Cardiac MRI (CMR) is an excellent modality for myocardial tissue characterization, allowing demonstration and quantification of myocardial damage using late Gadolinium enhancement (LGE) sequence. C Reactive Protein (CRP) has been shown to be a prognostic marker in lymphocytic myocarditis. The purpose of this study was to study the correlation between CRP levels and the extent of myocardial damage in patients diagnosed with myocarditis.The study cohort included 47 patients  admitted to the heart center with MRI proven acute myocarditis. Demographic, clinical, laboratory echocardiographic and CMR data was collected. CMR was performed using a 1.5 T scanner  using a standardized protocol including SSFP and LGE sequnces. LGE was quantified as percentage of the left ventricular (LV) mass. Patients were divided into two groups: LGE< 10% of LV mass and LGE> 10.1% of LV mass. These two groups were compared in regards to CRP levels and left ventricular (LV) function.CRP levels were positively correlated with the myocardial damage; in the LGE< 10% group CRP was 54.6±56, in the and LGE> 10.1% group CRP was 104±68 . This correlation was maintained also when CRP was divided into thirtailes . LV ejection fraction was 59.9%±6.7 VS 52.2%±12 for the lower and mid LGE thirtailes and upper LGE thirtaile, respectively No correlation was found between the extent of myocardial damage (% LGE) and the CPK and Troponin levels or any of the baseline characteristics table .Table 1LCRP was significantly and positively correlated with the extent of myocardial damage as quantified by CMR. It may serve as a simple yet valuable tool to predict LV damage and dysfunction in patients presenting with acute myocarditis.No external funding was used for this study.


Duchenne muscular dystrophy (DMD) is a progressive striated muscle disease that is characterized by skeletal muscle weakness with progressive respiratory and cardiac failure. Together respiratory and cardiac disease account for the majority of mortality in the DMD patient population. However, little is known regarding the effects of respiratory dysfunction on the dystrophic heart. The studies described here examine the effects of acute hypoxia on cardiac function. These studies demonstrate, for the first time, that a mouse model of DMD displays significant mortality following acute exposure to hypoxia. This mortality is characterized by a steady decline in systolic function. Retrospective analysis reveals that significant decreases in diastolic dysfunction, especially in the right ventricle, precede the decline in systolic pressure. The initial hemodynamic response to acute hypoxia in the mouse is similar to that observed in larger species, with significant increases in right ventricular afterload and decreases in left ventricular preload being observed. Significant increases in heart rate and contractility suggest hypoxia-induced activation of the sympathetic nervous system. These studies provide evidence that while hypoxia presents significant hemodynamic challenges to the dystrophic right ventricle, global cardiac dysfunction precedes hypoxia-induced mortality in the dystrophic heart. These findings are clinically relevant as the respiratory insufficiency evident in patients with DMD results in significant bouts of hypoxia. The results of these studies indicate that hypoxia may contribute to the acceleration of the heart disease in DMD patients. Importantly, hypoxia can be avoided through the use of ventilatory support. The increased CO2 results in a respiratory acidosis, which is partially compensated for by the kidneys. However, there is no alternative source of O2, thus the hypoxia present in dystrophic respiratory failure is particularly important.Duchenne muscular dystrophy (DMD) is a progressive disease of striated muscle deterioration. Initially presenting as skeletal muscle weakness, the disease advances resulting in the loss of ambulation early in the second decade of life and death in the third or fourth decade  mouse colonies were established from breeding pairs purchased from Jackson Laboratories  and maintained at the University of Minnesota. Genetic makeup of these colonies was maintained by replacing the breeding stock every four generations. Animals were fed standard chow diet ad libitum and were kept in a room with 12-h light and dark cycles. These studies used mice of both sexes aged 4–6 months. All procedures reported here were reviewed and approved by the University of Minnesota Institutional Animal Care and Use Committee.Control (C57BL/10) and mdx . This allowed tight control of the content of respiratory gases being inhaled. A 1.2-Fr pressure-volume catheter  was inserted into the left ventricle and 1.2-Fr pressure catheter  was inserted into the right ventricle, both through apical stab incisions. Mice were fitted with a pulse oximeter located on their right thigh . Following instrumentation, the isoflurane was set to 1%, a level sufficient to maintain deep sedation. Overall surgical time from induction to the beginning of the protocol was about 45 min. Gas mixtures were generated using a custom built device consisting of two flow meters, one controlling oxygen and the other controlling nitrogen. The gas mixtures were calibrated using a ProOx P110 oxygen sensor  with a correlation coefficient of 0.996. Respiratory rate was set to be the lowest rate that prevented respiratory effort in the anesthetized mice. Mortality was defined as a left ventricular systolic pressure of <40 mmHg.To assess the hemodynamic effects of hypoxia in the dystrophic mouse, biventricular cardiac catheterization was performed under normoxic and hypoxic conditions. Mice were instrumented as described previously  test to determine differences in survival. The box and whisker plots in several of the figures show the distribution of the data. In these plots, the box defines the 25–75 percentile spread, the line in the middle is the median, and the “+” is the mean. The lines extent out to the maximum and minimum values, however, points outside of 1.5 the interquartile distance are displayed separately, but are included in any relevant statistical comparisons.All data were analyzed using either R (R Core Team 2) of 100%. The FIO2 was decreased to 20% for 10 min and then finally to 10%. Detailed hemodynamic analysis was performed following 10 min at an FIO2 of 10%. This level of hypoxia results in a significant desaturation of hemoglobin in both wild type (98.1 ± 0.3% to 66.7 ± 4.5%) and dystrophic mice (97.7 ± 0.2% to 64.0 ± 3.4%). Importantly, there is no significant difference in the degree of hemoglobin desaturation observed between wild type and dystrophic mice, indicating an equivalent level of hypoxia.Recently published work demonstrates the increased level of fibrosis within the right ventricle of the mdx mouse  decline in parallel with LV systolic pressure. Furthermore, the measures of global cardiac function, stroke work and cardiac output, both begin to decline several minutes prior to the loss of LV systolic pressure or alterations of LV preload. Together these data support a model where hypoxia-induced cardiac decompensation begins with declines in diastolic function, initially in the right ventricle, perhaps secondary to the additional hemodynamic demands placed on this ventricle during hypoxia. However, this diastolic dysfunction is also observed in the left ventricle a few minutes later. Following these changes in diastolic function, several measures of LV systolic function begin to decline, in the absence of changes in LV preload. The observation that hypoxia results in diastolic dysfunction prior to declines in systolic function in both ventricles of the dystrophic heart, suggests that the hypoxia-induced hemodynamic changes in pulmonary vascular resistance do not contribute significantly to the cardiac decompensation observed in the hypoxic dystrophic heart. Hypoxia-induced declines in left ventricular preload would be expected to decrease systolic function initially. These data support a model whereby hypoxia induces biventricular reductions in cardiac function, initially presenting as diastolic dysfunction and followed by declines in contractile function.The nature of the mechanism of cardiac decompensation and death in mdx mice exposed to hypoxia is not clear. The data presented here provide a detailed hemodynamic picture leading up to the decline in left ventricular systolic function. This study and others  of young dystrophic mice is significantly decreased relative to wild type mice (Yasuda et al. In summary, the studies described here identify a novel hypoxia sensitivity of the dystrophic heart that affects both ventricles, suggesting some aspect of global cardiac dysfunction. Further studies are required to better understand the underlying mechanism by which hypoxia results in declines in cardiac function and eventual mortality. However, the observed hypoxia-induced cardiac decompensation observed in the mdx mouse raises important concerns regarding the role of hypoxia in the progression of dystrophic cardiomyopathy in DMD patients.None declared.


