Global left ventricular electromechanical dyssynchrony (GLVD) is uncoordinated LV contraction that reduces the extent of intrinsic energy transfer from the myocardium to the circulation leading to a reduction in peak LV pressure rise, prolonged total isovolumic time (t-IVT) and fall in stroke volume . This poA prospective analysis of retrospectively collected data in cardiothoracic ICU patients who underwent echocardiography was performed. In addition to epidemiological factors, echo data included comprehensive assessment of LV/RV systolic and diastolic function including Doppler analysis of isovolumic contraction/ relaxation, ejection time (ET) and filling time (FT). t-IVT was calculated as ) and the Tei Index as (ICT + IRT) / ET. t-IVT >14 second/minute and Tei index >0.48 were used to define GLVD . Data arP = 0.02). There was no difference in requirement for cardiorespiratory support between the two populations, but there were significant differences (no GLVD vs. GLVD) in requirement for pacing , atrial fibrillation , QRS duration (92.0 (80.0 to 120.0) vs. 116.5 (95.0 to 154.0), P = 0.01) and QTc (460.0 (416.0 to 498.5) vs. 477.5 (451.2 to 541.0), P = 0.02). There was no significant difference in ejection fraction (no GLVD 43.0 (35.0 to 49.5) vs. GLVD 39.6 (29.5 to 49.7), P = 0.43), mitral regurgitation , or any other measures of LV systolic or diastolic function between the two groups. There was good correlation between the two methods used to assess dyssynchrony .A total of 103 patients (63.5 ± 18.4 years), 65 male (63%), APACHE II score (14.6 ± 7.4) were included. The prevalence of GLVD was high  and associated with significantly increased mortality, 7.5% vs. 25% .


For each congenital heart defect (CHD) knowledge of morphological and functional variations is crucial in order to assess an individual case and initiate specific therapy, if necessary. Specific data are widely lacking. CMR-based values exist only for left ventricular (LV) and right ventricular (RV) volumes of children and adults with normal anatomy. Therefore, we sought to provide values for RV volumes, mass and function in children with Hypoplastic Left Heart Syndrome (HLHS) in order to be able to consider the defect specific variation.57 children  with HLHS were evaluated after surgical completion of Fontan-Circulation in a single center. Children with hemodynamic relevant lesions such as tricuspid- or neo-aortic-regurgitation as well as aortic stenosis were excluded. All examinations were performed in freely breathing deeply-sedated children. RV volumes and mass were measured in the end-systolic and end-diastolic phases on fast field echo cine images  acquired in a short axis planes as a stack of at least 10 contiguous, parallel slices covering the full length of the ventricle.Average volumetric data (mean±SD) are summarized in the table below. The end-systolic (ESV), end-diastolic (EDV) and stroke (SV) volume, as well as the myocardial mass (MM) were indexed to body surface area. No significant gender specific difference was found in young HLHS patients.Compared to normal values from healthy children drawn from the literature and from our own data base, children with HLHS have a higher myocardial mass  and larger end-systolic volume of the systemic ventricle . All remaining parameters, especially the end-diastolic volume , ejection fraction  and the cardiac index , are significantly smaller. Intra- and inter-observer variability of the measurements was in the range of 4% and 9% respectively.CMR data on ventricular volumes and their variability specific to patients with HLHS have excellent inter-observer variability and fill an important void in the current literature. These reference values allow evaluation of an individual patient to assess his congenital heart defect. Additionally, the data can serve as a basis for longitudinal studies, as the time course of systemic ventricular remodeling after surgical completition of the Fontan-Circulation has important implications for patient outcomes.


For many years the lung has been considered off-limits for ultrasound. However, it has been recently shown that lung ultrasound (LUS) may represent a useful tool for the evaluation of many pulmonary conditions in cardiovascular disease. The main application of LUS for the cardiologist is the assessment of B-lines. B-lines are reverberation artifacts, originating from water-thickened pulmonary interlobular septa. Multiple B-lines are present in pulmonary congestion, and may help in the detection, semiquantification and monitoring of extravascular lung water, in the differential diagnosis of dyspnea, and in the prognostic stratification of chronic heart failure and acute coronary syndromes. For many years ultrasound has not been employed for the evaluation of the lung . All diaThere are some anectodical reports on B-lines since the eighties ,4. In 19LUS examination can be performed using any commercially available 2-D scanner, with any transducer . There is no need for a second harmonic or Doppler imaging mode. The examination can be performed with any type of echographic platform, from fully equipped machines to pocket size ones . PatientIn a 1994 review on the assessment of EVLW, Lange stated that «The possibility to detect pulmonary edema before it becomes clinically apparent, is so inherently attractive that the effort to develop and validate such technique still continues after many years of tireless and relatively unrewarding attempts» . Chest XB-lines have been proposed as a reliable ultrasound technique for the assessment of pulmonary congestion in HF patients. The number of B-lines increases with worsening New York Heart Association (NYHA) functional class . SonograB-lines are very dynamic, as shown by their rapid increase after exercise, both in patients with and without left ventricular dysfunction . An "alvIn less than ten years, the proposal to use B-lines to evaluate pulmonary congestion in HF patients, has moved from the research setting to the clinical arena, and it is now entering recommendation papers ,24. ReceIn HF patients, LUS may also enable the detection of PE. Evaluation of PE is the more established application of LUS . The effThe recognition, quantification and monitoring of pulmonary congestion is important for the clinician at all stages of care of the HF patient. Accurate assessment of effectiveness of medical treatment is mandatory in these patients . Chest XB-lines have been proposed as a bedside, easy-to-use, alternative diagnostic tool for clinically monitoring pulmonary congestion in HF patients , as theyThe simplicity and low-techology of this examination makes it appealing also for an out-hospital office monitoring of HF patients. Pharmacological therapy could be tailored as soon as the patient, although asymptomatic, shows a significant increase in B-lines number. This could, at least in theory, prevent some new hospitalizations for worsening dyspnea, since symptoms would appear with some days of delay . The posPersistent hemodynamic congestion, that is not adequately recognised and treated before discharge, is associated with adverse clinical outcome in HF patients . On the In patients with acute coronary syndromes, the number of B-lines, associated to some very easy echocardiographic parameters of left and right cardiac function, provide a clear prognostic stratification in a composite end-point including death, non-fatal myocardial infarction and new admission for acute decompensated HF .From a practical point of view, B-lines assessment may be useful at all stages of HF management: in outpatients, to monitor increasing EVLW as a sign of impending decompensation, that is more reliable than body weight changes; for the primary diagnosis of acute HF syndromes, in patients admitted with acute dyspnea to the Emergency Room, where even an old, low-technology echographic device may allow B-lines detection; during hospitalization for risk stratification and to titrate therapies, and for prognostic stratification at discharge.Acute respiratory distress syndrome (ARDS) is a common syndrome of diffuse lung injury with a high mortality rate . DiffereAlthough not frequently, the cardiologist may sometimes need to differentiate ARDS from cardiogenic pulmonary edema, especially in Intensive Care Unit, in patients after cardiothoracic surgery. Bedside chest X-rays are often very difficult to interpret, whereas LUS is much less affected from being performed at bedside. Moreover, LUS may be of great help in resource-limited settings, where an early diagnosis of ARDS can be life-saving, as in high altitude pulmonary edema ,40 and aIn ARDS, LUS is useful not only in the diagnosis, but also in the follow-up: bedside LUS is able to adequately estimate lung recruitment induced by positive end-expiratory pressure (PEEP) , with a seashore sign  can occur after cardiothoracic surgery. Bedside chest X-ray may misdiagnose up to 30% of cases . Radiogrn Figure , panel An Figure , panel Bt of PTX . Howeverhe other ,  , Figure; moreoveEchocardiography is an essential tool for the cardiologist, providing a huge amount of information on both acute and chronic situations. The addition of LUS to echocardiography provides an additive insight on the eventual pulmonary involvement. The cardiopulmonary system is so interconnected, that an integrated approach is mandatory. Presence of multiple, diffuse, bilateral B-lines associated to left ventricular systolic and/or diastolic dysfunction or valvular heart disease is highly indicative of cardiogenic pulmonary congestion Figure . MoreovePresence of multiple, diffuse, bilateral B-lines, associated to a normal heart, indicates a non-cardiac cause of pulmonary edema, as acute lung injury (ALI)/ARDS, interstitial pneumonia; alternatively, especially in a chronic setting, it should pose the suspicion of pulmonary fibrosis Figure . It is iLUS is one of the easiest application of echography, much easier than echocardiography. Images patterns are readily teachable, and minimal didactic and image recognition skill sessions are needed . The leaLUS limitations are essentially patient dependent. Obese patients are frequently difficult to examine because of the thickness of their ribcage and soft tissues. The presence of subcutaneous emphysema or large thoracic dressings alters or precludes the propagation of ultrasound beams to the lung periphery.The main limitation of B-lines is the lack of specificity. As already mentioned, they are a sign of interstitial syndrome, therefore they are a very sensitive but not specific sign of cardiogenic pulmonary edema. How to distinguish the different etiologies of B-lines has been discussed. However, it must be always reminded that all instrumental data should be evaluated within the clinical context and integrated with patient's history. No single test alone allows to establish the diagnosis.Providing a reliable, simple and repeatable estimation of EVLW, B-lines assessment by LUS represents a new, helpful tool for the cardiologist, to be employed at all stages of the management of HF patients, and for the differential diagnosis of dyspnea. LUS can further help in the diagnosis of other pulmonary conditions, that may be challenging in a Cardiology or Cardiac Surgery Department. Adding LUS to echocardiography may help to differentiate the main causes of acute dyspnea.The author declares that they have no competing interests.Sonographic pattern of the normal lung: the horizontal hyperechoic line moving synchronously with respiration is the pleura.Click here for fileSonographic pattern of interstitial syndrome: multiple B-lines originate from the pleural line.Click here for file


