Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR.Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p < 0.05.There was a significant reduction in right ventricular volumes at 6 months post-ASD closure  and RVEF was significantly increased . There was a significant increase in the left ventricular volumes . However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure . Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant .ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures. Atrial septal defects (ASDs) are the most common congenital cardiac malformation first diagnosed in adults and account for approximately 10% of all congenital heart lesions . PatientSurgical repair of atrial septal defects has previously been shown to have excellent results in both medium and long term studies . In one Many adults with secundum ASDs are now able to have these defects closed percutaneously using septal occluder devices such as with the Amplatzer Septal Occluder (ASO), a self-expanding circular double disc that has a conjoint waist containing polytetrafluoroethylene (PTFE) and a nitinol mesh. This device has become an accepted alternative to surgical repair with studies comparing ASO device closure to surgical closure showing decreased complication rates, shorter hospital stays and greater cost-effectiveness . PercutaCardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. Thus, we sought to use CMR to assess ventricular and atrial volumes directly to document structural changes post-ASD closure.Consecutive patients with secundum atrial septal defects diagnosed on transthoracic and transoesophageal echocardiography with significant left to right shunt (>1.5:1) underwent CMR pre-ASD closure and 6 months post- ASD closure with the Amplatzer Septal Occluder. Only patients in sinus rhythm pre-ASD closure were included.All CMR studies were performed with subjects in the supine position using a 1.5 Tesla MRI scanner  and a phased array surface coil. For the ventricular image set, long-axis reference views were used for positioning 8 to 12 perpendicular ventricular short-axis slices from the level of the mitral valve to the left ventricular apex. Images were obtained during end-expiratory breath-hold (8 to 10 seconds) with retrospectively ECG-gated True-FISP (Fast Imaging with Steady-State Precession) sequences . Ventricular short axis slice thickness was 6 mm with intersection gaps of 4 mm, based on previous published studies . For theVentricular and atrial analyses were performed off-line with a proprietary software program . For the left ventricular (LV) data set, short-axis endocardial and epicardial contours were manually traced in end-diastole (at start of R-wave) and in end-systole . Papillary muscles and trabeculations were excluded from the ventricular volume and were included if contiguous with the myocardial mass. The basal slice was selected as the slice where the blood volume was surrounded by >50% of ventricular myocardium ,16. For A true three-dimensional atrial volume assessment technique was used, in which the endocardial borders were manually traced for both left and right atria in the horizontal long axis (four chamber) views in ventricular end-systole when atrial volume is maximal . BordersAll ASDs were closed with the Amplatzer Septal occluder . Procedures were performed under general anaesthesia with transoesophageal echocardiographic guidance and fluoroscopy. A sizing balloon was used to determine the stretched diameter of the ASD before selection and deployment of ASO device, as previously described . In brieCMR was repeated at 6 months from the time of the ASD closure, with the full dataset obtained to re-assess cardiac volumes and function . Two patients who went on to surgical closure of their ASDs due to size of the defect were excluded from the analysis and one patient did not attend the follow up scan. Follow up CMR studies were obtained in 20 patients.There was a significant reduction in right atrial volumes at 6 months post-ASD closure . Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant .There was a significant reduction in right ventricular volumes at 6 months post-ASD closure  and RVEF was significantly increased . Left ventricular volumes were significantly increased . There was no significant difference in LVEF and LV mass post-ASD closure (See Table Indexed right ventricular volumes (to body surface area) pre-ASD closure were greater than aged-matched controls at baseline , but were not significantly different to aged-matched controls post-ASD closure . Indexed left ventricular volumes and mass were not significantly different to aged-matched controls pre- or post- ASD closure  comparable to that in control subjects at 24 months following closure. However indexed RA area remained greater than in the control group. Decrease in indexed RA area over the first 12 months of follow-up was related to young age at time of closure .Global LV function has been shown to improve after percutaneous ASD closure. In a recent study, myocardial performance index (MPI), a measure of combined systolic and diastolic function  was signVentricular interdependence has been well described in echocardiography studies and highlights the important role of the inter-ventricular septum in RV and LV function. In RV volume overload, the septum bulges into and encroaches on the LV cavity and leads to impairment of LV filling. The right ventricle is also more compliant than the left ventricle so the left ventricle is relatively under filled. The mechanisms for decreased LV performance associated with RV volume overload include the mechanical disadvantage of a non-circular short axis configuration and changes in chamber and myocardial preload .Reduced LV systolic function associated with RV volume overload has been described -44. One Percutaneous device closure of the ASD avoids the confounding factors caused by surgery. In a study of 34 patients, LV ejection fraction obtained by echocardiography improved significantly from 54.9 to 62.1% (P < 0.001) .In our study, left ventricular volumes were reduced as compared to normal values, but increased 6 months post-closure of the ASD. This is similar to a recent study which looked at left ventricular dimensions with CMR post-ASD closure . In addiIn this study, formal assessment of shunt calculation by Qp:Qs was not performed on the baseline CMR studies initially. Therefore, we were unable to assess any relationships between degree of left to right shunting with changes in cardiac volumes after percutaneous ASD closure.Percutaneous ASD closure leads to normalisation of both RV and LV volumes using CMR. With a true volumetric CMR technique, we note that RA volume reduces significantly although the small LA volume reduction was not significant. This may have important implications for future risk of atrial arrhythmogenicity.The authors declare that they have no competing interests.KST participated in the study design, CMR data acquisition, analysis and manuscript preparation. BKD and AC participated in data analysis and manuscript revision. PM and KW were involved in CMR acquisition. MB, MIW, PJD, PS contributed to manuscript revision. SGW conceived the study, supervised the CMR acquisition and revised the manuscript. All authors read and approved the final manuscript.


Severe obesity is associated with an increased risk of coronary artery disease (CAD). Bariatric surgery is an effective procedure for long term weight management as well as reduction of comorbidities. Preoperative evaluation of cardiac operative risk may often be necessary but unfortunately standard imaging techniques are often suboptimal in these subjects. The purpose of this study was to demonstrate the feasibility, safety and utility of transesophageal dobutamine stress echocardiography (TE-DSE) using an adapted accelerated dobutamine infusion protocol in severely obese subjects with comorbidities being evaluated for bariatric surgery for assessing the presence of myocardial ischemia.2] with known or suspected CAD and being evaluated for bariatric surgery were recruited.Subjects with severe obesity [body mass index (BMI) >40 kg/m2 were enrolled in the study and underwent a TE-DSE. The accelerated dobutamine infusion protocol used was well tolerated. Eighteen (90%) subjects reached their target heart rate with a mean intubation time of 13 ± 4 minutes. Mean dobutamine dose was 31.5 ± 9.9 ug/kg/min while mean atropine dose was 0.5 ± 0.3 mg. TE-DSE was well tolerated by all subjects without complications including no significant arrhythmia, hypotension or reduction in blood arterial saturation. Two subjects had abnormal TE-DSE suggestive of myocardial ischemia. All patients underwent bariatric surgery with no documented cardiovascular complications.Twenty subjects (9M/11F), aged 50 ± 8 years (mean ± SD), weighing 141 ± 21 kg and with a BMI of 50 ± 5 kg/mTE-DSE using an accelerated infusion protocol is a safe and well tolerated imaging technique for the evaluation of suspected myocardial ischemia and cardiac operative risk in severely obese patients awaiting bariatric surgery. Moreover, the absence of myocardial ischemia on TE-DSE correlates well with a low operative risk of cardiac event. Severe obesity is associated with multiple comorbidities and an increased risk for coronary artery disease (CAD) since many risk factors for CAD are present in obese patients. Bariatric surgery is probably the most effective procedure for long term weight management as well as reduction of comorbidities in this population . It also2 demonstrated that transesophageal echocardiography is a safe and well tolerated procedure in this population [Transesophageal echocardiography provides superior quality cardiac imaging and transesophageal dobutamine stress echocardiography (TE-DSE) compares favourably with myocardial scintigraphy for the detection of myocardial ischemia in non severely obese patients . A studypulation . Moreovepulation  while a pulation . The pur2) were recruited between March 2006 to June 2007 from the bariatric surgery preoperative evaluation clinic. All patients were considered at high cardiovascular risk because of known CAD or suspected CAD on the basis of an abnormal resting ECG or the presence of at least 2 risk factors for CAD . Exclusion criteria included: recent acute coronary syndrome, uncompensated heart failure, uncontrolled ventricular or supraventricular arrhythmias, oral or oesophageal pathology, uncontrolled systemic hypertension or significant valvular heart disease. Twenty patients underwent a TE-DSE. Beta-blockers were stopped 48 hours before the stress test. The study was approved by the local hospital ethics committee in accordance with the Helsinki declaration and subjects gave signed informed consent.Twenty severely obese patients  using a multiplane probe. Antianginal medications were discontinued for at least 24 hours prior the study. Studies were performed after an overnight fast with patients in the left lateral decubitus position. Topical oropharyngeal anesthetic spray was used and light sedation was achieved with the use of intravenous midazolam  or diazepam  before the introduction of the transesophageal probe. All patients received supplemental oxygen through nasal prongs. Oxygen saturation was continuously monitored throughout the procedure using pulse oxymetry. A continuous 12-lead electrocardiogram monitored for arrhythmias or ST-segment modifications suggestive of myocardial ischemia. Blood pressure was measured non-invasively every 3 minutes throughout the procedure.Dobutamine