Arrhythmias figure prominently among the complications encountered in the varied and diverse population of patients with congenital heart disease, and are the leading cause of morbidity and mortality. The incidence generally increases as the patient ages, with multifactorial predisposing features that may include congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical or hypoxic stress, and residual or postoperative sequelae. The safe and effective management of arrhythmias in congenital heart disease requires a thorough appreciation for conduction system variants, arrhythmia mechanisms, underlying anatomy, and associated physiology. We, therefore, begin this review by presenting the scope of the problem, outlining therapeutic options, and summarizing congenital heart disease-related conduction system anomalies associated with disorders of the sinus node and AV conduction system. Arrhythmias encountered in common forms of congenital heart disease are subsequently discussed. In so doing, we touch upon issues related to risk stratification for sudden death, implantable cardiac devices, catheter ablation, and adjuvant surgical therapy. Congenital heart disease is the most common form of birth defect, with an estimated 1-2% of live newborns afflicted by moderate or severe types   . The incArrhythmias may reflect congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical and/or hypoxic stress, and/or residual or postoperative sequelae ,8.  The Importantly, arrhythmias may herald a changing hemodynamic profile and should generally prompt a detailed work-up. The care of the patient with congenital heart disease and arrhythmias may involve pharmacological therapy, catheter ablation, implantable cardiac devices, and surgical interventions.In the absence of specific evidence-based recommendations, pharmacological therapy is often guided by principles established in other forms of heart disease ,11. ThesAnatomical complexities and vascular access issues may complicate catheter-based interventions and implantation of pacemakers or implantable cardioverter-defibrillators (ICD) ,13,14. CWith the advent of three-dimensional electroanatomic mapping and advances in catheter technology permitting larger and deeper lesions, transcatheter ablation has emerged as a promising alternative for many patients with tachyarrhythmias.  While acute success rates in dedicated centers are high, recurrences and the onset of new arrhythmias remain problematic, particularly in patients with Fontan palliation.  In certain circumstances, arrhythmia surgery, usually performed in conjunction with cardiac surgery for other indications, may complement less invasive options.Most patients with congenital heart disease have a normally positioned sinus node. Exceptions include left juxtaposition of the atrial appendages, situs inversus, and heterotaxy syndromes. In left juxtaposition of the atrial appendages, both appendages are on the left side of the arterial pedicle . The sinThe AV conduction system may be displaced if atrial and ventricular septae are malaligned, AV arrangements are discordant, or if the heart is univentricular. As a general rule of thumb, if the AV conduction system is displaced, it also tends to be more fragile and susceptible to degeneration, placing patients at greater risk for AV block.In atrioventricular canal defects (AVCD), the AV node is displaced inferiorly and posteriorly  . The HisMacroreentrant atrial circuits are the most frequent arrhythmias encountered in patients with secundum and sinus venosus ASDs. In the absence of surgical repair, typical cavo-tricupsid isthmus-dependent atrial flutter is the most common form. In the presence of atriotomy incisions, sutures, and/or patches, non-isthmus dependent macroreentrant circuits may occur or coexist with typical flutter. Common substrates include macroreentry along the lateral right atrial wall and double-loop or figure-of-eight circuits  ,29.The incidence of atrial arrhythmias increases with age and has been reported in 20% of adults  ,31. AlthIn patients with unoperated VSDs, isolated premature ventricular contractions (PVC), couplets, and multiform PVCs are prevalent  . Non-susIn patients with AV canal defects, frequent ventricular ectopy has been described in 30%, while complex ventricular arrhythmias are predominantly confined to those with left ventricular dysfunction . PersistImportantly, since the AV node is displaced just anterior to the mouth of the coronary sinus, interventional electrophysiologists should be cautious when ablating in the right inferior paraseptal region. For patients with cavo-tricuspid isthmus-dependent macroreentry, lateral ablation lines are generally preferred to prevent AV block. With dual AV node physiology, the slow pathway has been located superior to the His bundle, with the fast pathway inferior to the displaced AV node, as shown in In patients with left ventricular outflow tract obstruction, ventricular arrhythmias have been related to severity of obstruction, increased wall stress, and left ventricular hypertrophy ,44-46. IPatients with L-TGA have notoriously fragile AV conduction systems.  In 107 patients with L-TGA and mean age of 22 years, complete AV block occurred in 22% . Risk ofIn Ebstein's anomaly, the atrialized portion of the right ventricle is morphologically and electrically right ventricle but functionally right atrium . MechaniRight-sided accessory pathways, classically associated with Ebstein's anomaly, have been reported in 25% and may be multiple ,54,55.  The Fontan procedure has undergone multiple modifications to become the treatment of choice for various forms of single ventricle physiology  . Sudden In general, the incidence of atrial tachyarrhythmias appears lower in patients with total cavo-pulmonary connections in comparison to classic right atrium to pulmonary artery connections. Studies comparing the relative incidence of atrial tachyarrhythmias in patients with lateral tunnel versus extracardiac conduits are ongoing. Overall, the most common arrhythmia is atrial macroreentry . AlthougPatients with failing Fontans and refractory atrial arrhythmias should be considered for surgical conversion to a total cavopulmonary connection with concomitant arrhythmia surgery. This typically includes debulking the right atrium, removing thrombus, excising right atrial scar tissue, epicardial pacemaker implantation, a modified right atrial Maze procedure and, in patients with prior documented atrial fibrillation, a left-sided Maze procedure as well . Case seThe frequency and nature of arrhythmias encountered in tetralogy of Fallot are related, in part, to the type of surgical correction. Repairs were initially performed by means of a ventricular incision. This approach was largely abandoned in favor of transatrial/transpulmonary access to reduce risk for potentially fatal ventricular tachyarrhythmias . The mosSudden cardiac death is the most common cause of mortality late after repair ,73. MonoImplantable cardioverter-defibrillators (ICD) are increasingly utilized in the primary and secondary prevention of sudden death in patients with tetralogy of Fallot, with patients experiencing relatively high rates of appropriate shocks  . For patAlthough arterial switch surgery has supplanted atrial redirection as the procedure of choice for D-TGA, most adults with D-TGA have had intraatrial baffle repairs of the Mustard or Senning variety. Sinus node dysfunction is highly prevalent with increasing age, with loss of sinus rhythm in 60% at 20 years  . In a meStudies are beginning to address the role of ICDs   and cardPatients with congenital heart disease represent a heterogeneous population with varied arrhythmic diagnoses and issues. The last decade has witnessed major advances in our understanding of arrhythmia mechanisms and therapeutic options. Sudden cardiac death of presumed arrhythmic etiology is the leading cause of mortality, particularly in patients with left-sided obstructive lesions, D-TGA and intraatrial baffles, tetralogy of Fallot, and severe systemic ventricular dysfunction. Sinus node dysfunction is common in left atrial isomerism and with Mustard, Senning, Glenn, or Fontan surgery. Complete AV block frequently occurs in patients with L-looped ventricles, left atrial isomerism, and AVCD. Atriotomy incisions, sutures, baffles, and conduits may predispose to the development of scar-based macroreentrant atrial circuits, as commonly encountered in surgically repaired ASD, Mustard and Senning baffles, tetralogy of Fallot, and Fontan palliation.ICDs and cardiac resynchronization therapy are increasingly utilized in patients with congenital heart disease. Unlike standard indications for patients without congenital heart disease, evidence supporting this technology is limited but growing. Guidelines have begun incorporating issues relevant to this patient population and targeted training programs are now offered. A thorough understanding of conduction system variants, arrhythmia mechanisms, underlying anatomy, and physiology is important to safely and effectively manage arrhythmias in this unique and diverse patient population.


