these agents are free of deleterious bioeffects. To date, such studies have confirmed the safety and utility of these agents. Ultimately, the clinical application of MCE must be tempered with the knowledge that the capacity of perfusion analysis is limited in myocardial segments such as the baso-lateral walls that are prone to greater errors.MCE is a rapid bedside method for assessing myocardial perfusion. Among other cardiovascular conditions, and as with other forms of perfusion imaging, MCE in MI provides significant diagnostic information both in the acute sense and with regard to revascularisation strategy. Ultimately, these microbubbles can also be generated carrying therapeutic agents or carrying receptors or ligands within their membranes. They may, therefore, provide a means to direct intravascular treatments specifically to the site of active disease, as envisaged by Ehrlich when he described his magic bullet therapy .Video S1Click here for additional data file.Normal variant; often an ethnic variant in African-American malesLeft ventricular hypertrophyPericarditisHyperkalaemiaBrugada syndromePeriresuscitationNeurological events Post-cardioversionPulmonary embolismCoronary thrombosis, due to coagulopathy Vasculitis CocaineCoronary spasmEmbolic events Congenital coronary anomaliesMetabolic toxicity Drug-induced infarction Pulmonary embolismNon-invasive perfusion imaging such as MCE, radionuclide techniques, dobutamine echocardiography, magnetic resonance, and positron emission tomography have all been shown to have value in diagnosing coronary artery disease.MCE is a new echocardiographic modality that relies on microbubbles to scatter ultrasound efficiently and hence improve imaging.Because they are confined to the vasculature, contrast agents provide a unique red-cells view of myocardial perfusion.By assessing rate of perfusion and myocardial volume, tissue perfusion, and hence myocardial viability, can be accurately quantified.An assessment of viability can guide immediate and subsequent treatment strategies in patients with a variety of cardiac conditions, including MI.Fast becoming the standard of care in the treatment of AMI, MCE provides prognostic value even for patients undergoing primary angioplasty.While indicated for only diagnostic purposes at present, the capacity to load microbubbles with active therapy (drug or gene) and rupture them at will with ultrasound at the site of disease promises that they will be used for directed therapeutic purposes.MCE carries a learning curve: the dissemination of MCE must be carried out with specific attention to technical excellence and training to ensure that existing trial results can be adequately translated to real-world patient care.When microbubbles are ultimately licensed, ascent of the learning curve, coupled with an appreciation of the myocardial segments and circumstances that may limit the accuracy of the technique, will ensure optimal patient outcomes.


Obstructive sleep apnoea (OSA) might cause right ventricular dysfunction and pulmonary hypertension. We aimed to determine the effects of nasal continuous positive airway pressure (CPAP) therapy on right ventricular myocardial performance index (MPI) in OSA patients without hypertension.49 subjects without hypertension, diabetes mellitus, any cardiac and pulmonary disease had overnight polysomnography and echocardiography. In 18 moderate-severe OSA (apnea-hypopnea index ≥ 15) patients, right ventricular free wall diameter (RVFWD) was measured by M-mode, and right ventricular MPI was calculated as (isovolumic contraction time+ isovolumic relaxation time) / pulmonary ejection time using Doppler at baseline and after 6 months CPAP therapy.2), but there was no change in either BMI or blood pressures after 6 months. Right ventricular end-diastolic and end-systolic diameters were in normal limits at baseline, and did not change after CPAP usage. Baseline RVFWD (7.1 ± 2.1 mm) significantly decreased after CPAP therapy . 15 of patients (83%) had right ventricular diastolic dysfunction at baseline, and it was completely improved in 11 of them (73%) by CPAP usage. Right ventricular global dysfunction was shown in 11 patients (61%) with a high MPI (62.2 ± 9.3%) at baseline; and MPI was significantly decreased after CPAP therapy , and it was completely corrected in 4 of them (36%).Mean age was 46.5 ± 4.9 year. Patients had high body mass index  in OSA patients without hypertension. The obstructive apneic event is associated with considerable breathing efforts against totally or partially occluded upper airway. Obstructive sleep apnoea (OSA) might lead to cardiovascular complications such as heart failure, left/right ventricular dysfunction, myocardial infarction, arrhythmias, systemic and pulmonary hypertension, that all increase morbidity and mortality -10. EarlDuring an obstructive apnea, large negative intrathoracic pressures are generated during inspiratory efforts, which increase transmural pressures across the myocardium, thus increasing afterload. An increase in preload and pulmonary congestion may also occur due to increased venous return. The presence of hypoxemia decreases oxygen delivery to the myocardium, which may promote angina and arrhythmias. Also, frequent arousals from sleep lead to increase sympathetic activity. Other responsible mechanisms include impaired vagal activity, increased platelet aggregability, insulin resistance, and endothelial dysfunction with reduced endogenous nitric oxide production . ContinuVentricular dysfunction could not be detected clinically, but could just be detected echocardiographically. Myocardial performance index (MPI) reflects both systolic and diastolic functions  of the ventricle ,19. In tIn the present study, we aimed to determine the effects of nasal CPAP after 6 months of therapy on right ventricular MPI in moderate-severe OSA patients without hypertension.49 subjects admitted to sleep clinic with symptoms of nocturnal snoring and/or excessive day-time sleepiness taken into the study. A detailed sleep and cardiovascular anamnesis of the patients were recorded. Sleep cycle, nutritional status, medications, alcohol usage and family anamnesis were also questioned. Epworth sleepiness scale (ESS)  was ques2).Physical examination was performed to all subjects at baseline and at 6 months. Systolic (SBP) and diastolic (DBP) blood pressures were measured in the sitting position on the right arm using a sphygmomanometer , after at least 5 min of rest. Hypertension was identified as blood pressure ≥ 140/90 mmHg or being used antihypertensive drugs. Heart rate per minute (HR) was measured in the sitting position, and body mass index (BMI) of the patients were calculated as weight divided to height square , arterial blood gas analysis  were performed to all patients at rest. A 12-leadsurface ECG was taken from every subject, and all of them were in sinus rhythm. Also, all of subjects underwent treadmill exercise test and, the test was normal for each subject.Symptoms of nocturnal snoring and/or excessive day-time sleepiness were accepted as inclusion criteria. Exclusion criteria of the study were the presence of 1- any known cardiac and lung disease, 2- hypertension, 3- diabetes mellitus, 4- angina pectoris, 5- atrial fibrillation or any arrhythmias, 6- chronic renal and hepatic diseases, 7- serum electrolytes imbalances.All patients underwent an entire night of diagnostic PSG while breathing room air, followed a second night of PSG with nasal CPAP titration . The porApnea was defined as total obstruction of oronasal airflow ≥ 10 seconds, an hypopnea was