was intravenously infused using an accelerated protocol with a starting dose of 10 ug/kg/min and increased every 2 minutes to 20, 30 and 40 ug/kg/min. Atropine sulphate was given intravenously in increments of 0.2 mg from the second stage of the dobutamine infusion (20 ug/kg/min) until 85% of the maximal heart rate (i.e. 220-age) was reached or up to a maximum of 1 mg. Images were obtained at each stage in the following sequence: 1) midesophageal four-chamber view at 0°, 2) midesophageal two-chamber view at 60°, 3) midesophageal three-chamber view at 120° and, 4) transgastric midpapillary short-axis view at 0°  but the majority of subjects (74%) had a least 3 risk factors for CAD and an abnormal metabolic profile (Table The accelerated dobutamine infusion protocol used was well tolerated. Eighteen (90%) subjects reached their target heart rate with a mean intubation time of 13 ± 4 minutes. Mean dobutamine dose was 31.5 ± 9.9 ug/kg/min while mean atropine dose was 0.5 ± 0.3 mg. Twenty patients  with a mean age of 50 ± 8 years and mean BMI of 50 ± 5 kg/mTE-DSE was well tolerated by all subjects with no complications including no significant arrhythmia, hypotension or reduction in blood arterial saturation. No patient develops clinical pneumonia-induced aspiration. Sedatives were administered to ensure subject's comfort (midazolam 10 ± 7 mg or diazepam 15 ± 6 mg). Seventeen patients (85%) required atropine to reach their target heart rate. Only 7 subjects (35%) had adequate transgastric images for the evaluation of left ventricular wall motion but transesophageal images were of diagnostic quality in all patients. At peak dose, 3 subjects complained of symptoms suggestive of myocardial ischemia. One patient developed ECG changes suggestive of myocardial ischemia (ST segment depression ≥ 1 mm) and 2 patients had new left ventricular wall motion abnormalities compatible with myocardial ischemia (hypokinesia)  was estimated at 23.9% in 2005 with approximately 4.8% considered to be severely obese (BMI > 40 kg/m2) [2 [Obesity has become an epidemic condition around the world and is associated with increased risk of CAD and risk factors for CAD  ,14. In tg/m2) [2 . Bariatrg/m2) [2 . Moreoveg/m2) [2 . Preoperg/m2) [2 . Also, eg/m2) [2 . Thus, c2) with 323 nonobese subjects, Garimella et al showed that the frequency of complications did not differ between both groups. Oxygen desaturation was infrequent when supplemental oxygen was used [2) with suspected CAD were not significantly different from those of nonobese individuals [2) and the use of large doses of sedatives, there were no complications including no significant hypotension or oxygen desaturation reinforcing the safety of TE-DSE in severely obese subjects. Only 35% of our subjects had adequate transgastric imaging. We propose that severe abdominal obesity might displace the stomach in a more anterior position resulting in altered probe contact. In fact, in a previous study of TE-DSE in nonobese subjects, 8% of patients had poor transgastric echocardiographic images related to the presence of hiatal hernia or gastroesophageal disease [Obese patients have a higher prevalence of systemic hypertension, CAD, and sleep apnea which could potentially increase the risk of complications during transoesophageal echocardiography. Also higher doses of sedatives are often necessary in this population which could further increase the risk of complications, including oxygen desaturation. In a study comparing transesophageal echocardiography in 341 obese subjects  results with positron emission tomography (PET), discordance was encountered with greater frequency in obese patients, mostly in the territories supplied by left anterior descending or right coronary arteries, as a result of more prominent attenuation artefacts [Assuming equal technical competence, the debate persists regarding which imaging modality between stress echocardiography and stress myocardial perfusion imaging is the most accurate for the diagnosis of CAD. In nonobese populations, TE-DSE has showed to be a useful technique in the evaluation of CAD with a sensitivity of 82 to 92% and a specificity of 93% when compared with coronary angiography ,20. In prtefacts . In a strtefacts . This coThere are some limitations inherent to our study. Without information on coronary arterial wall and lumen, for example by means of intravascular ultrasound or quantitative coronary angiography, it is speculative to comment on the accuracy of TE-DSE regarding the presence of clinically significant CAD in these patients (namely 50% stenosis on coronary angiography). At the very least, a larger study including more patients with coronary angiography should be performed before we can conclude on the validity of TE-DSE for the diagnosis of CAD in patients with severe obesity. Also since this study included only 20 patients, a larger study should be performed to assess and confirm the safety of this accelerated protocol of TE-DSE before its wide implantation in clinical practice.In conclusion, TE-DSE with an accelerated protocol is a safe and well tolerated imaging technique for the evaluation of suspected myocardial ischemia and cardiac operative risk in severely obese patients awaiting bariatric surgery. Moreover, the absence of myocardial ischemia on TE-DSE correlates well with a low operative risk of cardiac event.The authors declare that they have no competing interests.PP conceived the study, participated in its design and coordination and helped to draft the manuscript, he also performed statistical analysis. SL and MS participated in the design of the study, participated in the interpretation of the results and manuscript drafting. SB, MS, and MA performed TE-DSE measurements, participated in data collection, plots and calculations from ultrasound data. MT and JG participated in data collection and in the preparation of the manuscript. All authors read and approved the final manuscript.Video1 Rest 2 chamber. 2 chamber view TE-DSE (rest).Click here for fileVideo2 30 mg 2 chamber. 2 chamber view TE-DSE (30 mg).Click here for fileVideo3 Rest 3 chamber. 3 chamber view TE-DSE (rest).Click here for fileVideo4 30 mg 3 chamber. 3 chamber view TE-DSE (30 mg).Click here for fileVideo5 Rest 4 chamber. 4 chamber view TE-DSE (rest).Click here for fileVideo6 30 mg 4 chamber. 4 chamber view TE-DSE (30 mg).Click here for fileVideo7 Rest short axis. short axis view TE-DSE (rest).Click here for fileVideo8 30 mg short axis. short axis view TE-DSE (30 mg).Click here for file


Cardiovascular magnetic resonance (CMR) is currently the gold standard for assessing both global and regional myocardial function. New tools for quantifying regional function have been recently developed to characterize early myocardial dysfunction in order to improve the identification and management of individuals at risk for heart failure. Of particular interest is CMR myocardial tagging, a non-invasive technique for assessing regional function that provides a detailed and comprehensive examination of intra-myocardial motion and deformation. Given the current advances in gradient technology, image reconstruction techniques, and data analysis algorithms, CMR myocardial tagging has become the reference modality for evaluating multidimensional strain evolution in the human heart. This review presents an in depth discussion on the current clinical applications of CMR myocardial tagging and the increasingly important role of this technique for assessing subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes. Heart failure (HF) is the result of advanced myocardial dysfunction and continues to be a leading cause of morbidity and mortality in developed nations. In the United States alone, an estimated 5.3 million adults carry the diagnosis of HF and the disease prevalence continues to escalate with aging of the population. In addition to conferring a significant burden of illness to affected individuals, management of HF also imposes enormous expense to the health care system . TherefoTo this end, some of the most promising approaches to improved risk stratification involve using imaging modalities to detect early myocardial dysfunction. Assessment of global ventricular function - and its reduced indices, such as ejection fraction, are clearly strong predictors of future HF and poor prognosis. However, global measures are insensitive to reductions in regional performance, where even a normal ejection fraction can obscure significant underlying regional dysfunction. Thus, measures of regional function, such as quantification of myocardial strain and torsion, have emerged as more accurate tools for defining degrees of myocardial disease. Abnormalities in these measures of regional function can also serve as a more specific marker of subclinical myocardial dysfunction. Several techniques have been used to quantify regional myocardial function. Nuclear techniques  can provCurrently, cardiovascular magnetic resonance (CMR) tagging remains the reference standard for assessment of regional function . It remaQuantifying regional myocardial function, or regional deformation, originally required invasive surgical implantation of physical markers within the myocardium itself and then tracking their motion using external imaging. However, this method is impractical for clinical application and implanted markers tend to influence cardiac motion and thus distort the accuracy of measurements . In 1988See additional file Movie 1 demonstrating myocardial tagging covering the cardiac cycle. However, fading of the tag lines close to end-diastole, as a result of T1 tissue relaxation, has limited its application to the systolic part of the cardiac cycle. Although spoiled gradient echo imaging is the commonly used sequence for tag generation at the widely available 1.5T magnets, recent studies [Initially designed to analyze myocardial contraction during systole, tags are typically created upon detection of the QRS complex of the electrocardiogram (ECG). The resulting tags then follow myocardial motion during the cardiac cycle, thus reflecting the underlying myocardial deformation Figure . See add studies ,11 have  studies . ProvidiIn addition, current advances in gradient technology and acquisition techniques have greatly improved tagging temporal resolution. Currently, the most widely feasible temporal resolution is on the order of 15 - 20 msec, which is sufficient to detect peak systolic strain, the most extensively reported value in most clinical settings. However, a high temporal resolution actually becomes a critical issue especially when studying specific phases of the cardiac cycle that are characterized by rapid cardiac motion like the early diastolic filling phase in diastolic dysfunction, the early systolic emptying phase in conduction abnormalities as well as stress induced wall motion abnormalities . RecentlSee additional file cc)Movie 2 demonstrating color coded strain analysis of the tagged left ventricle using HARP; x-coordinate represents time frames, y-coordinate represents percent circumferential shortening  differential optical flow-based methods that track motion by assessment of the temporal and spatial changes of image intensity; b) tag segmentation methods based on tracking of tag lines as in Findtags  and SPAMWith the rising interest in computing 3D myocardial deformation maps, several techniques based on CMR tagging have been developed to quantify 3D strain through the acquisition of multiple orthogonal slices covering the whole volume of interest. The proposed methods used