Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities , chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levelsA 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2–V3 and ST-segment depression in leads V5–V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities.Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman. Takotsubo cardiomyopathy, also known as transient left ventricular (LV) apical ballooning syndrome, is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities, chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levels . The typA 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. Her cardiovascular risk factors were female sex, tobacco smoking, dyslipidemia and family history of coronary artery disease. Upon admission her blood pressure was 150/80 mmHg and the electrocardiogram (EKG) showed sinus tachycardia with 2–3 mm ST-segment elevation in leads V2–V3 and 1 mm ST-segment depression in leads V5–V6 Figure  and 2B. Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated . AlthougThe author(s) declare that they have no competing interests.ML collected the data relative to the Case Report; VZ assisted the patient in the CICU and composed the draft of the manuscript; SM participated in the preparation of the revised manuscript; FC collected the data relative to the Case Report; MM collected the data relative to the Case Report; SL performed the first echocardiogram; PA performed the second echocardiogram; AC performed the coronary angiography; DC helped in revising the manuscript draft; RF is head of the CICU and participated in the coordination and revision of the manuscript; CP is head of the Cath Lab and participated in the coordination and revision of the manuscript; SM is head of the Echo Lab and conceived the Case report and participated in the coordination, data analysis and elaboration and drafting of the manuscript. All authors read and approved the final manuscript.


Myocardial contractility can be investigated using longitudinal peak strain. It can be calculated using the Doppler-derived TDI method and the non-Doppler method based on tissue tracking on B-mode images. Both are validated and show good reproducibility, but no comparative analysis of their results has yet been conducted. This study analyzes the results obtained from the basal segments of the ventricular chambers in a group of athletes.30 regularly-trained athletes were submitted to an echocardiography at rest and after handgrip. Starting from the four-chamber view, overall myocardial function and regional velocities were evaluated. The images obtained were processed to determine strain in left and right ventricle basal segments. Strain was calculated using the TDI method and a validated "speckle tracking" or, more correctly, "feature tracking" algorithm. The statistical analysis included a Student's t-test (p < 0.05).The range of strain values obtained is in agreement with the data reported in the literature. In the left ventricle (LV) the average strain values of the basal segments calculated with TDI on IVS and LW at rest and after stress were: -21.05 ± 3.31; -20.41 ± 2.99 and -20.05 ± 2.61; -21.20 ± 2.37, respectively. In the right ventricle (RV) the same method gave IVS and LW strain values at rest of -22.22 ± 2.58 ; -24.42 ± 5.84, and after HG of -22.02 ± 5.20 ;-23.93 ± 6.34. The values obtained using feature tracking were: LV at rest -20.48 ± 2.65 for IVS, and -21.25 ± 2.85 for LW; LV after HG: -19.48 ± 3 for IVS and -21.69 ± 3.85 for LW. In RV at rest: -21.46 ± 3.25 for IVS and -24.13 ± 5.86 for LW; RV after HG: -24.79 ± 7.9 for IVS and -24.13 ± 7.0 for LW. Tissue Doppler and "feature tracking" methods showed the respective consistency of the results in the basal segments of myocardial ventricle walls.Provided that echographic imaging is good, strain can be computed in athletes by both Doppler-derived and tracking methods. It is technically feasible to use both -interchangeably, at least in basal segments. S), a measure of regional deformation, can be calculated from the gradient of velocity from Tissue Doppler Imaging . Comparisons among data were performed with Student's t test, p < 0.05. For intra-observer and inter-observer variability 95% limits of agreement were used.In all the athletes enrolled, the myocardial wall basal segments were analyzed using the two methods, and only the good-quality echocardiographic images were processed. One reason for exclusion was inability to obtain the ROI (region of interest) closely enough to the shape of the left and right ventricular endocardium, which would result in underestimation of data and their contamination by signal components outside the left ventricular cavity. The 4-chamber view was the one which allowed the best delineation of the ventricular cavity and the best detection of the endocardial border.2), confirming that the athletes were regularly trained. Heart rate and systolic blood pressure increased significantly after stress. The results of the echocardiographic parameters are reported in Table All the athletes maintained a normal EF % at rest and after stress, without any significant differences. The studied group showed a higher cardiac mass index than the upper limits of the normal range 132 ± 5 g/m ± 5 g/m2The results of the strain analysis performed with the two different methods are shown in Table In addition, we wish to note that the longitudinal strain in the athlete's heart appears to be higher in the right than in the left ventricle, although the statistical differences are not sufficient to draw any conclusion.Strain is considered a valid parameter for estimating myocardial contractility by deformation ,3 and twA careful comparison is feasible at least in interventricular septum (IVS) and lateral wall (LW) basal segments of left and right ventricles , where either method can be applied with equal accuracy, and the Doppler angle dependency does not interfere\souts with the TDI analysis. This study was conducted in a group of athletes that presented a high quality of the image where the tracking method was properly applied. Comparison was made of strain values as a major dimensionless measure of tissue contractility. The test was carried out both at rest and after handgrip stress to enhance variability and investigate the consistency of the results. It was found that Doppler-derived and "feature tracking" approaches show substantial agreement in the results, since no statistical differences were evident in the basal segments of either ventricle at rest and after HG effort. This study shows that, when high-quality images are recordable, the deformation of the basal heart segments at rest and after stress can be investigated by two different methods which lead to nearly the same results.The accurate identification of regional myocardial function in athletes by strain analysis is important for follow-up and management of the training itself. In this particular population, the physiological hypertrophy of the heart supports the hypothesis that longitudinal strain may present changes in basal segments that are nearly rectilinear. A mild increase in longitudinal strain values appears in the right more often than in the left ventricle, although a wider and heterogeneous group of athletes should be studied to investigate this particular trend. It should be remembered that the two methods present several limitations to a correct interpretation of the results that preclude routine use of the strain concept. The Doppler-derived method is limited by angle dependence, which makes it unable to evaluate LV deformation with uniform accuracy along the different ventricular walls and in the different echocardiographic projections. Feature tracking is performed on grey scale (B-mode) echocardiographic images where the local grey-scale pattern (including speckles) remains reasonably stable; unlike TDI, the velocity evaluated with this method is a vector, and does not therefore present any angle dependence. It can be applied with the same accuracy to the different myocardial regions; on the other hand it is a novel technique that requires further practical experience validation studies. Both methods are influenced by image quality, and in particular clinical conditions they can present limitations due to the physiological growth of the myocardial chambers, which prevents the perfect framing of the image in the echographic window.In conclusion, strain values computed with the TDI-derived method and the tissue tracking technique are equivalent in the basal segment. The former has more literature to support it, but is limited to basal and low-median segments. Tracking appears to open up possibilities of extending strain analysis to the whole of the myocardial wall. It might allow complete analysis of the development of myocardial contractile adaptation in athletes in training and during their career.The potential clinical applications of the two methods used to estimate myocardial contractility are not further explored here since this is not within the scope of the study and would necessarily imply the use of subjects with different pathologies.The author(s) declare that they have no competing interests.The initial idea for the study was of GG and LS and designed the study, and LS, GP, LT performed all the measurements and statistical analyses. LS wrote the manuscript and all the authors contributed to, read, and approved the final version.


Idiopathic outflow tract arrhythmias  can originate from the left ventricular (LV) epicardium (Epi-VT/PVCs), and radiofrequency (RF) energy applications from the aortic sinus of Valsalva can eliminate Epi-VT/PVCs in selected patients. Among the various ECG findings, the R-wave duration index and R/S amplitude index in leads V1 or V2 are useful for identifying Epi-VT/PVCs, and the Q-wave ratio of leads aVL to aVR and S-wave amplitude in lead V1 are useful for differentiating between an Epi-VT/PVC originating from the LV epicardium remote from the left sinus of Valsalva (LSV) and that from the LSV. Tissue tracking imaging is a promising modality for identifying the origin of OT-VT/PVCs and for differentiating between an Epi-VT/PVC originating from the LV epicardium remote from the LSV and that from the LSV.If the origin of the Epi-VT/PVC is identified within the LSV, coronary and aortic angiography should be performed to assess the anatomic relationships between the Epi-VT/PVC origin and coronary arteries and aortic valve before the RF energy delivery. To avoid potential complications, RF ablation should be performed at the LSV using a maximum power of 35 watts and maximum temperature of 55°C. Epicardial mapping through the coronary venous system and the presence of potentials recorded from the ablation site within the LSV and their changes before and after the RF energy applications may be useful for diagnosing Epi-VT/PVCs or predicting a successful catheter ablation from the LSV. Radiofrequency (RF) catheter ablation has been established as an effective and curative therapy for ventricular tachycardias (VTs) or symptomatic premature ventricular contractions (PVCs) originating from the outflow tract (OT-VT/PVCs) in structurally normal hearts -6. RecenCharacteristic ECG findings originating from each portion of the outflow tract and several ECG findings useful for differentiating an OT-VT/PVC from other OT-VT/PVCs originating from different portions of the outflow tract have been reported. The precordial R-wave transition ,6,19, QRst OT-VT/PVC and 2nd OT-VT/PVC, while the earliest ventricular activation during either the 1st or 2nd OT-VT/PVC was recorded from the LSV . A re. A re8].With an RF energy application from the LSV, some Epi-VT/PVCs can be abolished. However, RF catheter ablation within the LSV runs the risk of potential complications. Thus, attempting to diagnose these types of VT/PVCs non-invasively before the ablation procedure, performing detailed mapping and assessment of the electrograms obtained during the procedure, and obtaining a precise assessment of the anatomic relationships between the arrhythmia origin and coronary arteries and aortic valve, are crucial for avoiding futile RF applications from the LSV and the ensuing complications, and for successfully eliminating this type of Epi-VT/PVC.