When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance , arterial elastance, ventricular arterial coupling , and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo.Aims of this paper are: 1) to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2) to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3) to show examples of software testing in a way that proves its value.http://cctrainer.ifc.cnr.itThe informatics infrastructure is available on the web, linking to  BecauseD echocarOnce the electronic rest and stress data set is filled, the CCtrainer program will show that echo-measured volumes (plus standard assessment of heart rate and blood pressure) allow a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance Figure  arterialA computerized web-based system has been developed for data transfer, analysis and report phases. All the computer clients connect to the server merely by using a common web browser, without needing to install any specific software. Data and reports are anonymous, so secure protocols are not required.http://cctrainer.ifc.cnr.it.The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it. gives time and modalities of extending the time of program use. Only then can the user access his/her data in protected and reserved mode.When operating for the first time, a user need to get his/her user - password clicking on the "new user" button. The CCTRAINER calculation program is completely free for use during the first month of operations. Algorithms and data sheets can be freely downloaded. Values and indexes are obtained automatically by software processing. After the first month, to continue using the program each user must be registered by the server administrator who assigns him/her an account and an exclusive memory area on the database server. A user license could be purchased by bank transfer to the CNR. Page 1 of the WEB site In each training example the age, height, and weight will be filled in and body mass index and body surface area will be calculated. A complete data set to fill in the electronic sheet is shown in Table The blood pressure recording is made using a sphygmomanometer and the diaphragm of a standard stethoscope. The auscultatory pressure is obtained by inflating the cuff to a level approximately 30 mm Hg above the peak level of systolic blood pressure and evaluating Korotkoff's sounds. The systolic blood pressure is recorded as the point where the first tapping sound occurs for 2 consecutive beats. The right and left brachial arterial systolic blood pressures are compared and discrepancies greater than 5 mm Hg are reported .LV End-Diastolic Volume  is measured from the apical view by an experienced observer using 3 D echo or by apical 4- and 2-chamber views using (Simpson's rule) 2 D echo. The frame captured at the R-wave in ECG in triggered software is considered to be the end-diastolic frame ) + 1.9 (mmHg)Elevated filling pressures are the main physiologic consequence of diastolic dysfunction. Filling pressures are considered elevated when the mean pulmonary capillary wedge pressure is >12 mmHg or when the LV End-Diastolic Pressure is >16 mmHg. Using the septal E/e´ ratio, a ratio < 8 is usually associated with normal LV filling pressures, whereas a ratio >15 is associated with increased filling pressures ,55.A growing number of acute and chronic conditions have been associated with RV diastolic dysfunction, including both pressure and volume overload pathologies, primary lung disease, ischemic heart disease, congenital heart disease, cardiomyopathies, LV dysfunction (via ventricular interdependence), systemic diseases, and the physiologic aging process . The parTo test the WEB downloadable software for training in noninvasive cardiovascular hemodynamics, anonymous standard stress echo reports with baseline and stress measurements were submitted to 10 skilled echocardiographers (American Society of Echocardiography class III). Each echocardiographer was asked to calculate hemodynamic parameters starting from the sets of rest and stress measurements with two modalities Table . A firsthttp://cctrainer.ifc.cnr.it. Algorithms and data sheets can be freely downloaded by the WEB. Measures and indexes are obtained automatically by software processing. The exporting data in excel or SPSS format is possible for shorten calculations and to store data. Examples of the web downloadable "rest and stress parameters" electronic sheet is shown in Figure The informatics infrastructure is available on the web, linking to Clinical use of modern 3 D echocardiography is boosted by the marked reduction in acquisition time and the unique possibility of online rendering on the ultrasound system. The ability to visualize a virtual 3 D surface in real time - although limited to a sector size of about 30 degrees - offers new insights into cardiac pathomorphology even in patients with arrhythmias. Analysis of wide-angle 3 D datasets  is possible by combining the 3 D information of several -6 consecCombination with 3 D color Doppler data allows additional assessment of valvular function as well as determination of flow in the left ventricular outflow tract and across septal defects. Dedicated software systems and technologies have been developed based on high-performance computers designed for graphic handling of three-dimensional images by providing possibilities beyond those obtainable with 2 D echocardiography. Beyond this, echocardiography enables the cardiologist to measure and calculate over 30 different noninvasive parameters including cardiac chamber size, indices of left ventricular performance, and estimates of mean left atrial pressure. However, the entire procedure requires meticulous measurements and time-consuming calculations, particularly when some of the data must be corrected for heart rate or body size. Because of this, many busy noninvasive cardiac laboratories routinely calculate only a few selected parameters in most patients. This problem of calculation is strongly amplified in the stress echo lab, since the 30 different noninvasive parameters become 60 if we also have to calculate peak stress data, 90 if we want to calculate rest-peak stress changes, and even more if we want to graphically display results. Quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamic needs data to be implemented in formulas - and until now, little or nothing has been done to help cardiologists utilize these data practically in the everyday busy echocardiography lab. In this paper we have shown how a simple web downloadable calculation trainer could greatly simplify the use and speed of calculation of a complete set of cardiologic parameters.The success of imaging is high with pharmacologic stress but the feasibility is not established with exercise stress. The lower spatial and temporal resolution of 3 D imaging and artifacts introduced by suboptimal subvolume integration are limitations of the current 3 D technique. The ability to provide more planes for analysis has not been clearly shown to improve the accuracy of stress echocardiography. However, 3 D imaging eliminates apical foreshortening, which is common with 2 D imaging, and may improve detection of apical wall motion abnormalities. Development of automated image registration, quantitative analysis techniques, and single beat acquisition is needed to fully exploit the potential of 3 D imaging in the stress laboratory ,69.A potential limitation of this study is the lack of information regarding Doppler indexes of diastolic function or dysfunction during stress. Doppler echocardiography is the preferred method for non-invasive diastolic function assessment. In current practice, most diastolic function indexes are derived by visual inspection of transmitral E- and A-waves . HoweverThe E/e´ ratio has been applied for that objective. In subjects with normal myocardial relaxation, E and e´ velocities increase proportionally, and the E/e´ ratio remains unchanged or is reduced. However, in patients with impaired myocardial relaxation, the increase in e´ with exercise is much less than that of mitral E velocity, such that the E/e´ ratio increases. In that regard, E/e´ was shown to relate significantly to LV filling pressures during exercise, when Doppler echocardiography was acquired simultaneously with cardiac catheterization ,73.In cardiac patients, mitral E velocity increases with exertion and stays increased for a few minutes after the termination of exercise, whereas e´ velocity remains reduced at baseline, exercise, and recovery. Therefore, E and e´ velocities can be recorded after exercise, after 2 D images have been obtained for wall motion analysis. However, the paucity of clinical data and the potential limitations in patients with regional LV dysfunction, mitral valve disease, and atrial fibrillation preclude recommendations for its routine clinical use at this time ,55.The combination of a cutaneous operator independent force sensor and 3 D stress echo allows a highly feasible, fast and informative assessment of mitral inflow rate, which could be impaired in presence of diastolic dysfunction and provide insight on a novel form of diastolic stress echocardiography .2 - Mitral Opening interval (isovolumic relaxation) and the beginning of isovolumic contraction   list several functional parameters of the heart and vascular system at rest and during stress; 2) give typical values for systolic, diastolic and mean pressures in the systemic and pulmonary arterial system; 3) calculate arterial elastance from pressure and volume values, and know the steady (systemic vascular resistance) and pulsatile  components of the arterial elastance; 4) calculate left ventricular systolic elastance and the interaction of the LV with the arterial system, termed ventricular-arterial coupling, that is a central determinant of cardiovascular performance and cardiac energetics; 5) calculate pulmonary vascular resistance and pulmonary vascular capacitance; 6) calculate patterns of diastolic function and dysfunction at rest and during stress.2: aortic valve closure, aortic component of second sound; ASE: American Society of Echocardiography; BSA: Body surface area; C: Systemic arterial compliance; CO: Cardiac output; CI: Cardiac index; DBP: Diastolic blood pressure; Ea: Effective arterial elastance; Ees: Left ventricular elastance; EF: Ejection fraction; ESP: End systolic pressure; IVC: Inferior vena cava; IVCT: Isovolumic contraction time; IVRT: Isovolumic relaxation time; LV: Left ventricle; M1 : mitral component of first sound at time of mitral valve closure; MAP: Mean arterial pressure; P2 : pulmonary component of second sound; PA: Pulmonary artery; PADP: Pulmonary artery diastolic pressure; PAPP: Pulmonary artery pulse pressure; PCWP: Pulmonary capillary wedge pressure; PH: Pulmonary hypertension; PP: Pulse pressure; PVR: Pulmonary vascular resistance; PVC: Pulmonary vascular capacitance; RA: Right atrium; RV: Right ventricle; RVOT: Right ventricular outflow tract; RVSP: Right ventricular systolic pressure; SBP: Systolic blood pressure; SPAP: Systolic pulmonary artery pressure; SV: Stroke volume; SVR: Systemic vascular resistance; T1 : tricuspid valve closure, second component of first heart sound; 3 D: Three-dimensional; TR: Tricuspid regurgitation; TVI: Time velocity integral; 2 D: Two-dimensional; VAC: Ventricular arterial coupling.AThe authors declare that they have no competing interests.TB conceived this study, developed the SW system, performed the data analysis, and drafted the manuscript; DC participated in the development of the web system; GA contributed to data discussion; EPi contributed to the preparation of study design, data discussion, and critical revision of the manuscript. All authors read and approved the final manuscript.