various 3D model-based approaches to reconstruct the 3D motion of the left ventricle (LV) from tagging images ,20-22. HWithin the LV, the myofiber arrangement changes gradually from a right-handed helix in the subendocardium to a left-handed helix in the subepicardium, passing by a circumferential arrangement in the mid wall. Such complex fiber architecture results in complex patterns of deformation and changes in shape that are produced upon muscle contraction or relaxation . TaggingLo is the original fiber length before tag deformation and L is the current length.Each element of strain is, simply, a measurement of the fractional or the percent change of length in a specific direction where ECC) describes circumferential shortening in the short axis plane in a direction tangential to the epicardial surface; radial strain (ERR) describes myocardial thickening in a radial direction towards the center of the ventricle; and, longitudinal strain (ELL) represents base to apical shortening along the ventricular long axis. The RCL coordinate system is based on the cardiac geometry and, thus, is more convenient for clinical purposes [In 3D space, myocardial strain can be represented by two different coordinate systems: 1) The radial-fiber-crossfiber coordinate system, which is based on the fiber direction within the myocardial tissue and thus, requires a precise knowledge of fiber orientation angles , and 2) purposes .ECC, ERR, and ELL represent the normal strain elements of myocardial deformation in 3D space, whereas ERC, ERL, and ECL represent strain changes that occur in a plane between two of these three initially orthogonal normal directions known as shear strains [ECL, represents the shear in the circumferential - longitudinal plane and is usually referred to as torsion  E2, the minimum principal strain, represents the greatest shortening; and, 3) E3 represents the strain occurring perpendicular to E1 and E2 Principal strains have been used in tagging studies [α represents the angle between E2 and ECC; β represents the angle between E1 and ERR [Principal strains represent the maximum and minimum deformation occurring at a point in three orthogonal directions irrespective of cardiac geometry 1)  studies  and have and ERR .Strain rate (SR) represents the time derivative of strain values or, in other words, strain changes per unit time. Strain rate is calculated by taking the change in strain (S) between two time frames and dividing this by the time (t) difference between these two frames:Using strain rate analysis for evaluation of LV diastolic function, Edvardsen et al. , revealeDuring the systolic phase of each cardiac cycle, the contracting myofibers exert a wringing motion that assists in ejecting blood from the LV . This wrECC) is the most frequently computed parameter for quantifying regional function. This particular strain measure is favored, in part, due to myocardial geometry contributing an abundance of tagging data around the mid wall myocardial circumference compared to along the width of radial wall thickness [ECC data less sensitive to noise and more suitable for assessing the transmural strain gradient. In the normal heart, circumferential strain increases gradually from the base towards the apex. With respect to transverse regions, the greatest shortening is consistently observed in the anterior and lateral myocardial segments with the least deformation seen in the inferior wall. Additionally, ECC is seen to increase from epicardium towards endocardium. [Mid wall LV circumferential strain (hickness . This macardium. -36.ELL) has also been measured in multiple studies [ECC, ELL shows a transmural pattern that increases from epicardium to endocardium. Maximum radial strain (ERR), on the other hand, shows a degree of disparity in its reported values with no consistent pattern across different studies [ERR at the base particularly at the lateral segment, whereas Moore et al. [ERR increasing from base to apex. However, endocardial ERR was consistently higher than epicardial ERR Congruent with the general pattern of almost all other measures, maximum torsion angle also increases across the LV wall from epicardium towards the endocardium as well as from the base toward the apex in the normal heart.Maximum longitudinal LV strain . Using 2D displacement data from tagging to examine differences in the transmural distribution of myocardial shortening, Lumens et al. [When referring to expected normal patterns of regional myocardial deformation, consideration should always be made for the effects of aging. Fonseca et al.  and Oxens et al.  further ECC in the left anterior descending and right coronary territories, with dose dependent effect seen between LV function and smoking [p < 0.001). This finding remained significant even in the setting of preserved regional systolic function [Many individuals with underlying coronary artery disease are asymptomatic and go unnoticed before they present with major coronary events. Since atherosclerosis is the most important primary etiologic factor predisposing to the development of HF, the Multi-ethnic Study of Atherosclerosis (MESA) was initiated in 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease in a community-based population of 6,500 men and women of different racial/ethnic backgrounds. Harmonic phase analysis of myocardial tagged images proved highly reproducible in MESA for detecting silent myocardial dysfunction in asymptomatic populations . Using C smoking . With refunction , supportECC and its strain rate in the corresponding coronary territory, suggesting a link between coronary atherosclerosis and incipient regional dysfunction [ECC) among individuals free of known cardiovascular disease [p < 0.05) except in the inferior wall. In addition, greater IMT was associated with a lower diastolic strain rate, representing reduced diastolic function, in all regions (p < 0.01) except the anterior wall.Beyond their association with cardiovascular risk factors, changes in regional myocardial function also correlated with more specific markers of subclinical atherosclerosis in MESA. Coronary artery calcification burden, quantified by computed tomography, was related to reduced regional function . Increas disease ,46. In pGiven the strong association between regional myocardial dysfunction and markers of prevalent coronary disease, multiple studies have used tagging to further explore its relation with myocardial ischemia. Rosen et al.  examinedA particularly useful feature offered by myocardial tagging is its ability to provide a detailed assessment of contractile reserve in the setting of ischemia. Myocardial tagging, either independently or combined with the findings of gadolinium enhanced CMR, can also assess and predict the extent of functional recovery after successful reperfusion of a transmural myocardial infarction ,49. As wWhen comparing qualitative assessment of myocardial contractile reserve by CMR tissue tagging versus echocardiography, CMR had a similar sensitivity (82% versus 86%) but lower specificity (69% versus 87%). Overall accuracy was 76% for CMR and 85% for echo . Lower CIn addition to assessing contractile reserve in the setting of ischemia, myocardial tagging has made it possible for investigators to elucidate the mechanisms related to post-infarct ventricular remodeling. In particular, myocardial tagging is able to define changes in regional function involving the infarcted myocardium versus areas remote from the infarcted myocardium Figure . In the Non-ischemic dilated cardiomyopathies (DCM) are characterized by ventricular eccentric remodeling, increased ventricular volume, and globally reduced ventricular function. In a cohort of 13 DCM patients, Young et al. [p < 0.02 pre vs. post). Kanzaki et al. [p < 0.05) and apex , whereas the timing of peak rotation was earlier . Systolic torsion was characterized by a discontinuing counter rotation of the apex with respect to the base before end-systole. In addition, amplitude of peak systolic torsion was impaired in proportion to the degree of LV dysfunction. In a trial to assess cardiac mechanics and clinical outcome of PLV, 24 DCM patients underwent CMR tagging studies before and then 3 and 12 months after PLV. Circumferential LV shortening at three short axis levels was increased at both post-surgical time points. Thus, using these and similar methods, CMR tagging can serve as a useful tool for assessing the efficacy of various surgical as well as non-surgical interventions for DCM [g et al.  quantifii et al.  studied  for DCM .Hypertrophic cardiomyopathy (HCM) is the most frequently occurring genetic cardiomyopathy responsible for sudden cardiac death in young trained athletes. Underlying histological changes include myofibrillar disarray and abnormal intramural coronary vasculature [p < 0.01). Changes in myocardial contractility in the non-hypertrophied regions of HCM have been a subject of controversy. Therefore, to assess regional function in these non-hypertrophied regions, Mishiro et al. [ECC during systole and diastole in 8 HCM patients and 6 normal volunteers. In HCM patients, total systolic strains were reduced in the septal and inferior regions (p < 0.01 for both). On the other hand, early diastolic strain rates were significantly reduced in all regions, indicating slow and impaired filling function in HCM cases relative to controls.culature . While sculature  and Dongculature  observedo et al.  examinedo et al.  comparedp < 0.01), whereas a weak but significant correlation was detected between delayed enhancement and hypokinetic segments. Recently, Kim et al. [ECC was more substantially reduced in the regions displaying focal nodular enhancement patterns rather than in patchy enhanced regions.Myocardial tagging has also been used to explore the relation of regional dysfunction with areas of abnormal myocardial perfusion in HCM. In a prospective trial including 53 patients, Soler et al.  found gom et al.  demonstrMuscular dystrophies are a group of inherited diseases involving primarily the skeletal muscle leading to degeneration and progressive weakness. Cardiac involvement is not infrequent and can manifest as cardiomyopathy, conduction defects, and sudden death. In a study conducted by Ashford et al. [d et al. , regionaonset) and time to peak contraction (Tpeak) between the septum and lateral wall can be easily derived from all segments in a given cross section [Cardiac resynchronization therapy (CRT) is the treatment of choice for management of patients with ventricular dyssynchrony . Despite section ,38. Simi section . Moreove section -74 and e section  and pred section . Future Right ventricular (RV) function plays a pivotal prognostic role in a wide variety of diseases involving the heart as well as the lung. Thus, the application of CMR tagging has been extended to include assessments of RV regional function. It should be noted, however, that there are several technical challenges involved in applying CMR tagging analyses to the RV. For example, the very thin wall (<5 mm) of the normal RV offers less than the minimum optimal tag spacing (≥6 mm) and therefore limits the number of tag stripes that would be required for accurate quantification . NonetheIn light of the challenges associated with applying CMR tagging to the RV, several novel approaches have been developed. Using measures of percent segmental shortening, Klien et al.  observedIn conclusion, CMR tissue tagging is a powerful non-invasive diagnostic tool for quantifying regional systolic and diastolic myocardial function. Owing