This study explores the feasibility of non-invasive assessment of left ventricular volume and flow relationship throughout cardiac cycle employing echocardiographic methods.Nine healthy individuals and 3 patients with severe left-sided valvular abnormalities were subject to resting echocardiography with automated endocardial border detection allowing real-time estimation of left ventricular volume throughout the cardiac cycle. Global and regional (6 different left ventricular segments) estimates of flow-volume loops were subsequently constructed by plotting acquired instantaneous left ventricular 2-D area data (left ventricular volume) vs. their first derivatives (flow).Flow-volume loop estimates were obtainable in 75% of all echocardiographic images and displayed in normal individuals some regional morphological variation with more pronounced isovolumic events in the paraseptal segments and significantly delayed maximal systolic flow paraapically. In patients with aortic stenosis, maximal systolic flow occurred at a lower estimated left ventricular systolic volume whereas in mitral stenosis, maximal diastolic flow was observed at a higher estimated left ventricular diastolic volume. Aortic regurgitation caused a complex alteration of the estimated flow-volume loop shape during diastole.Non-invasive assessment of left ventricular flow-volume relationship with echocardiography is technically feasible and reveals the existence of regional variation in flow-volume loop morphology. Valvular abnormalities cause a clear and specific alteration of the estimates of the normal systolic or diastolic flow-volume pattern, likely reflecting the underlying pathophysiology. Flow-volume measurement is well established as a clinical measure of lung function through its ability to demonstrate the dynamic nature of an underlying obstructive or restrictive process . AlthougNon-invasive estimation of left ventricular flow-volume loops could be obtained using transthoracic echocardiography with continuous information of the left ventricular volume changes throughout the cardiac cycle. Since the left ventricular 2-dimensional (2-D) area as used in the Simpson's rule algorithm for the calculation of left ventricular ejection fraction  is relatThe aim of this study was to develop and explore the feasibility of a non-invasive estimation of left ventricular flow-volume relationship throughout the cardiac cycle with echocardiography according to the conceptual framework outlined above. The secondary aim was to identify normal ranges of global systolic and diastolic flow estimates and to assess the normal contributions of different left ventricular segments. In addition, examples of estimated flow-volume loops are provided in patients with left ventricular valvular disease to illustrate the applicability of such a non-invasive approach in these conditions.The study population consisted of nine individuals (5 men and 4 women), 39 ± 23 years old, without any signs of coronary artery disease and normal left ventricular function, and 3 patients  with severe valvular abnormalities  for demonstration of potential pathological flow-volume loop morphology. All the study participants were subject to resting echocardiography. Individuals with poor image quality, complex atrial or ventricular arrhythmias, or previous revascularisation were excluded from the study. The study was approved by the ethics committee at Karolinska Institutet – Huddinge University Hospital and all the study subjects gave their informed consent to participate.Echocardiographic imaging was performed with the subjects in left lateral position using a commercially available system . Images were obtained in the three standard apical views  using a standard 3 MHz transducer. Two-dimensional gray scale images with real-time left ventricular endocardial detection were stored digitally for subsequent off-line analysis.Using commercially available software , an ellipsoid region of interest (ROI) was defined so that the left ventricular endocardium could be encapsulated for the whole cardiac cycle while taking care to avoid inclusion of data external to the left ventricular cavity. The left ventricular endocardium was then automatically detected in real time for each frame throughout the cardiac cycle (100 frames/s). The left ventricular cavity thus delineated was subsequently displayed 'filled in' with orange pixels  during diastole  during systole  for Aediast, i.e. timing of Femaxdiast.TAesyst: Time interval (expressed as a fraction of diastole) for Aesyst, i.e. timing of Femaxsyst.Although the isovolumic systolic and diastolic events in flow-volume loops could be delineated . Continuous data are presented as mean and standard deviation while categorical data are presented as frequency. Mean values for each variable were compared by independent t-test and ANOVA. Frequency analysis between categories was achieved with the χWith the off-line software used, the time required to import, convert and analyse data, and to produce graphical presentation was 3–5 minutes.All individuals in the normal group had normal resting ventricular wall motion. Of the 36 echocardiographic images available for acquisition in this group, 28 (75%) provided sufficient resolution to allow adequate automated endocardial border detection. The 4-chamber view was most favorable in this respect with all the images obtained in this view allowing adequate delineation of the left ventricular cavity whereas the percentage of qualitatively satisfactory images in the two other views was lesser . There were several reasons for exclusion of images from analysis, sub-optimal image quality being the most prominent factor. Another important reason was inability to obtain the region of interest closely enough to the shape of the left ventricular endocardium throughout the cardiac cycle which fact would result in underestimation of global and regional data and their contamination with extraneous signal components from outside the left ventricular cavity. An irregular RR-interval of the cardiac cycle and poor breath holding resulted in poor reproducibility of the flow-volume loops and the corresponding images were therefore excluded from the analysis as well.Figure As illustrated in Figure Estimated regional flow-volume loops were more complex in their forms in comparison to the global ones and there occurred differences in curve morphology between the loops from different left ventricular cavity segments Figure . As can Adiast and Asyst, respectively) allowed the assessment of the dynamics of blood movement into and out of the ventricle, respectively. In currently studied healthy individuals without any significant intra-ventricular shunt, this integral was roughly the same for both the diastolic and systolic components of the estimated flow volume loop. No differences in this respect occurred between the different apical views either.Table Vemin values registered at the mid-ventricular level were significantly lower (p < 0.05) than those registered in the basal and apical levels. There was also a tendency toward lower Vemax at this level but the difference did not reach the level of statistical significance. On the other hand, the estimated maximal systolic and diastolic flow values, and the integrals of the systolic and diastolic components of the estimated regional loop were not significantly different in any of the three ventricular locations considered. Interestingly, there was a delay in estimated peak systolic flow noted in the apical segments compared to the basal segments (p = 0.05). In concordance with this delay, there was also an increased early systolic integral (Aesyst) in the regional apical loop prior to Femaxsyst (p < 0.00).With 24 regional segments available for analysis, it is not practical to show the results for all of the measured loop variables for each of these segments. Therefore, the segments were grouped before the analysis was performed. Table Despite the visual appearance of differing curve form, there were no significant differences for all estimated flow-volume loop variables between the left ventricular free wall and septal segments.Figure Femaxsyst occurred at a lower estimated left ventricular volume during systole consistent with impaired left ventricular emptying.In the presence of aortic stenosis, there was an alteration in the estimated flow-volume relationship during systole. Femaxdiast appeared at a higher estimated left ventricular volume during diastole compared with the normal individuals.In the case of mitral stenosis, the rate of filling of the left ventricle was notably altered and Finally, in the patient with severe aortic regurgitation, a complicated estimated flow-volume relationship was seen in diastole. This complex flow-volume pattern differed from what could be seen in the estimated normal global flow-volume loop, and thus reflected altered diastolic filling of the left ventricle in this valvular abnormality.This study explores the feasibility of a non-invasive assessment of left ventricular flow-volume relationship throughout the cardiac cycle using transthoracic echocardiography technique. The obtained results demonstrate that such an approach indeed can provide estimates of left ventricular flow-volume characteristics. Furthermore, software analysis of data could easily be automated and integrated in the echocardiographic equipment, thus enabling on-line presentation of the results. The estimated flow-volume loops derived from the acquired data provide physiologically intuitive information about the extent of peak diastolic and systolic blood flow, end diastolic and end systolic left ventricular volumes and their relationship to each other both in normal individuals and in patients with significant left-sided valvular pathology. Other ventricular events as, for example, the contribution of the atrial volume to diastolic filling may also be appreciated. In addition, the analysis of regional displacement of the cardiac walls suggests that there may be an asymmetrical pattern of myocardial deformation throughout the cardiac cycle that may, in part, mirror the current physiological concept of the left ventricular motion dynamics.The reliability of presented methodology is based on certain assumptions. Firstly, the assessment of changes of global left ventricular volume in the present study was obtained by measuring left ventricular 2-D areas in echocardiographic images and the measured 2-D areas were the same as those used for calculation of left ventricular volumes and ejection fraction with Simpson's rule algorithm . The SimThe use of left ventricular volumes in clinical practice is well documented , with enmean A; vmean : mean velocity, A : aortic valve area) by dividing consecutive derivative values of left ventricular area  by the corresponding Doppler-derived aortic velocities may become another possible application. The method also has the potential to be used as a quick communication interface, when comparing loops obtained at different occasions or in different patients. When comparing estimated flow-volume loops among the patients or during the course of disease in any given patient, not only the shape of the loop but also its actual position in the diagram may provide valuable information.The present methodological approach to demonstrate the relationship between left ventricular flow events and dynamic changes in ventricular volume may provide a novel opportunity to better understanding of cardiac (patho-)physiology. The estimated flow-volume loops may offer an attractive approach to the evaluation of varying degree of both systolic and diastolic dysfunction. Calculation of time-dependent estimate of the aortic valve area throughout the ejection period , and in diastole . Although the changes noted could be intuitively anticipated, the morphology of the estimated flow-volume loops could reflect the nature and severity of the underlying valvular pathology. In the case of aortic stenosis, the observed estimated maximal systolic flow occurring at lower than normally estimated left ventricular volume would indicate obstruction of the ventricular emptying that might be valvular or subvalvular. Similarly, the estimated maximal diastolic flow at higher estimated diastolic volume in the case of mitral stenosis reflects most probably restricted ventricular filling and a greater contribution of active filling during atrial contraction, or widening of the mitral orifice during late diastole. Finally, the complex pattern of the diastolic section of the estimated flow-volume loop in the patient with aortic regurgitation results most probably partly from rapid filling of the left ventricle in early diastole, and partly from equivalent of the Austin Flint phenomenon  on the mIn conclusion, non-invasive estimation of left ventricular flow-volume characteristics throughout the cardiac cycle using transthoracic echocardiography is technically feasible and offers physiological information that has not hitherto been readily available. The presented estimates of flow-volume loops reveal the existence of regional morphological variation that, if explored further, may lead to a deeper understanding of the complex physiology of the left ventricle and it would be of particular interest to see whether the segmental alteration of flow-volume loop estimates could identify coronary stenosis that is by and large a segmental  disease. Finally, severe left-sided valvular abnormalities cause a clear and specific alteration of the estimated normal systolic or diastolic flow-volume relationships that can be easy identified, supposedly reflecting the underlying hemodynamics specific for such abnormalities.The author(s) declare that they have no competing interests.LÅB initiated and designed the study. BL and PC performed all of the UL measurements. ES made all data conversions, plots and calculations from ultrasound data. BL, PC, JN and ES performed all the statistical analysis of the study. JN was responsible for the manuscript. All authors contributed to, read and approved the final manuscript.