Dilated cardiomyopathy is the most common type of the heart failure which can be characterized by impaired ventricular contractility. Mechanical circulatory support devices were introduced into practice for the heart failure patients to bridge the time between the decision to transplant and the actual transplantation which is not sufficient due to the state of donor organ supply. In this study, the hemodynamic response of a cardiovascular system that includes a dilated cardiomyopathic heart under support of a newly developed continuous flow left ventricular assist device—Heart Turcica Axial—was evaluated employing computer simulations. For the evaluation, a numerical model which describes the pressure-flow rate relations of Heart Turcica Axial, a cardiovascular system model describing the healthy and pathological hemodynamics, and a baroreflex model regulating the heart rate were used. Heart Turcica Axial was operated between 8000 rpm and 11000 rpm speeds with 1000 rpm increments for assessing the pump performance and response of the cardiovascular system. The results also give an insight about the range of the possible operating speeds of Heart Turcica Axial in a clinical application. Based on the findings, operating speed of Heart Turcica Axial should be between 10000 rpm and 11000 rpm. Dilated cardiomyopathy (DCM) is the most common type of nonischemic cardiomyopathy and a major cause of congestive heart failure , 2. It lDCM is conventionally treated with inotropic support, diuretics, and moderate exercise. When these methods fail, especially towards the final stage of the disease, heart transplantation is called for. With the current state of donor organ supply, many patients would not be treated, due to lack of a fitting donor organ. Furthermore, availability of a donor heart for urgent patients is not always timely. For these patients, to bridge the time between the decision to transplant and the actual transplantation, cardiac assist devices have been introduced into clinical practice .2, systolic arterial pressure is less than 90 mmHg, atrial pressure is higher than 20 mmHg, or the systemic vascular resistance is higher than 1.57 mmHgs/mL [Ventricular assist devices (VADs) are the devices supporting the failing ventricle partially or completely. Because of the native heart being kept in place in a VAD patient, the VADs can be used for bridge to transplantation or as a destination therapy. In some cases, the heart may regain its original function, so the pump support is only temporary, until the failing heart has recovered . GeneralmmHgs/mL , 16. CF-In this study, we aim to evaluate the hemodynamical response of a DCM cardiovascular system model under support of a newly developed CF-LVAD-Heart Turcica Axial (HTA) . The resThe baseline geometry of HTA includes an inducer at the inlet, a diffuser at the outlet, and a rotating impeller. These components were expressed using eleven design parameters. The design parameters were optimized using genetic algorithms in order to increase pressure rise at the outlet of the pump and reduce the wall shear stresses on the surface of the components for 6 L/min flow rate through the pump. The optimized geometries were assessed employing Computational Fluid Dynamics (CFD) analyses. The geometry generates the highest pressure rise at the outlet of the pump and lower wall shear stress on the components was selected as HTA CF-LVAD. The detailed information about the shape optimization and CFD analyses can be found in , 22.A model was chosen to estimate the pressure head of HTA using pump flow rate and operating speed and the coefficients were estimated using the results of the CFD analyses to describe HTA. This model is given as follows:pHTA  is the pressure difference across HTA and  QHTA  and  nHTA  are the flow rate through HTA and the operating speed of HTA, respectively.  k1  and  k2  are the estimated coefficients. The least squares approximation was used to estimate  k1  and  k2. Estimated values of  k1  and  k2  were 0.2380 mmHg mL−1 and 0.0032 mmHg s−2 with a root mean square error of 1.41 mmHg. The detailed information about the parameter estimation is given in [Here,  ΔE) model [e) and characteristic ventricular elastance of end-systole (Es) and end-diastole (Ed). One has the following:The cardiovascular system model includes ventricles, atria, heart valves, systemic arteries, systemic veins, pulmonary arteries and pulmonary veins. The ventricles were modeled using a time varying elastance (E) model . This mot  is the instantaneous time,  T1  and  T2  are the time instants, when the activation function becomes maximum and minimum, and  T  is the duration of a heartbeat. Left and right ventricles were modeled using the same equation with different  Es  values [Vlv), zero pressure filling volume of the left ventricle , and the elastance function (Elv). Model for the left ventricular pressure is given inHere,    values . PressurVlv) was described as the difference between flow rates through the mitral valve (Qmv) and aortic valve (Qav) as follows:A similar model was used for describing the right ventricular pressure considering the right ventricular elastance function, cavity volume, and zero pressure filling volume. Left ventricular volume (dpas/dt) and flow rate (dQas/dt) in the systemic arteries are given below. Qav  and  Qas  denote the flow rate through the aortic valve and the systemic arteries,  pas  and  pvs  denote the pressure in the systemic arteries and the systemic veins, and  Cas,  Ras, and  Las  are compliance, resistance and inertance in the systemic arterial model. Pressures and flow rates in the other compartments were modeled in a similar way. The heart valves were modeled as ideal diodes which allow only one-way blood flow. Flow rate through the aortic valve (Qav) is given inThe blood vessels and the atria were modeled considering the analogy between the electrical systems and the circulatory system . Model oRav  is the characteristic resistance of the aortic valve. Flow rate through the mitral, tricuspid, and pulmonary valves was described in a similar way. The electric analogue diagram of the cardiovascular system model is given in R), compliance (C), inertance (L), and elastances (E) are presented in Here,  −1 from 2.5 mmHg mL−1 in order to simulate a DCM condition in the cardiovascular system model.Dilated cardiomyopathy (DCM) was considered as the pathological case in the simulations. As mentioned before, in a DCM patient, contractions of the heart muscle weaken and left ventricular volume increases significantly while the ventricular stroke volume, systolic left ventricular and aortic pressures, cardiac output, and ejection fraction reduce . Left veHTA model and the circulatory system model were combined in order to simulate the CF-LVAD assistance by modifying the equations describing the left ventricular volume and systemic arterial pressure change as follows:pHTA  in  in the simulations for the healthy model. In the DCM model, the peak left ventricular pressure reduced to 97 mmHg while there was an increase in the diastolic pressure. Systolic and diastolic arterial pressures decreased as well in the DCM model. Right ventricular peak pressure and pulmonary arterial systolic and diastolic pressures increased. Ventricular stroke volumes decreased with the lowered elastance in the DCM model while left ventricular volume was higher than 200 mL over a cardiac cycle. Heart rate was 75 bpm and the cardiac output was 66.17 mL/s (3.97 L/min). The amplitude of the aortic valve flow was around 1000 mL/s in the healthy model while it reduced to 650 mL/s in the DCM model. The variation of the systemic arterial flow was between 60 mL/s and 110 mL/s in the healthy model. In the DCM model it changed between 50 mL/s and 85 mL/s.HTA was operated between 8000 rpm and 11000 rpm operating speeds with 1000 rpm intervals in the CF-LVAD integrated cardiovascular system model. The pressures in the ventricles and systemic and pulmonary arteries and ventricular volumes under HTA support are given in Left ventricular peak pressure becomes lower at relatively higher pump operating speeds in a CF-LVAD assisted failing heart. Also it is expected to have lower end-diastolic left ventricular pressure under relatively high pump operating speeds due to lowered preload , 29. HTAThe aim of supporting the impaired left ventricle with CF-LVAD is to increase the blood flow and mean arterial pressure to maintain the normal organ function in the body. There was an upward shift in the systemic arterial pressure signal that indicates the increased mean pressure in the systemic arteries under HTA support. However, amplitude of the systemic arterial pressure signal decreased under support of HTA. Left ventricular pressure remained below arterial pressure over a cardiac cycle at the pump speeds higher than 8000 rpm.High peak pressures in the right ventricle and the pulmonary arteries reduced under HTA support. HTA support did not have a significant effect on the end-diastolic right ventricular pressure like the amplitude of pulmonary arterial pressure signal.Left ventricular volume, which was higher than 200 mL in the DCM model, decreased significantly under HTA support. Left ventricular volume was in the healthy physiological range at 10000 rpm HTA operating speed . The strThe heart and the HTA operated together at 8000 rpm operating speed. The amplitude of the aortic valve flow signal was 250 mL/s at this speed. The aortic valve remained close over a cardiac cycle at the relatively higher operating speeds due to high pressure rise at the outlet of HTA. Therefore, there was no ejection through the aortic valve at these operating speeds. The pulsatility in the arterial flow was decreased due to lower left ventricular pressure with increasing pump speeds.Left ventricular pressure-volume loops give the information about the unloading of the left ventricle under CF-LVAD support. Left ventricular pressure volume loops under HTA support for the simulated operating speeds are given in Left ventricular pressure volume loop shifted to right because of the increased cavity volume in the DCM model. There was a reduction in its area because of the reduced systolic left ventricular pressure and stroke volume. Left ventricular pressure volume loop area which indicates the left ventricular stroke work is expected to decrease under CF-LVAD support due to continuous unloading of this heart chamber by the pump. Left ventricular stroke work decreased with increasing HTA operating speed due to higher level of unloading at the relatively higher speeds. Isovolumic contraction and relaxation phases disappeared due to continuous unloading of the ventricle under CF-LVAD support. Pressure volume loop area of the left ventricle was very small at 11000 rpm operating speed. This also indicates that further increase in the HTA operating speed may cause collapse of the ventricle due to suction.Flow rate through the pump is an important parameter in a CF-LVAD supported heart. Blood flow should not regurgitate through the pump for an efficient CF-LVAD support. This happens at the relatively lower pump operating speeds. At the relatively higher speeds, flow rate signal becomes less pulsatile. In the excessive pumping, left ventricle may collapse and flow rate signal through the pump may be distorted over a cardiac