This minireview discusses the evidence that the inhibition of p38 mitogen-activated protein kinases (p38 MAPKs) maybe of therapeutic value in heart failure. Most previous experimental studies, as well as past and ongoing clinical trials, have focussed on the role of p38 MAPKs in myocardial infarction and acute coronary syndromes. There is now growing evidence that these kinases are activated within the myocardium of the failing human heart and in the heart and blood vessels of animal models of heart failure. Furthermore, from a philosophical viewpoint the chronic activation of the adaptive stress pathways that lead to the activation of p38 MAPKs in heart failure is analogous to the chronic activation of the sympathetic, renin-aldosterone-angiotensin and neprilysin systems. These have provided some of the most effective therapies for heart failure. This minireview questions whether similar and synergistic advantages would follow the inhibition of p38 MAPKs. Heart failure, also referred to as chronic or congestive heart failure, is a progressive condition which occurs when the heart at a normal filling pressure is unable to pump sufficient blood to meet the body's requirements. The syndrome is multifaceted including abnormities in heart muscle, valves and/or pericardium as well as systemic disturbances in neuro-humoral, cytokine and/or vascular function Marks, . The chaThe mitogen-activated protein kinase p38 is a key Ser/Thr kinase that responds to a variety of the multifaceted abnormalities contributing to heart failure , responsible for the translocation of Ca2+ from the cytosol to the sarcoplasmic reticulum   are all attenuated, suggesting a pro-apoptotic role for p38  is an important substrate of p38 that is associated with heart failure; since cardiac fibrosis and dysfunction are diminished in MK2 knockout mice , show heart failure progression is accelerated with an increase in interstitial fibrosis, worsening ventricular function and early mortality , and IL-6, are elevated in, and may contribute to, heart failure. TNF-α levels increase in patients with advanced heart failure and correlate with prognosis , which could potentially benefit acute coronary syndrome (ACS) patients. Losmapimod is an anti-inflammatory medication which inhibits p38 and may improve vascular function and reduce subsequent cardiac events following ACS.Though further research is required on the mechanisms and consequences of p38 activation in heart failure, this review has discussed the substantial evidence for an important role of p38 in the development of heart failure and its potential as a therapeutic target.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Inflammation may be a key trigger in the accumulation of extracellular matrix that leads to fibrosis, abnormal myocardial relaxation, diastolic dysfunction and eventual heart failure with a preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a metabolically active organ releasing various adipokines and inflammatory mediators which may promote fibrosis in adjacent myocardium altering the structural properties of the ventricle leading to abnormal diastology. The aim of this study was to assess the relationship of EAT volume using cardiac magnetic resonance imaging (CMR) and parameters of diastolic dysfunction as assessed by 2D-transthoracic echocardiography (TTE) in patients with atrial fibrillation (AF).We conducted a retrospective study of 20 patients with AF who underwent CMR and TTE prior to ablation between 11/1/2010 and 10/17/2013 (Table Patients with elevated filling pressures (E/e' >15) had significantly higher EAT compared to those with normal filling pressures (E/e' <15) . By univariate analysis, EAT volume had a significant inverse correlation with e' sep , but not hypertension , or E/e' . EAT volume remained the only significant predictor of abnormal myocardial relaxation in a multivariate linear regression model incorporating age, BMI, LA volume, hypertension and coronary artery disease (p = 0.04).EAT volume quantified by CMR is independently associated with abnormal myocardial relaxation in patients with AF. EAT may serve as a novel therapeutic target to preserve diastolic function.None.


Measurement of myocardial extracellular volume fraction (ECV) with T1 mapping cardiac magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent enables the assessment of diffuse myocardial fibrosis. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be achieved with a primed contrast infusion (equilibrium contrast-CMR). In healthy volunteers it could be shown that a single bolus may also be sufficient to reach equilibrium. We hypothesized that equilibrium between blood and myocardium contrast distribution can be achieved with the bolus-only technique to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD).A study group of 23 patients with CHD  was compared with 17 healthy volunteers . Using modified Look-Locker inversion recovery (MOLLI) T1 mapping before application, 15 minutes after bolus injection, and during constant infusion of Gd-DOTA, T1 values were obtained for blood pool and myocardium of the interventricular septum (IVS), the left ventricular (LV) antero-/lateral wall, and the inferior or anterior wall of the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation.In CHD patients, correlation between ECV by bolus-only and infusion was strong for IVS, LV and RV . ECV of IVS, LV and RV by both techniques correlated strongly in healthy volunteers . Bland-Altman plots did not show significant bias between the techniques in patients and healthy volunteers for any of the analyzed regions .