to the inherent features of CMR tissue characterization and its multiplanar capabilities, CMR tagging is able to reveal previously undetected components of regional myocardial mechanical function and, thus, aid in the early detection and management of a wide range of myocardial disease processes. Moreover, ongoing developments in the technology, imaging techniques, and analytical tools used to implement CMR tagging will likely further advance current capabilities for performing sophisticated analyses of regional myocardial function. As such, myocardial tagging promises to continue to enhance our understanding of the mechanical complexities underlying the function of the normal and pathological heartDr Nael F. Osman is a founder and shareholder in Diagnosoft Inc. The terms of this arrangement have been approved by the Johns Hopkins University in accordance with its conflict of interest policies.MS and SC drafted the initial review article, MS performed the literature search, NO, DB and JL participated in the article organization, editing and final drafting of the manuscript. All authors read and approved the final manuscript.CMR: cardiovascular magnetic resonance; HF: heart failure; SPAMM: spatial modulation of magnetization; CSPAMM: complementary spatial modulation of magnetization; ECG: electrocardiogram; SSFP: steady state free precession; CNR: contrast to noise ratio; SNR: signal to noise ratio; 2D: Two dimensional; 3D: three dimensional; HARP: harmonic Phase; LV: left ventricle; RV: right ventricle; SR: strain rate; MESA: multi-ethnic study of atherosclerosis; IMT: intima-media thickness; PLV: partial left ventriculotomy; DCM: dilated cardiomyopathy; HCM: hypertrophic cardiomyopathy; CRT: cardiac resynchronization therapy.Movie 1. Demonstrating myocardial tagging covering the cardiac cycleClick here for fileMovie 2. Demonstrating color coded strain analysis of the tagged left ventricle using HARP; x-coordinate represents time frames, y-coordinate represents percent circumferential shortening (% Ecc)Click here for fileMovie 3. Original data usedClick here for file


Diabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels  and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.We enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 , TNF-alpha  and NT-pro- BNP  plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6  and TNF-alpha  remained significantly elevated in subjects with E/Em ratio ≥ 15.This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction. Diastolic heart failure and diabetes mellitus (DM) are contributors to mortality, hospitalization and medical costs in health care systems worldwide. Cardiovascular disease is the leading course of death among subjects with diabetes, accounting for over 60% of mortality. While DM is uniformly recognized as an important risk factor for the development of coronary artery disease and its complications, it is less well acknowledged that DM is a powerful and independent risk factor for the development and prognosis of heart failure independent of coronary artery disease (CAD) . Left veThere is increasing evidence that inflammation is involved in the pathophysiology of heart failure and diabetes -9. Most Little information is available about whether inflammation is involved in the development of LVDD as the earliest stage in the development of heart failure.Advantages in echocardiographic techniques have made it possible to comprehensively access LV diastolic function . Tissue This study was designed to explore the possible association between LVDD and proinflammation reflected by IL-6 and TNF-α levels in subjects with stable coronary artery disease.The present study is a substudy of a larger survey in which we investigated the relationship between diastolic dysfunction and cardiovascular autonomic neuropathy in 150 patients submitted for coronary angiography.41 subjects submitted for coronary angiography for stable or suspected coronary artery disease (CAD) were consecutively enrolled in this substudy. The protocol was approved by the local ethics committee, and signed informed consent was obtained from all patients. We excluded patients with hypertrophic obstructive cardiomyopathy, moderate-to-severe valvular disease, uncontrolled hypertension, atrial fibrillation or other severe arrhythmias. Oral glucose tolerance tests (OGTTs) were carried out according to the World Health Organization protocol as previously described. Echocardiography for the diagnosis of diastolic dysfunction was performed on a Philips IE33 Ultrasound System machine. Conventional transmitral flow was measured with pw-doppler. Early (E), atrial (A) transmitral peak flow velocities and the ratio (E/A) were measured. Pulsed wave TDI was performed at the junction of the LV wall with the medial mitral annulus end-expiratory. Early diastolic velocity (Em) was recorded. Ratio of E/Em was calculated. The E/Em ratio was used to classify LVDD. LVDD was defined as E/Em ratio ≥ 15, borderline diastolic function as E/Em between 8-14 and normal diastolic function as E/Em < 8 according to the guidelines of the ASE [®).Interleukin-6 and TNF-α were measured with high-sensitivity enzyme linked immunoassay . NT-pro Autonomic nervous function was assessed according to the guidelines of German diabetes association. Spectral analysis with Fourier transformation was performed. Therefore a commercially computer program (VariaCardio TF4-System) was used. The following tests were performed: (1) coefficient of variation of R-R intervals at rest, (2) spectral power in the very-low-frequency band, (3) spectral power in the LF band, (4) HRV during deep breathing, (5) maximum/minimum 30:15 ratio, (6) valsalva ratio, (7) postural change in systolic blood pressure. CAN is defined as the presence of ≥ 3 abnormalities among these 7 parameters.p value ≤ 0.05 was considered statistically significant. Comparison among the 2 groups of subjects for various parameters was performed by 1-way analysis of variance (ANOVA or t-test) when appropriate. Pearson's linear correlation coefficients were calculated for pairs of continuous variables, Spearman's correlations coefficient was used when data were not normally distributed. We first analyzed associations without any adjustments and then with adjustments for potential confounders by multiple linear regression for continuous and logistic regression for categorical variables.All analyses were performed using SPSS statistical software . The data are presented as mean +- SD unless otherwise specified. A The demographic variables of subjects with normal, borderline and increased E/Em ratio are shown in Figure In subjects without DM, an oGTT was performed. 21 (29%) of patients enrolled in the study had a history of diabetes. The oGTT showed impaired fasting glucose (IGT) or new detected Diabetes (NDM) in 32 (63%) of the included patients, only 11 (27%) of subjects enrolled in the study had normal glucose metabolism (NGT). In subjects with E/Em ratio ≥ 15, no patient was found with NGT. 16,7% had IGT or NDM and 66,7% known diabetes, respectively. Fasting glucose was 111 mg/dl in subjects with E/Em ratio ≥ 15 vs. 92 mg/dl and 90 mg/dl in those with borderline or normal E/Em ratio , whereas HbA1c was 6,9%, 6,2% and 6,1%, respectively .The mean Em velocity was 8,4 cm/s in subjects with E/Em ratio < 8, 7,0 cm/s in those with E/Em ratio 8-15 and 5,3 cm/s in those with E/Em ratio ≥ 15, respectively.and E/Em ratio was positively correlated with TNF-α levels . In the post-hoc analysis, patients with E/Em ratio > 15, classified as LVDD, had significantly higher IL-6 , TNF-α  compared to those with normal diastolic function  was found in 22% of the study group. Although statistically not significant, 60% of subjects with diastolic dysfunction defined as E/Em ratio ≥ 15 were found CAN+, whereas only 9% of subjects with normal left ventricular diastolic function were CAN+. In the subgroup with borderline diastolic function, 20% were diagnosed as CAN+. Of note, in patients CAN+, IL6 levels were significantly higher than in those CAN- . Although statistically not significant, TNF-α levels were also numerical higher .NT-pro-BNP levels were significantly higher in those with E/Em ratio > 15 compared to those with borderline E/Em ratio or normal diastolic function . In diabetics, NT-pro- BNP levels were 608 pg/ml vs. 229 pg/ml in non diabetics .We were able to demonstrate that LVDD and proinflammatory cytokines are associated in subjects with normal left ventricular systolic function. In particular increased plasma levels TNF-α and IL-6 seem to be correlated with impaired LVDD and more advanced left ventricular diastolic dysfunction. These data provide clinically important information on systemic immune abnormalities in subjects with LVDD. The Framingham Heart Study was the first to demonstrate an increased risk of heart failure in patients with diabetes . Since tIt has been demonstrated that IL-6 shows cardiodepressive properties . In patiProinflammatory cytokines are capable of modulating cardiovascular function by various mechanisms. It is now known that virtually every nucleated cell type in the myocardium, including the cardiac myocyte, is able to secrete proinflammatory cytokines in response to various myocardial damage or stressors. The expression of these cytokines can occur in absence of systemic immune activation.They partly act in a negative inotropic manner and cause changes in turnover of the extracellular matrix resulting in myocardial fibrosis. The proinflammatory cytokine TNF-α induces cardiodepressive effects and causes apoptosis . The devThere are some limitations in the present study. The consensus paper of the ESC  deals wiMoreover, we did not measure LA volume index and pulmonary vein velocities. These additional echo data might have been of interest especially in the cohort with E/Em ratio 8-14.Our study shows for the first time, to the best of our knowledge, a relationship between proinflammatory cytokines and abnormalities of diastolic performance in patients without clinical heart failure. The development of diastolic dysfunction and its possible sequelae diabetic cardiomyopathy is likely to be multifactorial, with putative mechanism including metabolic disturbances, insulin resistance, myocardial fibrosis, endothelial dysfunction, autonomic dysfunction and myocyte damage. Proinflammatory cytokines are involved in most if not all of these pathophysiological changes and might be a link between these abnormalities. At present, it is not clear which mechanism can explain the association between diastolic abnormalities and IL-6 and TNF-α-levels. The relationship between LV diastolic performance and the activation of immunoinflammatory system should be studied more thoroughly in the future both on experimental and clinical grounds.The authors declare that they have no competing interests.WD conceived of the study, participated in the study and drafted the manuscript and performed statistical analysis. RF participated in echocardiographic studies and participated in the study design of the study. LB participated in echocardiographic studies. AB participated in echocardiographic study. WN carried out the plasma analysis of IL6, TNF-α and BNP. TK carried out the plasma analysis of IL6, TNF-α and BNP. PE carried out the plasma analysis of IL6, TNF-α and biomarkers. TS participated in the study design of the study and performed statistical analysis. MCB participated in echocardiographic studies. ML participated in the study design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.