cycle. Flow rate through HTA between 8000 rpm and 11000 rpm pump operating speeds with 1000 rpm is increments given in Blood flow through HTA regurgitates at 8000 rpm and 9000 rpm operating speeds. At 10000 rpm regurgitation of the blood flow disappeared. However, the amplitude of the flow rate signal decreased. The amplitude of the flow rate signal was minimum at 11000 rpm HTA operating speed.The hemodynamic variables at the end of the systole and at the end of the diastole, together with the heart rate, mean pump output and the cardiac index for the healthy, DCM, and HTA supported cardiovascular system models is given in End-systolic pressure in the left ventricle decreased due to impaired contraction. Left ventricular end-systolic pressure decreased more under assistance of HTA due to continuous unloading of the left ventricle. High end-diastolic volume in the DCM model decreased under HTA support. It was 8 mmHg, at 11000 rpm HTA operating speed. End-systolic right ventricular pressure increased because of lowered afterload in the DCM model. This hemodynamic variable was reduced to below healthy level at 11000 rpm operating speed. In the DCM model, decrease of the end-diastolic right ventricular pressure was low with respect to healthy model. This parameter reached the healthy level at 10000 rpm operating speed under HTA support.At 8000 rpm pump operating speed, the mean arterial pressure became 83 mmHg by increasing 3 mmHg with respect to the DCM model. Under relatively higher speed CF-LVAD support, the systolic and mean arterial pressures increased more. However, the amplitude of the arterial pressure signal reduced which indicates a decrease in the arterial pressure pulsatility. The mean arterial pressure was 103 mmHg which was the same as the healthy level at 11000 rpm HTA operating speed. Mean pump output was at the same level as the healthy model at 11000 rpm HTA operating speed as well as the cardiac index. Keeping the mean arterial pressure and ejected mean blood at a certain level is very important to maintain the proper organ functions. Therefore, these parameters should be at the healthy level in mechanical circulatory device supported cardiovascular system. This parameter increased to level in the healthy model at 11000 rpm HTA operating speed.High systolic pulmonary arterial pressure in the DCM model reduced to healthy level at 10000 rpm HTA operating speed. Pulmonary arterial pressure at the diastole in DCM model was higher than the healthy model. This parameter decreased to healthy level at 10000 rpm HTA operating speed. The high end-systolic and end-diastolic volume in the left ventricle decreased under HTA support. The end-systolic volume reduced to the healthy level at 11000 rpm HTA speed while end-diastolic volume was lower than the level in healthy model. The end-diastolic volume increased while the end-systolic volume decreased with respect to DCM model under HTA support.In a DCM patient heart rate increases for maintaining the cardiac output and systemic arterial as in the healthy situation. In the DCM model heart rate became 75 bpm increasing by 10 bpm with respect to healthy model. HTA support caused a decrease in this parameter by increasing the afterload. At 10000 rpm operating speed, heart rate was 67 bpm.In this study, a numerical model was developed for describing the pressure-flow rate relation of a new CF-LVAD to evaluate the hemodynamic response of a DCM cardiovascular system model under support of this CF-LVAD. The CFD analyses were performed for the operating speeds between 5000 rpm and 15000 rpm. The reverse flow rate-pressure relation in the pump was assumed to have the same relation as the forward flow rate-pressure relation.The results also give an insight about the possible operating speed interval of this CF-LVAD in a patient. At 11000 rpm HTA operating speed the mean arterial pressure and, the mean pump output reached the same level as in the healthy model. However, left ventricular peak pressure was very low at this speed. The blood flow through HTA regurgitated at the operating speeds below 10000 rpm because of the relatively high pressure at the outlet of the pump. This should be avoided for achieving an efficient mechanical circulatory support in the patient. Therefore HTA should not operate at the speeds lower than 10000 rpm in a patient.Existence of the baroreflex model allowed us to evaluate the response of the cardiovascular system model with respect to changing heart rate. The effect of the CF-LVAD on the hemodynamical parameters without the model of baroreflex would be slightly different because of keeping the heart rate constant. This model also showed the effect of the HTA support on the heart rate.In a DCM patient, the total blood volume increases for maintaining the perfusion level . We did In a mechanical circulatory assist device supported heart myocardium recovers due to support. However, this recovery is not sufficient to maintain the perfusion without CF-LVAD assistance . In thisNormally, there is a range for the optimum operating speed for such a device in the clinical applications and the optimal pump speed is determined according to the hemodynamical data monitoring the cardiac index and the left ventricle size in a patient . The fin


Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate. In the past decade, cardiac resynchronization therapy (CRT) has become an important treatment option for symptomatic heart failure patients with reduced left ventricular (LV) ejection fraction and abnormal QRS duration mostly in the form of left bundle branch block (LBBB). Until recently, little was known about the pathophysiology of the conduction disease and its adverse effects on ventricular contractility. Large clinical trials have shown that CRT benefits most patients but approximately one third of patients to not show clinical or echocardiographic response. Furthermore, further analysis of these studies show that the amount of responders was considerably higher in patients with LBBB as compared with patients without this conduction disease . These aOne hundred years ago, Eppinger and Tothberger reported distinctive changes in QRS morphology after the destruction of only a small region in the interventricular septum in canine hearts . Since tisolated LBBB as discussed more extensively elsewhere in this edition [Investigation of the electrical activation during LBBB can be performed in patients but is limited by the presence of comorbidities and the lack of knowledge concerning the duration and extent of the lesion (or lesions). Animal models can be used to specifically investigate the effects of  edition . Example edition . As is a edition . The LV  edition , 12. In  edition . Narula  edition .Fig. 1TyThe varying conduction patterns could thus be caused by one or more of the following aspects: (1) the varying structure of the LBB, (2) variability in the location of the LBB “block”, being either a proximal lesion or a more distal and diffuse disease, (3) LV hypertrophy and fibrosis as associated cellular uncoupling can result in increasing QRS duration and a LBBB-like QRS morphology . The hetThe key clinical investigation to detect and evaluate the extent of ventricular conduction delay remains the surface electrocardiogram. To diagnose LBBB in patients, specific ECG criteria exist in addition to QRS width ≥120 ms such as a broad notched or slurred R wave in leads I, aVL, V5, and V6, an occasional RS pattern in V5 and V6 attributed to displaced transition of QRS complex, and absent q waves in leads I, V5, and V6  . Note thmax). QRS duration was weakly associated with reverse remodeling probability and this relationship was replaced by LVATmax in the multivariable model. A longer LVATmax at baseline was predictive of CRT response . The Selvester QRS score was used to quantify LV scar and a higher score was detrimental to volumetric response  [V1 and V2 in expected direction) was also predictive of CRT response. An alternative method to estimate LV electrical asynchrony is by calculating the delay between QRS onset and LV lead depolarization. Varma found in heart failure patients that this delay exceeded 100 ms in 87% of LBBB patients as compared to 45% of RBBB patients, even though there was no difference in QRS duration [In the past decade, most efforts focused on finding dyssynchrony parameters to predict CRT response were based on echocardiography, which are discussed later in this review. Interestingly, recent studies have revamped the interest in using the surface ECG for exactly that purpose. An example is the PROSPECT trial where multiple echocardiography derived dyssynchrony parameters were investigated, followed by a sub-study where various ECG parameters were tested , 25. In = 0.002) . The appduration . Singh eduration  showed tp = 0.01). This study confirmed that the benefit of CRT is more dependent on specific LV activation patterns rather than on total LV activation time, which could explain why LVATmax beyond 125 ms, and in some studies QRS duration, are poor individual predictors of response [Studies investigating electrocardiography beyond surface ECG or pacemaker lead electrograms are even scarcer because evaluation of cardiac electrical activation sequence by catheter mapping in CRT candidates is time-consuming, cumbersome, and not without risk. Lines of conduction block are seen in most LBBB patients as shown by endocardial (EnSite) and epicardial (ECGi) non-contact mapping studies , 12. Theresponse , 30.Although the underlying pathophysiological mechanisms of how LBBB induces left ventricular dysfunction remain to be clarified, LBBB yields a disturbance of mechanical coordination between the different regions of the left ventricular walls, especially between septum and lateral wall. Moreover, the extremely variable and relatively unpredictable nature of response to CRT remains puzzling. Transthoracic echocardiography represents a non-invasive method that has been used to address some of these issues. The first measurements such as interventricular mechanical delay, septal posterior wall motion delay and pulsed-wave, color-coded tissue Doppler imaging were all measures of myocardial regional mechanical delay in patients with heart failure and ventricular conduction delays  is calculated . This raMost studies show that CRT response is higher in non-ischemic patients , 44. A pIn line with the pre-clinical data, clinical response after CRT is assumed to involve three key factors: lead position (in relation to area of greatest delay or vicinity to scar tissue), the presence of discoordinate and inefficient area of myocardial contractility, and quantity/degree of scarred tissue. However, rapid, effective, and integrated assessment of these features in the diagnostic build-up of patients considered for CRT, remains an unresolved challenge. Furthermore, the present literature offering aid remains scanty. Some important single center studies have shown how measures derived from CMR may be of great use. The relation between scar and left ventricular lead deployment has been unveiled using CMR late gadolinium enhancement , 47. Thimax values. However, LV dP/dtmax at best LV endocardial sites was greater than conventional CRT. Given individual variations in etiology, severity, patterns of delayed ventricular activation, location of regions of scar, and extent of mitral regurgitation in heart failure, it seems indeed unlikely that one pacing site will “fit all”. Individual tailoring of endocardial CRT by searching the optimal pacing site within the endocardium is warranted. LV endocardial pacing in humans can be established through an atrial transseptal approach [Worthy to mention is the study by Delgado et al.  who haveapproach , 54 or aapproach . In the approach  might betrue left bundle branch block, coexists with adequate morphological and anatomical conditions to allow adequate CRT delivery. In the future, integrated multi-modality imaging presents the central and challenging task to transfer pre-clinical knowledge into clinical practice, hence further defining the complex mechanical and functional effects of LBBB. On the other hand, with the aid of endocardial LV pacing, with- or without RV pacing, patient-specific tailoring of CRT will likely increase therapy success.Left bundle branch block results in asynchronous electrical activation, which can be largely reversed by CRT, thus conferring favorable clinical effects. It is imperative that correct electrical substrate, preferably in the form of