The pathophysiology of diastolic dysfunction is complex, but can be simply described as impaired LV myocardial relaxation and/or increased LV stiffness. The objective of this study is to clarify true normal left ventricular (LV) diastolic function and early stage of diastolic dysfunction before relaxation abnormality develops in patients with normal LV diastolic function using simple diastolic wall strain (DWS) in South Korea.DWS which is a non-invasive, load-independent, and reproducible estimator of LV stiffness using two-dimensional echocardiography using the difference between posterior wall thickness in systole and diastole to approximate LV stiffness. A total of 349 consecutive patients with normal LV diastolic function by echocardiography were enrolled. According to DWS, patients were divided into two groups: high DWS (≥median 175) vs. low DWS (<median 174).Patients with low DWS were more obese and showed higher blood pressure, and had more prevalent hypertension and hyperlipidemia. In addition, those with low DWS had higher LV end-systolic volume, LV mass index, E/E’ and lower ejection fraction and E’ velocity. Among them, higher LVESV and LVMI were independently associated with low DWS.These data suggests that simple DWS might be helpful in identifying a subgroup of subtle diastolic dysfunction. Our data suggest that early change of diastolic dysfunction might start with abnormal LV geographic changes preceding functional changes. Left ventricular (LV) diastolic dysfunction is common in the general population, and is associated with incident heart failure and increased mortality , 2. The We conducted an observational cross-sectional study in which we enrolled 349 patients who met the criteria for normal LV diastolic function among 6,277 subjects who underwent transthoracic echocardiography at Kangnam Sacred Heart Hospital between April 2012 to May 2013 . We enrolled patients who met criteria for normal LV diastolic function as both E/A, E’/A’ ratio were 1.1 or higher, deceleration time (DT) was 142–220 ms, and septal E’ velocity was 10 cm/s or higher [3 − (LVEDD)3] − 13.6. Thereafter, the LV mass index (LVMI) was calculated and indexed to body surface area, and LV hypertrophy was defined by an LV mass index >95 g/m2 in women or >115 g/m2 in men. Calculation of relative wall thickness (RWT) by the formula 2× (PWTd)/LVEDD permits categorization of an increase in LV mass as either concentric (RWT >0.42) or eccentric (RWT ≤0.42) hypertrophy and allows identification of concentric remodeling  [TTE was performed using standard techniques with a 2.5-MHz transducer. The standard 2-D and Doppler echocardiography was performed using a commercially available echocardiographic machine . LV end-diastolic dimensions (LVEDD), end-diastolic interventricular septal thickness (IVSTd), and end-diastolic left ventricular posterior wall thickness (PWTd) were measured at end-diastole according to the standards established by the American Society of Echocardiography . LV EF wsed RWT) . Volumessed RWT) . Measurec RWT >0.2 or ecceMitral flow velocities were recorded in the apical four-chamber view. Mitral inflow measurements included the E/A ratio and the peak early (E) and peak late (A) flow velocities. The tissue Doppler of the mitral annulus movement was also obtained from the apical four-chamber view. A 1.5-mm sample volume was placed sequentially at the lateral and septal annular sites. The analysis was performed for early diastolic (E’) and late diastolic (A’) peak tissue velocities. As a noninvasive parameter for LV stiffness, the LV filling index (E/E’) was calculated by the ratio of transmitral flow velocity to annular velocity. Adequate mitral and tissue Doppler image (TDI) signals were recorded in all patients .A high-resolution B-mode ultrasound  equipped with a 7.5-MHz linear array transducer was used for carotid ultrasonography. In the longitudinal view, carotid intima-media thickness (IMT) was determined as the distance from the media adventitia interface to the intima lumen interface on the far wall in a region free of plaque . The exaPWV was measured using a VP-2000 automated device . The details of this device and the measurement method have been described elsewhere . Right aU test. Independent contributing factors to the DWS were investigated by multiple logistic regression analysis of significant variables in the univariate analysis. Variables that strongly influenced others were excluded from the multivariate analysis. Male and female were compared using each analysis. A p value <0.05 was considered significant. All data were analyzed using StatView software  was performed.Data are expressed as numbers and percentages for categorical variables, and mean ± standard deviation for continuous variables. Correlations between continuous variables and DWS were examined using Spearman’s correlation analysis. Patients were assigned based on the median DWS to either the low or the high (< or ≥ median DWS) group. Two groups were compared using Fisher’s exact test or Mann–Whitney’s The median (25th to 75th percentiles) DWS was 0.36 0.33–0.42) of the overall study population. In the previous adult study (mean age 56.7 ± 8.3 years), the normal value of the DWS was reported to be 0.40 ± 0.07 2 of the . Our medTable r = −0.168, p = 0.001) and LVMI . Scatterplots depicting the relationship between DWS and LVESV and LVMI are shown in Fig. When compared with patients with higher DWS, patients with lower DWS showed larger LV end-systolic dimension and end-systolic volume. In addition, LV mass index was much higher in patients with lower DWS. In terms of adverse LV remodeling, patients with lower DWS had more abnormal geometry. DWS was inversely correlated with LVESV (p < 0.001). In addition, E’ velocity also slightly but significantly lower  and E/E’ ratio was higher  in patients with lower DWS among indices reflective of diastolic function. Figure LV EF was slightly but significantly lower in patients with lower DWS  with marginal statistical significance. Carotid IMT was also slightly increased in patients with lower DWS.Among the whole population, on 140 patients carotid ultrasound was performed and on 72 patients baPWV was performed, and the results are shown in Table As shown in Table p < 0.001) and LVMI  and lower EF  were independently associated with lower DWS in patients with normal LV diastolic function.Higher BMI, elevated systolic and diastolic BP, increased LV ESV and LVMI, lower EF and E’, and higher E/E’ were parameters found related to lower DWS via univariate analysis. Among them, increased LVESV . We assume that this difference was mainly due to larger LVESV in patients with lower DWS. DWS was also correlated with some diastolic indices  like previous studies [According to our study, patients with lower DWS showed not only enlarged cardiac size but also diminished indices for both systolic and diastolic function. For starters, LVESD, LVESV, and LVMI were all larger in those with lower DWS. Therefore, eccentric LVH was more prevalent in those patients compared to patients with higher DWS. A previous study by Ohtani et al.  showed a studies , 5.p = 0.064). PWV is generally accepted as the most simple, non-invasive, and validated indicator of arterial stiffness [We also performed carotid ultrasound in 157 patients and baPWV in 79 patients. To mention conclusion first, there were no statistically significant differences between the two groups. However, patients with lower DWS had slightly increased mean carotid IMT and increased baPWV with marginal statistical significance (PWV 13.1 ± 17.1 vs. 14.2 ± 28.7 m/s, tiffness . It is atiffness , 20, diatiffness , end-statiffness , in eldetiffness , and thetiffness . Furthertiffness , which mThis study was, to the best of our knowledge, the first study to see early change of diastolic dysfunction among patients with normal LV diastolic function using DWS. Our study showed that lower DWS is associated with larger LVESV, LVMI with slightly decreased LV EF even in patients with normal LV diastolic function. In addition, those who had lower DWS were more obese and had more prevalent hypertension and hyperlipidemia. Therefore, our data suggests that adverse cardiac remodeling might occur before overt diastolic dysfunction occurs. Limitations include the lack of clinical outcomes. As mentioned earlier, further larger-scale prospective trials are needed to determine the relationship of DWS and clinical aspects in patients without overt heart disease. In addition, the lack of invasive gold standard measurement of diastolic stiffness should be mentioned for limitations.Our study shows that patients with lower DWS had larger LVESD, LVESV, and LVMI as a result of more prevalent eccentric LVH. In addition, LV EF was slightly but significantly lowered in patients with lower DWS, and E’ velocity was lower and E/E’ ratio was higher in patients with lower DWS. Among those parameters, increased LVESV, LVMI, and decreased EF were independently associated with decreased DWS in patients with normal LV diastolic function. Our data suggests that DWS might be helpful in detecting subtle diastolic dysfunction in patients with normal LV diastolic function, and this change starts with LV geometrical remodeling before functional changes.