defined as decrease of airflow at least 50%, and desaturation was accepted as a decrease of ≥ 4% in oxygen saturation . DesaturPatients with severe OSA were prescribed nasal CPAP , including use of a heated humidifier. The CPAP machines were equipped with compliance monitors that measured CPAP use, in order to observe CPAP usage/compliance at home. Routine troubleshooting took place in an effort to maximize compliance with nasal CPAP. Patients were considered to be CPAP compliant if they used CPAP an average ≥ 3.5 h per night at the 6-month follow-up.Echocardiograms were obtained following the diagnosis of OSA and prior to initiation of CPAP, and at 6 months. All measurements were performed with the subjects in the left lateral decubitus position by M mode, two dimensional (2D), and Doppler ultrasound echocardiography in the morning. The ultrasound equipment used was Contron Sigma Iris with a 2.5-MHz probe. The duration of the examination was at least 20 minutes. The ventricular diameters, volumes and functions were measured according to the recommendations of the American Society of Echocardiography . Basic mEarly (E) and atrial (A) trans-mitral/tricuspid maximal flow velocities, the ratio (E/A) and deceleration time (DT) of E was registered. Isovolumetric relaxation time (IVRT) was measured by the continuous wave Doppler technique. The velocity of mitral/tricuspid flow propagation (VPR) was estimated using color Doppler M-mode. The left/right ventricular MPI was calculated as (isovolumic contraction time of left/right ventricle + IVRT of left/right ventricle) / (aortic/pulmonary ejection time) by Doppler.Measurements are expressed as mean ± SD. A Wilcoxon test for related measurements was used to compare primary outcome variables of both IVS, LVPW, RVFWD and ventricular functions  at baseline and 6 months. Also, Mc Nemar chi-square test was used for comparison of number of obstructive sleep apnea patients without hypertension according to right ventricular hypertrophy and diastolic or global dysfunctions at baseline (before treatment) and after 6 months of CPAP usage. A p value of < 0.05 was regarded as significant.2), however there were no change in either BMI or blood pressures (BP) after 6 months  and 4 females (22%) with moderate-severe OSA without hypertension were included in the study. Mean age of patients was 46.5 ± 4.9 year. None of them were using alcohol, and 55% of them were smoking cigarettes. Baseline characteristics of OSA patients were shown in table 2O and 11.0 ± 2,3 cmH2O).The major reasons for noncompliance were mask discomfort or pressure intolerance. All subjects were offered heated humidity, and efforts were made in all subjects to improve comfort and compliance with therapy. Average CPAP pressure after 6 months of therapy did not change from the initial CPAP pressure that was prescribed  was significantly decreased after 6 months of CPAP usage , but it did not come to the normal limits, and it still reflected right ventricular global dysfunction (see table % was sigComparison of number of OSA patients without hypertension according to right ventricular hypertrophy (RVH) and diastolic or global dysfunctions at baseline (before treatment) and after 6 months of CPAP usage was shown in table In our previous studies, we showed right and left ventricular global dysfunctions in OSA patients with an increased MPI ,4. ArterIn our study, we excluded systemic hypertension, diabetes mellitus, coronary artery disease and any pulmonary diseases including chronic obstructive pulmonary disease, and there were no significant differences in BMI or BPs after 6 months of therapy. Thus, we assessed the ventricular structure and functions (MPI) in uncomplicated (isolated) OSA patients.Left ventricular systolic and/or diastolic functions provide prognostic information in the patients. In our study, left ventricular diameters and both systolic and diastolic functions of all subjects were in normal limits and did not significantly change after CPAP therapy. However, right ventricular free wall diameter significantly decreased after CPAP usage. Eleven of 15 patients having diastolic dysfunction (73%) and 4 of 11 patients having right ventricular global dysfunction (36%) completely improved by CPAP therapy.The relation of OSA to right heart structure and function is controversial. The prevalence of RVH by echocardiography in sleep apnea was ranged from 0 to 71% . In the The reasons for the disparate conclusions of the prior studies examining RVH, systolic function, and right ventricular enlargementare not certain. In a study, right atrial and ventricular dimensions, and right ventricular systolicfunction were not found to be significantly different betweensubjects with sleep-disordered breathing and the low respiratory disturbance index subjects, but this study indicated that sleep-disordered breathing was associated with increased right ventricular wall thickness in a general population . Right aIn many studies beneficial effect of CPAP on cardiac functions have been shown -37. ThesDoherty LS, et all. performed a long-term follow-up study of 168 patients with OSA who had begun receiving CPAP therapy at least 5 years previously, most of whom had been prospectively followed up, having been the subject of an earlier report on cardiovascular risk factors in OSA patients with the average follow-up period 7.5 years . They coOur study does not clarify the reasons of right ventricular diastolic and global dysfunctions in OSA patients without hypertension. Right ventricular diastolic filling is a complex event that is influenced by several factors, such as right ventricular relaxation, right ventricular compliance, right atrium contraction force and pulmonary artery resistance. Thus, right ventricular dysfunction might be the result of a variety of these impairments. In our study patients, intermittent nocturnal hypoxemia might have caused RVH and/or right ventricular dysfunction, since they had more hypoxic duration in their sleep with the highest percent of sleep duration below 90% of oxygen saturation.Since the systolic and diastolic dysfunction frequently coexist, it was shown that a combined measure of ventricular performance with calculation of MPI might be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. MPI is a simple and reproducible non-invasive method for diagnosis of ventricular global dysfunction in patients with OSA.In the present study, a very noticeable finding is the improvement of right ventricular free wall dimension and global dysfunction with a significantly decreased MPI by CPAP therapy, even if 6 months usage.OSA patients, especially having diastolic dysfunction, is in an increased risk of heart failure, since the systolic and diastolic dysfunction frequently coexist. A combined measure of ventricular performance with the calculation of MPI might be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. CPAP therapy significantly decreases right ventricular free wall thickness and improves global dysfunction with a significantly decreased MPI even if 6 months of CPAP usage. We consider that much longer-term usage of CPAP therapy may achieve complete improvement of right ventricular global dysfunction in patients with OSA.Small number of patients in our study population is an important study limitation to determine the effects of CPAP on RVH and right ventricular dysfunction. Also, our sleep clinic population may not reflect the findings in the general community. A larger population of study subjects would be helpful to determine the effects of CPAP on right ventricular structure and function.