Lindbergh.Pacemakers have evolved over a period of time trying to mimic the normal response rates, conduction and activation characteristics, though are still far from what nature has bestowed upon us. Better understanding of cardiac physiology and hemodynamics has led to current available pacing technology and we do recognize now that to achieve physiological pacing we should have an appropriate heart rate response, ventriculo-ventricular (VV) synchronization and atrio-ventricular (AV) synchronization.Patients receiving rate responsive pacemakers for sinus node dysfunction, in spite of using various sensors and rate response algorithms -5, stillRight ventricular (RV) pacing represents a non-physiological activation of the heart causing wide QRS (left bundle branch block) with electrical and mechanical VV dyssynchrony . Higher Optimal AV interval at rest ranges from 100 to 150 milliseconds. In normal individuals the AV interval shortens with increased heart rate during exercise in a predictable and linear fashion. Most pacemakers have a programmable shortening of AV delay at higher rates, the hemodynamic benefits of which have not yet been shown . Device An electrocardiogram based method to determine optimal AV interval is described by Sorajja et al  in this Based on echocardiographic parameters and natriuretic peptide levels, AV delay optimization is found to be beneficial in patients with normal LV function in short term small studies -25. TherAdopt the pace of nature:  her secret is patience  - Ralph Waldo EmersonLook deep into nature, and then you will understand everything better  - Albert Einstein


Recent advances in technology have provided the opportunity for off-line analysis of digital video-clips of two-dimensional (2-D) echocardiographic images.Commercially available software that follows the motion of cardiac structures during cardiac cycle computes both regional and global velocity, strain, and strain rate (SR).The present study aims to evaluate the clinical applicability of the software based on the tracking algorithm feature (studied for cardiology purposes) and to derive the reference values for longitudinal and circumferential strain and SR of the left ventricle in a normal population of children and young adults.45 healthy volunteers  underwent transthoracic echocardiographic examination; 2D cine-loops recordings of apical 4-four 4-chamber (4C) and 2-chamber (2C) views and short axis views were stored for off-line analysis.Computer analyses were performed using specific software relying on the algorithm of optical flow analysis, specifically designed to track the endocardial border, installed on a Windows™ based computer workstation. Inter and intra-observer variability was assessed.The feasibility of measurements obtained with tissue tracking system was higher in apical view  than in short axis view . Longitudinal systolic velocity decreased from base to apex in all subjects . Longitudinal strain and SR significantly increased from base to apex in all subjects . Similarly, circumferential strain and SR increased from base to apex .Values of global systolic SR, both longitudinal and circumferential, were significantly higher in children than in adults . No significant differences in longitudinal and circumferential systolic velocities were identified for any segment when comparing adults with children.This 2D based tissue tracking system used for computation is reliable and applicable in adults and children particularly for systolic events. Measured with this technology, we have established reference values for myocardial velocity, Strain and SR for both young adults and children. Accurate assessment of global and regional left ventricular function is essential for the evaluation and management of patients with heart disease. Recent developments have improved cardiac function quantification and it seems that both magnitude and temporal sequence of tissue deformation can provide additional information in known or suspected heart disease -3.-1 [Tissue Doppler Imaging (TDI) has been extensively applied in assessing and quantifying regional myocardial contractility -6 and va-1 .However, TDI being a Doppler based technique, its routine clinical use is limited by technical issues such as angle, signal noise and measure variability. When the angle between the velocity direction and the ultrasound beam is > 20°, the real velocity is underestimated. Since a correct alignment is not always possible, due to ventricular geometry, TDI derived measures will lose validity especially at the apical segments . RecentlSeveral 2D tissue tracking techniques are currently available and their difference is based on the type of algorithm employed; the first (and more investigated) method is known as "speckle tracking"  and the Forty-five healthy volunteers  were included in the study. Informed written consent and appropriate ethics approval were obtained. All subjects underwent clinical examination, 12-lead ECG recordings and systemic blood pressure recording. Subsequently, they underwent a complete transthoracic echocardiographic examination in left lateral decubitus. The exclusion criteria were: history of hypertension, diabetes, coronary artery disease, myocardial infarction, stroke, congenital heart disease, acquired valve disease, atrial fibrillation or congestive heart failure.Echocardiographic exams were performed with all subjects positioned in the left lateral decubitus, by the same operator (CB) using a MyLab50 echo machine  equipped with a multi-frequency 2.5–3.5 MHz transducer. 2D harmonic image cine-loops recordings (video clips) of apical 4C and 2C views and short axis views at mitral, papillary muscles and apical levels, with good quality ECG signal and a frame rate between 40–64 fps were acquired and stored for off-line analysis. Off-line computer based analysis of the video clips stored on the Esaote Mylab 50 were performed using XStrain™ software  installed on a Windows™ based computer work station. Relying on the algorithm of optical flow analysis specifically designed to track the endocardial border, XStrain™ is a dedicated software that derives longitudinal and circumferential myocardial velocity, ε and SR from the digitized 2D video clips. The endocardial border, drawn by the operator on an arbitrary single frame, is identified as a sequence of points. It is then automatically followed frame by frame by searching  for each single point, in the neighbourhood of maximum likelihood. For apical views an adaptive control is performed by the system; the control is based on the spatial coherence of the points with respect to the points fixed by the operator .For each point, the velocities are calculated and displayed both as vectors superimposed on the 2D images and as graphs plotted against time; ε and SR displayed for each point are deformation and deformation rate of the segment whose extreme points are the previous and the subsequent points with respect to the point analyzed Figure . Since pFor each patient, clip with the best border was chosen and processed as follows: a starting frame was chosen, usually in end diastole when endocardial border is better visible . Border tracking of the left ventricle was manually traced by an experienced operator in the recorded clips. In apical 4C and 2C views a total of 13 equidistant points were tracked in order to obtain a subdivision in 6 segments for each view. Points were tracked starting from the septal side of the mitral annulus in the apical 4C view  and with accuracy ,12. DiffThe feasibility of obtaining measurements with border tracking system, evaluated in all the 225 stored cine-loops, was higher in the apical long axis view (100% for systolic and 64% for diastolic events) than in the short axis view (70% for systolic and 52% for diastolic events).Inter-observer variability between two experienced operators was minimum; Correlation coefficient r = 0.8958, p < 0.0001, 95% Confidence interval for r = 0.8039 to 0.9460.b (accuracy) 0.9632.Intra-observer variability for CB was r = 0.9348, 95% Confidence interval for r = 0.8968 to 0.9591, p < 0.0001. Bias correction factor CValues of the longitudinal and circumferential velocities, in systole and diastole, measured in the overall population are reported in details in Table Even for circumferential ε and SR there was a significant increase of the values from base to apex calculated as global values for section in all subjects . Global systolic longitudinal Strain was significantly higher in children than in adults (22.18 ± 3.06 vs. -19.05 ± 3.05 p = 0.0020). Global systolic SR, both longitudinal and circumferential, was significantly higher in children than in adults . The differences in longitudinal and circumferential Strain and SR between adults and children were more significant for circumferential strain of the apical segments.Values of global systolic longitudinal and circumferential values of ε and strain rate are reported in Table TDI, it's derivatives, and 2D strain technologies suffer from an intrinsic limitation i.e. they have been put to clinical use long before their value has been demonstrated in various clinical settings. Currently, we can only make intra-population comparisons to assess changes induced by treatments that act on strain, strain rate and torsion like resynchronization therapy, drug therapy or surgery. In the near future we will have data on the clinical impact of such measurements and their clinical meaning. These measures actually assess cardiac mechanics and changes induced by loading conditions that are already well known from physiology and pathology point. But their great advantage, once technical accuracy has been achieved, is that they are easily and non-invasively applicable to large cardiac disease population.The 2D Strain tissue tracking method described as "Feature Tracking" has previously been employed in paediatric  and adulThe processing system used in this study is based on a mono-dimensional technology; this seems to be a more accurate system and this hypothesis has been verified in this study. The "Feature Tracking" system is highly reliable for systolic events and provides data for apical and short axis regions that TDI is unable to provide. This new 2D tissue tracking technology overcomes this limitation by analyzing displacement of all the points tracked in two spatial dimensions . This has the advantage of offering a correct strain computation even along curved segments.Limitations to our study are mostly software related and the fact that the analysis is based on 2D video clips. Any 2D based system that relies on tissue tracking needs good quality images (as young and cooperative subjects can offer); however, in clinical practice it may be more difficult to obtain a similar level of image quality and consequently the percentage of the feasibility of the measurements will go down. In our analysis we have done only partial observations about diastolic data since most of the video clips were recorded at a frame rate lower than 60 fps (between 40 to 60 fps) and this probably would have resulted in an underestimation of the peak values of those rapid events. The feasibility of these measurements was less in short axis views than in the long axis views: this could partially be consequent to the movements of the whole left ventricle in directions others than radial or circumferential, partially to the quality of the images and also to the tracking accuracy of the algorithm in short axis.The first issue is an intrinsic limitation of the 2D approach and it will probably be solved when the system will be applied to 3D echocardiography. On the other hand, rapid improvement in technology in terms of improved tracking of the algorithm and better lateral resolution of images even with higher image fps will enhance the results.The assessment for longitudinal systolic ε and SR was 100% in apical 4C views, but it fell to 73% for ε and 64% for SR in apical 2C view. This was mainly due to the poor lateral resolution in the apical anterior segment, which is the most difficult segment to demark with an endocardial border.Our results are very encouraging if we consider that in other studies  20% of the segments couldn't be processed . Referen2D strain technologies have demonstrated their value in several clinical conditions and now that they have been shown to be highly accurate and reproducible, they are going to be applied in the large cardiac disease population, substituting the TDI technology that gives consistent but limited information in respect to 2D based technology.Validation against MRI is recommended for all imaging technology and is widely considered to be the gold standard because it allows the measurement all three velocity vectors and thus analyzes regional strain in three dimensions; but the peak values obtained with MRI must also be considered carefully because this technique has a lower temporal resolution compared to echocardiography, and, with 30 fps it could underestimate both diastolic and systolic values, especially when heart rate is rapid, as occurs in children ,22.Having derived the normal values for pediatric and young adult population it is now important to open up this exciting new field of basic science to study physiology of the ventricular function and its change with the human growth. This will also be very useful in the clinical assessment of segmental and global ventricular function in congenital heart disease where other echocardiographic parameters are often less applicable.The major limitation of this study was that we were restricted in considering only the data for systolic events because the feasibility for diastolic events was consistently reduced, especially in short axis view. This was due to sub-optimal tracking followed by the algorithm but rapid evolution of ultrasound technology and improvement in software engineering will rapidly overcome this limitation.2D based tissue tracking system is highly reliable and applicable for the study of systolic events in adults and children. Reference values for children and adults have been derived for various segments of myocardium and significant difference between adults and children in longitudinal and circumferential Strain and SR has been demonstrated. This difference is more evident in the circumferential strain of the apical segments.The capability of this system to analyze curved segments as well as rectilinear segments consistently may provide valuable insights into physiology and patho-physiology of left ventricular function . It willCB acted as consultant to ESAOTE in the development of the clinical software.CB: Conceptualized and designed the study, executed all the echocardiographic exams, analyzed and interpreted the data, overviewed at the file processing and wrote the manuscript. AM: Reviewed the manuscript and made substantial contribution to the conception and design of the study. MDD: Reviewed the manuscript, made substantial contribution of data interpretation, contributed to the statistical analysis. BdeC: Contributed to drafting of the manuscript and statistical analysis. DN: Examined clinically all the subjects and participated in the post processing of echocardiographic files. EDA: Participated in the post processing of echocardiographic files and overviewed all data processing and collection. EL: Reviewed the manuscript for relevant intellectual content. MCH: Made substantial contribution to study conception and design. JSD: Reviewed the manuscript for relevant intellectual content. CA: Participated in the post processing of echocardiographic files and overviewed all data processing and collection. FM: Made substantial contribution to study conception and design. MC: Made substantial contribution to study conception and design.