Heart failure (HF) can be caused by left ventricular (LV) pump failure as well as by bradyarrhythmias. Hemodynamic differences between HF by LV pump failure and that by bradyarrhythmia have not been fully investigated. We hypothesized that HF by LV pump failure could be associated with both reduced cardiac output (CO) and increased LV filling pressure due to associated LV diastolic dysfunction, whereas HF by bradyarrhythmia could be associated with reduced CO but only modestly increased LV filling pressure due to the absence of LV diastolic dysfunction.In 39 patients with HF by LV pump failure (LV ejection fraction <35 %), 24 with HF by bradyarrhythmia, and 22 normal controls, LV volume, ejection fraction, stroke volume, left atrial volume, and early diastolic mitral valve flow to tissue annular velocity ratio (E/E′) were measured by echocardiography.2, n.s.), preserved LV diastolic function (E′) , less dilated end-systolic LA volume, and preserved E/E′ .Compared to patients with HF by LV pump failure, those with HF by bradyarrhythmia had significantly lower heart rates, less LV dilatation, preserved LV ejection fraction, preserved stroke volume, similarly reduced cardiac index (1.8 ± 0.4 vs. 1.6 ± 0.4 L/min/mHF by LV pump failure is characterized by both significantly reduced CO and increased LV filling pressure, whereas HF by bradyarrhythmia is characterized by a similar reduction in CO but only modestly increased LV filling pressure. Heart failure (HF) is a major cause of mortality and poor quality of life , 2. HF cLV pump failure with both systolic and diastolic dysfunction is known to cause both reduced cardiac output (CO) and elevated LV filling pressures or lung congestion , 5. BradSubjects consisted of 3 groups meeting the following criteria: (1) 39 consecutive patients who underwent echocardiography due to HF symptoms (dyspnea or fatigue) associated with LV pump failure, defined by an LV ejection fraction <35 % without other structural heart disease; (2) 24 consecutive patients admitted to the hospital due to HF symptoms associated with bradyarrhythmia (sinus bradycardia or atrioventricular block with QRS rate <50 beats/min) but without other structural heart disease or hypothyroidism; and (3) 22 age- and gender-matched healthy controls. The etiology of HF in the bradyarrhythmia group was confirmed by the disappearance of HF symptoms after pacemaker implantation. We collected other data including elements from the present and past history, reports of other blood tests, and interpretations of chest X-rays . None ofv2 + right atrial pressure), where v is the peak velocity of the TR jet (m/s); right atrial pressure was estimated from the diameter and breath-induced variability of the inferior vena cava [2/4. Velocity time integral (VTI) of LVOT flow was measured using the apical long-axis view. SV was determined as the product of the VTI and the LVOT cross-sectional area. CO was calculated as SV × heart rate [Two-dimensional and Doppler echocardiographic examinations were performed in all patients using a commercially available ultrasound machine . Echocardiography was performed on patients with pump failure at the time of the first hospital visit after the development of HF symptoms. Echocardiography was performed on patients with bradyarrhythmia on the day of admission or the next day. LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) were measured with apical 2- and 4-chamber images using the biplane Simpson’s method , and theena cava . In the ena cava . Mitral ena cava . The peaena cava –18. Stroart rate . The 2-dart rate , 21. Echp < 0.05. Risk factors and medications groups were compared by the Chi-square test.The results were expressed as mean and standard deviation and categorical data as absolute numbers and percentages. Comparisons of continuous variables among the 3 groups were performed by Scheffe’s test. Statistical significance was established at p < 0.001), lower incidence of taking beta-blockers (p < 0.05), reduced heart rate (p < 0.001), and increased systolic blood pressure (p < 0.05). Compared to patients with LV pump failure, those with bradyarrhythmia had a significantly lower incidence of abnormal X-ray, including increased heart size, interstitial edema, intraalveolar edema and pleural effusion, and lower BNP and NT-proBNP levels.The clinical characteristics of the study population are presented in Table p < 0.05) and it tended to be increased in the bradyarrhythmia group, but without reaching statistical significance (Table p < 0.001). Compared to controls, only the LV pump failure group had a significant reduction in the LV ejection fraction by definition (p < 0.001). Compared to controls, the SV index was significantly reduced in patients with LV pump failure (p < 0.05). The SV index tended to be greater in patients with bradyarrhythmia compared to controls, but without reaching statistical significance. Compared to controls, the CO index was significantly and similarly reduced in both groups (p < 0.05), and there was no significant difference between the 2 groups. Compared to patients with LV pump failure, those with bradyarrhythmia had lower increase in TR velocity (p < 0.05) and sPAP (p < 0.005). The mitral regurgitation (MR) vena contracta dimension was significantly increased in both groups and was significantly less pronounced in patients with bradyarrhythmia (p < 0.001). Mitral E velocity and E/A was significantly increased in patients with LV pump failure (p < 0.05). E-wave deceleration time (E-DcT) was significantly decreased in patients with LV pump failure (p < 0.05). Mitral annular tissue E velocity was significantly reduced only in patients with LV pump failure (p < 0.05). Consequently, the early diastolic mitral flow to tissue velocity ratio (E/E′) was significantly increased only in patients with LV pump failure (p < 0.001). Compared to controls, both the LV pump failure and bradyarrhythmia groups had significantly increased LA volume indices (p < 0.05). Compared to the LV pump failure group, patients with bradyarrhythmia had significantly less pronounced LA dilatation (p < 0.05). LV global longitudinal strain was significantly decreased in patients with LV pump failure (p < 0.05), while patients with bradyarrhythmia even had increased LV global longitudinal strain compared to controls (p < 0.05).Compared to controls, LV end-diastolic volume index (LVEDVI) was significantly increased in the LV pump failure groups  with considerably increased LV filling pressures (LV end-diastolic pressure of 21 ± 6 mmHg) in patients with LV pump failure. Stack et al. [2 in patients with bradyarrhythmia. These studies support the results of the present study. Our study has also demonstrated the association or dissociation of LV diastolic dysfunction in patients with LV pump failure and those with bradyarrhythmia.Both LV pump failure and bradyarrhythmia are known to cause HF with reduced CO and/or increased LV filling pressure , 4, 6. Hk et al.  demonstrThis study has demonstrated that both reduced CO and increased LV filling pressures can be prominent in patients with LV pump failure, whereas increased LV filling pressures is only modest in patients with HF due to bradyarrhythmia. Therefore, a marked increase in LV filling pressures in patients with bradyarrhythmia may suggest associated LV pump failure or other causes of elevated LV filling pressures. It may also be useful to expect that pacing to increase the heart rate in patients with bradyarrhythmia may markedly increase CO, whereas it may not result in a satisfactory improvement in elevated LV filling pressures. In this study, indices of LV mechanical function, including ejection fraction, SV, and mitral annular tissue E′ velocity, were all preserved or even augmented in patients with bradyarrhythmia. These findings suggest compensatory LV mechanical adaptation to reduced heart rate. If indices of LV mechanical function were reduced in patients with bradyarrhythmia, this finding may suggest the presence of associated LV structural disease other than bradyarrhythmia.Although echocardiography is largely established as a modality to accurately measure SV or CO , 25, echThese results suggest that heart failure (HF) due to left ventricular (LV) pump failure is characterized by both a significant reduction in cardiac output (CO) and increased LV filling pressure, whereas HF by bradyarrhythmia is characterized by a similar reduction in cardiac output but only a modest increase in LV filling pressure.


Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet.In 146 subjects with non-ischemic dilated cardiomyopathy  LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula.p < 0.05), presence of LGE  and LAS  were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points.The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters. Non-ischemic dilated cardiomyopathy (NIDCM) is the second most common aetiology of heart failure and a leading indication for heart transplantation , 2. AlthDue to its excellent intrinsic blood-to-tissue contrast and high reproducibility, cardiovascular magnetic resonance (CMR) is nowadays considered as the non-invasive gold standard for the evaluation of left ventricular (LV) function . AdditioThe assessment of myocardial strain provides additional prognostic value in heart failure patients –18. LateLately, we established long axis strain (LAS) in CMR as a reliable and fast assessable parameter for LV global longitudinal function which provides high sensitivity and specificity in discriminating patients with cardiomyopathies from healthy subjects without the necessity of any additional offline deformation analysis software tools and without application of gadolinium contrast agents. Moreover, LAS analysis shows good inter- and intraobserver agreement and can be performed much faster than FTI derived strain analysis . HoweverThe aim of the present study was to evaluate whether LAS assessed with CMR offers prognostic information besides standard CMR parameters in patients with NIDCM.2 was added as an exclusion criterion for administration of intravenous CMR contrast agents after July 2007.Our study population consisted initially of 210 consecutive patients with NIDCM who were prospectively included in our study after referral to the ‘Cardiomyopathy Center’ at the University Hospital Heidelberg between May 2005 and November 2009. 64 patients had an LVEF over 45 % and were therefore excluded. LAS was analyzed retrospectively in 146 patients. A part of the population was previously reported . CMR wasThe diagnosis of NIDCM was based on the 1995 World Health Organization/International Society and Federation of Cardiology criteria . Inclusiprimary endpoint of our study. Cardiac events together with the occurrence of hospitalization due to congestive heart failure were used as a secondary endpoint. In case of patients undergoing heart transplantation, the follow-up data was censored at the time of transplantation. In case of several simultaneous cardiac events per patient, the worst event was selected . Otherwise, only the first event for each patient was included in the analysis for composite end-points. Personnel unaware of the CMR results contacted each subject or an immediate family member for acquisition of the follow-up data.Cardiac death, heart transplantation and sudden cardiac death aborted by appropriate ICD discharge due to ventricular tachycardia or fibrillation were defined as hard cardiac events building the Standard CMR was performed on a 1.5T clinical scanner  equipped with a cardiac phased array receiver coil. Cine images were obtained using a breath-hold segmented-k-space balanced fast-field echo sequence (SSFP) employing retrospective ECG gating in long axis planes  as well as in contiguous short axis slices covering the whole ventricles from the annulus of the atrioventricular valves to the apex, with 35 phases per cardiac cycle. All analyses were performed on a commercially available workstation . Results for ventricular volumes, ejection fraction and LV myocardial mass were derived from short axis slices. The presence of late gadolinium enhancement was evaluated by two independent observers experienced in CMR, who were blinded to clinical data and outcome. To exclude artefact, LGE was deemed present only if visible in two orthogonal views. Left ventricular global function index (LVGFI) was assessed as described previously .Values for LAS were assessed in 2 and 4 chamber views by measuring displacement of the mitral annulus. The distance between the epicardial border of the LV apex and the middle of a line connecting the origins of the mitral valve leaflets was measured in both end-systole and end-diastole. The value in percentage for LAS was finally determined according to the strain formula:Mean values in 2- and 4-chamber views were calculated. All values were assessed with the IntelliSpace Portal (ISP) workspace . An example of the technique in a patient with a severe NIDCM is shown in Fig. For calculation of intra- and interobserver variability 20 single measurements were used. To examine intraobserver variability, a sample of 20 randomly selected CMR scans for the measurement of LAS were randomly selected for masked review by the same investigator. The same studies were analysed by a co-investigator, who was blinded to the clinical information and the results of the first investigation, in order to measure interobserver variability.t-test was used. Proportions of categorical were compared using Chi-squared test. Survival curves were plotted using the Kaplan-Meier method and p-values were determined by log-rank testing. The calculation of optimal cut-off values was carried out by receiver operating characteristics (ROC) analysis. Cox proportional hazards models were used for uni- and multivariate analysis, which yielded hazard ratios (HR) and the corresponding 95 % confidence intervals (CI). P-values <0.05 were regarded as significantly different. After successful testing for normal distribution with Shapiro-Wilk test, correlation coefficients were expressed as Pearson’s r.Statistical analysis was carried out using the software solution MedCalc . Continuous variables are expressed as mean ± standard deviation. For the comparison of means between groups, two-tailed Student’s n = 34). The baseline characteristics of the study population are shown in Table p < 0.0001).One-hundred-forty-six patients were included for data collection. During a follow-up period of 4.3 ± 2.0 years, 24 hard cardiac events occurred , declared as primary endpoint. Further 10 patients were admitted to the hospital due to severe heart failure symptoms during the follow-up period . Kaplan-Meier curves for the primary and secondary endpoint concerning the whole study cohort are shown in Fig. p = 0.006), LVEDV/BSA  and the presence of LGE  remained the only significant parameters regarding the primary endpoint (Table p = 0.009), surpassing LVEDV/BSA and LGE. To further test the predictive power of LAS we performed a sequential Cox regression analysis regarding the primary endpoint. Hereby, the addition of LAS to a model including LGE and the LVEDV/BSA led to a significant increase in the predictive power of this model . In this study, LAS was measured in a similar approach as previously described by us and was found to be a significant predictor for cardiac events in a multi-ethnic population . Lately,r = 0.97), on the other hand the patients in our collective have low LVEF values (29.3 ± 11.0 %), which may also explain why LVEF is not as strong as in other studies.Compared to the studies mentioned above we evaluated a parameter which has several advantages particularly for usage in clinical routine. Major drawbacks of FTI strain analysis are the need of a specific post-processing software tool and an elaborate manual marking of the myocardial borders. By