This pilot study was performed to evaluate whether virtual reality is applicable for three-dimensional echocardiography and if three-dimensional echocardiographic 'holograms' have the potential to become a clinically useful tool.Three-dimensional echocardiographic data sets from 2 normal subjects and from 4 patients with a mitral valve pathological condition were included in the study. The three-dimensional data sets were acquired with the Philips Sonos 7500 echo-system and transferred to the BARCO  I-space. Ten independent observers assessed the 6 three-dimensional data sets with and without mitral valve pathology. After 10 minutes' instruction in the I-Space, all of the observers could use the virtual pointer that is necessary to create cut planes in the hologram.The 10 independent observers correctly assessed the normal and pathological mitral valve in the holograms .this report shows that dynamic holographic imaging of three-dimensional echocardiographic data is feasible. However, the applicability and use-fullness of this technology in clinical practice is still limited. Evaluation of intracardiac anatomy from multiple two-dimensional echocardiographic images requires a mental conceptualisation process that is complicated by cardiac dynamics -3. CurreData sets from normal subjects and from patients with mitral valve disease, referred for a diagnostic echocardiogram, were selected with the aim of gathering a representative series of mitral valve pathological conditions with sufficient image quality. For this feasibility study, we selected 3D data sets of clinical conditions which have advantage of 3D perspective: (1) two patients with a normal mitral valve, (2) a patient with a mitral valve prolaps of the P2 segment of the posterior leaflet, (3) a patient with mitral valve stenosis, (4) a patient with hypertrophic obstructive cardiomyopathy and systolic anterior motion of the mitral valve, and (5) a patient with an atrioventricular septal defect (AVSD) where there is a commissure present between the superior and inferior bridging leaflets. Ten observers , who were blinded for the type of mitral valve morphology, were instructed to assess mitral valve anatomy/pathology and function.The 3D data sets were acquired with the Philips Sonos 7500 echo system  equipped with a 3D data acquisition software package. Real-time 3D echocardiographic (RT-3DE) acquisition was done with ECG gating and in an end-expiratory breath-hold, lasting 6 to 8 seconds (depending on the heart rate). The 3D image data was stored on CD-ROM in DICOM 3.0 format and transferred to the computer  driving the I-space.The BARCO  I-space installed at the ErasmusMC, is a so-called four-walled CAVE(tm)-like virtual reality system figure . In the The observers were instructed to create several cut plane in the hologram. For the analysis of the mitral valve, two opposite views were reconstructed: 1) a view from the left atrium towards the atrioventricular junction, allowing a "surgical view" of the mitral valve, and 2) a view from the left ventricular apex toward the mitral valve. The observers were asked to assess in these views, the anterior and posterior leaflets, and subvalvular apparatus for possible pathology .The 3D data sets of the 6 patients with normal or abnormal mitral valve anatomy were transformed to 3D holographic heart models. Once the transformation method had been developed, the time required to create a hologram from the 3D data set varied from 1 to 3 minutes. Figure In the generated 3D hologram of a normal mitral valve , the mitThis report presents a novel approach for visualisation of dynamic 3D echocardiographic data, known as virtual reality. The 3D echocardiographic data sets generated by a commercial available echo machine can be visualised as a dynamic hologram inside the I-Space. Until now, the 3D echocardiographic reconstructions could only be seen on a 2D screen, but virtual reality makes it possible to 'dive' into the actual 3D anatomy of the heart. We show that professionals, familiar with intracardiac anatomy, can learn how to handle the technique and cut through these holograms within 10 minutes. Subsequently, they were all able to correctly diagnose the intracardiac anatomy or pathology of the mitral valve. At the moment, I-Space technology is only available in a few dedicated research centres throughout the world. Therefore, the combination of the 3D echocardiography and virtual reality is very uncommon and the applicability and usefulness in clinical practice is still limited. However, in our opinion, it has potential and one can think of possible applications in the future.Virtual reality provides a unique resource for education of intracardiac anatomy in general and/or specific cardiac structures. Especially for all professionals for whom detailed knowledge of the intracardiac anatomy is essential, virtual reality might lead to a better understanding of the intracardiac anatomy. With the growth of minimal invasive cardiac surgery and interventional procedures, the interest for simulation of the heart hologram as a training tool has increased. We believe that dynamic 3D echocardiography in virtual reality has the potential for wider applicability in providing a preview of real intracardiac anatomy. With the I-Space technology, the complex anatomy, pathology and dynamic changes of the heart are appropriately visualised in a virtual heart model, which increases the accessibility and availability of virtual reality for clinical practice. In order to be integrated into clinical practice, this application should be able to run on smaller virtual reality systems, either based on a single projection surface, or on a monitor (CRT or LCD).The author(s) declare that they have no competing interest.AEB conceived the study, and participated in acquisition and analysis of the data and drafted the manuscript. AK participated in acquisition and analysis of the data and drafted the manuscript. FM drafted the manuscript and revised it with important intellectual content. JM carried out the 3D echocardiographic assessments and participated in the drafting of the manuscript. MS revised the manuscript with important intellectual content. PS revised the manuscript with important intellectual content. AJB conceived the study, and revised the manuscript with important intellectual content and gave final approval of the version to be published. All authors read and approved the final manuscript.Demonstration of the I-Space. The film shows a researcher going into the I-Space wearing a lightweight pair of polarised glasses and demonstrates the head/hand movements that allow a natural interaction with the images that are displayed.Click here for fileDemonstration of a heart hologram in the I-Space.Click here for fileDemonstration of a 3D echocardiogram from a normal mitral valve viewed from the left ventricular apex to the base of the heart.Click here for file