Rheumatic and congenital heart diseases account for the majority of hospital admissions for cardiac patients in India. Tetralogy of Fallot is the most common congenital heart disease with survival to adulthood. Infective endocarditis accounts for 4% of admissions to a specialized unit for adult patients with a congenital heart lesion. This report is unique in that a severe stenotic lesion of the mitral valve, probably of rheumatic aetiology, was noted in an adult male with Tetralogy of Fallot.An unusual association of rheumatic mitral stenosis in an adult Indian male patient aged 35 years with Tetralogy of Fallot and subacute bacterial endocarditis of the aortic valve is presented.In this case report the diagnostic implications, hemodynamic and therapeutic consequences of mitral stenosis in Tetralogy of Fallot are discussed. In addition, the morbidity and mortality of infective endocarditis in adult patients with congenital heart disease are summarized. The risk of a coincident rheumatic process in patients with congenital heart disease is highlighted and the need for careful attention to this possibility during primary and follow-up evaluation of such patients emphasized. Rheumatic and congenital heart diseases account for about 65% of total cardiac admissions in India and the prevalence rate of rheumatic heart disease is reported as 0.5 to 0.67 per 1000 ,3. We diTF remains the most common type of congenital heart lesion seen beyond infancy and childhood with about 5% of patients surviving to the age of 40 years. Aortic regurgitation may occur in affected patients in or beyond the second decade of life, and this may predispose to infective endocarditis [Atrial fibrillation is an uncommon rhythm disturbance in TF. However, mitral stenosis may predispose the patient to atrial fibrillation, with disastrous hemodynamic consequences. The possibility of left atrial clot formation and embolic stroke may add to central nervous system complications such as cerebral thromboses and abscesses that occur as a result of a widespread tendency to spontaneous arterial thrombosis secondary to a hypercoagulable state in adult TF .The low pulmonary blood flow situation in TF, with a consequent decrease in the left atrial flow, tends to result in a small left atrium and left ventricle. Mitral stenosis results in a further reduction of the left ventricular end diastolic volume, which is an important risk factor for early death after repair . MyocardInfective endocarditis accounts for 4% of admissions to a specialized unit for adult patients with a congenital heart lesion. Predisposing events identified include a dental procedure, systemic sepsis or prior cardiac surgery . The aorA male aged 35 years with a history of cyanosis from early childhood was referred for evaluation of low grade fever and worsening breathlessness on exertion. There was no history of a recent dental or surgical procedure. General physical examination revealed a moderately nourished individual with central cyanosis and grade IV clubbing. The jugular venous pulse was elevated. The pulse was regular with a rate of 100 beats per minute and a collapsing character. The blood pressure was 120/60 mmHg. On precordial examination the first heart sound was palpable. Auscultation revealed a loud first heart sound, single second heart sound and an apical opening snap. Additional findings included ejection systolic and early diastolic murmurs at the left sternal border and a mid-diastolic murmur with pre-systolic accentuation at the apex. The lungs were clear. Abdominal examination revealed a tender enlarged liver. There was no enlarged spleen. Pulse oximetry showed a room air oxygen saturation of 78%. Chest X-ray revealed enlarged heart, pulmonary oligemia and no evidence of pulmonary venous hypertension. Electrocardiogram revealed sinus rhythm, normal PR interval, right axis deviation, left atrial enlargement and right ventricular hypertrophy.2. There was no mitral regurgitation. The peak and mean gradients across the valve were 36 and 21 mmHg respectively (Figure An echocardiogram revealed a large malaligned ventricular septal defect with 60% aortic override. The aortic valve was trileaflet with a vegetation on the right coronary cusp Figure . The mity Figure  and the A final diagnosis of TF, subacute bacterial endocarditis of the aortic valve and severe mitral stenosis, probably of rheumatic etiology, was considered. Endocarditis with aortic regurgitation added to the hemodynamic burden and the patient succumbed to infective complications during the course of stabilization.Although there was no definitive evidence of prior streptococcal infection, the clinical profile and the echocardiographic findings suggest an acquired rheumatic etiology in our patient. Congenital mitral stenosis can present with some leaflet thickening and commissural fusion; however, its association with TF is extremely rare . Fifty pAbout 50% of patients with rheumatic heart disease may not have a prior history of rheumatic fever  and recuThis report draws attention to an interesting association of rheumatic mitral stenosis in TF and highlights the possibility of a coexistent rheumatic lesion in patients with congenital heart disease.The authors declare that they have no competing interests.GVR, NKP and MD carried out the diagnostic evaluation and stabilization. CSK was responsible for drafting the manuscript, its revision and preparation of illustrations. Final edits were carried out by NKP. All the authors read and approved the final manuscript.Written informed consent was obtained from the patient's next-of-kin for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Transient left ventricular dysfunction syndrome (TLVDS), or Tako-Tsubo cardiomyopathy (TC), is a clinical entity in which patients present with features of acute coronary syndrome, electrocardiogram abnormalities, and transient left ventricular  dysfunction. Patients usually recover from this condition four to six weeks after the event. The etiology or triggering factors of TC remains unknown. Various triggering factors have been associated with this syndrome, with one of the most recent being malignancies. In this case report we present a postmenopausal female with underlying advanced malignancy who presented with TC. This is consistent with a recent hypothesis that in addition to currently known triggering factors, malignancies might well trigger TC in the context of a stressor or paraneoplastic phenomenon. Other names include stress-induced cardiomyopathy, apical ballooning syndrome, ampulla cardiomyopathy, or Broken Heart syndrome. It was first thought to be restricted to the apex of the left ventricle, hence the name “apical”; however, we now have evidence that other parts of the left ventricle, as well as the right ventricle, are involved [Tako-Tsubo cardiomyopathy (TC) is a clinical entity first described in 1991 by Dote et al. [involved , 3. TherThere continues to be a constant evolution in our understanding of this unique condition as far as etiology, pathophysiology, and triggering factors are concerned. There are no large randomized or cohort studies available. Most of the information known comes from case reports and case series. Current incidence is unknown; however, some studies estimate 1% to 2% of all patients present with acute coronary syndrome, which puts the incidence at 7,000 to 14,000 cases per year. The condition is common in postmenopausal women, with a mean age of 58 to 75 years, and <3% under age 50 [Triggering factors and their mechanisms continue to generate deep clinical interest. Recent retrospective studies , 6 have A 66-year-old woman with hyperlipidemia and hypertension presented with acute onset of chest pressure. She denied any shortness of breath, diaphoresis, palpitations, presyncopal, or syncopal symptoms. She had no cardiac or diabetic history. She did not have regular medical care. Clinically she was in mild distress with tachycardia at 120 bpm. Other vital signs were within normal limits. Physical examination was normal except for positive stool Guaiac test. Laboratory values were troponin I 6.5 ng/mL, creatinine kinase (isoenzyme—MB) 28.4 ng/mL, white blood cell count (WBC) 19600/uL with 0% bands, hemoglobin 10.9 g/dL, hematocrit 32.7%, normal platelets, alanine transaminase 36 U/L, aspartate transaminase 44 U/L, total alkaline phosphatase 234 U/L, sodium 133 mmol/L, and potassium 3.3 mmol/L.Electrocardiogram (ECG) showed ST segment elevation in precordial leads V2-V3 . Chest XBecause of her positive Guaiac test and mild anemia, she was advised to return in four weeks for a diagnostic colonoscopy. Colonoscopy revealed a colorectal mass with colonic obstruction. Histopathology was consistent with a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen and pelvis revealed stage IV adenocarcinoma for which an exploratory laparotomy with diverting sigmoid colostomy and mucous fistula was performed. This was followed by adjuvant chemotherapy with FOLFOX  regime. She is currently having a sixth cycle. Repeat echocardiography at four weeks postcardiac event showed improved ejection fraction (60%) and resolution of the anteroapical akinesia. Final diagnosis was TC possibly triggered by underlying advanced malignancy.The pathophysiology of TC remains largely unknown, but various hypotheses have been put forward including, but not limited to, autonomic dysfunction resulting in catecholamine-induced myocardial injury. In 70% of patients there is a triggering factor  identified. Additional hypotheses include catecholamine-induced myocardial stunning, ischemia-mediated stunning due to coronary vasospasm, and myocarditis . The preThe most supported hypothesis is the catecholamine-induced myocardial stunning, as evidenced by the elevated levels of catecholamine prevalent in patients presenting with TC. Endomyocardial biopsies done in symptomatic patients have shown features of catecholamine toxicity . In thisRecently Burgdorf et al.  observedWhat makes our case more interesting is the close relationship known to exist between adrenoceptor dysregulation and proliferation of adenocarcinoma cells, especially breast and colon , 13. It Most patients present with symptoms of acute coronary syndrome, chest pain, shortness of breath, cardiac enzyme elevation (mild), ST segment elevation, T wave inversion, or QT prolongation. Rare presenting symptoms include syncope, cardiac arrest, cardiogenic shock, or congestive failure. Patients in the intensive care unit might have pulmonary edema. Unique to this entity is preceding emotional or physical stress, although this is absent in about 30% of cases. Echocardiography reveals regional wall motion abnormalities. Definitive diagnosis is made on cardiac catheterization, which reveals two classical features: normal coronary arteries and aneurismal dilatation or ballooning of apical segment of the left ventricle (LV), appearing like a Japanese octopus trap on ventriculography. Other variants described are apical sparing or inverted tako-tsubo.Various diagnostic criteria exist, none of which has been adopted universally. The common criteria used are the proposed Mayo Clinic criteria, initially proposed by Bybee et al.  but receManagement is supportive. Since by the time of diagnosis most patients are on treatment for acute coronary syndrome, this is usually continued. The benefit of beta-blockers is unknown although theoretically, since they have an anti-catecholamine effect, they are given, especially those with both alpha- and beta-receptor blockade, like carvedilol. Diuretics are recommended for heart failure. Precautions must be taken to avoid thrombolysis as it might cause harm. Short-term anticoagulation can be given to patients who present with atrial fibrillation or thrombus formation . AspirinComplications include left ventricular free-wall rupture, ventricular arrhythmias, mitral regurgitation, left ventricular mural thrombus formation, dynamic intraventricular obstruction, and death , 14–19. This case hence raises two other interesting clinical issues. The first issue concerns which level of the troponin I elevation is clinically useful, and whether a degree of elevation matters. In this patient the troponin I elevation was not what we can refer to as modest, yet she did meet the modified Mayo Clinic diagnostic criteria. This challenges the clinical emphasis placed on “modest” troponin I elevation. The second issue is that the studies by Elesber  and Burg