Mean platelet volume has been associated with stroke in patients with atrial fibrillation. However, its role as a predictor of left atrial stasis, assessed by transesophageal echocardiography, in patients with non-valvular atrial fibrillation has not yet been clarified.Single center cross-sectional study comprising 427 patients admitted to the emergency department due to symptomatic atrial fibrillation and undergoing transesophageal echocardiogram evaluation for exclusion of left atrial appendage thrombus before cardioversion. All patients had a complete blood count performed in the 12 hours prior to transesophageal echocardiogram. Markers of left atrial stasis were sought: left atrial appendage thrombus, dense spontaneous echocardiographic contrast and low flow velocities in the left atrial appendage. The presence of at least one of the former markers of left atrial stasis was designated left atrial abnormality. Binary logistic multivariate analysis was used for obtaining models for the prediction of transesophageal echocardiogram endpoints.Left atrial appendage thrombus was found in 12.2%, dense spontaneous echocardiographic contrast in 29.7%, low flow velocities in 15.3% and left atrial abnormality in 34.2%. Mean platelet volume (exp β = 3.41 p = 0.048) alongside with previous stroke or transient ischemic attack (exp β = 5.35 p = 0.005) and troponin I (exp β = 5.07 p = 0.041) were independent predictors of left atrial appendage thrombus. Mean platelet volume was also incorporated in the predictive models of dense spontaneous echocardiographic contrast, low flow velocities and left atrial abnormality, adding predictive value to clinical, echocardiographic and laboratory variables.These findings suggest that mean platelet volume may be associated with the presence of markers of left atrial stasis, reinforcing a likely cardioembolic mechanism for its association with stroke in patients with non-valvular atrial fibrillation. Thromboembolism is one of the most feared complications of atrial fibrillation (AF) . It may 2 score.The possibility of using biomarkers for thromboembolic risk stratification of patients with atrial fibrillation is a field of growing interest. The role of mean platelet volume (MPV) as a predictive marker of stroke in patients with AF has been recently suggested by Ha and colleagues . In thisVery recently, it was also shown in a case–control study that stroke patients with AF displayed higher MPV levels than patients with AF without stroke history of stroke . These aHowever, the precise mechanism underlying this relationship  is not completely understood. It is thought that at least 90% of thrombi in patients with AF originate in the left atrial appendage . Other mThe association of MPV with the different markers of left atrial stasis (i.e. its role as a marker of increased risk of cardioembolic stroke) in patients with non-valvular AF has not yet been addressed.To test the accuracy of MPV for predicting markers of left atrial stasis, detected while using transesophageal echocardiogram, in patients with non-valvular AF.A single center cross-sectional study was conducted using the following inclusion and exclusion criteria for the definition of the assessed population:Inclusion criteria:– All patients undergoing echocardiographic assessment, comprising both transesophageal and transthoracic echocardiogram, due to symptomatic AF leading to admission to the Emergency Department during a 36 months period.Step-wise exclusion criteria:– Lack of assessment of MPV in the 12 hours immediately before the echocardiographic assessment.– Valvular AF, defined as rheumatic heart disease, prosthetic heart valve or previous valve repair and moderate to severe mitral or aortic valve stenosis or regurgitation.– Presence of ongoing infection.– Diagnosis of acute myocardial infarction during the index event or in the previous month.Among a total of 611 subjects, 507 had performed a complete blood count 12 hours prior to transesophageal echocardiogram and were selected for possible inclusion the purpose of our investigation. Among these, 28 subjects with valvular AF, 49 with concomitant infection and 3 with final diagnosis of acute myocardial infarction were excluded from analysis. Our study population included the remaining 427 patients. All subjects provided their informed consent to undergo the necessary investigations and to allow the usage of their data for research purposes, preserving their anonymity.Baseline overall group characterization with demographic, anthropometric, clinical, laboratory and echocardiographic data, alongside with information on medication was obtained for all patients. Data was retrospectively retrieved from clinical records . This study was conducted with the approval of our Institution’s Cardiology Department Supervisor and Ethics Committee.Fatkin et al. [Transthoracic and transesophageal echocardiogram were performed using a GE Vivid 7 echocardiograph alongside with M4S (1.5–4.0 MHz) and 6 T phased array multiplane transesophageal (2.9–7.0 MHz) probes. All examinations were performed by two cardiologists with accreditation in transthoracic and transesophageal echocardiography by the European Society of Cardiology. Transesophageal echocardiogram was performed without anesthesia or sedation in more than 97% of patients. Images were later reanalyzed using the GE Health Care EchoPac Dimension software, PC version 108.1.4. Left atrium volume was measured using the single-plane area length method. On transesophageal echocardiogram, the left atrium and left atrial appendage were imaged in different tomographic planes to detect the presence of LAAT and DSEC. Spontaneous echo contrast was classified according to the classification (1 to 4+) proposed by The cardiologists performing the transthoracic and transesophageal echocardiogram were blinded for the lab results and clinical information of the patients other than the fact that they were in AF and there was need for excluding transesophageal echocardiogram changes that could contraindicate cardioversion.After venous blood was drawn, it was immediately transferred into our hospital’s laboratory using an automatic internal tube transference system directly connected from different parts of the hospital into the laboratory. On average laboratory measures were performed within 15 minutes of venous blood sampling.3/μL; platelets – 150 to 400 ×103/μL; plaquetocrit – 16.7 to 29.3%; MPV 8.17 to 9.65 fL; platelet distribution width (PDW) 14.7 to 17.4%.Automated blood cell counting was performed using the Cell-Dyn Sapphire Hematology Analyzer from Abbot Diagnostics. Reference range values for complete blood count data according to local calibration from our hospital’s laboratory were: hemoglobin – 13.0 to 17.5 g/dL; leukocytes – 4.0 to 10.0 × 10PASW Statistics version 18.0 was used for descriptive and inferential statistical analysis. Comparisons were performed according to the presence/absence of all markers of left atrial stasis. Chi-square was used for nominal variables and Student’s t-test was used for comparison of continuous variables, where appropriate; the Levene’s test was used in order to check the homogeneity of variance; equivalent non-parametric tests were used when Kolmogorov-Smirnov was in favor of absence of normal distribution. Results with p < 0.05 were regarded as significant.Univariate analysis was performed using the chi-square test. Predictors from univariate analysis were used for obtaining logistic regression models  that could predict all the transesophageal echocardiogram endpoints: LAAT, DSEC, LFV and LA ABN.2 vs. < 60 ml/m2[2 vs. < 27.0 Kg/m2[Continuous variables such as left ventricle ejection fraction (LVEF), and MPV were converted into ordinal variables and then used in the logistic regression analysis. Established cutoff points according to data available in the literature were: ≥ 55% vs. < 55%  and < 40 60 ml/m2; MPV > 9 60 ml/m2; body ma7.0 Kg/m2. When cu2 and CHA2DS2-VASc values were 2.1 ± 1.2 and 3.7 ± 1.7, respectively. Only 147 patients (34.4%) were under oral anticoagulation and 73 of these (49.7%) had an INR ≥ 2.0. In 38.6% (n = 165) of subjects there was no previously known history of AF.The patients’ baseline clinical, echocardiographic and laboratory characterization is shown on Table 95%CI 1.004-2.901), a higher CHADS2 score and were more frequently medicated with angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers. These patients also displayed lower platelet count levels, higher rise in troponin I levels and a more dilated left atrium and left ventricle.Comparisons of patients with MPV ≤ vs > 9.4 fL are shown on Table The following prevalence of markers of left atrial stasis was found on transesophageal echocardiogram: LAAT in 12.2%, DSEC in 29.7%, LFV in 15.3% and LA ABN in 34.2% (Table 3/uL (sensitivity = 46.8% and specificity = 67.6%) and  ≥ 3.23 mm/m2 (sensitivity = 58.3% and specificity = 75.1%), respectively.After the analysis of ROC curves concerning the discrimination of LAAT, the following cutoff values for platelet count and indexed left ventricle diastolic diameter were found: ≥ 240 × 10On univariate analysis MPV was a predictor of all markers of left atrial stasis. Congestive heart failure, stroke or TIA, AF episode duration, platelet count, troponin I, iLVdd, iLAV and LVEF were among the other predictors of LAAT on univariate analysis.Predictors of DSEC, LFV and LA ABN on univariate analysis are shown on Table On logistic regression, MPV remained an independent predictor of all markers of left atrial stasis, adding predictive value to clinical variables , troponin I and echocardiographic parameters  that were also included in the predictive models Table .MPV was the only variable that could independently predict the presence of all markers of left atrial stasis.2 score , echocardiographic parameters  and other biomarkers (troponin I), as far as prediction of all transesophageal echocardiogram markers of left atrial stasis are concerned.Our data shows that MPV was associated to an increased prevalence of LAAT, DSEC, LVF and LA ABN, echocardiographic markers that are known to associate with cardioembolic stroke and an adverse prognosis in patients with AF. Thus, on logistic regression multivariate analysis MPV was able to add additive predictive value to clinical parameters from the CHADSThese results suggest that the recently described increased prevalence of stroke in patients with AF and elevated MPV  is possiFirst, in patients undergoing