contrast, even in clinical routine LAS can be measured rapidly based on standard SSFP sequences. Not only being a readily available parameter, our study could show that LAS has significant prognostic value in patients with NIDCM. LAS values > −5.0 % were significantly associated with a higher rate of cardiac events irrespectively of the presence of LGE. This is in concordance with our previous study on FTI where we could show that longitudinal strain surpasses LGE in predicting outcome . LAS mayRegarding LAS, we observed no single cardiac event in patients with LAS values better than −10 %. Based on this information we created a scoring system for risk stratification based on LAS and well-established, standard CMR parameters. We decided to use LVEF and not LVEDV/BSA for our risk stratification model because LVEF is still the most established parameter for risk stratification in patients with NIDCM and in a multivariate model including LVEF, LAS and LGE significantly associated with the endpoint (data not shown). We believe that for clinical routine LVEF may be better applicable than LVEDV/BSA.Hereby, we observed that detection of any LGE, LVEF below 35 % and LAS > −10 %, while each feature counted as one point in our scoring system, is highly associated with cardiac events. In patients without these risk features (score = 0) no events were observed during the follow-up period. Although, several studies suggest that longitudinal function outperforms the LVEF in predicting survival in cardiomyopathies , we hereLAS was analyzed retrospectively. LAS does exclusively represent LV longitudinal strain and does not provide information about strain rate, intra-myocardial strain or circumferential and radial strain, which may better reflect cardiac function in certain circumstances. Apart from LAS, no further strain measurements were performed. Extracellular volume could not be analyzed, as T1 mapping was not available in this study.Moreover, LAS was exclusively evaluated in NIDCM patients with EF below 45 %. The applicability of LAS on patients with mild form of NIDCM has not been evaluated and has to be tested in further studies.LAS is a rapidly determinable parameter which can be assessed easily from routinely acquired, contrast-agent free cine SSFP sequences. A reduced LAS is significantly associated with the occurrence of cardiac events. Accordingly, LAS is of high prognostic value in patients with NIDCM besides LGE and LVEDV/BSA. The scoring model presented in this work, which combines LVEF and LGE - the most established CMR parameters- and LAS, may help to improve risk stratification in NIDCM.NIDCM, non-ischemic dilated cardiomyopathy; LVEF, left ventricular ejection fraction; CMR, cardiovascular magnetic resonance; LGE, late gadolinium enhancement; FTI, feature tracking imaging; LAS, long axis strain; ICD, implantable cardioverter defibrillator; SCD, sudden cardiac death; SSFP, steady state free precession; LVGFI, left ventricular global function index; ISP, IntelliSpace Portal; ROC, receiver operating characteristics; HR, hazard ratio; CI, confidence interval; AUC, area under the curve; LVEDV, left ventricular enddiastolic volume; BSA, body surface area; GLS, global longitudinal strain


Parkinson’s disease (PD) is characterized by dopaminergic (DA) neuron death in the substantia nigra (SN) and subsequent striatal adaptations. Mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) are widely used as a model for PD. To assess the validity of the MPTP mouse model for PD pathogenesis, we here identify the biological processes that are dysregulated in both human PD and MPTP-treated mice. Gene enrichment analysis of published differentially expressed messenger RNAs (mRNAs) in the SN of PD patients and MPTP-treated mice revealed an enrichment of gene categories related to motor dysfunction and neurodegeneration. In the PD striatum, a similar enrichment was found, whereas in the striatum of MPTP mice, acute processes linked to epilepsy were selectively enriched shortly following MPTP treatment. More importantly, we integrated the proteins encoded by the differentially expressed mRNAs into molecular landscapes showing PD pathogenesis-implicated processes only in the SN, including vesicular trafficking, exocytosis, mitochondrial apoptosis, and DA neuron-specific transcription, but not in the striatum. We conclude that the current use of the MPTP mouse as a model for studying the molecular processes in PD pathogenesis is more valid for SN than striatal mechanisms in PD. This novel insight has important practical implications for future studies using this model to investigate PD pathogenesis and evaluate the efficacy of new treatments.The online version of this article (doi:10.1007/s12035-015-9103-8) contains supplementary material, which is available to authorized users. Furthermore, based on proteins encoded by the mRNAs that were differentially expressed in both PD patients and MPTP mice, molecular landscapes of interacting proteins were built for both the SN and striatum. These landscapes represent molecular mechanisms that are shared between PD and MPTP toxicity. Together, these analyses will help to understand and value experimental findings in the MPTP mouse in the light of human PD pathogenesis.www.genesifter.com) using robust microarray analysis (RMA). The Benjamini-Hochberg method was then used to correct for multiple comparisons, and only mRNAs with a fold change (FC) of ≥1.2 or ≤−1.2 and a corrected p value <0.05 were considered to be differentially expressed and used for the subsequent gene enrichment analysis, as described below. If no raw data was available, our inclusion criteria were the following: (1) correction for multiple testing was performed, with a corrected p value <0.05 and the correction method was explicitly mentioned; and (2) an mRNA expression FC of ≥1.2 or ≤−1.2. Only protein-coding mRNAs were included in our analyses.Available genome-wide mRNA expression data from multiple previously published studies were used to generate a list of differentially expressed transcripts in the postmortem SN and striatum of PD patients and MPTP-treated mice, studied at various time points following MPTP treatment. If raw expression data was available at the Gene Expression Omnibus (GEO) site, this data was reanalyzed in GeneSifter (www.ingenuity.com) was used to identify enriched gene categories in the lists of differentially expressed mRNAs in the SN and striatum of both human PD patients and MPTP-treated mice and in the lists of overlapping mRNAs that were differentially expressed in the SN or striatum of both PD patients and MPTP mice. Ingenuity assigns genes and their corresponding mRNAs/proteins to (sub)categories of functional classes, e.g., “diseases and disorders” and “molecular and cellular functions.” For these analyses, only functional categories and pathways with significant enrichment  and containing two or more genes were taken into account.The Ingenuity pathway analysis software package (http://www.uniprot.org/uniprot) [http://www.ncbi.nlm.nih.gov/sites/entrez). Based on these findings and applying an approach similar to the one we used previously to build landscapes based on genome-wide association data [www.serif.com) was used to draw the landscape figures.Subsequently, the mRNAs that were differentially expressed in the SN and striatum of both PD patients