Predischarge defibrillation threshold testing is often performed a few days after ICD implantation in order to validate defibrillation thresholds obtained at the time of implant. Ventricular fibrillation is induced with such testing and causes an increase in serum Brain Natriuretic Peptide (BNP) levels. BNP is an indicator for cardiac stress. We wanted to examine the feasibility to alter the trend of BNP after predischarge testing in VVI, DDD and CRT ICD's.We measured BNP before predischarge testing and 5, 10, 20 and 40 minutes after predischarge testing in 13 groups with each 20 patients. We evaluated patients without post shock pacing and patients with a post shock pacing frequency of 60, 70, 80, 90 and 100 bpm and a duration of 30 and 60 sec as well as a post shock pacing frequency of 80 and 90 bpm and a duration of 120 sec post shock pacing.Patients without post shock pacing showed the highest BNP during the follow-up. The percentage values of BNP increased consistent significantly after 5 minutes compared with BNP before predischarge testing. The percentage values of BNP trend was significantly lower with a post shock pacing of 90 bpm and duration of 60 sec. In addition, we excluded a cardiac necrosis by predischarge testing because of similar values of myoglobin, cardiac troponin I and creatine kinase during the follow-up.Our results suggested that post shock pacing with 90 bpm and duration of 60 sec as the best optimized post shock pacing frequency and duration for VVI, DDD and CRT ICD's. A reduction of cardiac stress is going to be achieved with the optimization of the post shock pacing frequency and duration. The efficacy to treat life threatening ventricular arrhythmias is a generally accepted function of implantable cardioverter defibrillators (ICD's) -4. The tIncreased ventricular wall tension causes a rapid release of messenger ribonucleic of BNP . FurtherThe Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial showed that a long-term ventricular pacing impaired the left ventricular function . But it In our former study we showed a doubling of BNP 5 minutes after predischarge testing with a heterogeneous post shock pacing frequency and duration . The purWe included 780 consecutive patients  with VVI-ICD, DDD-ICD or CRT-ICD (260 of each device) during predischarge testing from November 2004 to June 2006. A serum creatinine > 1.5 mg/dl was an exclusion criterion because of possible influence of BNP .The following ICD systems were used: CRT in 260 patients, DDD in 260 patients and VVI in 260 patients. Several ICD's were used: Biotronik Kronos (180), Lexos (3), Lumos (36) and Belos (3); Medtronic Marquis (6), En Trust (201), Sentry (14) and Maximo (6); Guidant Contak (42), Ventak Prizm (1) and Vitality (48); St. Jude Medical Atlas (240). The transvenous endocardial leads were inserted via the cephalic or subclavian vein and positioned under fluoroscopy in subpectoral position in all patients.There existed different company depended post shock pacing frequencies and durations of the ICD devices. We calculated the lowest common multiple of the post shock pacing frequency as 60, 70, 80, 90 and 100 bpm and of the shock pacing duration of 30 and 60 seconds. We established 10 groups of patients with a homogenous post shock pacing frequency and one group without post shock pacing (nonPSP). We first examined the groups  without post shock pacing. After that we examined the groups  with post shock pacing frequency of 60 bpm and a shock pacing duration of 30 seconds. After completion of each group we examined the next group with increased post shock pacing frequency . After completion of the shock pacing duration of 30 seconds we repeated this procedure with a shock pacing duration of 60 seconds and further of 120 seconds. We extended the post shock pacing duration to duration of 120 sec in the best two pacing frequency groups. Thus we achieved 13 homogenous groups with a defined post shock pacing frequency and post shock pacing duration. On the basis of our previous study [BNP  was measured directly before and 5, 10, 20 and 40 minutes after predischarge testing similar to our previous study . In addiThe local medical ethics committee approved the study protocol and all patients gave written, informed consent before entering the study.The patients were fasting and received no intravenous diuretic in the morning. We performed a short-term anaesthesia with propofol and midazolam in all patients. Ventricular fibrillation was induced by T wave shock. We defined the duration of ventricular fibrillation as interval between the induction of ventricular fibrillation with T wave shock and the termination of ventricular fibrillation with biphasic shock of the ICD. We monitored (Siemens SC 7000) the patients with ECG Holter before and for a period of 15 minutes after predischarge testing. All patients with CRT-ICD were tested in paced rhythm. Patients with single or dual chamber ICD were tested with intrinsic QRS. All patients with dual chamber ICD were tested with a long AV interval of 300 msec in order to achieve an intrinsic QRS. We included only patients who were successfully defibrillated with the first initial delivered shock energy in order to achieve the same condition for all patients in our study.Using a Phillips ultrasonic device  biplanar left ventricular end-diastolic and end-systolic cavity volumes were calculated with Simpson's rule  from paiAll data are presented as mean values ± standard deviation. Datasets were tested for normal distribution. Differences between the categorical variables were evaluated for statistical significance using chi-square test or Fisher's exact test, and Student't test for comparing continuous variables excepting BNP value, as its distribution was skew. Here, the Mann-Whitney U test was employed. As a result of the high standard deviation of real BNP values we calculated the percentage alterations of BNP. The BNP value before predischarge testing was equated with 100% for evaluation of percentage alterations. For comparisons of trends of BNP (%), myoglobin, cardiac troponin I and creatine kinase the Bonferroni-Holm test was performed. A measuring of the linear association between two variables was evaluated using Pearson correlation coefficient and all statistical tests were two-tailed. A P value < 0.05 was considered statistically significant. The statistical package used was SPSS 12.0 for Windows.All consecutive patients were included in our study. There were no significant differences in baseline clinical values between the 39 groups. The demographic data were presented in The result of the predischarge testing was similar between the groups . VentricWe observed an increase of BNP after five minutes after predischarge testing  followed by a decrease compared with BNP before predischarge testing in all patients . In addiThere was also observed an increase of percentage values of BNP after five minutes followed by a decrease of BNP . The groThe trend of the cardiac enzymes  showed no significant increase after predischarge testing .We observed no correlation between the trend of BNP, myoglobin, cardiac troponin I, creatine kinase or other value . We found a negative correlation between BNP before predischarge testing and left ventricular ejection fraction . Our results supported considering the percentage values of BNP an optimized post shock pacing frequency with 90 bpm and duration with 60 sec. Therefore a reduction of cardiac stress was achieved by the optimization of the post shock pacing. In addition, a cardiac ischemia or a correlation between the trends of BNP with other values was excluded.In the present study we showed the well-known increase of BNP after predischarge testing with a following consistent decrease of BNP as a result of ventricle wall tension ,8,15,16.Our results were not contrary to the results of DAVID or an analysis of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II concerning a deterioration of heart failure due to ventricular pacing ,17. A frVentricular fibrillation caused a cardiac low output with an increase of left ventricular end-diastolic pressure and dilation of the right and left ventricle ,19,20. BAn optimised hemodynamics might improve the clinical outcome with optimal post shock pacing after termination of ventricular arrhythmias. Our results showed an improvement of hemodynamic after termination of ventricular arrhythmias. The present  study examined only a short time period. Prospective trials are needed for the improvement of clinical outcome in patients with optimised post shock pacing.In the present study we also excluded a myocardial necrosis with similar values of myoglobin, cardiac troponin I and creatine kinase . Other aWe could not exclude a dilution of our BNP values because blood samples were taken from a peripheral intravenous catheter. Furthermore a myocardial necrosis in the further follow-up might be available because an increase of myoglobin, cardiac troponin I and creatine kinase was observed two hours after defibrillation threshold validation -23. We fWe found an optimized post shock pacing frequency of 90 bpm and duration with 60 sec. A reduction of cardiac stress is going to be achieved with the optimization of the post shock pacing frequency and duration. The clinical outcome might be improved by optimized post shock pacing.