Sustained chronic tachyarrhythmias often cause a deterioration of cardiac function known as tachycardia-induced cardiomyopathy or tachycardiomyopathy . It has A 13-year-old girl was admitted with a chief complaint of orthopnea. She had been born with the congenital anomalies of spina bifida and common cloacae. At birth, an artificial anal and urinal plasties had been performed. At the age of 11 her urinary and anal tracts had been surgically separated. After the operation she has been doing well, but at the age of 13, orthopnea and edema of the lower extremities was noticed. She was referred to pediatrics and diagnosed as having congestive heart failure with atrial tachycardia. Digitalis, verapamil, and a small dose of metoprolol were not effective in controlling her arrhythmia, so she was referred to our department for further evaluation and treatment.Physical examination indicated a small build  with underdevelopment of the lower extremities. Chest X-ray revealed marked cardiomegaly with a cardio-thoracic ratio of 77 % . On echoAt first we sought to perform an electrophysiological study, but the venous approach for catheterization was quite difficult since the development of her bilateral femoral vein had been hindered by the operation for her congenital genito-urinal abnormality. Furthermore, the patient and her family were reluctant to accept invasive examination or treatment. Thereafter, we decided to prescribe pilsicainide at an initial dose of 25 mg, and within 2 hours her ectopic atrial tachycardia was converted to a sinus rhythm. It was maintained by a daily dose of 75 mg pilsicainide from that day onward. After 3 months, chest X-rays showed an improvement of the cardiothoracic ratio to 46% , while hCoined by Gallagher JJ  , the teFenelon et al  further There is no definite answer to the precise mechanism of tachycardiomyopathy in the clinical setting ,9. SeverTomita et al  investigIn chronic-paced animal models, the response to beta-adrenergic stimulation is known to be blunted. This may also be related to a decrease in the density of the beta-adrenergic receptors ,15. ThesRegarding other cellular functions, chronic SVT induced cardiomyopathy in swine was associated with decreased Na-K ATPase activity and glycoside receptor density and affinity ,22. SpinA recent experimental study indicated that antioxidant vitamins such as beta-carotene, ascorbic acid and alpha-tocopherol reduced tissue oxidative stress in congestive heart failure and attenuated the associated cardiac dysfunction in a rabbit model. In addition, they also attenuated beta-receptor down regulation and sympathetic nerve terminal abnormalities. Therefore, it was emphasized that antioxidant therapy may be an efficacious method in treating human congestive heart failure .In a pig model of tachycardiomyopathy, Spinale et al  observedIn relation to the basic mechanisms of myocardial cell hypertrophy, Clemo et al  tested tA detailed summary of the functional and neurohumoral spectra of experimental tachycardiomyopathy is described by Fenelon et al . in theiIn addition, recent studies elucidated that the progression of tachycardiomyopathy to heart failure facilitates ionic channel remodeling and it may contribute the generation of ventricular tachyarrhythmias. There have been many studies related to the ionic remodeling (K+ and Ca2+) of ventricular myocytes in experimental animals by rapid-pacing induced heart failure ,30. A reIn clinical situations, tachycardiomyopathy is induced by various supraventricular and ventricular arrhythmias. Particularly in childhood, ectopic atrial tachycardia (EAT), a permanent form of junctional reciprocating tachycardia (PJRT) are most prevalently observed, which they are often incessant and refractory to antiarrhythmic drugs, and this commonly results in tachycardiomyopathy .Human tachycardiomyopathy is considered to be similar to the mechanisms of most experimental models. A small number of studies suggest a hemodynamical changes in patients with tachycardiomyopathy . They arPaelinck B et al   reportedOther factors related to LV function; age, underlying heart disease, drugs, irregurality of ventricular rhythm, short atrioventricular interval of less than 100ms are emphasized, yet remain to be determined .Regarding the mechanism of functional mitral regurgitation in tachycardiomyopathy, Timek TA et al  studied A definite diagnosis of tachycardiomyopathy is sometimes difficult. A correct diagnosis can only be made by a normalization or improvement of the impairment of LV function after control of the tachyarrhythmias. However, it is also a fact that tachyarrhythmia control does not always bring about the improvement of LV function in patients with tachycardiomyopathy, and may simply reflect the irreversible stage of tachycardiomyopathy and complicate the diagnosis. Thus, no specific methods are available to identify the presence of tachycardiomyopathy at present. Therefore, it is important to suspect the existence of this condition from its history and clinical findings.Fenelon et al   proposedThe basic concept for the treatment of tachycardiomyopathy is in controling the heart rate. The appropriate heart rate is beneficial for patients with tachycardia-induced heart failure. The usual approaches for tachycardiomyopathy are by both pharmacological and non-pharmacological treatments.In pharmacological therapy, drug choice depends on the underlying arrhythmias. In supraventricular tachycardia, digitalis or a Ca2+ antagonist (verapamil) are the common drugs of choice. Hayano M, et al  reportedUsually, class I anti-arrhythmic drugs have a negative inotropic effect and therefore, the clinical use of these drugs for tachycardiomyopathy should be carefully decided according to the patient's background. The case presented  here also had ectopic atrial tachycardiamyopathy, which was successfully treated with pilsicainide. This drug is a class Ic drug with a strong sodium channel blocking action and has a relatively short half-life compared to other Ic agents. In addition, a single oral dose is often effective for terminating supraventricular arrhythmias. For these reasons we cautiously administrated a single oral dose of pilsicainide (25mg), and it eventually terminated the EAT. Sinus rhythm was maintained at a dose of 75 mg/day and dramatic improvement of cardiac function was observed. Thus, if for some reason, catheter ablation cannot be performed as the first-line of therapy, class Ic drugs, including pilsicainide are an available option for the treatment of EAT-induced cardiomyopathy, provided that the patient is carefully observed.In pediatric cases, EAT or PJRT is often incessant and commonly results in tachycardiomyopathy.  Amiodarone is the only available drug for patients with impaired LV function and tachyarrhythmias.40 In pediatric cases, EAT or PJRT is often incessant and commonly results in tachycardiomyopathy. Chen R.P-C . reporteSince the introduction of radiofrequency (RF) ablation, the treatment of tachyarrhythmias has been safely performed and favorable results have been obtained. Simultaneously, it has been proven that the cure or control of tachyarrhythmia could improve LV function and heart failure in patitents with tachycardiomyopathy. Targeted arrhythmias are wide ranging, including EAT , PSVT orRF ablation can even be used successfully even in a cardiac transplant patient with atial tachycardia-induced cardiomyopathy .Similary, a surgical treatment is also effective for patients who received operations to cure the tachyarrhythmias. Giorgi LV et al  reportedGenerally, if tachyarrhythmias are properly treated, cardiac function will recover. In bacic study, the recovery of LV systolic function requires about 2 weeks from the termination of pacing. However, in clinical situations, this may be quite variable both spatially and temporally because the length of tachycardia and underlying heart diseases are different in each patient.The diagnosis of tachycardia-induced cardiomyopathy is not always simple, but we should start therapy if the patient suffers from congestive heart failure with tachyarrhythmias. This is because LV dysfunction may be recover after adequate treatment and it is the only way to make a definite diagnosis of tachycardiomyopathy.