and MPTP-treated mice were analyzed in more depth. Guided by the results of the Ingenuity enrichment analyses, the literature was searched for the (putative) function of all the proteins encoded by the mRNAs overlapping between human PD and the MPTP mouse, as well as their functional interactions, using the UniProt Knowledgebase (uniprot)  and PubMion data , 6, we tIn this study, we analyzed with gene enrichment approaches and systematic literature searches published datasets of differentially expressed transcripts in SN and striatum of PD patients and MPTP-treated mice that met our criteria for inclusion  cell death and other acute, MPTP toxicity-related processes, including (dys)regulation of inflammatory responses and immunity-related cells, and endometriosis. At 72 h after MPTP injection, the most significantly enriched categories shift towards those enriched within the PD patient striatal data, i.e., categories related to PD-like motor symptoms and neuronal/synaptic function Table .both human PD patients and the MPTP mouse model comprise a combination of the enriched “diseases and disorders” categories identified in human PD and MPTP-treated mice as summarized above, i.e., relating to both movement disorders and epilepsy  biological processes involved. While in the SN of PD patients, enriched molecular and cellular functions relate to neuronal and synaptic functions, functional themes pertaining to cell growth and death predominate in the MPTP mouse model. This discrepancy could well reflect the differences between the protracted processes of neurodegeneration in PD, as well as simultaneous compensatory neuroplastic mechanisms, compared to the acute MPTP toxicity in mice. Moreover, the biological processes that overlap between the SN of both PD patients and MPTP-treated mice mainly relate to neuronal/synaptic function and  cell death, while the molecular signaling cascades involved regulate DA synthesis and recycling, endocytosis and exocytosis of (DA-containing) synaptic vesicles, and cytoskeleton-dependent synaptic remodeling. These biological processes have been implicated in the pathogenesis of PD before –10. ProtAs opposed to the SN findings, the categories that were most significantly enriched within the differentially expressed striatal mRNAs did not unequivocally overlap between human PD and mouse MPTP-induced toxicity. In PD, they are related to PD-associated motor symptoms, but in the MPTP-treated mouse striatum, the enriched categories depend on the length of the time period between MPTP treatment and transcriptional profiling. Early  after MPTP injection, the most significantly enriched disease categories within the mouse striatal mRNA expression data are not related to motor dysfunction but to epilepsy. Epilepsy is a known acute side effect of MPTP injection in mice  and is dThus, our transcriptome analyses and molecular landscapes indicate that the MPTP mouse constitutes a valid model for the chronic molecular and pathological changes that occur in the SN of PD patients and hence of the PD phenotype that is associated with these changes. However, this is less obvious for the striatum, because early after MPTP injection, enriched categories and functions encompass mainly processes that are not directly related to PD. It appears that human PD pathogenesis in the striatum is better recapitulated at the molecular level in the MPTP-treated mouse model 72 h postinjection and perhaps even later. Effects of the level of chronicity of the dosing regimen on markers of DA neurotransmission—e.g., TH expression and striatal DA levels—and behavioral outcome have been reported before –23, but In addition to the acutely toxic nature of early MPTP-induced pathology, there may be several other explanations for the apparent discrepancy between the striatal PD pathogenesis and MPTP toxicity. First, presynaptic DA denervation may result in enriched processes that are different between humans and mice due to species specificity. For example, similar degrees of DA degeneration in humans and mice do not result in similar phenotypic severity  and clinThe principal differences between the chronological orders of events in PD-linked neurodegeneration versus MPTP-induced toxicity are summarized in Fig. Together, our findings provide further evidence that the molecular changes in the SN of MPTP-treated mice correspond to the observed alterations in the SN of PD patients. However, for a proper reflection of the molecular changes occurring during PD pathogenesis in the striatum, the time point of studying the changes following MPTP treatment is crucial. Further transcriptome studies are needed to determine whether waiting longer than 72 h would indeed provide a better construct validity for human PD pathogenesis and whether there is an optimal time frame following MPTP injection to assess striatal PD pathology in the MPTP mouse model. Such knowledge will have important practical implications for the use of the MPTP mouse as a model for PD and for PD drug testing.ESM 1(PDF 346 kb)Below is the link to the electronic supplementary material.


To develop and evaluate a non-invasive 3D model of Myocardial Wall Stress (MWS) in subjects with severe aortic valve stenosis (AVS).We studied 20 subjects (71±10 years) with severe AVS including 19 with a preserved ejection fraction (EF) and 14 elderly controls (59±6 years). All subjects underwent within 4 hours, transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) as well as applanation tonometry of the carotid artery immediately after CMR examination. CMR included an ECG gated cine SSFP acquisition of left ventricular (LV) short axis slices, positioned regularly and without inter-slice gap between base and apex. Carotid tonometry, by adjusting by the mean brachial pressure obtained during CMR acquisition is a reliable measurement of central aortic blood pressure. 3D MWS can provide a LV afterload estimate which is well known to be strongly related to EF, except in case of depressed contractility. Evaluation of 3D MWS relied on the combination of: 1) a geometrical factor (GF), estimated according to myocardial thickness and LV cavity radius, while accounting for the 3D curvature of the LV, and 2) LV peak systolic pressure provided by tonometric measurement and Doppler maximal transvalvular pressure gradient.For all patients, TTE revealed the presence of severe AVS according to ESC criteria . When compared to 3D MWS evaluation of controls, GF indicated a significant decrease in patients with AVS  whereas 3D MWS remained equivalent between the two groups. These data reflect LV adaptation to pressure overload, leading to an overall normalization of MWS in severe AVSwith preserved EF. Furthermore, our 3D model of MWS is strongly related to EF , reflecting the robustness of this non-invasive method based on CMR and applanation tonometry.This 3D non-invasive evaluation of MWS based on CMR and carotid tonometry was able to characterize LV adaptation to pressure overload in severe AVS. Since, MWS provides a LV afterload estimate, which is strongly related to EF, except in case of depressed contractility, future studies should be performed to reveal the particular usefulness of such non-invasive 3D MWS for prediction of recovery after aortic valve replacement in subjects with low EF.This study was funded by Assistance Publique dex Hôpitaux de Paris.