procedures like cardioversion or AF ablation, a transesophageal echocardiogram (a semi-invasive and highly uncomfortable exam for most patients) is frequently needed in order to rule out the presence of LAAT. By proving the association of MPV with this type of marker, we may contribute to the future development of probabilistic risk scores, combining several variables, that may allow the selection of patients who can be spared this examination (since they are very low risk), or identify those that are very high risk, and therefore must necessarily perform it to prevent thromboembolic complications related to the procedure.Second, a possible explanation for the association of MPV with stroke could be the increased platelet reactivity leading to peripheral thrombi formation. By showing that this may, in fact, be due to cardioembolism, adequate therapeutic interventions may be pursued or developed for targeting these alterations in patients with AF who test positive for this marker.Third, novel biomarkers are now being tested in patients with AF in order to improve thromboembolic risk stratification . By demoLarger platelets are thought to be younger, more reactive and more thrombogenic ,15. MPV The only investigation assessing the relation between left atrial stasis markers (focusing only on LAAT) and MPV provided negative results towards an association . Still, Based on investigations concerning the composition of spontaneous echocardiographic contrast (thought to be composed of aggregated activated platelets and leucocytes ) we are 2[2DS2-VASc score [Thromboembolic risk stratification of patients with AF is currently based on clinical schemes: the CHADS2 and CHA2Sc score . In our Sc score  that disTroponin I has already been associated both with thromboembolism  and withAs far as echocardiographic assessment of the left ventricle is concerned, evidence has been more robustly in favor of an association between both LVEF and LAAT ,25 and bTo best of our knowledge this is the first report of an association between MPV with markers of left atrial stasis. In face of these results, we may hypothesize that mean platelet volume may be used in the future for assessing patients that are candidates to procedures like catheter ablation or cardioversion of atrial fibrillation. Moreover, these data support the need of its prospective assessment for risk stratification of AF. Due to its wide availability and low cost, mean platelet volume is a potential candidate for this setting.A low prevalence of patients undergoing oral anticoagulation was found in our sample. Still, we reinforce that 165 patients (38.6%) had no previous diagnosis of AF. If we consider only patients with previously known AF the prevalence of patients undergoing oral anticoagulation rises steeply to 56.1% (147 out of 262). Therefore, our results can be applied to patients presenting to the emergency department due to symptomatic AF, but probably not to different subsets of patients, like those undergoing percutaneous AF ablation, who have an expected very high prevalence of oral anticoagulation.Patients over age of 75 displayed a lower prevalence of DSEC on univariate analysis, that was not confirmed after correction for other variables. This may be due to a selection bias, as we only select elderly patients who are very symptomatic and have a preserved biological age for the transesophageal echocardiogram and subsequent cardioversion strategy. As they usually have less risk factors and less severe disease than frail elderly who are directly referred to rate control strategy, this leads to the observed trend for lower prevalence of some markers of left atrial stasis in the transesophageal echocardiogram plus rhythm control strategy.73 patients (17.1%) had no evaluation of left atrial appendage flow velocities. This was due to technical reasons (echocardiographic data being classified as unsuitable for the accurate assessment of flow velocities) or lack of probe tolerance by the patients (sedation was used in less than 3% of patients). In these subjects, transesophageal echocardiogram was performed without measurement of left atrial appendage flow velocities if the presence of LAAT and DSEC could be excluded right away.Our results, using left atrial stasis markers, suggest that mean platelet volume are associated with the presence of left atrial stasis in non-valvular atrial fibrillation. These findings support the likely role of a cardioembolic mechanism in the association between mean platelet volume and stroke in patients with non-valvular atrial fibrillation, reinforcing the possible usefulness of anticoagulation in this patient subset.Further prospective investigations  will be necessary to confirm the plausibility and role of mean platelet volume as a part of risk models aiming to discriminate the presence of left atrial appendage thrombus in atrial fibrillation patients undergoing procedures like percutaneous ablation or cardioversion.AF: Atrial fibrillation; DSEC: Dense spontaneous echocardiographic contrast; LAAT: Left atrial appendage thrombus; LFV: Low flow velocities; MPV: Mean platelet volume; TIA: Transient ischemic attack; LVEF: Left ventricle ejection fraction.The authors declared that they have no competing interest.RP designed the study, draft collected data and wrote the first of the manuscript; AF, LP, AF, SB and JP, collected data and critically revised the first draft of the manuscript; JT and AB performed and analyzed all echocardiograms and revised the first draft of the manuscript; AMLM helped in the design of the study, interpretation of data and revised the first draft of the manuscript. All authors read, revised and accepted the final version of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/13/40/prepub


Data are scarce on long-term effects of Bentall procedure on left ventricular systolic function and functional status. Aim was to assess long-term effects of Bentall procedure on left ventricular (LV) systolic function and functional status.Study group consisted of 90 consecutive patients who were operated using elective Bentall procedure for the aneurysm of the ascending aorta and aortic valve disease from 1997 to 2003 in a single tertiary care center. Patients were followed for eight years for mortality, LV ejection fraction and volume indices, as well as functional capacity as assessed by NYHA class. Echocardiographic measurements were made according to the recommendations given by the American Society of Echocardiography.Study group consisted of 71 male and 19 female patients, mean age 54+/-10 years. There were no operative deaths. Survival rate was 73.3% during eight-year follow-up (11 cardiac and 13 non-cardiac deaths). Echocardiography was performed before index procedure and after 96+/-9 months. Statistically significant improvement in the LV ejection fraction was noted at follow-up examinations as compared to preoperative values . Similarly, statistically significant reduction in the LV end-systolic  and end-diastolic volumes  were observed. NYHA class improved from baseline during the follow-up . Univariate analysis identified ejection fraction on admission and the presence of postoperative complications as predictors of long-term LV ejection fraction.Bentall procedure significantly improves long-term LV systolic function and functional status.


The presence of late gadolinium enhancement (LGE) is related to cardiac remodeling and poorer prognosis in ischemic and non-ischemic cardiomyopathies. Non-invasive LGE- cardiovascular magnetic resonance (LGE-CMR) is able to detect infarct-typical and -atypical patterns of LGE after heart transplantation (HTX), mainly due to post HTX coronary artery vasculopathy (CAV) and myocarditis. In this study, we sought to describe the influence of the presence and patterns of both LGE forms on left ventricular (LV) remodeling after HTX.153 HTX patients were divided into 3 groups depending on the presence and pattern of LGE . 146 patients received coronary angiography within 4 weeks after CMR for assessment of CAV. Vector-ECG gated 32-channel parallel imaging cine SSFP sequences for standard imaging plane and LV volumetry acquisition were acquired on a 1.5T Whole Body MRI scanner . LGE-CMR (Gadolinium:0.2 mmol/kg) imaging was performed and analyzed blindly by two experienced observers. Patients were divided according to the presence and patterns of LGE. CAV was divided into three groups:1=mild;2=moderate;3=severe post transplant coronary artery disease. Data were expressed as mean and standard deviation or percentage. Groups were compared using Chi Square for categorical data and ANOVA or Kruskal-Wallis tests for continuous variables. P-values ≤ 0.05 were considered statistically significant.Overall, 135 patients (88%) presented patterns of LGE, whereas infarct-atypical patterns were more prevalent (66%). Group II showed significantly lower ejection fractions (56±12%) when compared to group I (63 ± 8%) and III  but significantly increased end-diastolic (83±26ml/m2) volumes/BSA  and end-systolic volumes/BSA (38±21ml/m2 vs. group I=26±8ml/m2 and III=28±5ml/m2; p<0,001, Figure The presence of infarct-typical LGE-CMR is related to negative post HTX remodeling revealing lower ejection fractions and increased volumes in patients after HTX. Future studies are warranted to evaluate the long-term effect of infarct-typical and atypical patterns on future post HTX outcomes.none


D corresponding to VTCs ranged between 2.05 and 2.2 and varied as a function of time during the cardiac cycle. Fractal dimension is highest at diastole and lowest at peak systole with the change being significantly different (P < 0.003). This variation of D when plotted against stroke volume  revealed an active VTC role due to hysteresis in the loop. Physically the hysteresis in the D-V loop indicates a new mechanical function of VTCs as structures that provide mechanical leverage during early systolic ejection through contraction. VTC relaxation is noted to occur during late diastole at larger ventricular volume. D-V loop of VTCs quantifies VTC function. A new dynamic physical role of VTCs is suggested by way of mechanical leverage, as opposed to the traditionally accepted passive role.The ventricular-blood interface is geometrically complex due to the presence of ventricular trabeculae carneae (VTC). We introduce a new image-based framework to quantify VTC function using high-resolution computed tomography (CT) imaging and offer new insights into the active role of VTCs during ejection. High-resolution Cine CT scans of a patient with normal cardiac function were acquired at a resolution of 0.77 mm per pixel at 10 phases of the cardiac cycle. The images were segmented and the VTC surface was obtained by triangulating the segmented data. Fractal dimension of the VTC surface was calculated for each cardiac phase as a function of scale size using the box-counting algorithm. The fractal dimension,  In this study, we introduce a technique to determine and quantify active ventricular trabeculae carneae (VTC) function through clinical computed tomography (CT) imaging and examine VTC contributions to systolic and diastolic function of the ventricle. While quantifying macroscopic or gross properties of the pumping chambers and heart valves, such as size, overall shape, and valve performance indices are well established spanning over many imaging modalities, no quantitative noninvasive image-based methodology exists to characterize the function of the small-scale fingerlike