Assessment of cardiac preload is important for clinical management of some emergencies related to hypovolemia. Effects of acute simulated hypovolemia on Doppler blood flow velocity indices of tricuspid valve (TV) and superior vena cava (SVC) were investigated in order to find sensitive Doppler indices for predicting right ventricular preload.Doppler flow patterns of SVC and TV in 12 healthy young men were examined by transthoracic echocardiography (TTE) during graded lower body negative pressure (LBNP) of up to -60 mm Hg which simulated acute hypovolemia. Peak velocities of all waves and their related ratios (SVC S/D and tricuspid E/A) were measured, calculated and statistically analyzed.p < 0.001).Except for the velocity of tricuspid A wave, velocities of all waves and their related ratios declined during volume decentralization. Of all indices measured, the peak velocities of S wave and AR wave in SVC correlated most strongly with levels of LBNP (r = -0.744 and -0.771, The S and AR velocities are of good values in assessing right ventricular preload. Monitoring SVC flow may provide a relatively noninvasive means to assess direct changes in right ventricular preload. In many critical clinical situations such as septic shock or cardiac surgery, hypovolemia may lead to cardiovascular failure by decreasing cardiac preload. In this situation, volume expansion is necessary for improving hemodynamic condition. However, excessive volume loading is harmful to the body. Therefore, it is important to find some new reliable indices to evaluate cardiac preload and to predict fluid responsiveness. Though many related indices have been introduced into clinical practice for this use, they are invasive and lack of sensitivity, and often with conflicting results ,2. The DTwelve young healthy male volunteers aged 21–24 years (mean age 23 ± 1y) were enrolled in this experiment. All the volunteers were normotensive and were not taking any medications. All of them were fully informed of the aim and protocol of the investigation. Approval of the Ethic Committee of the Fourth Military Medical University was obtained.Isolated preload reduction was obtained by means of graded LBNP. The device for lower body suction has been described in detail elsewhere. BrieflyThe participants began by lying supine on a laboratory bed with their legs and hips sealed in the LBNP chamber. The LBNP protocol included an initial 10-min period of baseline rest in supine position, followed by progressive -10 mmHg-graded negative pressure of up to -60 mmHg at intervals of 2 minutes. The LBNP was released to 0 mmHg (baseline level) soon after reaching -60 mmHg for 2 minutes. All the subjects were able to tolerate this protocol without any adverse effects. Doppler measurements were made at baseline, each level of negative pressure and 3 minutes after LBNP was released to 0 mmHg. Systolic and diastolic arterial pressures (SAP and DAP) as well as heart rate (HR) were simultaneously recorded from the dominant arm by means of an automatic device .All transthoracic echocardiographic examinations were performed by one experienced operator (G.P.) using a commercially available equipment  and a multi-Hertz sector probe 3V2c (H3.5 MHz) in basal condition and at each step of LBNP . With the subject in supine position, images were obtained from standard projections. Pulsed-wave Doppler echocardiography was performed with simultaneous electrocardiogram and respiratory recording. Flow velocities of SVC were measured from the right supraclavicular fossa. The sample volume size was 5 mm and the depth of the sample volume was 2 cm below the bifurcation of SVC  and volumetric variables [intrathoracic blood volume index (ITBI) and left ventricular end-diastolic area index (LVEDAI)] have been studied extensively. EchocarThe effects of LV preload on the pulmonary venous flow (PVF) have been well studied . It has p < 0.001). These results showed that the indices derived from SVC predicted fluid responsiveness more sensitively than those from TV. The reason may be that the flow patterns of SVC recorded from the right supraclavicular fossa are more clear and with less noise than the flow patterns of TV recorded from the parasternal 4-chamber view, and the sample position of SVC is stationary and less affected by the motion and condition of heart However, few investigations were made upon the effects of changes in RV preload on velocities of SVC and TV. Our results indicated that all waves of SVC, E wave of TV, the ratio S/D and E/A decreased with the acute blood volume decentralization, whilst the HR increased, with no significant change in A wave of TV and arterial blood pressure. Of all variables measured, the S and AR velocities of SVC appeared to be the most sensitive indices of blood volume depletion  which decreases with loss of the blood volume. Whilst A velocity of TV changed little, because the pressure difference between right ventricle and right atrium remained unchanged and A velocity is mainly determined by the atrial contraction. Furthermore, there was no obvious change of right ventricular compliance which will not induce significant change of A wave.When the LBNP was released to 0 mmHg (baseline), all indices measured except for HR returned to their baseline levels. This demonstrated that the results can also be applied in the situation of blood volume restitution.Our results underline the superiority of Doppler indices from SVC to detect hypovolemia and predict preload responsiveness over those from TV measured by transthoracic echocardiography. The S and AR velocities are of good value in assessing right ventricular preload. Monitoring SVC flow may provide a relatively noninvasive means to assess directional changes in right ventricular preload.The present study may involve certain limitations. First, no other related invasive indices were measured simultaneously to compare with the Doppler indices. Second, the subjects only limited to the healthy young men. It is not yet defined if these indices, as validated in the healthy subjects, may be applied also in patients with cardiovascular diseases.The author(s) declare that they have no competing interests.JL and TC designed the study. JL performed echocardiographic examinations and drafted the manuscript. YY participated in the LBNP test. YD and LY performed the statistical analysis. All authors read and approved the final manuscript.


The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated.Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin.With chronic left ventricular dysfunction, a reduced left ventricular ejection fraction  and increased index of myocardial performance  due to isovolumic contraction time lengthening and shortened left ventricular ejection time were noted. Dobutamine increased ejection fraction (p < 0.001), reduced left ventricular end diastolic pressure (p < 0.01), and reduced the index of myocardial performance  due to isovolumic contraction time, isovolumic relaxation time, and left ventricular ejection time shortening. Digoxin increased ejection fraction (p < 0.05), reduced left ventricular end diastolic pressure (p < 0.05), and reduced the index of myocardial performance  due to isovolumic contraction time shortening (p < 0.001). Both dobutamine and digoxin lengthened the diastolic filling period (p < 0.01).Increased inotropy with digoxin and dobutamine reduced the index of myocardial performance in dogs with left ventricular dysfunction. Shortened isovolumic contraction time, increased diastolic filling period, and reduced left ventricular end diastolic pressure with digoxin may provide insight into its efficacy in heart failure. The index of myocardial performance (IMP), calculated as the sum of the isovolumic relaxation time (IRT) and isovolumic contraction time (ICT) divided by the left ventricular (LV) ejection time (LVET), has been utilized as a combined systolic-diastolic index that is prognostic in patients with dilated cardiomyopathy  and postSystematic evaluations of IMP in the normal and abnormal left ventricle have recently been performed using a canine model of chronic ischemic LV dysfunction. IMP was demonstrated to be preload and afterload dependent but not heart rate dependent ,10. In tDigoxin, an oral inotropic agent, also has beneficial symptomatic effects in heart failure patients with either reduced or preserved LV function . HoweverThe goals of this study were:  to deterThe animals used in this study were maintained in accordance with the guidelines of the Committee on Animal Studies at Wayne State University School of Medicine and with the position of the American Heart Association on research animal use. The protocol was approved by the Animal Investigation Committee of Wayne State University. Anesthesia was induced in 10 conditioned mongrel dogs (16–24 kg) with intramuscular morphine sulfate (1.5 mg/kg) and acepromazine (1.1 mg/kg) followed in 15 minutes by 30 mg/kg of intravenous ketamine hydrochloride. Maintenance anesthesia was produced by intravenous morphine sulfate (1.5 mg/kg/hr) and pentobarbital (3 mg/kg/hr). The dogs were intubated and artificially ventilated with a Harvard respirator using room air. Using fluoroscopic guidance, two 7F high fidelity catheters (Millar Instruments) were introduced via the right carotid artery and advanced to the left ventricle and ascending aorta. A #7 multipurpose Judkins catheter was introduced through a sheath (Cordis) into the right femoral artery and advanced into the left coronary ostium. Continuous electrocardiographic monitoring was performed using lead II. At held end expiration, ECG, LV pressures, dP/dT, and central aortic pressures were obtained at 100 mm/s using an 8 channel physiologic recorder (Gould). Simultaneous 2 dimensional echocardiograms and Doppler were obtained from with the use of a phased array echocardiograph (Aloka 880). Transesophageal 4 chamber view was obtained from a 5 MHz probe placed in the mid-esophagus. Both transaortic and transmitral pulsed Doppler recordings were obtained from the LV outflow tract and from beyond the tips of the mitral leaflets in the left ventricle at 100 mm/s. Mitral regurgitation was assessed from the 4-chamber view as the size of the maximal color flow jet divided by the left atrial area.Ischemic LV dysfunction was induced by left main coronary artery plastic microsphere injections (58 ± 2 microns) (3M) injected in boluses of 17,500 microspheres every 5–10 minutes until the peak positive dP/dT was reduced by 25% and the LV end diastolic pressure was >12 mm Hg. LV dysfunction  was produced in 45–60 minutes with only mild mitral regurgitation . This approach ultimately leads to a model of chronic LV dysfunction where the extent of LV dysfunction may be titrated [At 8 weeks post coronary microsphere embolization, the animals were anaesthetized, intubated, instrumented, and ventilated as above. Using fluoroscopy, a #7 thermodilution catheter and a #5 bipolar pacing wire were advanced from the left internal jugular vein to the pulmonary artery and right atrium respectively. Atrial pacing commenced 10 beats above baseline rate with a PR interval <160 msec. Transthoracic and transesophageal echocardiography and Doppler were obtained as above. Continuous electrocardiographic monitoring was performed using lead II. The above