Because cardiomyopathy is the leading cause of death in diabetic patients, the determination of myocardial function in diabetes mellitus is essential. In the present study, we provide an integrated approach, using noninvasive echocardiography and invasive hemodynamics to assess early changes in myocardial function of diabetic rats.Diabetes was induced by streptozotocin injection . After 30 days, echocardiography (noninvasive) at rest and invasive left ventricular (LV) cannulation at rest, during and after volume overload, were performed in diabetic  and control rats . The Student t test was performed to compare metabolic and echocardiographic differences between groups at 30 days. ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P < 0.05 for all tests.Diabetes impaired LV systolic function expressed by reduced fractional shortening, ejection fraction, and velocity of circumferential fiber shortening compared with that in the control group. The diabetic LV diastolic dysfunction was evidenced by diminished E-waves and increased A-waves and isovolumic relaxation time. The myocardial performance index was greater in diabetic compared with control rats, indicating impairment in diastolic and systolic function. The LV systolic pressure was reduced and the LV end-diastolic pressure was increased at rest in diabetic rats. The volume overload increased LVEDP in both groups, while LVEDP remained increased after volume overload only in diabetic rats.These results suggest that STZ-diabetes induces systolic and diastolic dysfunction at rest, and reduces the capacity for cardiac adjustment to volume overload. In addition, it was also demonstrated that rodent echocardiography can be a useful, clinically relevant tool for the study of initial diabetic cardiomyopathy manifestations in asymptomatic patients. Diabetes is a chronic metabolic disorder associated with secondary complications in the cardiovascular system and autonomic control in humans and animals -4. DiabeDifferent methodologies have been used to investigate systolic and diastolic function in diabetic patients and rats. Assessment of cardiac function in experimental diabetes has relied on ex vivo  or in viMale Wistar rats (230 – 260 g) were obtained from the animal facilities at the University of São Paulo Medical School, São Paulo, Brazil. The rats received standard laboratory chow and water ad libitum. They were housed in individual cages in a temperature-controlled room (22°C) with a 12-h dark-light cycle. All procedures and protocols used were in accordance with the Guidelines for Ethical Care of Experimental Animals and were approved by the International Animal Care and Use Committee.The rats were randomly assigned to 1 of 2 groups: control , diabetic . Animals were made diabetic by a single injection of STZ  dissolved in citrate buffer, pH 4.5. Food was withheld from the rats for 6 hours before STZ injection. Control rats received a placebo  after a similar fasting period.Twenty-four hour urine was collected 29 days after diabetes induction. Animals were placed in a metabolic cage and were allowed free access to food and water during the collection period. Urine was collected and centrifuged at 1,000 g for 10 minutes to remove particles, and the volume was recorded. Urine samples were stored at -20°C for biochemistry analysis .a", from the cessation to onset of mitral inflow, is equal to the sum of the isovolumic contraction time, ET and isovolumic relaxation time. Ejection time "b" is derived from the duration of the LV outflow Doppler velocity profile. The MPI was calculated with the formula (a-b)/b.Echocardiographic indices were obtained according to the recommendations of the American Society of Echocardiography. Transthoracic echocardiography was performed in control and diabetic animals at 30 days, by double-blind observers with the use of a SEQUOIA 512 , which offers a 10–13 MHz multifrequency linear transducer. Images were obtained with the transducer on each animal's shaved chest . To optimize the image, a transmission gel was used between the transducer and the animal's chest . Animals were scanned from below, at a 2-cm depth with focus optimized at 1 cm. All measurements were based on the average of 3 consecutive cardiac cycles. Rats were anesthetized with a combination of ketamine hydrochloride 50 mg/kg and xylazine 10 mg/kg IP. Wall thickness and LV dimensions were obtained from a short-axis view at the level of the papillary muscles. LV mass was calculated by using the following formula, assuming a spherical LV geometry and validated in rats: LV mass = 1,047 × [(LVd+PWd+IVSd)3 - LVd3], where 1,047 is the specific gravity of muscle, LVd is LV end-diastolic diameter, PWd is end-diastolic posterior wall thickness and IVSd is end-diastolic interventricular septum thickness. In addition, another index of morphology was evaluated, the relative wall thickness (RWT), which is expressed by 2 × PWD/LVd. It represents the relation between the LV cavity in diastole and the LV posterior wall. LV fractional shortening was calculated as (LVd-LVs)/LVd × 100, where LVs is LV end-systolic diameter. Two-dimensional guided pulsed-wave Doppler recordings of LV inflow were obtained from the apical 4-chamber view. Maximal early diastolic peak velocity (E) and late peak velocity (A) were derived from mitral inflow. The LV outflow tract velocity was measured just below the aortic valve, from an apical 5-chamber view. The velocity of circumferential fiber shortening (VCF) was measured following the formula (LVd-LVs)/(LVd × ET), where ET is the ejection time. The sample volume was then placed between the mitral valve and LV outflow tract so that the aortic valve closure line and the onset of mitral flow could be clearly identified. Isovolumic relaxation time (IVRT) was taken from aortic valve closure to the onset of mitral flow. Global cardiac function was evaluated by using the Myocardial