Left atrium (LA) plays an important role in left ventricular filling. It is well known that right ventricular apical pacing has unfavorable effects on ventricular systolic and diastolic performance. The aim of this study is to evaluate the LA mechanical functions with 2D echocardiography in patients with a permanent pacemaker after short time ventricular pacing.Echocardiographic examination was performed in 38 patients  with dual chamber pacemakers or defibrillators  before and after 4 hours > 90% ventricular pacing at 70 beats per minute in DDD mode with an optimal AV interval. Left atrial volumes (LAV) including at the time of mitral valve opening (Vmax), at closure (Vmin), and at the onset of atrial systole (Volp) were measured. The passive emptying, conduit, active emptying and total emptying volume, stroke volumes were also calculated.No significant differences were noted at baseline and after pacing for absolute Vmax, Volp, passive emptying, conduit, active emptying, total emptying volumes as well as the volumes indexed to body surface area (p >0.05).Short - time RV pacing seems to have no acute effects on left atrial mechanical functions.  The left atrium (LA) serves as a reservoir during ventricular systole, as a conduit during early diastole, and as an active contractile chamber that augment left ventricular filling in late diastole. Changes in LA and mechanic functions are associated with adverse clinical events such as atrial fibrillation, stroke, diastolic dysfunction, left ventricular failure -4. AsyncEchocardiography is the most commonly used non-invasive imaging technique for estimation of LA mechanical functions. The aim of the present study was to evaluate the acute effects of short time right ventricular AV sequentional pacing on LA mechanical functions based on 2D echocardiography.The study protocol was approved by the Baskent University Faculty of Medicine Ethics Committee. All patients provided written informed consent prior to participation in the study. The study population consisted of 38 patients with AV sequential pacemakers or defibrillators (ICD) with electrodes positioned in the RV apex and the right atrial appendage. Exclusion criteria included ≥ 20% ventricular pacing within the previous 6 months, atrial fibrillation (AF), atrial flutter, atrioventricular block, or pacemaker rhythm at the time of the study, previous hospitalization due to heart failure within the previous 3 months, ICD shocks within the previous month, significant valvular lesions, and poor imaging quality that precluded satisfactory echocardiographic assessment. All participants underwent conventional 2D echocardiography. LA passive emptying volume = Vmax-Volp;LA passive emptying fraction = LA passive emptying volume/Vmax x 100;LA conduit volume = LV stroke volume-(Vmax-Vmin);LA active emptying volume = Volp-Vmin;LA active emptying fraction = LA active emptying volume/Volp x 100;LA total emptying volume = (Vmax-Vmin).LA total emptying fraction = LA total emptying volume/Vmax x 100.Atrial volumes were indexed to body surface area (BSA) in all patients.Patients were imaged with an Acuson XP-256  machine equipped with a multi-frequency transducer in the left lateral decubitus position. The left atrial diameter was measured from the parasternal long axis, and the left atrial volumes were traced and calculated by means of a modified Simpson method from apical 4- and 2- chamber views according to the guidelines of the American College of Cardiology, American Heart Association, and American Society of Echocardiography . Left veAfter baseline echocardiographic evaluation, AV delay of the pacemakers was shortened at an optimal AV interval in which the paced rhythm at a heart rate of 70 beats per minute was achieved during the observation period of 5 minutes. After the observation period the patients left on paced rhythm during 4 h. After 4 h the pacemaker parameters were reprogrammed to their original settings and echocardiographic examinations were repeated. The percentage of ventricular paced beats was assessed by pacemaker telemetry. SPSS v.9.0 software  was used for statistical analyses. Continuous variables with normal distribution were compared using the unpaired Student's t-test and are presented as mean ± SD. Continuous variables with abnormal distribution were compared using the Mann-Whitney U test. Echocardiographic measurements before and after short-time pacing were compared by means of the Wilcoxon signed-rank test. Categorical data were reported as frequencies and percentages. A p value < 0.05 was considered statistically significant.2  which is a criteria for severe LA dilatation according to The American Society of Echocardiography was present in 9 (23.7%) patients  [The study population consisted of 38  patients, mean age 63.0 ± 10.9 years. Four (10.5%) patients had a pacemaker with VDD mode. The indications for pacemakers and/or ICDs were sick sinus syndrome in 22 (58.0%) patients, symptomatic sinus bradycardia in 1 (2.6%) patient, idiopathic ventricular tachycardia in 4 (10.5%) patients, ischemic ventricular tachycardia in 11 (28.9%) patients. Baseline atrial pacing was 11%, and ventricular pacing was 15%. Patient characteristics and echocardiographic data are listed in  in 9 23.% patientNo significant difference was noted after short time pacing for absolute Vmax, Volp. Total emptying volume, passive emptying volume, active emptying volume, and conduit volume, as well as volumes indexed to BSA did not changed after short time pacing  .The purpose of the present study was to investigate the effects of short-time right ventricular apical pacing on LA mechanical functions based on 2D echocardiography. In this study, we have demonstrated that LA mechanical functions did not change significantly after 4-h right ventricular apical pacing.Recent studies showed the unfavorable effects of asynchronous ventricular activation induced by ventricular pacing on ventricular functions  -11. DataRecent studies have shown that left atrial enlargement obtained from echocardiography is a good predictor of cardiovascular outcomes -3. HowevOur study has several limitations. First, LA volumes and mechanical functions were only investigated with 2D echocardiography. However, LA volume calculated by the biplane method has been shown to have a close correlation with that calculated by cine computed tomography, biplane angiography and with conventional 3D reconstruction which may not be feasible for routine clinical practice -18. SecoShort time AV sequentional RV apical pacing seems to have no acute effects on LA mechanical functions when evaluated with on 2D echocardiographic evaluation. However, large and prospective studies, and other invasive or noninvasive methods such as tissue Doppler, strain, strain rate, hemodynamic measurements to evaluate atrial mechanical functions are required to confirm our findings.