hemodynamic, echocardiographic, and Doppler parameters were obtained after 10 minutes of steady state atrial pacing. Dobutamine was infused at a rate of 2–2.5 micrograms/kg/minute for 15 minutes. Care was taken to adjust the rate of infusion to ensure that atrial pacing was maintained. The above parameters were then obtained. The infusion was discontinued and the dogs were observed until hemodynamics and echocardiographic assessment of LV systolic function returned to the pre-dobutamine LV dysfunction baseline. The above parameters were then obtained as a baseline for digoxin therapy. The vessels were repaired, and the animals were recovered.On the following day, each dog received 0.02 mg/kg/digoxin in their food daily to a maximal dose of 0.25 mg digoxin for 4 weeks ,14. At 1LV dysfunction was induced in 8 additional dogs as described above. At 8 and 12 weeks post embolization, the dogs were instrumented as described above. Hemodynamics, echocardiography, spectral, and color Doppler were obtained at baseline and with atrial pacing 10 beats above baseline. The same atrial rate was used for each dog at 8 and 12 weeks post embolization.For all stages and time periods, LV pressures, dP/dT, cardiac outputs, and aortic pressures were measured from the average of 3 consecutive cycles at held end expiration. The time constant of LV pressure decline was calculated using the Weiss method . LV end For all stages and time periods, all Doppler indices were measured from the average of 3 consecutive cycles at held end expiration. From transmitral Doppler indices, peak rapid filling velocity (E) and peak atrial filling velocity (A) were measured. The E/A ratio was calculated. The rapid filling deceleration time was calculated as the time interval from the peak rapid filling velocity to the time mitral flow decelerated to the zero baseline. The tracing was extrapolated to the zero baseline if atrial filling commenced prior to mitral flow fully decelerating to zero. Diastolic, rapid filling, and atrial filling velocity integrals were determined. Mitral regurgitation was assessed using the ratio of the maximal color flow jet area in the left atrium during systole divided by the left atrial area.From the transmitral pulsed Doppler, the time interval between the end of mitral filling and the onset of mitral filling was determined ("a"). From transaortic pulsed Doppler, the time interval from the beginning of aortic flow to the end of aortic flow was determined ("b" or LVET). The IMP can be calculated asIMP = (a-b)/bTo determine the IRT, the time from the R wave to the end of aortic flow was subtracted from the R wave to the onset of mitral flow interval. As "a-b" represents total isovolumic time, the ICT is the difference between IRT and "a-b" . The ICTIntraobserver variability for calculation of IMP was determined from 25 randomly selected stages. Each determination was performed 4 weeks apart. The average difference between determinations was 0.008 ± 0.002. Intraobserver and interobserver variability for LV echocardiographic volume was determined by selecting end diastolic and end systolic frames from the echocardiogram of 10 previously studied dogs. Each frame was analyzed 3 weeks apart by 2 observers (see acknowledgement). The average difference for end diastolic or end systolic volume was 2.2 ± 0.9 cc for intraobserver variability and 3.4 ± 1.7 cc for interobserver variability.All data was expressed as mean ± standard deviation. Differences between a variable among stages was assessed using paired T testing. A p < 0.05 was considered to be significant.th chronic LV dysfunction, LV volumes, LV mass, heart rate, and LV end diastolic pressure were increased. Ejection fraction and peak +dP/dT declined. Parameters of relaxation (Tau and E/A) were also abnormal as compared to baseline. The deceleration time was also shortened suggesting reduced LV chamber compliance. This finding may be secondary to the interstitial and replacement fibrosis seen in the myocardium with this model of chronic LV dysfunction [Table function . IMP wasTable Table IMP has been identified as a useful prognostic parameter following acute myocardial ,17,18 inBoth inotropic agents significantly increased peak +dP/dT and LV ejection fraction though the effect of digoxin was smaller. IMP was markedly reduced with dobutamine infusion with reductions in both ICT and IRT despite a reduction in LVET. The reduction in ICT was >70% and due to a combination of prolongation of time to mitral closure (12 msec) and shortening of time to onset of aortic flow (18 msec). Similarly oral digoxin for 1 month resulted in a reduction in the IMP due to a 61% reduction in ICT. Shortening of the ICT was likely related to the prolongation of the time to mitral closure (24 msec). With both agents, LV filling pressures declined and the diastolic filling period increased suggesting that reductions in total isovolumic time resulted in greater time for diastolic filling. With dobutamine, stroke volume increased and relaxation improved allowing a greater filling volume to enter a more relaxed left ventricle with lower resultant filling pressures. With digoxin, stroke volume also increased and was associated with a longer diastolic filling period resulting in a lower LV filling pressure. This finding with digoxin is intriguing as its use in patients with preserved LV function (ejection fraction >40%) has been both advocated and questioned ,21.a model of LV dysfunction in which a positive inotrope is administered or a negative inotrope administered in a model with normal LV function.Using a swine model, LaCorte  demonstrHowever, the relationship between contractile alterations and IMP is less well delineated in the left ventricle with reduced LV function. Most information regarding the effects of contractile alterations are based on an acute ischemic episode from a normal resting LV function . There aAs this is an experimental study, the applicability of these findings and relation to intact humans is always a limitation. The general anesthesia utilized may influence the results. However, this anesthesia regimen has been utilized in multiple experimental studies ,10,12 anThough IMP has been demonstrated to be load dependent ,10, it cIn conclusion, the effect of increasing inotropic stimulation in a model of mild chronic canine LV dysfunction was determined. Increasing inotropy with digoxin and dobutamine reduced IMP primarily due to ICT shortening. Dobutamine had the additional effects of IRT and LVET shortening. Of note, a shortened ICT, increased diastolic filling period, and reduced LV end diastolic pressure with digoxin may provide insight into its efficacy in heart failure.ICT = isovolumic contraction timeIMP = Index of myocardial performanceIRT = isovolumic relaxationLV = left ventricularLVET = left ventricular ejection timeThe author(s) declare that they have no competing interests.As this is a single author paper, the author designed, acquired and analyzed the data. The author drafted and wrote the manuscript.


Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the µg/mL range with half-lives of 10–20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the µg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of  Bacillus anthracis is a spore-forming, Gram-positive bacterium and is the causative agent of anthrax. Infection by inhalation of B. anthracis spores can result in a mortality rate of up to 80% of Bacillus anthracis infections as a cause of human and animal disease and its notoriety as an agent of biological warfare, exactly how the bacteria kill the host is unclear. Although aggressive antibiotic therapy can prevent bacterial growth, infected individuals still die, most probably due to high concentrations of anthrax toxins already accumulated in the body Bacillus anthracis vegetative bacteria secrete three proteins—protective antigen (PA), lethal factor (LF), and edema factor (EF) which combine to form anthrax lethal toxin  and anthrax edema toxin  2+-metalloprotease which specifically cleaves the NH2-termini of mitogen-activated protein kinase kinases (MEKs) resulting in their inactivation Bacillus anthracis infection by prophylactic treatment with antibodies or vaccines to anthrax toxins In the 2001 bioterrorism anthrax experience, patients with inhalational anthrax developed refratory hypotension Newer methods used in this study to dissect the pathophysiology of shock in unrestrained rodents include instrumentation with intra-aortic catheter probes connected to telemetry units and transthoracic echocardiography with state-of-the-art ultrasound technology. These methods permit dissection of the contribution of the heart, blood volume and blood vessels to cardiac output and blood pressure.Examination of toxicity in Sprague Dawley rats was performed by an intravenous injection of different doses of LeTx and EdTx and mortality . SurvivaTo determine half-life and plasma levels of PA following injection, rats were administered various doses of LeTx (2:1 ratios of PA/LF) and EdTx (2:1 ratios of PA/EF) via the tail-vein injection. The LeTx was given as single bolus infusions using doses of 0.024 mg PA+0.012 mg LF, 0.03 mg PA+0.015 mg LF, 0.032 mg PA+0.016 mg LF, 0.04 mg PA+0.02 mg LF in 500 µL phosphate-buffered saline (PBS). EdTx was given as single bolus infusions of 0.15 mg PA+0.075 mg EF in 500 µL PBS. After various times (0–250 min) blood samples were collected and plasma levels of PA were analyzed using ELISA, as described in the methods. As shown in Hemodynamic parameters were measured by telemetry of conscious Sprague Dawley rats that were treated with single intravenous bolus infusions of toxins. Radiofrequency measurements of baseline heart rate and blood pressures were recorded for 72 hr, after which rats were administered tail-vein injections of LeTx (0.03 mg PA+0.015 mg LF), EdTx (0.15 mg PA+0.075 mg EF) or PBS (control). Bradycardia and hypotension developed in rats within 1 hr after exposure to LeTx . The rapEchocardiographic parameters including velocity of propagation (Vp), left ventricular diastolic area (LVAd), left ventricular systolic area (LVAs), heart rate were monitored at different times post anthrax toxin bolus iv infusion . LeTx trEdTx treated rat hearts showed significant increases in heart rate compared to controls at one and two hr post-injection . Heart rThe studies presented here provide the first detailed analyses of cardiovascular toxicity induced by purified anthrax toxins in a rat model. Both toxins induce significant hypotension. Importantly, LeTx and EdTx appear to produce the hypotension by affecting different parts of the cardiovascular system. Serum levels of toxins were measurable in all tested rats. Lethality and hypotension were associated with doses of toxins that produced peak PA levels in the µg/mL range. This is consistent with the measurements of toxin levels in spore-infected animals LeTx rapidly induced acute myocardial dysfunction similar to that observed with fulminant myocarditis with significant increases in the LV systolic area, LV diastolic area, and ventricular compliance. Left ventricular dilatation was expected from acute myocardial dysfunction such as fulminant myocarditis. Increased ventricular compliance is implied by the increased Vp. Ogawa reported that Vp was positively correlated with stroke