Performance Index (MPI), which is the ratio of total time spent in isovolumic activity (isovolumic contraction time and isovolumic relaxation time) to the ejection time (ET). These Doppler time intervals were measured from the mitral inflow and LV outflow time intervals. Interval "LV function was measured also invasively in anesthetized rats . One catheter of PE-50 was inserted into the right carotid artery and advanced into the LV, and a second catheter of PE-50 was inserted into the jugular vein for saline and drug administration. Ventricular pressure signals were measured with a transducer and conditioner  and digitally recorded (5 min) with a data acquisition system . The recorded data were analyzed on a beat-to-beat basis to quantify changes in LV pressure. The following indices were obtained: heart rate (HR), LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and maximum rate of LV pressure rise and fall (+dP/dt max and -dP/dt max). After LV pressure basal records, the LV function was recorded during a volume overload protocol performed by an injection of saline (0.27 mL/min/kg) during 3 minutes adapted from Souza's study . Accordit test was performed to compare metabolic and echocardiographic differences between different groups. Two-way ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P < 0.05 for all tests.Data are reported as means ± SEM, and the Student P < 0.0001) but also polydipsia , polyuria , glucosuria , proteinuria , and uremia . Body weight was reduced in the diabetic group (270 ± 8 g) compared with weight in the control group .Rats treated with STZ not only developed hyperglycemia  during diastole increased , and the thickness of the interventricular septum and of the posterior wall during diastole decreased  in diabetic rats in relation to control rats. RWT was significantly lower in diabetic (0.27 ± 0.016) than in control rats . LV systolic function, as expressed by fractional shortening (%) , ejection fraction (%)  and VCF (circ/sec)  was reduced in diabetic group compared with that in the control group. LV diastolic function was observed after 30 days of STZ-induced diabetes, as expressed by reduced E-wave (m/s)  and increased A-wave (m/s)  in diabetic animals when compared with control animals. The diabetic group had a reduced E/A ratio (1.33 ± 0.09) compared with the control group . Deceleration time of E-wave   and IVRT (ms)  were increased in the diabetic group compared with the control group, reflecting early diastolic dysfunction by slow relaxation. Statistical comparison of normalized EDT and IVRT by HR during echocardiography corroborated differences between groups observed using their absolute values. MPI was greater in the diabetic group (0.41 ± 0.014) compared with that in the control group .As can be seen in Table During and after volume overload, the differences in LV function between groups remained the same as in the baseline period. However, the LVEDP increased in both groups during and after volume overload compared with their respective baseline values. Only diabetic rats showed an increase in LVEDP values in the post volume overload period in relation to LVEDP values during the volume overload period Table .The present study provides an integrated approach to the assessment of diabetic cardiac function in rats, using both noninvasive echocardiography and invasive hemodynamic evaluation; it provides important new insights into the pathophysiology of diabetic cardiomyopathy. The present data confirm our preliminary findings that STZ diabetes induces hyperglycemia, weight loss, and bradycardia. However, the major finding of this study is that rats with 30 days of STZ-induced-diabetes had impairment in cardiac structure and function as evidenced noninvasively by echocardiography and invasively by LV catheterization, and also that this LV dysfunction was exacerbated by volume overload.Echocardiographic measurements of cardiac function and structure in the present experiments demonstrated both LV systolic and diastolic dysfunction in 30-day diabetic rats. In fact, several investigators have shown abnormalities in LV systolic function, diastolic function, and complaints in humans -12 and rLV cavity dilatation accompanied by no changes in wall thickness has been observed previously after 35 and 75 days  and 12 wMPI is a simple and nongeometric index that combines systolic and diastolic functions independently of heart rate, not requiring frequency based normalization . The impDent et al  demonstrIn addition, our results show impairment in cardiac responses during and after volume overload in STZ-induced rats. A similar increase in LVEDP observed in control rats in the present experiments was previously demonstrated in the early stages of volume overload induced by A-V fistula in control rats . HoweverStudies that have examined both systolic and diastolic dysfunction in diabetes suggest that the latter is more susceptible to preclinical changes. Diastolic dysfunction is not just a defect in active relaxation, but also in passive stiffness of the left ventricle . The echUsing the STZ model of diabetes, we have demonstrated that rodent echocardiography can be useful, because sensitive changes in systolic and diastolic performance were detected and markedly confirmed by in vivo direct LV measurements. Changes reported in the present experiments in cardiac performance are highly predictive of clinical findings, and further illustrate the value of this model of diabetic cardiomyopathy.LV: left ventricleSTZ: streptozotocinAP: arterial pressureHR: heart rateLVd: left ventricle end-diastolic diameterLVs: left ventricle end-systolic diameterPWd: end-diastolic posterior wall thicknessIVSd: end-diastolic interventricular septum thicknessRWT: relative wall thicknessE: maximal early diastolic peak velocityA: late peak velocityVCF: velocity of circumferential fiber shorteningET: ejection timeIVRT: isovolumic relaxation timeMPI: myocardial performance indexLVSP: left ventricular systolic pressureLVEDP: left ventricular end-diastolic pressure+dP/dt max: maximum positive values of first derivative of left ventricular pressure over time-dP/dt max: maximum negative values of first derivative of left ventricular pressure over timeEDT: deceleration time of E-waveThe author(s) declare that they have no competing interests.All authors have equally contributed to the conception and drafting of the manuscript.