Miyoshi myopathy (MM) is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR).Five consecutive MM patients  in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique.All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS) was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects . Four patients showed fibrosis by LGE. The reduced PSLS lesion detected by 2D strain tended to be in the same area as that which showed fibrosis by LGE.Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up. DYSF) gene resulting in severe to complete deficiency of dysferlin expression[Miyoshi Myopathy (MM) is a distinct form of muscular dystrophy caused by mutations within the dysferlin  in whom a DYSF gene mutation and distal myopathy was documented gave written informed consent. Five healthy subjects (mean age 43.8 ± 12.7 years) were enrolled as age-matched controls. The institutional review board of the Samsung Medical Center approved this study. The recommendations of the revised version of the Declaration of Helsinki were met. Cardiac involvement was investigated with conventional methods using standard 12-channel surface-electrocardiography (ECG), transthoracic echocardiography, and CMR.Transthoracic echocardiograms were performed with a commercially available echocardiographic instrument . A standard comprehensive M-mode, 2-D echocardiogram and echocardiographic Doppler studies were performed. Examinations included measurements of left ventricular (LV) volume and ejection fraction (EF), using the biplane disc method, and the left atrial volume index. All measurements were made according to the recommendations of the American Society of Echocardiography. Mitral inflow was obtained by pulsed-wave Doppler echocardiography, with the sample volume between mitral leaflet tips during diastole, and mitral annulus velocities were obtained from the septal and lateral annulus by tissue Doppler imaging. All measurements were performed over three cardiac cycles and then averaged.Global LV longitudinal strain was assessed using the automated function imaging (AFI) technique, which provides a new imaging modality based on 2-dimensional longitudinal strain imaging-7. LongiAll patients were scanned using a 1.5-T scanner . Criteria for exclusion from the study included generally accepted contraindication to CMR, but no patient had to be excluded. CMR focused on the detection of fibrosis (LGE). Volumetric evaluation of LV mass, volume, and EF by manual tracing were performed. Various pulse sequences were used for imaging. ECG-gated double inversion-recovery images (TE = 10 ms), triple inversion-recovery images (TE = 100 msec), transverse or short-axial breath-hold cine MR images  were usually obtained before contrast injection. After injection of contrast material , post injection images were obtained using late myocardial imaging  with suppression of the normal myocardial signals 5, 10, and 15 minutes later. A Look-Locker sequence was applied to determine optimal inversion time for myocardial nulling before delayed myocardial imaging in every instance.Data are reported as mean ± standard deviation. We used unpaired 2-sided t test to assess differences between groups (patients with MM vs controls) for normally distributed continous data. Parametric Man-Whitey test were used if data were nor normally distributed. All analyses were performed using commercially available software  and a p value < 0.05 was considered significant.The history, laboratory, and clinical data of the patients are shown in Table All patients were in sinus rhythm. Left ventricular hypertrophy (LVH) was present in two patients (patients #2 and #4). In patient #2, left anterior fascicular block was also detected.The data from standard echocardiography are summarized in Table Table There were no difference between patients with MM and age-matched healthy controls regarding age, sex, blood pressure, and heart rate. Echocardiographic parameters, including LVEDD, LVESD, LVEF, E, A, E/A ratio, E', and E/E' ratio were not significantly different between MM patients and control subjects. For 2D strain parameters, global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum PSLS, basal inferior septum PSLS, mid anterior PSLS, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects   is an autosomal recessive distal myopathy characterized by early adult onset. MM is believed to spare the heart. However, recently, few case of cardiac involvement in MM reported. In our study, subclinical cardiac involvement was detected by 2D stain and LGE. Although most of patients had preserved LVEF, segmental PSLS was decreased in three patients by 2D strain and fibrosis was shown in four patients by LGE. In patient #1, there was discrepancy the abnormality between 2D strain and LGE. 2D strain was decreased in the basal to mid inferolateral area, but there were fibrosis in mid anterolateral area in LGE. In patient #2, segmental PSLS was decreased in the basal to mid anterolateral wall and there was focal fibrosis in same area. In patient #3, 2D strain and LGE were normal. In patient #4, 2D strain was decreased in inferior and basal anteroseptal area and there were fibrosis in inferior and mid wall basal anteroseptal area. Particularly in patient #4, it is reasonable that the abnormal results in the inferior area could be related to ischemic heart disease. Cardiac CT angiography showed non-significant stenosis (about 40%) in the right coronary artery. Considering the result of cardiac CT angiography, abnormality of the anteroseptal area was not be related to ischemic heart disease. The reduced PSLS detected by 2D strain tended to be in the same area as that which showed fibrosis in LGE in patient #2 and #4 among 5 patients. In patient #5, there was only focal septal fibrosis in LGE with normal 2D strain. It seems like nonspecific septal fibrosis in patient #5.Myocardial strain imaging is useful for quantitative assessment of regional wall motion of the left ventricle. In our study, myocardial strain profile in MM patients with apparently normal 2-dimensional echocardiography were abnormal. Myocardial strain abnormalities are prevalent MM patients despite normal EF. Therefore, abnormal strain value would be early indicators of abnormal cardiac function in MM. Detection of such strain abnormalities might allow a better identification of MM cardiac dysfunction and might provide useful surrogate index to assess therapeutic efficacy. MM patients should be carefully evaluated for cardiac involvement using by conventional echocardiography, 2D strain and/or CMR. Any cardiac dysfunction should be promptly treated according to current guidelines. If the treatment were effective, decreased cardiac strain profile might be improved in follow up study. Further studies with long-term follow-up with a larger patient population are needed to determine the role of myocardial strain in preclinical diagnosis of myocardial impairment in MM. In other myopathies, such as Duchenne muscular dystrophy (DMD), patients with normal LV function showed myocardial strain profiles at the posterolateral wall of the LV that were different from those in healthy controls, suggesting abnormal myocardial contraction . An earlet al [et al [CMR has better sensitivity and could be used to assess ventricular size and function as well as to evaluate the characteristics of myocardial tissue. Specifically, LGE is used to evaluate myocardial fibrosis, which is present in dystrophinopathy patients. Silva et al  demonstrl [et al  demonstrl [et al ,12.The impact of subclinical cardiac involvement in MM remains to be assessed. Importantly, most MM patients may remain asymptomatic for years in spite of the progression of cardiac dysfunction because of their limited daily activities. Early detection of latent myocardial involvement before heart failure symptoms appear would be beneficial for delaying the progression of heart failure in MM. Therefore, follow-up is required. The findings of 2D strain and LGE are almost identical in MM patients. Thus, 2D strain and LGE could suggest subclinical early cardiac involvement and could be a noninvasive diagnostic screening test for evaluation of cardiac involvement in MM patients. Early recognition of cardiac involvement in MM is warranted, because adequate and appropriate therapy influences the further management and disease course of patients with primary myopathies .There are several limitations to our study. First, our sample size was small. Although additional studies would be necessary to establish further the cardiac involvement in MM, the rarity of the disease may preclude a large-scale trial. Second, both of patient #2 and #4 had a history of hypertension and diabetes mellitus (DM). The durations of DM for patients #2 and #4 were 10 years and 22 years, respectively. It is possible that the cardiac involvement is not associated with the primary myopathy but rather with other risk factors, such as DM and hypertension. In patient #4, cardiac CT angiography showed mild stenosis (about 40%) in the right coronary artery. Considering the result of cardiac CT angiography, abnormality of the anteroseptal area was not related to ischemic heart disease. To exclude coronary artery disease, coronary angiography should be performed. Third, we did not obtain cardiac biopsies for definite confirmation of cardiac involvement in the MM patients.2D strain echo and LGE CMR were abnormal in Miyoshi myopathy patients with preserved left ventricular function and no overt heart failure symptoms. 2D strain and LGE could constitute a new diagnostic test to detect preclinical cardiac involvement in Miyoshi myopathy patients before the onset of overt cardiomyopathy.The authors declare that they have no competing interests.ERC carried out the studies and drafted the manuscript, SJP assisted in conception and design, data analysis and interpretation and drafting of the manuscript, YHC helped with conception and design, revising it critically for important intellectual content, DRR, SAC and JOC provided analysis and interpretation of data, SCL, SWP, BJK, DKK and JKO revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.Cardiovascular Magnetic resonance - Late gadolinium enhancement inversion recovery images in the short-axis view.Click here for fileCardiovascular Magnetic resonance - Late gadolinium enhancement inversion recovery images in the short-axis view.Click here for file