volume, heart rate and left ventricular compliance Both observations are consistent with published results of toxin-induced rodent hypotension. Mice intravenously infused with LeTx developed malaise and death by 60–100 hr Previous reports support a critical role for mitogen activated protein kinase (MAPK) signaling in the heart. Tissue culture studies with antisense molecules and knockout mice show cardiomyocyte injury with impaired MEK1/2-ERK1/2 kinase activities The observed cardiovascular defects induced by anthrax toxins were dependent on the presence of two toxin components (PA+LF or PA+EF). Rats received IV infusion of LF alone survived and showed no symptom of hypotension (data not shown). Previous studies have demonstrated that, in the absence of PA, injection of EF does not cause any symptom in treated animals Combinations of LeTx and EdTx as occurs in systemic anthrax infections would be predicted to generate more severe and irreversible hypotension due to an inability of either the heart or blood vessels to respond to lesions in the other organ. Preliminary studies with combinations of EdTx and LeTx show worse hypotension and greater lethality In summary, these results suggest that the pathophysiology of anthrax shock may be closely linked with circulating toxins and involve both a rapid reduction in left ventricular preload and systolic function. Intervention to rescue animals and patients with anthrax shock will need to address both of these cardiovascular lesions. Rodents and other species provide an excellent system to test new therapeutics for this devastating disease.Anthrax toxin components PA, LF and EF were produced at over 95% purity with low endotoxin level as previously described ad libitum. The colony room lights were regulated on a 12:12-h light-dark cycle. Care and use of animals were designed in accordance with National Institutes of Health and American Association for the Accreditation of Laboratory Animal Care (AAALAC) guidelines, and approved by the Scott and White Memorial Hospital/Texas A and M University System Health Science Center Institutional Animal Care and Use Committee. Rats received bolus intravenous 500 µL infusions of sterile PBS, LeTx or EdTx.Male Sprague-Dawley rats weighing between 180 and 230 g were purchased from Charles River Laboratories  and allowed a one-week acclimation period after arrival to the animal facilities at Scott and White before experimentation or surgical procedures. Rat weights at the time of experiments were 250 to 300 g. Animals were housed two per polycarbonate tub with wood shavings and allowed food (Purina Rat Chow) and tap water Groups of three to twelve animals received intravenous injections of various doses of LeTx, EdTx, or toxin subcomponent. Animals were monitored post-injection hourly for eight hours and then every twelve hr for activity, posture, eating and drinking, and hair condition. Moribund animals were euthanized. Kaplan-Meier survival curves were compared by the log-rank test.2SO4 and absorbance measured at 450 nm on a VERSAmax microplate reader . Each test was performed in triplicate and the average of the data points was plotted using GraphPad Prism 4 . Curved-fits were calculated with one phase exponential decay equation: Y = Span (e−kX)+Plateau, k is elimination rate constant. The PA assay had a range of 3.91 ng/mL to 500 ng/mL with the inter-assay and intra-assay coefficients of variation less than 15%.Clearance of PA from the circulation of Sprague Dawley rats was determined following intravenous tail-vein injection of toxin into three rats. Tail-vein blood samples (100–200 µL) were collected at 15, 20, 30, 90, 100, 168, 240 and 1440 min-post injection, after which serum was harvested by sedimentation . Aliquots of serum were stored at−80°C until assayed. ELISA plates  were incubated  with capture anti-PA antibody (2 µg/mL of 14B7) Radio frequency devices were implanted for independent monitoring of blood pressure or heart rate using devices from Data Sciences Int.  as described Echocardiography was used to determine effects of LeTx and EdTx on cardiac function. At 12–24 hr prior to toxin administration, rats were subjected to echocardiography to establish baselines and exclude any animals with abnormal cardiac function. We used a previously established echocardiography protocol Data were averaged and shown as means±standard error of mean (S.E.). Two sample differences were analyzed using Student's unpaired t test. All calculated P values were two tailed, and a value of P<0.05 was considered to indicate statistical significance. For rats that died overnight, statistical analysis was based on the last observed post-infusion time point.


Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation. In the last decade cancer therapy (CT) has shown a terrific progress leading to an important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of patients with cancer includes multiple combinations of drugs, radiation therapy and surgery. Many of these therapies produce potential adverse cardiac reactions which can negatively affect the quality of life as well as the prognosis of oncologic patients.In this view, the early detection of cardiotoxicity due to CT is a critical issue in the clinical setting, in order to interrupt or modulate appropriately CT and even to sustain ventricular performance by cardiac drugs. The traditional screening of patients with cancer includes cardiologic examination, and both EKG and Doppler echocardiography at rest. The monitoring of cardiovascular toxicity might be more accurate by using endomyocardial biopsy  which isDuring time echocardiography is emerged as the choice test for noninvasive evaluation of cardiac disease due to cancer therapy. This tool is essential for the evaluation of left ventricular (LV) systolic and diastolic dysfunction, pericardial disease, myocardial damage and detailed information of valvular heart disease. Nevertherless, Doppler echocardiographic examination is routinely planned only at the beginning of CT in order to document a normal LV systolic function. Further echocardiographic controls during CT are performed only as a consequence of the onset of cardiac symptoms and/or signs, in particular following the administration of recognized cardiotoxic drugs or the radiation therapy. On these grounds, these review attempts to demonstrate the clinical need of serial Doppler echocardiographic evaluation and the potential impact of advanced ultrasound technologies in patients undergoing CT.Cardiovascular toxicity gives its expression in silent  or overt  events. Pre-clinical toxicity may be diagnosed by histopathological or biochemical techniques and, even, by detailed imaging techniques. The grading system proposed by the World Health Organization to standardize the report of adverse effects due to CT does not consider laboratory or modern imaging changes  while thAnthracyclines , the best studied anticancer drugs, widely used for several hematologic and solid tumors, have a recognized cardiotoxicity, which may be acute and/or late. Acute cardiotoxicity develops producing non-specific EKG abnormalities but sometimes also cardiac symptoms. Late cardiotoxicity is cumulative , dose-related and may determine LV systolic dysfunction until congestive heart failure (CHF). The mechanism underlying this dysfunction is consequence of a direct myocardial damage induced by the formation of free radicals [Alkylators , commonly used for several solid tumors and lymphomas, may induce cardiac complications including heart failure, myocarditis and pericarditis [Antimetabolities , widely used in the treatment of solid tumors, may produce ischemic syndrome , arrhythmias and cardiomyopathy [Antimicrotubule Agents , applied to the treatment of several solid tumors, may induce arrhythmias, thrombosis and myocardial ischemia [Cytokines , used for treatment of metastatic renal carcinoma and melanoma, can results in arterial hypotension, vascular leak syndrome, arrhythmias, cardiomyopathy and vascular thrombosis [All-trans Retinoic Acid, a vitamine A derivative approved for acute promyelocytic leukemia, induces a syndrome characterized by fever, dyspnoea, arterial hypotension and pericardial/pleural effusion within the first 21 days [Arsenic Trioxide, used for refractory or relapsed acute promyelocitic leukemia, provokes QT-interval prolongation and arrhythmias in more than 50% of treated patients but can determine also fluid retention  [Imatinib Mesylate, a specific inhibitor of BCR-ABL tyrosine kinase used for chronic myelogenous leukemia and other malignancies, is associated with a significant incidence of fluid retention [Etoposide, mainly used for refractory testicular tumors and small-cell lung carcinoma, is arterial hypotension but myocardial ischemia may be observed [Monoclonal Antibodies , modernly applied for treatment of some hematologic malignancies and solid tumors, have toxicity profiles specific to the blocked receptors but all produces arterial hypotension [Cardiovascular effects associated with CT agents are listed in Table radicals . It has radicals  but thiscarditis . The meccarditis . The totcarditis . Cisplatcarditis . Reportemyopathy . Of notemyopathy . Antimicischemia . Of noterombosis . The tre 21 days , with de 21 days . Arsenicffusion) . Imatinietention . The mosotension . In thisotension .radiation therapy is applied for CT of lymphoma, breast cancer, thymoma, high and low respiratory ways, esophageal and gastric lesions. Its damage may involve all cardiac structures  and peripheral vessels, with variable onset modalities, in relation with dose, irradiation modality, contemporary administration of chemotherapic agents (in particular doxorubicin) and baseline patient's clinical condition [The ondition . Cardiovondition ,26. Thesondition . Of inteondition ,27. Periondition ,29. ImpoTable EKG represents the traditional support and completion to the clinical examination also for patients undergoing CT but EKG abnormalities are often non specific in this clinical setting. This is particularly true for anthracycline-induced acute toxicity, where non-specific ST-segment and T-wave changes, decreased QRS voltage and QT-interval prolongation have been described. Chronic anthracycline cardiotoxicity (even many years after the completion of therapy) manifests often as life-threatening arrhythmias . 