projections known as trabeculae carneae. Trabeculations are particularly prominent in the ventricles and are known to originate during early embryonic development when woven cardiac fibers are “compacted” into a solid, continuous structure  determine and quantify any dynamic VTC function via high-resolution computed tomography, and (2) report new mechanistic insight that had not been previously conceptualized with respect to VTC dynamics in a healthy heart. By accomplishing both of these aims, a methodology and baseline measurements are established for assessing trabecular function. Furthermore, reducing such measurements to a simple, quantifiable parameter – fractal dimension – could enable clinicians to much more easily interpret complex imaging data.D(λ) is a measure that quantifies precisely the dimensionality of such objects as a function of scale size λ. Thus, a surface which appears 2D at the 1-mm scale range may appear to be more 3D  at a larger scale. To be precise, D(λ) quantifies the exact dimensionality of the object, which for the case of the human lung, or the ventricular surface is a number between 1 and 3, and not necessarily equal to the integer value of 2. Such analysis tools have also been previously used to characterize electrocardiogram (ECG) data with clinical utility  object with an area associated as a measure of its size. Similarly, a three-dimensional (3D) object is associated with volume as a measure of its size. Nevertheless, nature consists of surfaces that are extremely convoluted in a way that even though these surfaces exist within a finite volume, their surface area is extremely large. The ventricle contains such a surface, and while it has not before been studied using fractal geometry, it is an excellent candidate for such analysis. This is due to its complex topology, subtle changes in which are virtually undetectable without the use of fractal tools. Examples of other cardiovascular structures or phenomena with similar geometric properties that have been analyzed via fractal geometry include the lung Buchman , arteriaD(λ) is a function of scale size, λ. This interface consists of the outline of VTCs and the papillary muscles. A full 3D model of this surface  is the number of boxes of size D(λ), needed to fully cover the interface. D(λ) was determined for a range of scales, from ∼0% to 50% of the total/longest length scale of the ventricle. The D(λ) profiles obtained as a function of cardiac phase represent the temporal variations in the multi-fractal properties of the VTC interface structure.We begin with the notion of the ventricular-blood interface being modeled as a scale-dependent multi-fractal object whose fractal dimension, see Fig.  was acqusee Fig. , which eA validation study was carried out to verify the accuracy of our in-house code. Fractals with known dimension values were created, and the box-counting dimension was computed and compared to the known dimension. Because these theoretical shapes are generated through an iterative procedure, the box-counting dimension was computed at multiple iterations. Results are presented in Figure D(λ) profiles of the ventricle during five key phases of the cardiac cycle. As seen in the figure, the fractal dimension of the VTC surface is indeed scale dependent. The concave down profiles indicate that the complexity of the interface  is highest at an intermediate scale corresponding to where D(λ) profile achieves a local maximum. From the figure D(λ) is maximum at relatively low scales where λ ∼3–6 mm. This scale range is consistent with the anatomical size of VTCs structures  illustrate a general temporal trend. During ventricular systole, D(λ) consistently decreases with respect to time with the reversal of this trend in ventricular diastole.Figure D(λ) averaged over a range of scales. This was achieved by averaging or “binning” the D(λ) profiles of Figure D(λ) defined over these scale ranges are shown in Figure P < 0.003) during systolic ejection, which occurs within the initial 40% of the cardiac cycle followed by the more gradual increase in dimension during diastole. The temporal variation in dimension at the large scale is not statistically significant.To better understand the time-dependent complexity in the shape of VTC structures over the cardiac cycle, we further examine these changes by segregating the temporal response of D(λ) analysis to observable changes in the geometry of the interface, we present 2D slices along the long and short axes  means there must be a change in the number of boxes ). For this to occur, a fractal surface must alter its geometry to take up either more or less space. Because a fractal surface is made up of a number of features that determine its space-filling capacity, it must alter these features to change its box count, and therefore its dimension. A surface can achieve this in three ways: by changing (1) feature frequency, (2) feature size, or (3) feature complexity. By features, we refer to projections or cavities that define the VTCs relative to the overall shape of the ventricular-blood interface. Illustrations of these three ways are depicted in Figure h, frequency s, and spanning an overall length of L as shown in Figure Vtot is dependent on the amplitude, h, of a feature, it shows that variations in feature size indeed cause a volume displacement. Figure Here we attempt to offer a physical explanation behind this observation. The physical argument is that when the VTC interface changes its dimension, it must actively displace blood, and therefore perform a portion of the pressure-volume work/energy transferred to the blood. A physical heuristic argument supporting this notion can be made by examining the definition of fractal dimension as described by the box-counting algorithm . However, with the gain of momentum, the gear ratio can be shifted in order to yield larger displacement without the need for such large forces. The observations presented here are very similar. Systolic ejection of blood appears to be achieved by changing the small-scale geometric features to minimize mechanical effort. The Law of Laplace states that, to develop a certain pressure inside the ventricle, less muscular tension is required for a region of high curvature as opposed to one of low curvature Burton . As the In summary, we have presented new insight into the physical role of the complex anatomical features called VTCs that are present on the ventricular-blood interface in the human heart. Given the complexity of their geometry, the tools of fractal geometry have been utilized to quantitatively describe the anatomical changes in VTC geometry over the cardiac cycle. We show that the significant changes in multi-fractal dimension at the VTC length scales describe a mechanism to enhance mechanical leverage to initiate ejection during early systole. These results are the first of its kind to describe the complex biomechanical role of VTCs in the physiology of ventricular ejection phase. Future work is obviously needed to better understand the clinical relevance of the above findings with respect to factors such as age, gender, status of heart disease, etc. in large patient databases. The limitation of this study is that it only offers a novel hypothesis regarding the potentially new mechanical role of VTCs in cardiac pumping.


Compared with adults, cardiac emergencies are infrequent in children and clinical presentation is often quite variable. In adults, cardiac emergencies are most commonly related to complications of coronary artery disease; however, in pediatric cases, the coronaries are only rarely the underlying problem. Pediatric cardiac emergencies comprise a range of pathology including but not limited to undiagnosed congenital heart disease in the infant; complications of palliated congenital heart disease in children; arrhythmias related to underlying cardiac pathology in the teenager and acquired heart disease. The emergency room physician and pediatric intensivist will usually be the first and second lines of care for pediatric cardiac emergencies and thus it is imperative that they have knowledge of the diverse presentations of cardiac disease in order to increase the likelihood of delivering early appropriate therapy and referral. The objective of this review is to outline cardiac emergencies in the pediatric population and contrast the presentation with adults. In adults, cardiac disease is not uncommon and the majority of causes of sudden cardiac death are due to atherosclerotic coronary artery disease. However,Congenital heart diseases (CHD) are rare conditions, and the mortality is highest among infants and children and among the severe cardiac defects, such as hypoplastic left heart syndrome (HLHS). In the majority of the cases, mortality can be attributed to the underlying heart defect. Infants Left-sided obstructive lesions include HLHS, critical aortic stenosis, and coarctation of the aorta represent 12.4% of CHD. In HLHS 2 content.Right-sided obstructive lesions such as severe tetralogy of Fallot and pulmonary atresia with intact ventricular septum depend on ductal patency to provide blood flow to the pulmonary artery. As the ductus closes, infants develop progressive and rapid cyanosis not improved with oxygen administration and respiratory distress. Prostaglandins should be started immediately to reopen the ductus arteriosus in order to provide pulmonary blood flow through left to right shunting (aorta across the PDA to pulmonary artery), as opposed to the right to left shunt on left-sided obstructive lesions. In these lesions, 100% oxygen is useful to improve pulmonary blood flow and increase dissolved OWhereas ductal dependent lesions typically present early after ductal closure within the first two weeks of life, other CHD usually present in four-six weeks after birth when the pulmonary vascular resistance has fallen, such as a large ventricular septal defect. CongestiALCAPA  is a typSome patients with ALCAPA may survive undetected through adolescence and adulthood due to the development of significant collateral circulation from the right coronary artery to the LCA. However, these collaterals may not be sufficient to perfuse the left ventricle, and these patients are at risk of chronic mitral regurgitation, ischemic cardiomyopathy, and sudden cardiac death from malignant ventricular arrhythmias in 80-90% of cases.8Myocarditis is an often insidious, inflammatory disease of the myocardium preceded by a non-specific flu-like illness. Myocarditis may have a fulminant presentation characterized by acute severe hemodynamic compromise with severe congestive heart failure or cardiogenic shock. It is the most common cause of dilated cardiomyopathy in children. The sympCardiomyopathies are a heterogeneous group of myocardial diseases that causes significant disability and death. They are characterized by inappropriate ventricular hypertrophy or dilatation and are associated with electrical dysfunction or systolic and/or diastolic ventricular dysfunction.Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by dilation of the left ventricle and systolic dysfunction. Progressive heart failure ensues with resultant sudden and heart failure related death. DCM is the most common reason for heart transplantation in children and adults. In children, myocarditis is the most frequently identified cause followed by neuromuscular diseases, whereas 2325Unfortunately cardiac arrest and sudden death may be the first presentation of Hypertrophic cardiomyopathy (HCM) . It is t29Arrhythmias are far more common among adults than children, but are equally as important for the clinician be able to recognize the abnormal rhythm, respond immediately and treat appropriately. Of adults presenting to the emergency room with an acute myocardial infarction, 90% have a rhythm abnormality and 25% have a conduction disturbance. Most pedThe tachyarrhythmias can be characterized as supraventricular or ventricular. The most common symptomatic pediatric arrhythmia is supraventricular tachycardia (SVT) with an incidence of 1 in every 250 to 1,000 children. In infants, half are due to idiopathic causes, a quarter caused by congenital heart disease such as Ebstein’s anomaly, and 10-20% due to Wolff-Parkinson-White (WPW) syndrome, a type of AV reentrant tachycardia characterized on EKG by a delta wave, wide QRS, and short PR interval. It should be suspected if there is a regular and rapid heart rate usually greater than 180 bpm in older children and greater than 220 bpm in infants34 On theVentricular fibrillation (VF) and pulseless ventricular tachycardia (VT) are the common causes of cardiac arrest in adults and often due to coronary artery disease. Fourteen percent of children compared to 23% of adults had VF or pulseless VT as the first documented rhythm during in-hospital cardiac arrest. However,On EKG, VT is a wide QRS complex tachycardia that can be monomorphic or polymorphic, and VF has a fine or coarse chaotic rhythm with no discernible QRS complexes. Defibrillation is the treatment for VT/VF along with prompt and effective CPR. There is42Kawasaki disease does not usually present as a critical emergency; however, timely recognition and treatment can prevent the leading cause of acquired heart disease in children in the United States and fataChildren with a protracted febrile illness greater than five days with two to three of the clinical features of Kawasaki, incomplete Kawasaki should be considered. Moreover, the AHA recommends that an infant less than six months with fever greater than seven days and laboratory signs of systemic inflammation even without clinical features should have an echocardiogram. MortalitAortic dissection is rare in infants and children, and is associated with inherited disorders such as Marfan syndrome and other connective tissue disorders, and after balloon dilation of coarctation and re-coarctation, complication of cardiopulmonary bypass at the aortic cannulation site, and in young adults with a bicuspid aortic valve and ascending aortic dilation.51 In conThe clinical presentation in aortic dissection will vary based on the origin and extension of the dissection. Typically, there is abrupt onset of sharp pain that may change in location, followed by congestive cardiac failure due to severe aortic regurgitation. Patients may present with syncope, cardiac tamponade, stroke, limb ischemia with pulse deficits, paraplegia, and if renal or mesenteric arteries are involved may result in oliguria/anuria or have persistent abdominal pain. A diastolic murmur of aortic regurgitation and the typical wide pulse pressure is present in half of patients with proximal dissection. Aortic rupture into the pericardium with cardiac tamponade  or the pleural space are indications for surgical emergencies.A detailed history and physical exam should be performed; a patient with stigmata of Marfan syndrome or other connective tissue disease would raise the index of suspicion for dissection compared to other possible diagnoses . An EKG is important to differentiate acute myocardial infarction to prevent the administration of thrombolytic therapy that would be detrimental in aortic dissection. Although, 20% of patients with dissection involving the ascending aorta have evidence of ischemia or infarction as the dissection extends into the coronary ostium, and in this situation, additional imaging studies should be preformed to confirm the dissection if the index of suspicion is high. Diverse imaging modalities can be used to detect aortic dissection. Transthoracic and transesophageal echocardiography can be useful in the emergency room and operating room for emergent decision making. CT scans are the most often used technique in patients with suspected aortic dissection and have a high sensitivity and specificity. Branch vessel involvement can be accurately identified with contrast angiography, and should be used in patients with neurological symptoms, acute renal failure, and limb and mesenteric ischemia.Patients should be in an intensive care unit with blood pressure and heart rate monitoring. Fluid repletion, pain relief (e.g. morphine) and blood pressure lowering drugs, starting with a beta blocker and adding intravenous sodium nitroprusside for severe hypertension are important initial therapies. Surgical management in children is guided by similar principles as adults, with the emphasis on prophylactic intervention in patients with underlying dilation to prevent dissection.Pulmonary embolism (PE) is an uncommon cardiovascular emergency in children, although relatively common in adults. However, adolescent females with collagen vascular diseases or on birth control increase the risk as well as the increasing population of obese teenagers. Acute but often reversible right ventricular failure can result from pulmonary arterial occlusion by thromboemboli. The hemodynamic consequences of PE results when large and/or multiple emboli  acutely increase pulmonary vascular resistance, and the afterload that the right ventricular has to pump against is too high leading to RV failure. This can lead to sudden death or syncope with systemic hypotension that might progress to shock and death from acute RV collapse. The mortality rate is higher in children and they are more likely to be diagnosed at autopsy, where approximately 60% presented with sudden death. The most common predisposing factors were central venous catheters, malignancy, cardiac or other major surgery, and infection/sepsis. FurthermThe goal of diagnosis and appropriate treatment is to decrease mortality by preventing potentially lethal recurrent large thrombi. Clinical signs, symptoms and laboratory studies are not sensitive or specific to confirm or exclude PE, but should increase the index of suspicion to proceed with additional imaging. Such as, an electrocardiogram may show RV strain , but this finding is not specific to PE and may be present in other causes of RV strain.Diagnostic imaging include venous ultrasonography to detect DVT; echocardiography to detect right heart thrombi, a right to left shunt through a patent foramen ovale (an indication of elevated right sided pressures), and right ventricular dysfunction  findings which were associated with greater than two-fold increased risk of PE-related mortality; V/Q lungHeparin followed by oral anticoagulation therapy is the standard treatment for PE. In children, the use of thrombolytic therapy, such as tissue plasminogen activator (tPA), and surgical or transvenous catheter embolectomy may be considered in hemodynamically unstable patients at high risk of death due to RV failure. This can quickly reduce the RV afterload by recanalization of the occluded pulmonary arterial bed.While there are some similarities in cardiac disease in children and adults, there are some very important differences as well. Clinicians who care for children, even occasionally, should be aware of diseases that are unique to children  as well as the clinical presentations that are more unique to children . In addition, they should be aware of some of the approaches to therapy that differ from that of adults with cardiac disease . Prompt recognition and treatment of cardiac emergencies and consultation of pediatric intensivists and cardiologists in children can lead to improved outcomes.


Edge-to-edge repair of the mitral valve (MV) has been described as a viable option used for the surgical management of mitral regurgitation (MR). Based on the significant changes in MV geometry associated with this technique, we hypothesized that edge-to-edge MV repairs are associated with higher intraoperative transmitral pressure gradients (TMPG) compared to conventional methods.Patient records and intraoperative transesophageal echocardiography (TEE) examinations of 552 consecutive patients undergoing MV repair at a single institution over a three year period were assessed. After separation from cardiopulmonary bypass (CPB), peak and mean TMPG were recorded for each patient and subsequently analyzed.84 patients (15%) underwent edge-to-edge MV repair. Peak and mean TMPG were significantly higher compared to gradients in patients undergoing conventional repairs: 10.7±0.5 mmHg vs 7.1±0.2 mmHg; P<0.0001 and 4.3±0.2 mmHg vs 2.8±0.1 mmHg; P<0.0001. Only patients with mean TMPG ≥7 mmHg (n = 9) required prompt reoperation for iatrogenic mitral stenosis (MS). No differences in peak and mean TMPG were observed among edge-to-edge repairs performed in isolation, compared to those performed in combination with annuloplasty: 11.0±0.7 mmHg vs 10.3±0.6 mmHg and 4.4±0.3 mmHg vs 4.3±0.3 mmHg. There were no differences in TMPG between various types of annuloplasty techniques used in combination with the edge-to-edge repairs.Edge-to-edge MV repairs are associated with higher intraoperative peak and mean TMPG after separation from CPB compared to conventional repair techniques. Unless gradients are severely elevated, these findings are not necessarily suggestive of iatrogenic MS. Thus, in the immediate postoperative period mildly elevated TMPG can be expected and tolerated after edge-to-edge mitral repairs. Cardiac surgical intervention for the treatment of significant mitral regurgitation (MR) currently involves a wide variety of techniques. Over the last two decades there has been a shift in surgical management with increasing emphasis on mitral valve (MV) repair over replacement due to purported advantageous patient outcomes The edge-to-edge surgical technique, also referred to as ‘Alfieri stitch’, was introduced in the early 1990's An important concern during MV repair is the potential for acute, iatrogenic MS. The estimation of diastolic pressure gradients conventionally derived from a transmitral flow velocity spectral Doppler profile using the simplified Bernoulli equation correlates well with invasive measurements, and is considered a Level 1 recommendation in assessing the stenotic MV 552 consecutive patients who underwent MV repair for MR over a three-year period at the Brigham and Women's Hospital, Boston and who had intraoperative, post-CPB transmitral Doppler flow velocity profiles recorded during routinely performed TEE were included in this analysis. Data were collected prospectively as part of a Brigham and Women's Hospital and Partners Human Research Committee–approved protocol, with a waiver of informed consent to review the patients' medical records. The records were reviewed for patient demographics, type of surgical procedure, type of MV repair, intraoperative TEE examination data, and incidence and indication for MV reoperation prior to hospital discharge.Comprehensive routinely performed intraoperative TEE examinations were conducted with multiplane TEE probes . Peak TMPG were calculated using the simplified Bernoulli equation and derived mean TMPG were obtained from transmitral diastolic Doppler flow velocity curves by continuous-wave Doppler obtained in a midesophageal four chamber view following successful wean from CPB. TEE examinations were electronically recorded and analyzed off-line by two physicians with extensive experience in perioperative TEE. Peak and mean TMPG were obtained from the average of separate measurements of post-CPB transmitral Doppler flow velocity profiles obtained over three consecutive heart beats. As PHT measurements have been previously shown to greatly vary within this patient population, this parameter was omitted from the analysis As previously described, the decision to reoperate was made on a case-by-case basis weighing operative considerations and individual patient factors Demographics were tabulated and descriptive statistics computed. Numerical results are expressed as mean ±SEM. The echocardiographic data from the two independent analyses were averaged. Mean values for echocardiographic parameters were analyzed by unpaired t-test with the use of Graph Pad Prism 5 software for Windows . When numerical P values are not specified, P<0.05 was considered significant.552 consecutive patients who underwent MV repair and had interpretable Doppler exams were included in this analysis. An additional 26 patients were excluded as they had insufficient TEE recordings to measure TMPG. There were no demographic and preoperative differences found between Alfieri and non-Alfieri repairs with a male-to-female patient ratio of approximately 2∶1. The majority of patients (>75%) in both groups underwent mitral repairs alone or in combination with CABG . 