Objective. The purpose of this study was to establish the outlook for fetuses diagnosed with complete atrioventricular septal defect (cAVSD) prenatally and its relation to additional cardiac, extracardiac, and chromosomal abnormalities. Methods. We retrospectively reviewed fetal echocardiograms diagnosed with cAVSD from January 2002 to December 2007, comparing fetuses with and without aneuploidy. Results. Complete antrioventricular septal defect was confirmed in 62 fetuses. Mean maternal age was 28.79 ± 4.78 years (range 20–38). Mean gestational age was 23.69 ± 5.48 weeks (range 12–38). Fetal karyotype was known in all fetuses. An abnormal karyotype was found in 21 fetuses. Complete AVSD occurred without any other intracardiac abnormality in 28 fetuses. Extracardiac anomalies were present in 38 fetuses. As for pregnancy outcomes, there were 36 (58%) terminations of pregnancy and 4 (6.4%) intrauterine fetal deaths. In these four fetuses, complex cAVSD was associated with atrioventricular block (one case), heterotaxy (one case), and fetal hydrops (two cases). Of the 22 live births, 5 were neonatal deaths without surgery while 17 babies underwentsurgery and 13 have survived to date. The mean survival age was 53 ± 4 months (range 22–64 m). Conclusion. AVSD is associated with chromosomal, other cardiac, and extracardiac abnormalities. The detection of these abnormalities is important in order to give the best indication of the likely outcome when counselling parents. Atrioventricular septal defects (AVSDs) also known as endocardial cushion defects involve the septal portions of the mitral and tricuspid valves and the adjacent atrial and ventricular septum . It is aPrenatal detection of cAVSD is very important because it is usually associated with chromosomal abnormalities such as Trisomy 21, which occurs in at least 50% of all cases . It is oThe purpose of this retrospective study was conducted to estimate the frequency of other cardiac, extracardiac, and chromosomal anomalies and neonatal outcomes in fetuses with cAVSD diagnosed in our maternal perinatal units.This was a retrospective study conducted between January 2002 and December 2007 at the Department of Maternal Fetal Medicine of the Bakirkoy Women and Children's Teaching Hospital and the Department of Maternal Fetal Medicine of the Sulaymaniye Women's Teaching Hospital. These hospitals serve as a tertiary referral center in Istanbul. We reviewed all 62 cases of complete atrioventricular septal defects diagnosed prenatally. Ultrasound examinations were carried out using a Voluson 730 Expert . All patients underwent two dimensional, color and pulsed Doppler echocardiography. M-mode tracing was used in case of arrhythmias and whenever necessary. The diagnosis of an atrioventricular septal defect relies on the following sonographic markers: (1) atrioventricular valves inserting into a common junction or in a linear fashion instead of the normal differential insertion; (2) a large defect “discontinuity” located in the cushion zone of the atrioventricular septum; (3) atrial and ventricular septal defects of varying size; (4) aorta “unsprung” from the crux of the heart; (5) unstable floating “kicking” crux .μg every 6 hours.Prenatal karyotyping was offered to all parents and performed in all cases. The mothers choosing to continue the pregnancy were followed up and were examined usually twice or three times after diagnosis. The neonates were studied after birth. If the parents opted for termination of the pregnancy, postmortem examination of the fetus was advised. All parents agreed to proceed a postmortem examination. The vaginal misoprostol dose for pregnancy termination is usually 200 Details of the cardiac anatomy were determined from prenatal and postnatal echocardiograms or other postnatal investigations, from surgical findings or at autopsy. Extracardiac abnormalities and syndromes that were detected prenatally or only became apparent postnatally were noted.The relative size of the ventricles was classified as approximately equal in size, right ventricle substantially larger than the left (dominant right/Hypoplasia of the left heart) or left ventricle substantially larger than the right (dominant left/Hypoplasia of the right heart). Left isomerism was diagnosed in the presence of azygos continuation of an interrupted inferior vena cava and/or fetal heart block, supported by structural heart disease and viscerocardiac heterotaxy . A diagnosis of right isomerism was made in the presence of a combination of complete atrioventricular septal defect and/or viscerocardiac heterotaxy and/or juxtaposition of inferior vena cava and aorta on the same side of the spine.The cases were analyzed for associated cardiac and noncardiac anomalies, karyotyp7e, and obstetric and neonatal outcomes. Isolated cAVSD was defined as an isolated lesion at the fetal echocardiogram. A diagnosis of complex CAVSD was only considered when additional intracardiac malformation was seen at the fetal echocardiogram. Demographic data including maternal age, parity, gestational age at diagnosis, and reason for referral were also noted. t test was used for normal distributed variables in the analysis of continuous variables and Mann Whitney U test was used for abnormally distributed variables. Relative risk (RR) with 95% confidence interval (CI) was calculated. A P value of less than .05 was considered statistically significant.MedCalc 9.3 program was used for statistical analysis. Normal distribution of continuous variables was assessed by Kolmogrov-Smimov test. Chi-square analysis was used for analysis of categoric variables, Student-We reviewed all 62 cases of complete atrioventricular septal defect diagnosed prenatally. In all cases the diagnosis was confirmed by postmortem examination or postnatal examination. Demographic data are presented in P =.60; RR: 0.71; 95% CI: 0.25–1.97]. Also there was not any statistical significance in the frequency of chromosomal anomalies between the two groups . Associated extracardiac anomalies were present in 38 cases (63.3%). There was a single extracardiac anomaly in 12 fetuses, two anomalies in 10 cases and >2 in 16 cases. Associated extracardiac anomalies by apparatus are shown in Fetal karyotype was known in all fetuses. Chromosomal anomalies were detected in 21 fetuses (33%): ten had trisomy 21, seven had trisomy 18, three had trisomy 13, and one had triploidy. As for pregnancy outcomes, there were 36 (58%) terminations of pregnancy and 4 (6.4%) intrauterine fetal deaths. Detailed information about these four cases are summarized in Atrioventricular septal defects (AVSDs) are characterized by defects in the atrial and ventricular septum immediately above and below the atrioventricular (AV) valves . Traditionally, this congenital abnormality has also been referred to as AV canal defect, endocardial cushion defect, persistent atrioventricular ostium, and canalis atrioventricularis communis. The defects usually involve the AV valves to some degree, and the pathophysiology of the lesion depends on the extent of shunting at both the atrial and ventricular levels as well as regurgitation from the involved valves. When limited to the atrial septum, the condition is called an ostium primum atrial septal defect (primum ASD) or partial AVSD. Complete AVSDs combine deficiency of both the atrial and ventricular septum with severe abnormality of the mitral and tricuspid valves, creating what is in essence a common AV valve that serves both ventricles .An AVSD is a common cardiac condition detected prenatally, accounting for 17 percent of diagnosis in the Allan and Sharland series and approximately 4 to 5 percent of congenital heart disease in live births .Antenatal diagnosis of complete atrioventricular septal defects is not always easy. When the atrial and septal defects are large, the four-chamber view reveals an obvious deficiency of the central core structures of the heart. Color Doppler ultrasound can be useful in that it facilitates the visualization of the central opening of the single atrioventricular valve. The atria may be dilated as a consequence of atrioventricular insufficiency. In such cases, color and pulsed Doppler ultrasound allow the identification of the regurgitant jet –6.When an AVSD is detected, a complete sequential analysis of the heart is mandatory. Because AVSDs are frequently associated with other cardiac defects. In our study, atrioventricular septal defect was associated with other cardiac anomalies in 34 fetuses 54.8%). Huggon et al. reported 301 fetuses with AVSD. Additional cardiac abnormalities were noted in 146 (48%) of these cases . Friedbe%. HuggonMany of the larger studies reported 13–72% association of AVSD with extracardiac anomalies , 9. In tStudies indicate 37–58% association of AVSD with chromosomal anomalies, especially trisomy 21 , 10. TheP = 1.00; RR: 0.86; 95% CI: 0.30–2.50]. We have no explanation for the difference between the studies. Trisomy 18 was less frequent in our series. Triploidy occurred in two cases with associated other intracardiac lesions. Deletion of 46q4 occurred only in one case without any other associated intracardiac lesions.Fesslova et al. reported that aneupoidy was a strong predictor for AVSD as an isolated cardiac defect . Huggon  Careful examination of the abdominal organs and the systemic veins is essential in the fetus with an AVSD to rule our visceral heterotaxy. This syndome is strongly predictive of a normal karyotype. However in this series, left isomerism and right isomerism were demonstrated in 12 fetuses with AVSD, and abnormal karyotype was found 5 in 12 fetuses (three with trisomy 18 and two with trisomy 13). In all these patients maternal age was above 35, and they were all endogamous. Also there are several reports on the association of cardiosplenic syndrome and chromosomal abnormalities, mainly microdeletion of chromosome 22q11, trisomy 18, and trisomy 13 , 12–14. The natural history of complete AVSD is not well understood, since it is unusual for patients with this condition to be treated without surgical intervention. Nevertheless, the addition of an intracardiac shunt at the ventricular level, combined with the atrial level shunt and AV valve insufficiency, makes this a particularly morbid lesion with high mortality if left untreated. A few small series have confirmed this suspicion and suggest that 80% of patients who do not undergosurgery will die by 2 years of age , 16.In the study of Machado et al. which included all fetuses diagnosed with AVSD, only four of the 29 fetuses survived . Huggon The outcome of fetal cAVSD continues to depend on associated lesions, both cardiac, and extracardiac, with a continuing high incidence of pregnancy termination and neonatal death . In our In conclusion, cAVSD is associated with chromosomal, other cardiac and extracardiac abnormalities. When the diagnosis of cAVSD is made in fetal life, karyotype and a detailed anatomical survey should be offered in every case. The detection of these abnormalities is important in order to give the best indication of the likely outcome when counselling parents.