5-FluorToday, the widely used non-invasive method of monitoring cardiotoxicity of CT is certainly represented by Doppler echocardiography which allows to identify the main forms of cardiac involvement in cancer patient: LV (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, and carotid artery lesions.LV dysfunction which may progress until overt congestive heart failure [2 + average mediastinum irradiation dose = 21 Gy = 21 Sv = 210.000 chest x-rays) did not show significant changes of M-mode derived LV end-diastolic diameter, end-systolic diameter and EF but identified regional wall motion abnormalities (hypokinesis) by 2D assessment [2) [2) cyclophoshamide [2 + paclitaxel 200 mg/m2 showed reduction of two-dimensional EF from baseline median value of 60% to median value of 50% after 8 courses [The form of CT-related cardiac involvement of the greatest interest and concern among oncologists and cardiologists is  failure . LV endo failure . The diasessment . The chrsessment . Early psessment . Figure sessment ,48. In tsessment . Serial ment [2) . The echoshamide . Advance courses . Hypokin courses . Of inte courses , the sam courses . Echocar courses . The eff courses . Worthy  courses . Data co courses .valvular heart disease, developing as chronic CT of chemotherapic agents, concerns mainly anthracycline treatment. In a population of 305 patients (median age = 14 years), treated with a cumulative dose ranging 140–450 mg/m2 for childhood malignancy, color flow Doppler detection of mitral regurgitation was evident in 34 patients (11.6%) compared with only 1.8% of a normal population of similar age (p < 0.0001) [Also the documentation of  0.0001) . Since i 0.0001) , echocar 0.0001)  After a  0.0001) . The ech 0.0001)  observed 0.0001) .Pericarditis and pericardial effusion can be also due to chemotherapy and, above all, to radiation therapy [Malignant pericardial disease is a serious but not uncommon problem seen in patients with cancer, usually due to metastatic spread of the underlying malignancy.  therapy . The pat therapy ,65. Radi therapy ,67. Acut therapy  and late therapy ,70 after therapy  while th therapy  takes in therapy . The seacarotid arterial disease occurs frequently in young patients following head and neck radiation therapy. Doppler-echo scan of carotid arteries allowed to detect increased intima-media thickness in 24% of 42 survivors of Hodgkin lymphoma who had undergone radiation therapy more than 5 years earlier and one patient had greater than 70% stenosis of both common carotid arteries [Asymptomatic arteries . This fiarteries . In thisarteries .All together, these findings highlight the ultrasound ability to unmask cardiovascular abnormalities in symptomatic as well as in asymptomatic patients undergoing CT. It emerges also by our retrospective experience including 148 echocardiographic observations from patients referring to our echo-lab for hematologic malignancies and showing CT-related abnormalities of LV function, pericardium and heart valves .2) and had normal LV structure and function at rest, did not show significant modifications during a modified/accelerated dobutamine protocol . On the other hand, Hamada et al, by using high-dose dobutamine (30 mg/Kg/min), evidenced alteration of posterior wall thickness, fractional shortening and transmitral E/A ratio in patients treated by high-dose anthracycline and free of cardiologic symptoms (81).Dobutamine stress echocardiography was tested in several studies to detect subclinical abnormalities of LV function induced by anthracycline cardiotoxicity -81 but tStress echocardiography, an optimal tool to unmask coronary artery disease in the general population, remains important also in patients treated by some chemotherapic agents  and in particular by radiation therapy, which is able to provoke accelerated coronary atherosclerosis. Experiences dealing with the use of stress echocardiography in this clinical setting are, however, lacking until now.Some high-tech ultrasound tools as Integrated Backscatter (IBS) and Tissue Doppler have been used with the aim to identify subclinical alterations of both LV structure and function in patients treated by CT.th hour of treatment compared with 0th hour but returned near the baseline values at day 15 (p = 0.003), suggesting a reversible, acute 5-fluorouracile toxicity [2 of doxorubicin, this decrease being higher in patients treated by moderate and high-dose than in those undergoing low dose [Analysis of acoustic intensity of the backscattered signal consists of the omni-directional scattering energy redirected back to the transducer, with different intensity according to the density of the reflecting tissue . IBS, whtoxicity . In additoxicity , cyclic-low dose .2). In these patients also myocardial systolic dysfunction was evident, in presence of normal EF [IBS requires time-expensive, off-line analysis and normalization for the pericardial interface, inducing possible artifacts. In contrast, pulsed Tissue Doppler may be easily performed during a standard Doppler echocardiographic examination by using a high-pass filter and placing a sample volume on a given region of interest . It has ormal EF ,92. Simiormal EF , while nAn useful tool to identify early markers of pulmonary congestion following to heart failure could be represented by the ultrasound "lung comet", an echocardiographic sign detectable with the ultrasound scan of anterior and lateral chest . It is visualized as multiple comet-tails fanning out from the lung surface . It origA large amount of data demonstrate how Doppler echocardiography represents the election tool not only for baseline cardiologic screening but also for follow-up of the oncologic patients during and after the completion of CT. In relation with its low cost, feasibility and reliability to diagnose LV systolic and diastolic dysfunction, regional wall motion abnormalities, valve disease, pericardial abnormalities and carotid lesions, the ultrasound examination appears very useful to identify and monitor CT-related cardiac conditions over time. This is really crucial when using some chemotherapic agents as anthracyclines, which have early but, most importantly, late and very late, cumulative cardiac toxicity. The late cardiac toxicity may be stopped or at least blunted by a prompt pharmacological intervention. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation. Under these circumstances and given the high likelihood of diagnosing significant cardiovascular pathologies, an ultrasound screening 10 years after irradiation is recommendable also in patients who remain asymptomatic and should be extended to the exploration of carotid arteries in patients undergoing mantle irradiation. In all the cases the performance of Doppler-echo examination should be very flexible, prone to the assessment of multiple parameters of LV systolic and diastolic function , to the detection and grading of valvular heart disease, to the visualization of overall pericardium by multiple views and even to the measure of carotid intima-media thickness Table . Bio-humThe author(s) declare that they have no competing interests.


Right ventricular hypertrophy (RVH) is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase . Saline treated animals served as controls .2), but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC βI and PKC ε from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC ε was unchanged. Translocation of PKC α and βII were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con.Nine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 ± 1.18 vs. Con 5.14 ± 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 μmThese data suggest that PKC βI, ε and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH. Emphysema affects nearly 3 million people and is responsible for nearly 16,000 deaths per year in the United States . The proEven though many studies have identified a critical role for many protein kinase C isoforms  and extracellular regulated kinase (ERK) 1/2 in the pathogenesis of left ventricular hypertrophy, very few studies have examined these kinases in RVH. It has been previously reported that PKC α, βI, and δ activation is increased in RVH due to pulmonary artery constriction, and PKCGiven the numerous human and animal studies identifying PKC and ERK1/2 as critical mediators of left ventricular hypertrophy -12, and 2 vs. 2695 μM2)  Figure  as was mEchocardiographic assessment documented progressive right ventricular enlargement over time in the Emp hamsters, with significantly greater right ventricular internal dimension (RVID) vs. Con after nine months of emphysema Figure . HistoloThere was a significant correlation (r = 0.68) between the RVID and lung volume measured Figure . Only trThere was a mild, but statistically significant increase in right ventricular systolic pressure (RVSP) after nine months of emphysema Figure , Table 1No differences were detected in translocation of PKC isoforms α and βII between Emp and Con hamsters, as evidenced by the unchanged membrane-to-cytosol ratio Figure . There wRV homogenates from Emp hamsters had increased phospho-ERK1/2 levels, resulting in a 34% increase in the ratio of phospho ERK1/2 to ERK1/2 Figure . Total JDespite the morbidity and mortality, associated with right heart failure, the pathogenesis of right ventricular hypertrophy has been studied much less than left ventricular disease. Evidence from clinical observations and animal studies suggest that the right ventricle does not respond to stress in precisely the same fashion as the left ventricle. Most patients with L-transposition of the great arteries, a condition in which the anatomic right ventricle serves as the systemic ventricle from birth, eventually develop severe RV failure. This usually occurs before the age of 30 . Thus, cin situ thrombosis and polycythemia may play a role as well  was instilled intratracheally using a 27-gauge hypodermic needle as previously described .Parameters of cardiac structure and function were determined with transthoracic echocardiography (n = 8 con and n = 10 Emp hamsters) as previously described ,36. HamsFollowing the final echo (nine months after elastase treatment) while still under anesthesia with chloral hydrate the right jugular vein was exposed and a temperature-calibrated 1.4 F micromanometer-tipped catheter (Millar Instruments) was inserted into the vein and advanced in retrograde fashion into the right ventricle. Heart rate, right ventricular pressure and first derivative of pressure (dP/dt) were recorded.2 and stored separately at -80°C until further analysis. A saline displacement technique was used to measure excised lung volume at 0-cm H2O airway pressure as previously described . Samples were then sonicated twice on ice and centrifuged at 11,000 × g for 10 mins at 4°C. Supernatants were recovered and stored at -80°C for subsequent immunoblotting. Protein concentration of RV lysate was determined using a Bio Rad Protein assay  with bovine serum albumin (BSA) as a standard.Electrophoresis and transfer of proteins to PVDF membranes were done as previously described ,29. GelsFor all data except echocardiographic data, an unpaired Student t-test was performed to detect the difference between Emp and Con animals using SPSS V. 10 for Macintosh . For changes in echocardiographic parameters over time, a general linear model with repeated measures was used. Pearson's correlation coefficient was used to describe the relationship among the echocardiographic variables, hemodynamic data, and gross anatomical measurements. Significance was accepted at p ≤ 0.05 for all tests. All values are expressed as mean ± SD.TJ helped supervise the scientific direction of project, assisted with immunoblots, conducted histology studies, analyzed immublots, histology, myocyte, animal morphometrical data, and drafted the manuscript. EA conducted serial echocardiographs and analysis, and drafted the manuscript. LD did the immunoblots and assisted in data analysis. JA determined myocyte dimensions. SEL helped supervise the scientific direction of the project, assisted with the echocardiographs and analysis, and helped draft the manuscript. JPM conceived of the study, prepared the hamster model, assisted in echocardiographs, and helped draft the manuscript.