Although left bundle branch block (LBBB) alters the electrical activation of the heart, it is unknown how it might change the process of myocardial coordination (MC) and how it may affect the left ventricular (LV) systolic function. The present study assessed the effects of LBBB on MC in patients with LBBB with and without dilated (DCMP) or ischemic cardiomyopathy (ICMP).Tissue Doppler echocardiography (TDE) was performed in 86 individuals: 21 with isolated LBBB, 26 patients with DCMP + LBBB, 19 patients with ICMP + LBBB and in 20 healthy individuals (Controls). MC was assessed analyzing the myocardial velocity profiles obtained from six basal segments of the LV using TDE. The LV systolic function was assessed by standard two-dimensional echocardiography and by TDE.Severe alterations in MC were observed in subjects with LBBB as compared with controls ; these derangements were even worse in patients with DCMP and ICMP . Some parameters of MC differed significantly between DCMP and ICMP (P < 0.01). A good or very good correlation coefficient was found between variables of MC and variables of LV systolic function.LBBB induces severe derangement in the process of MC that are more pronounced in patients with cardiomyopathies and that significantly correlates with the LV systolic function. The assessment of MC may help in the evaluation of the etiology of dilated cardiomyopathy. Left bundle branch block (LBBB) alters the pattern of electrical activation of the heart -4 and diThe studied population consisted of 86 individuals: 21 with isolated LBBB but otherwise healthy, 26 patients with DCMP and LBBB, 19 patients with ICMP and LBBB, and 20 healthy individuals (Controls). The controls, being part of a study in the geriatric population, were asEchocardiography was performed with a System V™ equipment  using a 2.5-MHz probe for image acquisition. The images were acquired in parasternal long and short axis as well as in apical four- and two-chamber projections. Left atrial and LV dimensions and function were assessed by standard methods and LV volumes and ejection fraction were calculated by the Simpson's method, averaging values from three consecutive cardiac cycles.Images were obtained from the apical four and two-chamber views as well as from the apical long-axis view. The pulse repetition frequency and the ultrasound sector beam image width and depth were modulated to avoid the Nyqvist's upper frequency while obtaining images with at least 100 frames per second. Five consecutive cardiac cycles were acquired during post-expiratory apnea in each of the above-mentioned projections and the images were analyzed off-line using an EchoPAC™ 6.3.6 software .electro-mechanical delay time, the electro-hemodynamic delay time, the isovolumic contraction time, the ejection time and the isovolumic relaxation time. The electro-mechanical delay time was defined as the time interval between the start of the QRS complex and the beginning of the mechanical activity on the myocardial velocity curve. The electro-hemodynamic delay time was defined as the time interval between the start of the QRS complex and the beginning of the ejection time. The isovolumic contraction time was calculated by subtracting the electro-mechanical delay time from the electro-hemodynamic delay time. The ejection time was defined as the time interval between the opening and closure of the aortic valve characterized by the descent of the myocardial velocity profile curve to the baseline. The isovolumic relaxation time was defined as the time interval between the closure of the aortic valve and the opening of the mitral valve characterized by the beginning of the E' wave; when a post-systolic velocity was present, the beginning of the isovolumic relaxation time was measured at the peak of that velocity. Using TDE, the LV systolic function was calculated by means of the peak systolic velocity (PSV) of all LV walls and by the temporal integration of the PSV curve, a measure of the A-V plane displacement that assess the longitudinal LV systolic function. All the above-mentioned measures are expressed as the average of the values obtained at each of the basal segments of the six LV walls.A 2 mm sample volume was placed at the basal segment of the LV near the A-V plane in the following walls: the posterior septum and lateral walls (in the 4-chamber view), inferior and anterior walls (in the two-chamber view), and posterior wall and anterior septum . As previously described and as sP value < 0.05 was considered statistically significant.The values are expressed as means ± standard deviation. ANOVA was used to test differences among groups, followed by the Tukey test for post-hoc comparisons between groups. The correlation coefficient was used to establish relationships between variables expressing the LVSF and variables expressing MC. A As shown in table electro-mechanical delay time was shorter in the Controls group than in the other groups ; however, this interval was similar among LBBB, DCMP and ICMP groups. The electro-hemodynamic delay time was shorter in the Controls group than in the other groups ; it was also shorter in the DCMP and ICMP groups as compared with the LBBB group (P < 0.01 for both comparisons), and shorter in the ICMP group than in the DCMP group (P < 0.01). Findings similar to these were observed with respect to the isovolumic relaxation time. The isovolumic contraction time was shorter in the Controls group than in the other groups ; it was shorter in the ICMP and the DCMP groups as compared with the LBBB group (P < 0.01 for both comparisons), but was similar in the DCMP and the ICMP groups. Findings similar to these were observed with respect to the ejection time. The PSV was higher in the Controls group as compared with the other groups ; it was lower in the DCMP and ICMP groups as compared with the LBBB group (P < 0.01 for both comparisons), but it was similar in the DCMP and ICMP groups. Findings similar to these were observed for the A-V plane displacement variable.Table isovolumic relaxation time and the PSV  LBBB considerably alters MC as evidenced by a prolongation of the electro-mechanical delay time, the electro-hemodynamic delay time, the isovolumic contraction time and the isovolumic relaxation time, and by a shortening of the ejection time; 2) In patients with DCMP and ICMP these derangements were more pronounced; 3) Some variables, viz. the electro-hemodynamic delay time and the isovolumic relaxation time made it possible to differentiate patients from the DCMP and the ICMP groups; 4) A good or very good coefficient of correlation was found between variables of MC and of LV systolic function demonstrating that the larger the derangement in MC, the poorer the LV systolic function. The present findings may explain the mechanisms of poorer LV systolic function and the poorer prognosis in patients with cardiomyopathies with LBBB than in those without LBBB -13.As known, the myocardial coupling and uncoupling processes (electro-hemodynamic delay time and the isovolumic relaxation time) are energy demanding, indicatThe good correlation coefficient between the variables of MC and LV systolic function does not necessarily establish a cause-effect relationship between them, though it is probable that the poor or the lack of MC found in patients with LBBB and cardiomyopathies could be an additional cause of deterioration of LV systolic function seen in these patients. The intrinsic poor contractile function together with the hemodynamic imbalance induced by the inter- and intra-ventricular dyssynchrony usually observed in these patients are additional known factors for poor LV systolic function. To what extent the lack of MC or the inter- and intra-ventricular dyssynchrony contribute to the deterioration of the LV systolic function and to what extent these processes coexist is difficult to ascertain. Surely all these mechanisms  alone or together play an important role in the deterioration of LV systolic function.Though some parameters of MC were more altered in patients with DCMP than in patients with ICMP, the current results cannot yet be used to make the differential diagnosis of these entities. The findings may, however, lead to future investigations for testing new hypothesis; for example, although the coupling and uncoupling processes were more prolonged in patients with DCMP than in those with ICMP, the LV systolic function was poorer in the last group as compared with the former . This apparent contradiction may be explained by the fact that patients with DCMP may have a myocardial contractile reserve that is larger than in patients with ICMP. It could then be hypothesized that patients with moderately depressed myocardial contractile reserve but severely depressed MC (patients with DCMP) may better respond to CRT than those with severely depressed myocardial contractile reserve but with only moderately depressed MC (patients with ICMP). Indeed, the subgroup analysis of some cohort studies,32 and oAlthough TDE has not been used to select patients for CRT in large randomized clinical trials, this technique together with other methods have been used to estimate the results of such therapy,34-37. HAs the main aim of the present study was to evaluate the effects of LBBB on MC and of it's repercussion on LV systolic function, the study did not include patients with cardiomyopathies without LBBB; therefore we could not assess the degree of MC and it's effect on LVSF in that group of patients, as shown in previous studies ,46. AlthLBBB introduces severe derangements in the process of MC that are more pronounced in patients with cardiomyopathies. There are good correlations between the variables expressing MC and LV systolic function, indicating that these processes are closely related irrespective of background pathologies associated with LBBB, and that one important determinant of deterioration of LV systolic function could be the degree of loss of MC. The electrophysiological, electromechanical, and hydraulic events that represent MC may help to differentiate patients with DCMP from those with ICMP and that may be used as additional criteria for patient selection for CRT.A-V: Atrio-Ventricular; DCMP: Dilated cardiomyopathy of unknown origin; EHDT: Electro-hemodynamic delay time; EMDT: Electro-mechanical delay time; ET: Ejection time; ICMP: Ischemic cardiomyopathy of ischemic origin; IVCT: Isovolumic contraction time; IVRT: Isovolumic relaxation time; LBBB: Left bundle branch block; LV: Left ventricle (ventricular); MC: Myocardial coordination; PSV: Peak systolic velocity; TDE: Tissue Doppler Echocardiography.MQ: Made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; mainly responisble for drafting the manuscript and gave final approval of the version to be published. SS: Contributed with data acquisition and interpretation, participated in drafting process and approved the final version. SG: Contributed with data acquisition and interpretation, statistical analysis, participated in drafting process and approved the final version. LÅB: Made substantial contributions to conception and design, participated in drafting process and approved the final version. FdF: Contributed with data acquisition and interpretation, statistical analysis, participated in drafting process and approved the final version. VB: Made substantial contributions to conception and design, participated in drafting process and approved the final version.