The ninth edition of the congress of the European Association of Echocardiography (EAE) (former working group of Echocardiography) held in Florence has just finished with a great success of participant attendance (2.842) and abstract submissions. Hot topics at EuroEcho 9 were: 1-live 3-dimensional echocardiography and surgical decision making; in pediatric cardiology; in resynchronization therapy 2- stress echocardiography beyond wall motion: from valve diseases to contractility to coronary flow reserve to diastolic function; 3- pulmonary cardiogenic interstitial thickening recognized by ultrasonic lung comets; 4- the "proven clinical inefficacy" of the many technologies sold as breakthrough: color kinesis, tissue characterization, strain rate, tissue Doppler, applied to stress echocardiography. The Meeting of the European Association of Echocardiography (EuroEcho9) that took place in Florence from December 6th to 10th, has just finished achieving the record of abstract submissions and participant attendance (2.842). The interest on ultrasound technologies is very high and is still increasing over time in relation to its widespread employment, often outside the cardiological community. This is a brief report on what went on for those who could not attend the meeting or could not follow all the sessions.During the opening ceremony, the president Alan Fraser announced the result of the recent elections for a new member in the Board. The winner was Prof. Albert Varga from Szeged, Hungary. He has an outstanding curriculum characterized by some key publications on safety of stress echocardiography and evaluating new protocols for the detection of myocardial viability. His election is very welcome inside the Board since he represents an independent and highly appreciated voice of the new European Union countries. For the first time the Association employed a completely electronic voting system (different from the previous one that was conducted via e-mail). The electoral system employed by the Association allows that any echocardiographist from any associated country member (the membership of countries to the European Association does not correspond to the 25 members of the European Union but is much larger), can submit his/her resume to the Board. The candidatures do not go through a selection system unless more than five candidates apply for the same position, as stated in the bylaws of the Association. In that particular case the Board will select the best profiles that would fit for that position. The electronic vote posed some technical problems (many physicians found the access a little bit too complicated) but the time allowed for voting was long enough to overcome these limitations. This is an open and transparent way to have access to the Board independent of country of origin and power of the echo working groups. In fact, if it is true that the two societies with the largest number of members in Europe  do have three members each in the Board, it is also true that much smaller working groups were able to elect their representatives such as Romania or Hungary. In the near future a new election for two critical positions, secretary of the Association and President will be held. It would be advisable that the endorsement of the national working groups and/or societies for candidatures were optional and not mandatory: the need for the support of national societies might exclude those who do not lead an active political life in their home societies but nonetheless can represent large sections of the European scientific community on the basis of their curriculum. This problem might be overcome with the institution of a co-membership fee that would make all the national working groups constituent bodies of EAE.During the ceremony it was announced with great emphasis the imminent submission to the European Heart Journal of a position paper on the future of non-invasive imaging modalities in cardiovascular diagnosis. The joint statement will be signed by Alan Fraser and Petros Nihoyannopoulos on behalf of the EAE, Peter Buser and Jürg Schwitter on behalf of the Working Group on Cardiovascular Magnetic Resonance, Jeroen Bax and Juhani Knuuti on behalf of the Working Group on Nuclear Cardiology; Radiology Associations were invited to join among the authors in order to have a widespread acceptance, of general criteria to be applied every time an imaging technique is employed in the clinical practice. The first draft made available to the members of the Board of EAE raised many questions with an overwhelming feeling of not having taken any position regarding imaging modalities. The general view stems from the idea that all the techniques were created equal and can be used in the same clinical setting provided that they are non-invasive and performed by cardiologists. In fact, "no competition among modalities" is the key phrase of the paper. Too little to provide clearer indications to a cardiological community that is pressured between marketing forces giving birth to the latest high-tech indispensable machine and a scientific community unable to speak up sound and loud on the many conceivable limitations and risks of imaging techniques. The aim of the paper should be to create the intellectual and political framework to move from the culture of waste to the culture of responsibility and safety, in which the only possible competition of imaging modalities should be run on the basis of their cost-effectiveness, biological risks, safety, with the ultimate scope of providing key clinical and additive information to the patient .NonethelThe EuroEcho9 programme was designed to address some difficult clinical diagnoses in echocardiography such as rare and infiltrative diseases or secondary cardiomyopathies. A special attention was given to the use of echo in intensive care unit and in the surgical setting as a support for continuing monitoring of valve heart surgery. This is my personal evaluation of the best sessions, it is not meant to be objective , but only to provide suggestions on those areas of research that seemed to be more original : 1 – live 3D echocardiography in particular when used in congenital heart diseases and as a support in interventional pediatric cardiology; it is becoming an important mean in the surgical theatre  and its Accreditation in echocardiography has become a very important activity for the Association and the success of the exams, this year also in transesophageal echocardiography in association with European Association of Cardiothoracic Anaesthesiologists (EACTA), is measured by the increasing number of echocardiographists attending the theoretical part. In Florence 31 out of 48 echocardiographists passed the theoretical part of the TTE exam and 37 out 45 of the TEE exam. Kevin Fox and Bogdan Popescu are the masterminds behind this honorable activity. The presence of Luc Mertens inside the Board of EAE as a non-voting member brought clear advantages to the Association such as the first exam in accreditation in congenital heart disease that will be held in Prague, on December 2006, during EuroEcho 10 in association with the European Association for Pediatric Cardiologist (AEPC) and Grown-Up Congenital Heart Disease working group (GUCH). It would be advisable that the National societies and/or working groups recognized the European accreditation exam in order to avoid two parallel processes with different criteria and procedures.What is missing from the general picture of European echocardiography? The words of Richard Feynman, the physics Nobel Prize, are of help: what is missing is the "perfectly reasonable deviations from the beaten track" . What isWe should give the echocardiographic scientific and clinical community clear positions and some more "eccentric" (non mainstream) research. Let's keep in mind the warning of Bernard Lown: "Technology in medicine is frequently untested scientifically, often applied without data relating to cost benefit, and driven by market forces rather than by patient needs" . It shouMorphological evaluation of a mitral valve by 3D echocardiography.Click here for fileApical 4 chamber view of a 70 years old patient with moderate mitral insufficiency in resting conditionClick here for fileand at exercise peak stress (100 w) with the worsening of the grade of mitral insufficiency.Click here for fileCardiogenic ultrasound lung comets.Click here for file