Current pacing practice is undergoing continuous and substantial changes. Initially pacing had an exclusively palliative role, since it was reserved for patients developing complete heart block or severe symptomatic bradycardia. With the appearance of novel pacing indications such as pacing for heart failure and atrial fibrillation, the effect of pacing site on cardiac function has become a critically important issue and a subject for consideration. It seems that the classical pacing site in the right ventricular apex is no longer the gold standard because of possible disadvantageous effects on cardiac function. The aim of this review article is to discuss the effect of right ventricular apical pacing on cardiac function including cellular and hemodynamic changes. We also aim to discuss the role of alternative pacing sites in the light of cardiac function. One of the most challenging tasks of modern pacing is to optimise or at least stabilize cardiac performance. This is clearly dependent on the important factors of chronotropic function, the quality of AV synchrony, the ventricular activation sequence and ventricular pacing site. Over the last 40 years stimulation of the right ventricular apex became the standard method for pacing the ventricles because it is a stable and easily accessible site, and usually provides appropriate sensing and threshold parameters ,2. AlthoThe aim of this review is to provide insights into understanding how the pacing site may influence cardiac function. This may have an impact on selection of alternative locations for the right ventricular lead when preservation or even improvement of left ventricular function seems to be important for the patient.During ventricular pacing the impulse conduction occurs predominantly through the working myocardium and the normal conduction system is bypassed. During right ventricular pacing the right ventricle is activated first followed by trans-septal activation of the left ventricle, then the remaining part of the left ventricle is activated. The QRS duration is increased, due to a combination of slow trans-septal activation , and delayed activation of the remaining part of the left ventricle . A partiFor many years the attention given to optimising the atrio-ventricular delay during dual chamber pacing has delayed an understanding of the importance of the effect of pacing site on global and regional myocardial function. This is despite the fact that diminished ventricular function during pacing at the right ventricular apex has been known for decades from numerous animal and human studies -10. VentExperimental animal data have also indicated that right ventricular apical pacing may decrease regional myocardial blood flow within the interventricular septum ,15. ProlAcute clinical studies show that atrial pacing with preserved atrio-ventricular conduction and normal intraventricular conduction ensure better pump function at rest and a low pacing rates than DDD pacing with a restricted AV interval . BecausePatients with permanent atrial fibrillation undergoing AV node ablation and VVIR pacemaker implantation are optimal subjects for studying the effect of right ventricular apical pacing on left ventricular function for two reasons. First of all, these patients have no AV conduction, therefore the effect of AV delay does not influence the results; the effect of pacing site on the function could be studied independently. The other obvious reason is related to the concept of tachycardiomyopathy . A relatAs shown in previous trials, pacing of the right ventricular apex  reduces LV function more than pacing the high ventricular septum or at LV sites ,9,38. SiIn conclusion, the ventricular pacing site has a major effect on ventricular function. It influences hemodynamics, initiates cellular changes and alters myocardial perfusion. These changes might result in left ventricular dysfunction in a considerable number of patients. Since the patients who develop dysfunction with pacing cannot be predicted according to our present knowledge, selection of alternative pacing sites, when the preservation and improvement of left ventricular function is important, should be considered during the routine clinical practice.


Fifty-three patients underwent complete clinical history, electrocardiogram, Holter and transthoracic echocardiogram. Forty patients (75%) were in class I/II of the New York Heart Association, and 13 (25%) in class III/IV. Ventricular and supraventricular escape beats were found in 40% and 26.4%, respectively. Holter showed premature ventricular contractions in 32% and sustained ventricular tachycardia in 7.5%. Ventricular noncompaction was an isolated finding in 74% of cases and was associated with other congenital heart disease in 26%. Noncompacted ventricular myocardium involved only left ventricle in 62% of the patients and both ventricles in 38%. The mean ratio of noncompacted to compacted myocardial layers at the site of maximal wall thickness was 3.4 ± 0.87 mm (range 2.2–7.5). The presence of ventricular noncompaction in more than three segments was associated with a functional class greater than II and ventricular arrhythmia with demonstrable statistical significance by χa) Noncompacted cardiomyopathy is a congenital pathological entity that can occur in isolated form or associated with other heart disease and often involves both ventricles. b) A ratio of noncompacted to compacted myocardium greater than 3 and involvement of three or more segments are indicators of poor prognosis. c) Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular noncompaction and establish prognostic factors. XII appear trabeculated or sinusoidal pouches in both cardiac ventricles . One is Isolated noncompaction of the ventricular myocardium was first reported by Chin in 1990 . In thesNoncompacted myocardium can be considered an inherited congenital alformation since the genes responsible for its development have been identified on chromosome 11p15  or as muThe clinical manifestations of noncompacted cardiomyopathy are variable. Patients may be asymptomatic or may demonstrate evidence of congestive heart failure, arrhythmias or systemic emboli ,21,23,24The echocardiogram is the diagnostic procedure of choice, and diagnosis is based on established criteria . ContrasHowever, diagnosis is sometimes overlooked or delayed because this disease is rare and not well-known . This ocVentricular noncompaction involving three or more segments was found in 80% of the cases. Left ventricular apical, inferior and lateral walls were predominantly affected. Ventricular noncompaction was initially reported only in middle and apical portions of the left ventricle. However, in a minority of patients it also affected basal segments. A finding relevant to our series is that patients with a noncompacted:compacted ratio greater than 3 and ventricular noncompaction in three or more segments are in functional class III/IV rather than functional class I/II. For patients in functional class III/IV with ventricular arrhythmia and noncompaction of three or more segments, probability of survival to 9 months was 75%. Probability of survival to 15 months in these patients was 48%  Noncompacted cardiomyopathy is a congenital malformation that can occur as an isolated entity or associated with other pathologies of the heart and can often involve both ventricles.b) A ratio of noncompacted:compacted wall greater than 3 and involvement of three or more segments are signs of poor prognosis associated with greater clinical deterioration  and ventricular arrhythmias.c) Inasmuch as the clinical picture does not provide sufficiently specific evidence to establish the diagnosis, the echocardiogram is the diagnostic cornerstone. It makes it possible to document noncompacted ventricular myocardium and to identify the factors of poor prognosis.


Readers of a certain age may remember Mighty Mouse singing, “Here I come to save the day!” as he raced in to save the innocent from evildoers. Fanciful as his cartoon antics may have seemed at the time (it first aired in the 1950s), the TV show's creators weren't so off the mark. There's still no evidence of superhero behavior in real mice, but in a new study, Timothy E. Holy and Zhongsheng Guo show that mice have a gift for song.Much of what we know about the biology of song and song learning comes from research on songbirds, but birds are difficult subjects for genetic studies. Song commonly figures in courtship rituals among birds, insects, and frogs, but such behavior in mammals had been restricted to whales, bats, and humans. Evidence of similar behavior in the mouse—a long-established genetic model, often referred to as the pocket human—could open whole new avenues of research into the genetic contributions to song and song learning.To a lay person, the vocal stylings of rodents appear restricted to squeaks and chatter. But mouse social encounters prompt many vocalizations; some are audible to humans, such as the distress calls of pups, and some aren't, such as the ultrasonic calls of males presented with females or urine pheromones. Previous studies characterized the situations that prompt these vocalizations, but did not detail their acoustics. In this study, Holy and Guo went beyond the conditions that prompt rodent discourse to focus on the sounds themselves. Far from random patter, male ultrasonic calls contain complex passages with long sequences composed of diverse syllable types. 10.1371/journal.pbio.0030386.sa004.) To bolster this subjective conclusion, the authors then undertook a quantitative analysis of the sounds.The authors used cotton swabs coated with either female mouse urine, male mouse urine, or a combination of the two to elicit the male mouse's ultrasonic sounds, and then recorded their vocal responses. The authors manipulated the recordings to hear the ultrasonics. One approach used a slow playback (at one-sixteenth of the recorded speed), but this distorted the temporal structure of the sounds, and the calls sounded like low, intermittent whistles. The other dropped the pitch to an audible level without interfering with the time sequence—the pitch-shifted recording sounds remarkably like birdsong. —all in keeping with previous reports. To determine whether these frequency jumps, or pitch changes, followed a stereotyped pattern or occurred randomly, the authors first analyzed a set of 750 syllables produced by one mouse in a single 210-second trial. They identified discrete clusters of pitch changes, including two clusters with stereotyped jumps to or from a low frequency, which they called low jumps. Repeating the trial and analysis with 45 different mice produced similar results, indicating that the pitch changes are a universal feature of mouse ultrasonic vocalizations.Liza GrossThese pitch jumps formed three distinct categories, which together with two other techniques—borrowed from previous research in birdsong, speech, and pattern recognition—confirmed that syllables are naturally grouped by their pitch changes. The syllables, in turn, occurred in complex sequences that, in some cases, constituted regularly repeated motifs. Syllables with low jumps were repeated in blocks, and phrases tended to be introduced with syllables containing no pitch jumps at all. Since the mice produced multiple syllable types arranged in regular, repeated time signatures, their vocalizations meet the definition of song. Finally, the authors showed that individual males produced songs distinct from those of other males. “The richness and diversity of mouse song appear to approach that of many songbirds,” Holy and Guo write. And just like songbirds, the mice appear to be singing their own tune. Future studies can begin to unravel the physiological basis and mechanics of ultrasonic mouse song—and perhaps decipher the messages encoded in the notes and melody. —