Prognosis after opening the obstructed coronary artery in acute myocardial infarction (AMI) is influenced by several factors. In routine clinical practice, revascularization is considered to be successful when the restoration of epicardial blood-flow is complete. However, the patent epicardial artery does not always provide functional recovery in the myocardium. There are two visual angiographic grades to assess myocardial perfusion: myocardial blush grade (MBG) and TIMI myocardial perfusion grade (TMP). The aim of our study was to compare these two parameters, how they correlate with short-term indicators of myocardial damage.The two visual grades were assessed along with enzymatic infarct size as creatine kinase release (CK), echocardiographic left ventricular ejection fraction (LVEF), and ST-segment resolution (STR) in 62 patients with acute myocardial infarction and successful revascularization.R= − 0.687, P<0.001; LVEF: R=0.586, P<0.001; STR: R=0.574, P<0.001). MBG also showed significant correlations with clinical measurements, except for enzymatic infarct size .Better correlation was found with TMP in case of all clinical parameters (CK: Our findings suggest that the clearance of the dye (described by TMP) is more characteristic to myocardial recovery after AMI, than maximal contrast density (described by MBG) in the clinical practice. Functional recovery of the myocardium after acute myocardial infarction (AMI) and recanalization of the occluded coronary artery by primary coronary intervention (PCI) are influenced by several factors including pain-to-balloon time, myocardial capacity for regeneration, and microembolization distal to the thrombus. In routine clinical practice, reperfusion treatment is considered to be successful when restoration of the epicardial blood-flow is complete.In current clinical practice, successful recanalization of AMI is described by an increase in blood-flow in the epicardial artery characterized by thrombolysis in myocardial infarction (TIMI) flow grade ,2. HowevVan 't Hof et al. described the first angiographic grading method for the assessment of myocardial perfusion . A new pAfter demonstrating a high correlation between recovery of myocardial function after AMI and visual perfusion grading (both MBG and TMP), they have been widely used as an end-point in clinical studies evaluating effectiveness of interventional tools and other therapeutic methods. However, no reports have been found to evaluate and compare these visual grading scales on the same population.The present prospective study comprised 62 patients with ST-segment elevation myocardial infarction (STEMI) treated by PCI. Patients were enrolled by the following inclusion criteria: 1) pain-to-balloon time <12 h; 2) ST-segment elevation >0.1 mV in at least three contiguous electrocardiographic leads; 3) occluded coronary artery on the diagnostic angiogram (TIMI grade 0 flow) that is at least 2 mm in diameter and supplies a medium to large myocardial area; 4) successfully opened coronary artery after PCI (TIMI grade 3 flow); 5) ability of the patient to co-operate. Patients who were unconscious, or showed signs of cardiogenic shock, or had visible collateral circulation to the infarct-related myocardial region have been excluded from the study. Demographic and clinical data of patients are shown in Angiographic parameters were assessed on an AI 1000  work station. For the determination of perfusion grades of the area at risk, the final angiogram of the coronary intervention was performed under the following criteria: 1) motion of the patient or the table should be avoided; 2) the patient should hold breath for the time of the recording; 3) the field of view is to be set to contain the whole supplied area of the vessel of interest. All coronary angiograms met with these criteria. The same non-ionic contrast material  was used for all angiograms injected by a manual injector, the contrast quantity was 6.84±0.97 mL (mean±SD), the injection rate was 3.04±0.34 mL/s. Angiograms were recorded on an Innova 2000™  system, and images were stored in 512×512 size 8-bit, greyscale, uncompressed format.Echocardiographic measurements were performed 3 days after the primary PCI to assess left ventricular ejection fraction (LVEF). Twelve-lead electrocardiograms were recorded at the beginning of PCI and 90 minutes later. ST-resolution was defined as a decrease of ST-segment at 90 minutes compared to the first measurement in the lead with highest ST-segment elevation, expressed as percentage of initial ST-elevation. Blood creatine kinase (CK) enzyme levels were measured 6, 12, 24, and 48 hours after the PCI. These four measurements were summed up to assess total enzymatic infarct size.MBG and TMP were graded in a random sequence independently by two cardiologists experienced in analysis of angiograms, who were blinded to all other clinical data. Final values for each patient were based on consensus between the observers. Patient groups of grades 0 and 1 of both MBG and TMP were united in statistical analysis, due to identical definitions in MBG 0 and TMP 1. See P <0.05 was considered to be statistically significant. Our results were obtained by Spearman's rank correlation at a confidence interval of 95%.All statistical tests were performed with MedCalc software package . A value of R= − 0.687, P<0.001) with TMP, but not with MBG  as shown in R=0.389, P=0.002) and TMP . TMP showed a stronger correlation as shown in R=0.348, P=0.006) and had a stronger relation to TMP   , which iThe main finding of the present study is that TMP has a stronger correlation to enzymatic infarction size, LVEF, and ST-resolution than MBG has; however, both grades show the same tendency when compared to other clinical parameters of AMI patients after PCI. These results suggest that clearance dynamics of dye from the microvasculature (classified by TMP grade) gives more precise information on indicators of myocardial viability than absolute density of the myocardial blush (classified by MBG).In animal models, the change of density as a function of time was found to correlate better with effective tissue perfusion than the absolute value of contrast density. Pijls et al. investigated the relationship between epicardial blood-flow, measured with Doppler flowmetry, and densitometric parameters on the angiogram . They foThe importance of this is further emphasized by the difference in back-flow of the contrast material to the aorta in different angiograms, which may influence maximal contrast density as observed in the myocardial area. Visual evaluation of maximal density may also be corrupted by automatic image processing of the angiographic computer system . Image processing results in different brightness of images recorded in different projections, which further limits comparison of affected and healthy areas.In contrast with these findings, MBG is more widely used in the literature than TMP to evaluate new interventional devices –13 and oAs a limitation of this study, it should be noted that the extent of necrosis in AMI is a function of several factors, e.g. pain-to-balloon time, existing collaterals, and technical success of the procedure. This should be taken into consideration when discussing the results of this single-centre study, with a limited number of patients. Our patient population was younger, with few diabetics, smokers, and hypertensives, compared to other studies. A follow-up study on these patients, as well as multi-centre studies, should be carried out to provide further evidence on our conclusions.In conclusion, examination of contrast density in the myocardium with coronary angiography provides important information on myocardial viability and, with this, on the evaluation of recanalization success. Dynamics of contrast density is more informative than the level of maximal contrast density. Since visual estimation is subjective, angiographic evaluation by experienced and independent physicians is of primary importance.


Novel cardiovascular magnetic resonance (CMR) techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR protocols to humans is rarely possible, while validation in humans is often difficult, slow and occasionally not possible due to ethical considerations. The aim of this study is to overcome these limitations by introducing an MR-compatible, free beating, blood-perfused, isolated pig heart model for the development of novel CMR methodology.6 hearts were perfused outside of the MR environment to establish preparation stability. Coronary perfusion pressure (CPP), coronary blood flow (CBF), left ventricular pressure (LVP), arterial blood gas and electrolyte composition were monitored over 4 hours. Further hearts were perfused within 3T (n = 3) and 1.5T (n = 3) clinical MR scanners, and characterised using functional (CINE), perfusion and late gadolinium enhancement (LGE) imaging. Perfusion imaging was performed globally and selectively for the right (RCA) and left coronary artery (LCA). In one heart the RCA perfusion territory was determined and compared to infarct size after coronary occlusion.All physiological parameters measured remained stable and within normal ranges. The model proved amenable to CMR at both field strengths using typical clinical acquisitions. There was good agreement between the RCA perfusion territory measured by selective first pass perfusion and LGE after coronary occlusion (37% versus 36% of the LV respectively).This flexible model allows imaging of cardiac function in a controllable, beating, human-sized heart using clinical MR systems. It should aid further development, validation and clinical translation of novel CMR methodologies, and imaging sequences. Coronary artery disease (CAD) with subsequent myocardial infarction and heart failure constitutes a leading cause of death in the western world . MyocardCardiovascular magnetic resonance (CMR) is being used increasingly in the diagnosis and assessment of CAD as it has the unique capability of assessing myocardial function, viability and perfusion in one session . It alsoNovel CMR techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR imaging protocols to humans is rarely possible. On the other hand, validation of novel imaging techniques in humans, for example quantitative perfusion, novel sequences, optimized contrast agent injection schemes or responses to alterations of blood flow requires large patient populations and is occasionally not possible for ethical reasons.In order to observe cardiovascular physiology and pathophysiology in a controlled fashion, complex experimental models are necessary to mimic the human situation as closely as possible. The porcine heart closely resembles the human heart from the point of view of size, physiology and anatomy and consequently pigs are frequently used for in vivo cardiovascular research .Oscar Langendorff introduced a model of retrograde perfusion of mammalian hearts via the Aorta with Krebs Henseleit solution in 1895 -12.in situ physiological cardiac function ex vivo . Thi. Thi8]. Despite making the system MR compatible we were able to keep the short tubing and the small volume of the circuit. This is important as it allows the use of a mixture of autologous blood and crystalloid solution with near normal haematocrit and haemoglobin without the need for donor or support animals. Perfusion with blood leads to more stable function and less oedema compared to crystalloid solution perfusion .The main disadvantages of this model are the less physiological environment compared to in vivo experiments, the ischaemic period after heart removal and the high associated costs.For studies of myocardial perfusion rapid recirculation of contrast is prevented in the current model. This is an oversimplification of in vivo conditions but allows for repeated perfusion scans. In addition contrast arrival time was longer compared with in vivo as a consequence of distribution and dilution in the inflow-tubing. Whether this influences quantitative perfusion analysis with CMR needs to be investigated.As this was a feasibility study we did not perform metabolic assessment of the 6 hearts we perfused in the magnets. Therefore stable physiological function was assumed on the basis of the previously performed validation experiments. Future trials aiming to answer specific questions need to include metabolic measurements relevant to the nature of the hypothesis and to assure stable, robust and reproducible conditions for the specific scientific question.We performed a proof of concept study to demonstrate the feasibility of the model in the MR environment and thus we did not perform systematic statistical analysis.The current work demonstrates for the first time the feasibility of operating and imaging an isolated beating porcine heart preparation in a clinical MR scanner. The technical design of this isolated pig heart model allows ex vivo simulation and imaging of cardiac function. This novel system provides excellent control of physiological parameters and allows validation of novel techniques against gold standards and easy translation of the methods to patients using identical equipment and imaging sequences.Tobias Schaeffter served as a Consultant to Philips Healthcare. Eike Nagel received minor consultancy fees from GE and Philips Healthcare and minor speaker honoraria from GE, Philips Healthcare, and Bayer Schering Pharma. The other authors declare that they have no competing interests'.AS carried out the perfusion studies, designed and implemented the MR compatible model and drafted the manuscript. IG carried out the perfusion studies and substantially contributed to the design of the MR compatible model. AC carried out the perfusion studies, designed and implemented the MR compatible model. RS participated in the design of the MR compatible model and helped with the perfusion studies. MI helped with the perfusion studies, and participated in the study design. GH and NN helped with the perfusion studies. GM and DP participated in the study design and helped to draft the manuscript. TS participated in the sequence alignment and helped to draft the manuscript. EN designed and implemented the MR compatible model and drafted the manuscript. All authors read and approved the final manuscript.