Radix Astragali is believed to be the active component in treating heart failure. The present study aims to examine the effects of ASI on cardiovascular parameters in long-term heart failure in rats.Astragaloside IV (ASI) in Using echocardiographic and haemodynamic measurements, we studied the effects of ASI on congestive heart failure (CHF) induced by ligation of the left coronary artery in rats.ASI  attenuated the decline of fractional shortening (FS). The peak derivatives of the left ventricle (LV) pressure (dp/dt) in ASI-treated groups significantly increased. Both LV internal diameters in diastole (LVIDd) and in systole (LVIDs) decreased significantly after ASI treatment (0.3 and 1.0 mg/kg/day). ASI (1.0 mg/kg/day) attenuated the decrease of LV systolic pressure (LVSP). ASI treatment inhibited compensatory hypertrophy of myocardial cells and lowered the number of apoptotic myocytes.ASI improved cardiac functions as measured by cardiovascular parameters. Radix Astragali (Huangqi) is a Chinese herbal medicine reported to improve the left ventricular function and mitigating the cardiac hypertrophy in heart failure patients [Heart failure is a major cause of morbidity and mortality around the world and remains a serious outcome of myocardial infarction (MI). patients -5. Recenpatients -10. ASI patients  further patients .Recent studies showed that cardiac hypertrophy and apoptosis were correlated with the severity of CHF ,14. CardThe present study aims to examine the effects of ASI on cardiovascular parameters in long-term heart failure as an outcome of MI in rats.in vivo. Quinapril was supplied by the Shanghai Institute of Pharmaceutical Industry (certificate no.051).Wistar rats weighting 228.3 ± 13.0 g (203–272 g) were housed at 22 ± 2°C in a temperature-regulated room equipped with an automatic 12:12 hour photoperiod and were provided with food and water. ASI is colourless needles crystallized from Astragaloside by ethyl acetate-ethanol, melting point 295–300°C, purity>95%. ASI was dissolved in 20% dimethylsulfoxide (<0.05%) and diluted with normal saline (NS) when studied et al. [MI in Wistar rats was induced by coronary ligation. Through a thoracotomy on the left side, the heart was exteriorized and extensive MI was induced by ligation of the left coronary artery according to Tonnessen et al. . Animalset al. ,19 whereWe used a commercially available echocardiography  equipped with a 10 MHz linear transducer. The animals, with shaved chests, were placed in supine position. The transducer was placed gently on the left. Two-dimensional (2D) images of the left ventricle (LV) were obtained in both parasternal long-axis and short-axis views at a frame rate of 130 Hz. M-mode tracings were recorded at the level of the papillary muscles with 2D guidance. LV wall thickness and cavity diameters were measured outside the infarcted area by M-mode, through the largest diameters of the ventricle. Each image consisted of 24 consecutive heart cycles and the focus area was 0–40 mm from the transducer. Fractional shortening (FS), in percentage, was calculated according to the following formula:where LVIDd is the LV internal diameter in diastole, and LVIDs is the LV internal diameter in systole . LV inteAn F-2  catheter with pressure-transducer was inserted through the right carotid artery into the aorta to determine the mean arterial blood pressure. The catheter was subsequently advanced further into the LV, and end-diastolic pressure (LVEDP) and systolic pressure (LVSP) were recorded. The transducer was connected to a polygraph  and a data acquisition workstation  to a computer running Acknowledge (version 3.7.1). LVEDP was read directly from the pressure curve as being the diastolic pressure immediately preceding the pressure rise associated with LV contraction. Peak positive and peak negative first derivatives of the LV pressure (+LVdp/dt and -LVdp/dt) were calculated with the Acknowledge software.After haemodynamic measurements, the rats were subsequently euthanized by excision of the heart. The atria and ventricles were sectioned, separated and weighted. The infarcted area (scar tissue) was excised with care from the non-infarcted LV to avoid contamination of viable myocardial tissue by necrotic tissue. The infarction size was estimated by weighing the excised scar tissue. The non-infarcted LV from the CHF rats was further sectioned by separating the tissue contiguous to the infarcted area  and the tissue distal to the infarcted area (interventricular septum). A piece of the apical part of the nonischemic interventricular septum was processed separately for histochemical analysis of apoptosis. The right tibia of each rat was isolated and its length measured . MyocardP values < 0.05 are considered to be statistically significant.Data are expressed as mean ± standard deviation (SD). The statistical significance between groups was evaluated by a one-way analysis of variance (ANOVA) with SAS software . P < 0.05, P < 0.001 and P < -0.001). Two weeks after the administration of ASI (at a dose of 1.0 mg/kg/day), the decline of the FS was attenuated (P < 0.05). The dp/dt in the ASI-treated groups (0.3 and 1.0 mg/kg/day) significantly increased compared with the model group (P < 0.05 and P < 0.01) , the decline of the FS was attenuated  Tables .LV geometry in various groups was analyzed with echocardiography Table . The finP < 0.01) compared with the model group. The rats in the model group displayed higher wall stress of LV. ASI (1.0 mg/kg/day) significantly lowered the wall stress by 22% (P < 0.05) compared with the model group.LVSP in the model group was 21% lower than that in the sham group, while LVEDP in the model group increased markedly, suggesting severe cardiac dysfunction in the CHF rats after coronary artery ligation Table . ASI  treatment compared with the model group Table .in situ TUNEL staining of mycardial sections. Apoptosis was observed in the CHF rats with an increased level of Bax protein. Compared with the model group, both apoptotic cells and Bax proteins were reduced markedly after two weeks of ASI treatment (1.0 mg/kg/day) (Table Assessment of apoptotic cell death was performed with y) Table .CHF is a serious outcome of MI. Many rats may die from serious ischemia after induction of acute MI by coronary artery ligation. However, rats suffering from slight ischemia may develop CHF. In the present study, surgery was performed on 141 rats, among which 48 rats died within 24 hours  and 61 rats developed CHF according to echocardiographic criteria for CHF . The ratP < 0.001); LVIDd and LVIDs increased markedly from 4.8 ± 1.2 mm and 1.5 ± 0.5 to 7.0 ± 1.1 mm and 4.8 ± 1.0 mm respectively (P < 0.001). These results are consistent with the findings by Oie et al. [Routinely used on humans, echocardiography is emerging as a noninvasive method for evaluating global systolic cardiac function and LV dimensions in rats -27. In te et al. .The mechanism of heart failure remains mostly unclear. The loss of cardiomyocytes may play an important role in causing heart failure . ApoptosA previous study showed that quinapril significantly suppressed the incidence of apoptotic myocytes around the necrotic region . In the The present study showed that ASI improved cardiac functions, inhibited compensatory hypertrophy of myocardial cells and lowered the number of apoptotic myocytes.ASI: Astragaloside IV; Bax: Bcl-2 associated X protein; CHF: congestive heart failure; FS: fractional shortening; IVSs: interventricular septum thickness at end-systole; LA: left atrium; LV: left ventricle; LVIDd: left ventricle internal diameter in diastole; LVIDs: left ventricle internal diameter in systole; LVEDP: left ventricle end-diastolic pressure; -LVPWs: posterior wall thickness at end-systole; -LVSP: left ventricle systolic pressure; -MI: myocardial infarction; RA: right atrium; RV: right ventricle; SD: standard deviation; TL: tibial length; wt: weight.The authors declare that they have no competing interests.ZYZ, WTW, FW and KRZ drafted the manuscript and performed the experiments. WRX and YMH prepared reagents for the experiments. LDT supervised this work and revised the manuscript. All authors read and approved the final version of the manuscript.


Sir,On the occasion of the recent publication about the interesting case report of postpartum cardiomyopathy (PPCM), we woulA 42-year-old woman, with medical treatment for hyperthyroidism, eutopic delivery a week before, and gestoses in the last 2 weeks of gestation, turned up in the emergency department of our hospital referring progressive dyspnea that ended up in dyspnea being at rest accompanied with orthopnea and paroxysmal nocturnal dyspnea.On arrival in the emergency department, she was conscious, her blood pressure was 160/100 mmHg, and she presented tachycardia and taquipnea. Chest radiograph showed an image of acute pulmonary edema. Echocardiography revealed severe left ventricular dysfunction (LVEF 20%), normal left ventricular end diastolic dimension, and mild mitral regurgitation. In spite of the conventional treatment for AHF with diuretics and vasodilators, the patient did not improve, and was given mechanical ventilation and vasoactive drugs because of hypotension.In this critical situation, she was transferred to the intensive care unit. In the presence of AHF refractory to the habitual treatment, administration of a continuos levosimendan infusion at 0.1 μg/kg/min during 24 h was decided. The patient evolved favorably; therefore, a few hours later, vasoactive drugs could be interrupted and subsequently extubation was carried out.On the fourth day, she was discharged to the ward. The echocardiography on the fifth day revealed an LVEF improvement (30%). She went home on the ninth day and 3 months later a new echocardiography showed an LVEF of 50%.PPCM is a rare cause of AHF in the last months of pregnancy or within 5 months after delivery, in the absence of demonstrable preexisting cardiac disease and identifiable cause, which determines cardiac failure, with echocardiographic evidence of left ventricular systolic dysfunction.3There is no specific treatment for this disease. In general, the treatment of PPCM is similar to that of other forms of AHF. However, in the literature there are few cases that describe the satisfactory use of levosimendan in PPCM, with improved myocardial performance associated with hemodynamic and symptom improvement, and a recovery of left ventricular function.454Levosimendan—calcium sensitizer—increases myocardial contractility without increasing oxygen requirements, and also induces peripheral and coronary vasodilation through the opening of ATP-sensitive potassium channels in vascular smooth muscle. Because levosimendan does not increase intracellular calcium levels, it is less likely than traditional inotropes to have deleterious effects on cardiac myocyte relaxation, cell survival, and arrhythmia induction.In spite of its short half-life, effects are long-lasting due to the active metabolite OR-1896, which has an elimination half-life of 70–80 h in patients with heart failure.565At present, although there exists literature about the beneficial effects of levosimendan in PPCM, it is also true that the reported cases are sparing and that the only treatment based on scientific evidence is the habitual used in AHF.


Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. Methamphetamine is a synthetic amine commonly used as a recreational drug because of its stimulant effects. Its use has increased nationwide  and receRecovery of left ventricular dysfunction in patients with methamphetamine-induced cardiomyopathy has been described -9. HowevCardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been show to identify myocardial fibrosis in ischemic and non-ischemic cardiomyopathies ,14 and pWe herein report a case of recovery of left ventricular function in a patient with methamphetamine-associated cardiomyopathy demonstrated using LGE.2 saturation was 99% on room air. Cardiac examination revealed a JVP of 12 cm and a 3/6 holosystolic murmur best heard at the apex without respiratory variation. She had no organomegaly or ascites and her extremities had 2+ pitting edema. Her laboratory data demonstrated a sodium of 138 mEq/L, creatinine of 1.1, and serum troponin of 0.11 (ng/ml). A chest X-ray showed cardiomegaly, an electrocardiogram showed left ventricular hypertrophy and ST-T wave abnormalities. Two-dimensional echocardiography showed reduced systolic function (Figure A 44 year old woman presented to the emergency department with 3 days of peripheral edema, paroxysmal nocturnal dyspnea, and dyspnea on exertion. She denied chest pain, fever, rashes and/or recent viral illnesses. She had no recent exposure to ill contacts or foreign travel. Her review of systems was otherwise unremarkable. Her past medical history consisted of pregnancy related hypertension 4 years prior that required no therapy after delivery. Her social history consisted of 15 years of inhaled methamphetamine and tobacco use. She denied alcohol or other street drug use. She was taking no medications at time of presentation. Her surgical history consisted of one normal child delivery 4 years prior, a tubal ligation and tonsillectomy. Physical examination revealed a blood pressure of 159/109 mmHg, pulse of 109 bpm, and a temperature of 36.3°C. Her arterial OAfter informed consent, she underwent LGE using standard techniques . BrieflyEchocardiography and CMR both showed a reduced ejection fraction, calculated at 37% using quantitative analysis of GRE images. There was no LGE Figure . She wasFollowing 6 months of medical therapy and decreased use of methamphetamine, she again was evaluated for signs and symptoms of heart failure. At this time, she had improved clinically to functional class I. Echocardiography showed a normal ejection fraction and quantitative CMR showed an ejection fraction of 64% Figure . Left veThis patient illustrates the potential use of LGE as a tool to predict whether patients with methamphetamine-associated cardiomyopathy can recover left ventricular function with appropriate medical therapy. In this instance, the absence of gadolinium enhancement was consistent with an absence of macroscopic regions of fibrosis and hence, no irreversible myocardial injury.Methamphetamine is a sympathomimetic agent that mediates its cardiovascular effects through excessive release of norepinephrine and blockade of reuptake at the sympathetic synaptic receptors . This syWhile the extent of fibrosis defined by LGE predicts recovery of left ventricular function in patients with coronary artery disease and myocardial infarction , there aIn the specific case of this patient with methamphetamine-associated cardiomyopathy, the LGE study did not demonstrate any enhancement, consistent with an absence of significant fibrosis. Left ventricular function recovered with 6 months of medical therapy and decreased drug abuse. While it is unknown whether, in a larger cohort of patients, the absence or presence of CMR identified fibrosis would predict recovery, the benign LGE findings in this patient likely portended a favorable outcome.The authors declare that they have no competing interests.JEL and SS analyzed the data and wrote the manuscript. KK and SS conceived of the study, and participated in its design and coordination. GC participated in the acquisition of the data. MB participated in the acquisition and analysis of the data. All authors read and approved the final manuscript.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Assessment of ventricular dyssynchrony in patients with heart failure is used for selecting candidates for cardiac resynchronization therapy (CRT). The patterns of regional distribution of dyssynchrony in a population with LBBB with and without heart failure have not been well delineated. This aspect forms the object of the study.Tissue Doppler Imaging (TDI) data of consecutive patients with heart failure and LBBB (Group A) was compared with those with LBBB and normal LV function (Group B). All patients had standard 2D-echocardigraphic examination and TDI. Tissue velocity curves obtained by placing sample volumes in opposing basal and mid segments of septal, lateral, inferior, anterior and posterior walls were analyzed. Inter ventricular dyssynchrony (IVD) was assessed by the difference between aortic and pulmonary pre ejection intervals. LV dyssynchrony (LVD) was assessed by the difference in times to peak velocity. A delay of ≥ 40 msec was considered significant for presence of IVD and LVD.There were 103 patients in Group A and 25 in Group B. The mean QRS duration and PR intervals respectively were 146 ± 25 vs. 152±20 msec and 182± 47 vs. 165±36 msec. (p=NS) LVEF in the 2 groups were . Prevalence of dyssynchrony in the HF group compared to Group B was 72% vs. 16%, (P< 0.01). Lateral wall dyssynchrony in the 2 groups was 37% vs. 0% (p< 0.01) while septal dyssynchrony was 16% vs. 16% (p- NS).72% of heart failure patients with LBBB have documented dyssynchrony on TDI, which has a heterogeneous regional distribution. Dyssynchrony may be seen in LBBB and normal hearts but it is does not involve the lateral wall. Septal dyssynchrony in heart failure patients may not have the same significance as lateral wall delay. Cardiac resynchronization therapy (CRT) has proven to be beneficial in drug refractory heart failure patients for alleviation of symptoms, improving quality of life, decreasing hospitalizations and mortality -4. Most This prospective study was undertaken to assess the patterns of interventricular and left ventricular dyssynchrony (LVD) in patients with complete LBBB and heart failure. This data was compared with the dyssynchrony patterns of 25 subjects with LBBB having normal ventricular function. Consecutive patients with heart failure referred for assessment of ventricular dyssynchrony by TDI and fulfilling the inclusion and exclusion criteria were studied. All patients were also subjected to a standard 2D echocardiogram prior to TDI. Individuals declared normal at annual routine physical examination but having LBBB on ECG were selected for comparison .Patients aged 18 and abovePatients with symptomatic heart failureLVEF ≤ 40% by 2 D echocardiogramComplete LBBB on surface ECGPredominant valvular heart diseasePredominant diastolic heart failureAcute coronary syndromes in the last 3 monthsRecent revascularization in the last 3 monthsPatients with atrial fibrillationAsymptomatic consenting adults with a complete LBBB (QRS duration >  120 msec) and a normal 2D echocardiographic study were included. None of them had hypertension, coronary artery disease or pulmonary disease.Standard echocardiography, including Doppler studies was performed with Vivid 5, GE Vingmed Ultrasound, Horten, Norway. The left ventricular end-diastolic volume, left ventricular end-systolic volume and ejection fraction were assessed by biplane Simpson's equation using the apical four- and two chamber views. Standard methods were used to assess cardiac output, Tei Index and severity of mitral regurgitation.Tissue Doppler imaging was performed by using apical four chamber, apical two chamber and parasternal long axis views for the long axis motion of the ventricles -10. Two-Interventricular dyssynchrony was evaluated by assessing the extent of interventricular mechanical delay (IVMD), defined as the time difference between left and right ventricular pre-ejection intervals. (Q to aortic flow and Q to pulmonary flow). An IVMD of > 40 msec was considered indicative of interventricular dyssynchrony. LVD was assessed from measurements of time intervals between the onset of the QRS complex and the peak regional velocity of myocardial systolic shortening, considered as a surrogate for regional electromechanical coupling intervals. Time intervals were measured in opposing basal and mid LV segments. Intraventricular (LV) dyssynchrony was determined as the difference between the longest and shortest electromechanical coupling times in the opposing basal septal, lateral, anterior, inferior and posterior segments of the LV. Any difference of 40 msec or more was considered indicative of presence intraventricular dyssynchrony. Statistical analysis was done by commercially available package MINITAB version 13. Continuous variables are expressed as mean + 1 standard deviation and were compared by unpaired Student t test. Discrete variables were compared using chi square test. For all comparisons, the difference between the 2 groups was considered significant at a level of 5%.Of the 233 heart failure patients referred for TDI 103 had complete LBBB and formed the cohort for this study. The baseline characteristics of the 103 patients and 25 controls with LBBB are summarized in Prevalence of dyssynchrony in heart failure patients varies depending on methodology and cut off values used. In our study we measured LVD from onset of QRS to peak of respective tissue velocity curve and used a cutoff value of 40 msec. This value was obtained by assessment of 20 normal individuals in our lab and was greater than 2 SD of LVD. This study documented LVD in 72% of heart failure patients with LBBB, thus showing a lack of consistent correlation between presence of dyssynchrony assessed by TDI and complete LBBB and reinforces the observation that a wide QRS does not always predict dyssynchrony  -13. An iLV dyssynchrony is present in 72% of heart failure population with complete LBBB. The regional distribution patterns of dyssynchrony are heterogenous. Lateral wall delay is seen only in heart failure patients while septal delay is present similarly in heart failure patients and normal individuals with LBBB. Prospective follow up of this population may result in correlation of dyssynchrony patterns and development of LV dysfunction.