J) and examined the cardiac involvement.Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations.The cardiac phenotypes of eight CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age.Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and histopathology. These findings imply that studies of CXMDJ may reveal not only another causative mechanism of the deep Q-waves but also more information on the pathogenesis in the dystrophin-deficient heart.Cardiac involvement in CXMD Duchenne muscular dystrophy (DMD) is a common and lethal genetic disease characterized by progressive muscle wasting. It is an X-linked recessive disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin . The absLike dystrophin-deficient skeletal muscle, dystrophin-deficient cardiac muscle is replaced by fibrotic or fatty tissue, especially in the left ventricular posterobasal wall region -11. Atromdx) mouse and the Golden retriever-based muscular dystrophy dog (GRMD) have been used for elucidation of the pathogenesis and development of therapy for DMD. The phenotypes of GRMD are more similar to DMD than that of the mdx mouse [et al. [J) [J, involvement of the temporalis and limb muscles is observed from 2 months of age, and macroglossia, dysphagia, drooling, and joint contracture are apparent from 4 months of age; the phenotypes of CXMDJ are thus almost comparable to GRMD [J using electrocardiography, echocardiography, and pathological examinations. Abnormalities on echocardiogram and cardiac pathology were detected from 12 months of age; however, the distinct deep Q-waves in leads II, III, and aVF on ECG were consistently observed by 6–7 months of age in all CXMDJ dogs examined. The cardiac phenotypes of CXMDJ were identical to but milder than those of GRMD described in the literature. Thus, CXMDJ may also be a suitable animal model for elucidation of the above-mentioned problems.To date, the X-linked muscular dystrophy  . In CXMD to GRMD . In thisJ) breeding colony was established [J breeding colony at the General Animal Research Facility, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)  or the Chugai Research Institute for Medical Science, Inc. . The clinical and histopathological characteristics, except for cardiac involvement, of CXMDJ dogs were recently described [We imported frozen GRMD semen and artificially inseminated a Beagle bitch. The carriers produced were mated with unrelated Beagles, and a Beagle-based canine X-linked muscular dystrophy .J  and one normal littermate (III-301MN) dogs at 2, 3, 4, 6, 9, 12, 15, 18, and 21 months of age, and the heart rate (HR), intervals of PQ and QRS, and Q/R ratios were measured. However, in normal control and in CXMDJ, Q waves were not prominent in leads aVR and aVL, therefore, we measured the Q/R ratios in leads I, II, III and aVF. Next, we compared the HR, intervals of PQ and QRS, or Q/R ratios in I, II, III and aVF in eight CXMDJ and four normal dogs at 6–7 months of age.Leads I, II, III, aVR, aVL and aVF were recorded in the right lateral recumbency using an ECG-922 electrocardiograph  . All ECGJ dogs using M-mode echocardiography. We calculated the M-mode parameters based on multiple measurements of 5 consecutive heart cycles, or 3 or 5 representative heart cycles. We examined the parameters mentioned above and myocardial echogenicity in two CXMDJ  and one normal littermate (III-301MN) dogs at 2, 3, 4, 6, 9, 12, 15, 18, and 21 months of age. We also examined the parameters mentioned above and myocardial echogenicity in six CXMDJ  and three normal dogs  at the time point just before euthanasia. Among those dogs, myocardial echogenicity in one CXMDJ (III-D02MA) and its normal littermate (III-D03MN), and another CXMDJ (III-D08MA) dogs were also examined at various time points.M-mode and two-dimensional echocardiography was performed using an EUB-8000 echocardiograph . The thickness of the interventricular septum (IVS) and left ventricular posterior wall (LVPW) at end-diastole, left ventricular internal dimension at end-diastole (LVIDd) and systole (LVIDs), and fractional shortening (FS) were examined on normal and CXMDAll dogs in this study underwent cardiac histological analysis. After a dog was given an overdose of intravenous pentobarbital, the whole heart was removed and immediately fixed in 15% buffered formalin. Formalin-fixed hearts were cross-sectioned, and samples were taken from the right and left ventricles at the apical papillary muscle and basal levels . The tissue blocks were embedded in paraffin, and 10 μm sections were stained with hematoxylin and eosin or Masson's trichrome stain. Photographs were taken with a DAS Mikroskop LEITZ DMRB microscope , using a digital still camera system HC-2500 .t test was used to evaluate differences between the two groups. A p value of less than 0.05 was considered to indicate statistical significance.Data are expressed as means +/- SE. Student's J except for cardiac phenotypes [J dog examined. We evaluated body and heart weight, the ratio of heart to body weight, and serum CK in eight CXMDJ and four normal male dogs aged 6–21 months just before euthanasia . One 9-month-old CXMDJ dog, III-D55MA, did not show any signs of respiratory or cardiac failure. When we tried to record a routine ECG of the dog, the dog struggled to escape from recording and then ceased moving. Immediately afterwards, we recorded ECG and the monitor showed an idioventricular rhythm. The dog died despite attempted cardiopulmonary resuscitation.We recently reported the detailed clinical and histopathological characteristics of CXMDenotypes . None ofJ dogs, but not in the normal littermates, as shown in Fig. J dogs at 6–7 months of age, the HR, and intervals of PQ and QRS were not different between the two groups of dogs  were not different from those in a normal littermate (III-301MN) by sequential analysis with advancing age  by 6–7 months of age and that they correlated with histologically recognizable areas of mineralization and corresponded to the progression of fibrosis [J dogs showed a hyperechoic lesion in the left ventricular posterior wall, but the rest had not by the age of 6–7 months , although III-D08MA showed a hyperechoic lesion at 5 months of age or older , which occurs as a secondary loss in dystrophin deficiency, decreased cardiac inflammation and fibrosis resulting in amelioration of both cardiac function and electrocardiographic abnormalities, including deep Q-waves [et al. suggested that the alteration of a particular ionic current by lack of specific membrane proteins associated with dystrophin might participate in electrocardiographic changes [J will be very useful to elucidate aspects of the dystrophin-deficient heart, but we may recognize that a longer period of time would be required to complete cardiac phenotypes in CXMDJ.The prominent deep Q-waves seen in both DMD and GRMD have been attributed to a reduction in or a loss of electromotive force caused by scarring of the posterobasal region of the left ventricle ,9,17. In Q-waves . PerloffJ are comparable to but milder than those of GRMD. Furthermore, we found for the first time that the distinct deep Q-waves precede detection of the left ventricular posterobasal lesion by echocardiography or histopathology. CXMDJ may provide not only new insights into the mechanisms causing the abnormal Q-waves but also more information on the pathogenesis in the dystrophin-deficient heart.We demonstrated that the cardiac phenotypes of CXMDThe author(s) declare that they have no competing interests.NY and NU carried out the electrocardiographic, echocardiographic, and pathological examination and drafted the manuscript. YF performed the electrocardiographic study. MY, KY and MRW participated in the necropsy and pathological examination. MN, YS, MT and AT participated in the maintenance of the dog colony and the design of the study. NM performed the pathological examination. YW participated in the design of the study. AN participated in the statistical analysis and drafted manuscript. ST participated in the design, planning and coordination of the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow . Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited. The congenital heart lesion more commonly known today as hypoplastic left heart syndrome (HLHS) was initially termed hypoplasia of the aortic tract complex by Lev in 1952 [Hypoplastic left heart syndrome refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. The severity of outflow obstruction, the left heart structures involved, and the degree of left ventricular and aortic hypoplasia, may vary among patients, resulting in a spectrum of patients with varying levels of severity .The syndrome has been reported to occur in approximately 0.016 to 0.036% of all live births -7. It acNewborn infants generally are born at full term, and initially appear healthy. With closure of the arterial duct, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure.A small subset of patients have restriction of blood flow from the left to right atrium because of an inadequate or absent atrial communication. Such restriction to flow of blood from the left to right atrium can result in severe left atrial hypertension, and decreased blood flow into the right atrium and the dominant right ventricle, resulting in decreased flows into both the systemic and pulmonary circulations. These patients present with cardiogenic shock and profound cyanosis at birth, and are likely die in the absence of an intervention, such as catheter-based or surgical septostomy, performed soon after birth, to relieve obstruction or to create a means of communication in the atrial septum, allowing decompression of the left atrium and free flow of blood from the left atrium into the right atrium.The embryologic cause, as in the case of most congenitally malformed hearts, is not fully known. Early epidemiologic studies report a multifactorial influence to be the cause of up to 90% of cardiac anomalies, with a recurrence rate in further offspring of 2% to 6% . AssociaChromosomal aberrations account for about 6% of all congenitally malformed hearts. Many genetic and hereditary diseases are associated with such congenital malformations, although the causative mechanism is unknown. Prospective studies using chromosomal analysis have suggested that some malformations may be the result of a single gene defect .In the case of hypoplasia of the left heart, the resulting multiple anomalies may result from either the multifactorial factors described above, or from a reduction of left ventricular inflow or outflow during fetal development.The most useful diagnostic modality is the echocardiogram, which may help confirm the diagnosis, and as well as diagnose basic variability in anatomic structures within this anatomically heterogenous population. Information collected should include the size of the inter-atrial communication, function of the atrioventricular valve, and the size of the ascending aorta, as these are useful measurements for stratifying the options for treatment. Although the electrocardiogram is non-specific, many patients display right ventricular hypertrophy, and have paucity of left ventricular forces. Chest radiographs are not diagnostic, and cardiac catheterization is only needed if an intervention such as creation or enlargement of the inter-atrial communication is required .The clinical presentation may resemble those of neonates with other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow. These conditions may include critical aortic stenosis, coarctation of the aorta, interrupted aortic arch. As with hypoplasia of the left heart, their clinical presentation is cardiogenic shock following closure of the arterial duct. Other non-structural cardiac diseases, with clinical presentation in a shock-like state, such as neonatal myocarditis and neonatal sepsis, should also be included in the differential diagnosis. These conditions can be easily differentiated by echocardiography.Upon diagnosis, both genetic counseling and testing should be offered to both parents. Multiple genetic syndromes have been reported, including Turner's syndrome, Noonan's syndrome, Smith-Lemli-Opitz syndrome, Holt-Oram syndrome, and many others ,14. OverThe syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation -16. Furtet al., recently evaluated outcomes for 251 children during 1997, with 17 managed by primary cardiac transplantation, and 234 by stages palliation, and showed that death occurred more frequently in those undergoing primary cardiac transplantation, with 42% dying, compared with those undergoing the Norwood operation, of whom 35% died [Afflicted children require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major treatment modalities. These are primary cardiac transplantation, or a series of staged functionally univentricular palliations . The fun35% died . The morFor patients undergoing functionally univentricular palliation, leading to creation of the Fontan circulation, the highest risk of mortality is following the initial operation, with up to three-tenths of patients dying in some reported series . The NorThe second stage of palliation is called the bi-directional Glenn operation. This consists of anastomosis of the superior caval vein to the right pulmonary artery, and takedown of the systemic-to-pulmonary arterial shunt or conduit . ResultsA number of unresolved questions continue to surround management and treatment . DespiteAnother ongoing discussion, less in the United States of America than in Europe, involves the option of no intervention, known as compassionate care, and otherwise described as passive euthanasia. Until 1980, when the Norwood procedure was introduced, compassionate care was the only option available to infants born with the syndrome. Recent studies seem to suggest most diagnosed infants now initially undergo a surgical intervention, but it is not clear if the option of lack of intervention is discussed with families at the time of initial pre- or postnatal diagnosis -49.Comprehensive counseling by the health care team is a critical component of care for the family of a child born with hypoplastic left heart syndrome. A review of the current outcomes of surgical intervention, as well as studies describing neurological and developmental outcomes, will guide families in their choice of treatment, or lack of treatment. For families who elect to have surgical intervention, care for their afflicted child is associated with numerous hospitalizations, services of a multidisciplinary team of specialists, and use of both advanced and innovative technology. The significant financial burden, or out of pocket expenses, that the family will incur should also be part of the preparation. Additional outside support can be provided by directing families to support groups available for families who have a child with congenital cardiac disease, and other online resources.As a result of advanced technology, refined surgical techniques, and catheter-based interventions, the mortality in the short term has improved dramatically for children born with hypoplasia of the left heart. The syndrome, nonetheless, it is still considered one of the most complex congenital cardiac malformations to manage. Many unresolved questions regarding treatment, and long-term functional and cognitive outcomes, remain for these children. Further information on these topics is required appropriately to guide discussions with families regarding initial options for treatment, long-term survival, and quality of life.