84 15%.Inter- and intraobserver variability of gradient measurements were minimal with Pearson's r and 95% CI of 0.989  for peak TMPG and 0.964  for mean TMPG. Patients in the edge-to-edge repair group had mean and peak TMPG of 4.3±0.2 mmHg and 10.7±0.5 mmHg, respectively. These Doppler-derived gradients were significantly higher than mean and peak TMPG in patients following conventional repairs: 2.8±0.1 mmHg and 7.1±0.2 mmHg, P<0.0001 . There wTMPG measurements reliably predicted the occurrence of iatrogenic MS requiring prompt reoperation in our previous study While MV repair remains the preferential technique for surgical approaches to MV disease, a wide variety of techniques have been recommended based upon the mechanism and etiology of disease, as well as surgeon and institutional preferences. The edge-to-edge or ‘Alfieri’ procedure is convenient because it can be performed efficiently, and can be applied to a variety of regurgitant lesions and is technically less demanding 2), the edge-to-edge technique did not result in higher TMPG compared to traditional Carpentier-type repairs: the mean mitral gradients at rest were not significantly different between the two groups (3.8 vs 3.3 mmHg). At peak exercise, the increase in TMPG pressure gradients and maximum oxygen uptake were also comparable between both groups. It was hence postulated that artificially created double-orifice valves still follow physiologic principles during exercise with adequate valvular reserve in response to increased cardiac output. However, the application of these findings to the intraoperative setting remains unclear.Several studies have addressed the question of the hemodynamic effects of edge-to-edge repair as well as postoperative MV function and functional reserve at rest and during exercise. The hemodynamic performance of the double-orifice mitral valve seems to depend more on total valve area and cardiac output than on the change in geometry  Barring any patient-specific contraindications, TEE is a safe imaging modality that is commonly used in cardiac surgery TMPG obtained by Doppler echocardiography are a reliable postoperative diagnostic tool in patients with mean gradients usually <5 mmHg as determined by TTE In conclusion, mean TMPG of approximately 4 mmHg and peak TMPG of approximately 10 mmHg obtained intraoperatively immediately after mitral valve edge-to-edge repairs appear to be well tolerated even though they are reproducibly higher compared to TMPG after conventional mitral valve repairs. Mean TMPG in the range of 5 to 7 mmHg may warrant a thorough discussion regarding further intraoperative management with the cardiac surgeon. The individual patient's risks and benefits of prolonging the surgical procedure to correct rather than tolerate a mild degree of intraoperative MS need to be carefully weighed. Although not pathognomonic for iatrogenic MS, patients experiencing mean gradients exceeding 7 mmHg should be monitored vigilantly in the postoperative period, and remain at the highest risk for requiring a surgical correction independent of the previous repair type. Given the potential advantages of direct orifice area measurement and its independence from transmitral blood flow, improvements in two- and three-dimensional TEE may further facilitate the diagnosis of intraoperative mitral pathologies.


Previous studies have shown that there is a circadian variation in the incidence of acute myocardial infarction. The aim of this study is to examine the circadian rhythms of acute myocardial infarction in patients with type 2 diabetes.1016 consecutive patients admitted to a coronary care unit with acute ST elevation myocardial infarction were studied from January 2004 to December 2008. All patients were divided into two groups according to with or without diabetes. Admission rates were calculated according to the 6-hour interval of the day (circadian rhythm). The data were analyzed for variations within subgroups. In diabetic group, number of patients in the first to fourth quarters was 38, 45, 43, 46 respectively (NS). The corresponding figures for the controls were 174, 295, 183, 192 (P<0.01). The difference between the two groups was significant (P<0.02).There is no a significant circadian variation in the onset of acute myocardial infarction in diabetic subjects. Circadian variation of the onset of acute myocardial infarction (AMI) has been reported by some studies and may carry important pathophysiologic implications. Some studies show an increased onset in the morning between 6:00 AM and 12:00 noon. Furthermore, a secondary peak in the late evening has also been reported in some studies.1Diabetes neuropathy occurs in approximately 16~50% of individuals with long-standing type 1 and type 2 diabetes. It may manifest as polyneuropathy, mononeuropathyConsecutive patients admitted to the cardiac care unit (CCU) of Xuanwu hospital with ST segment elevation myocardial infarction (STEMI) between January 2004 and December 2008 were enrolled. Inclusion criteria were: age greater than or equal to 18 and diagnosis of STEMI. STEMI was diagnosed if two of the following criteria were present: (1) the presence of ischemic pain or other symptoms lasting ≥30 minutes; (2) ST-segment elevation of ≥ 2 mm in at least 2 contiguous precordial leads, ST-segment elevation of ≥1mm in at least 2 inferior leads , or new left bundlebranch block; (3) an increase in serum MB isoenzyme of creatine kinase(CKMB) to more than twice the upper limit of normal. Exclusion criteria: (1) myocardial infarction occurring after invasive coronary artery procedures such as percutaneous coronary intervention(PCI) or coronary artery bypass grafting history of myocardial infarction; (3) causes of myocardial infarction without coronary atherosclerosis.All subjects were assigned into two groups according to with or without diabetes.The diagnosis of type 2 diabetes mellitus was based on history of treatment with hypoglycemic agents and/or fasting blood glucose >126 mg/dl.We divided the day in into four 6-h intervals from 0:00 to 5:59, 6:00 to 11:59, 12:00 to 17:59, and 18:00 to 23:59 and calculated number of patients in each interval.For each patient enrolled, the structured data form was completed by experienced cardiologists within 72 hours after admission.Clinical features were obtained from coronary care unit admission logs and other medical documentation, including: (1) baseline data: age, gender, systolic and diastolic blood pressure, heart rate, smoking, history of disease . Duration from onset to emergency room was calculated. (2) laboratory examination: white cell count (WBC), total cholestrol, peak of MB isoenzyme of creatine kinase, serum potassium, blood glucose, serum creatinine (CRE). Fasting blood samples for laboratory measurements were obtained early in the morning after overnight fasting within 24h of admission. Left ventricle ejection fraction (LVEF) was measured by ultrasonic cardiogram (UCG) within 24 hours of admission. (3) Clinical outcome: Killip Class, in-hospital mortality.The hypothesis that the number of diabetes patients with infarction during each time interval was equal to an expected frequency was tested using a χ2 goodness of fit analysis. The χ2 test was used to assess the significance of circadian variation between the two groups.Among 1016 subjects enrolled in this study, 172 were diagnosed as diabetes. Compared with the control group, diabetes patients were elder and more female. There was no significant difference on level of serum creatinine and left ventricular ejection fraction between two groups. Diabetes patients had more comorbidities and worse in-hospital outcome. Proportion of patients taking β adrenergic receptor blockers before onset of MI was similar between two groups .The 6-h interval of AMI onset was shown in Circadian variation has been demonstrated in several types of acute cardiovascular disease, including acute myocardial infarction, sudden cardiac death, silent ambulatory ischemia, and thrombotic stroke. The morning peak of incidence of AMI is related to some known daily rhythms. It is well known that a surge in sympathetic activity and vagal withdrawal occurs after waking accompanying by increase of plasma levels of catecholamine, renin and cortisol . As a result, higher level of heart rate, blood pressure, coronary vascular tone, platelet aggregability and a lower level of fibrinolytic activity are observed during the early morning hours. These changes may increase shear forces in the coronary arterial bed, thus promoting plaque disruption and causing unstable angina and AMI. Also, a morning increase in platelet reactivity may make a thrombus more likely to grow and cause symptoms.A studyThe mechanism of change of circadian pattern in the onset of AMI among diabetic subjects is unclear. It can be related to the blunting of diurnal variation in physiological variables. Autonomic nervous system plays an important role in determining the circadian pattern of cardiovascular events. It suggests that in patients with diabetes, abnormalities in the circadian rhythm of autonomic tone may be responsible for the altered temporal onset of cardiovascular events.14As a result of autonomic neuropathy, the rhythm of sympathovagal balance is significantly attenuated in patients with diabetes compared with those without diabetes. The morning rise in platelet aggregability has been reported to be lost in diabetic patients by some investigators. Plasminogen activator inhibitor 1 and von Willebrand factor show no circadian variation in patients with diabetes.17However, there were also conflicted reports. Behar showed the preponderance of the morning peak persisted in patients with diabetes mellitus.The lack of circadian variation in the onset of acute myocardial infarction may have therapeutic implications. As cardio-protective medication has been shown to exert its effect mainly by diminishing the morning peak in acute myocardial infarction, the optimal timing of such medication may differ in diabetic subjects from their non-diabetic counterparts.22