Cardiovascular magnetic resonance feature tracking (CMR-FT) offers quantification of myocardial deformation from routine cine images. However, data using CMR-FT to quantify left ventricular (LV) torsion and diastolic recoil are not yet available. We therefore sought to evaluate the feasibility and reproducibility of CMR-FT to quantify LV torsion and peak recoil rate using an optimal anatomical approach.−1·min−1) in 10 healthy volunteers. Rotational displacement was analysed for all slices. A complete 3D-LV rotational model was developed using linear interpolation between adjacent slices. Torsion was defined as the difference between apical and basal rotation, divided by slice distance. Depending on the distance between the most apical (defined as 0% LV distance) and basal (defined as 100% LV distance) slices, four different models for the calculation of torsion were examined: Model-1 (25–75%), Model-2 (0–100%), Model-3 (25–100%) and Model-4 (0–75%). Analysis included subendocardial, subepicardial and global torsion and recoil rate .Short-axis cine stacks were acquired at rest and during dobutamine stimulation . Reproducibility was sufficient for all parameters as determined by Bland-Altman analysis, intraclass correlation coefficients and coefficient of variation.Quantification of torsion and recoil rate was feasible in all subjects. There was no significant difference between the different models at rest. However, only Model-1 (25–75%) discriminated between rest and stress (Global Torsion: 2.7±1.5°cmCMR-FT based derivation of myocardial torsion and recoil rate is feasible and reproducible at rest and with dobutamine stress. Using an optimal anatomical approach measuring rotation at 25% and 75% apical and basal LV locations allows effective quantification of torsion and recoil dynamics. Application of these new measures of deformation by CMR-FT should next be explored in disease states. The prevalence of heart failure including systolic and diastolic functional impairments continues to increase representing a major health problem Left ventricular (LV) systolic torsion and diastolic recoil describe the myocardial twisting and untwisting motion resulting from apical counter-clockwise and basal clockwise rotation during systole . Torsion and recoil rate have shown to be sensitive markers for systolic and diastolic dysfunction We therefore aimed to first develop a model that allows uniform selection of apical and basal slices at standardized LV levels and to evaluate its feasibility and reproducibility to quantify LV systolic torsion and diastolic recoil at rest and during dobutamine stress using CMR-FT.Ten healthy volunteers underwent CMR on a 1.5 Tesla scanner . The study protocol was approved by the Institutional Review Board at the University of Nebraska Medical Center and complies with the Declaration of Helsinki. Written informed consent was obtained from all participants.−1·min−1 of dobutamine.All CMR measurements were performed in the supine position using a 5-channel cardiac surface coil. LV dimensions and function were assessed with an ECG- gated SSFP cine sequence during brief periods of breath-holding in 12 to 14 equidistant short-axis planes  completely covering the LV. The field of view was 360×480 mm and matrix size 196×172. Dobutamine stress imaging was performed as previously described −1·min−1 of dobutamine stress. Furthermore, heart rate and mean blood pressure were measured at rest and with both levels of dobutamine stimulation.End-diastolic (EDV) and end-systolic volume (ESV), stroke volume (SV), ejection fraction and cardiac index (CI), were calculated using MassK-Mode in QMass Version 7.6 . Ventricular volumes were adjusted to body surface area. All parameters were analysed at rest, 10 and 20 µg·kgMyocardial feature tracking was performed using dedicated software . All short-axis slices were included in the analysis between the most apical slice showing LV cavity at end-systole and the most basal slice including a complete circumference of myocardium at end-systole. LV endocardial and epicardial borders were manually traced in all slices using a point-and-click approach with the initial contour set at end-diastole. Endocardial and epicardial border surfaces were manually delineated and the automated tracking algorithm was applied. The software automatically tracks 48 subendocardial and subepicardial tissue voxels throughout the cardiac cycle. Tracking performance was visually reviewed to ensure accurate tracking of the ventricular myocardium. In case of insufficient border tracking manual adjustments were made to the initial contour and the algorithm was reapplied. Tracking was repeated for three times in each short-axis view and results were based on the average of the three repeated measures.φapex) and clockwise rotation at the base (φbase) divided by the inter-slice distance (D) Torsion and peak recoil rate were calculated using MATLAB software . Averaged LV rotation profiles were calculated from the angular displacement of all 48 tissue voxels in all slices. LV rotation was averaged across the three repeated measurements. The rotation of points that would typically be located in between adjacent slices was linearly interpolated resulting in a complete 3D LV model of angular displacement Figure 1andThe distance (D) was calculated as the sum of the slice thickness (8 mm) and gap (1–2 mm) of imaging planes that were located in between the basal and apical slices where rotation was measured Statistical analysis was performed using Microsoft Excel and IBM SPSS Statistics version 22 for Macintosh. Data are expressed as mean (± standard deviation). Differences of torsion and peak recoil rate calculated between models 1–4 were assessed by the Friedman test. Pairwise comparisons between variables at rest and with increasing levels of dobutamine were evaluated using the Wilcoxon test. All statistical tests with p values <0.05 were considered statistically significant.Two independent observers analysed all cases to assess inter-observer variability (JTK & AS). Intra-observer variability was derived from the repeated analysis by the first observer (JTK) after four weeks. The intra- and inter-observer variability were assessed by intraclass correlation coefficients (ICC) using a model of absolute agreement. Agreement was considered excellent when ICC>0.74, good when ICC = 0.60–0.74, fair when ICC = 0.40–0.59, and poor when ICC<0.4 The image quality was sufficient to perform CMR-FT in all subjects and for all slices at rest and during dobutamine stress. CMR-FT post-processing took 10 to 12 minutes for a LV short-axis stack on average including adjustments if necessary. Participant demographics are summarised in −1·min−1 of dobutamine. Stroke volume increased significantly between rest and both levels of dobutamine, whilst no further increase was observed between 10 and 20 µg·kg−1·min−1 of dobutamine , 5.8±0.7 cm (model 2) and 4.4±0.5 cm (model 3 and 4). There was no significant difference of endocardial, epicardial or global torsion and endocardial and global recoil rate between the models 1–4 at rest. Results are displayed in −1·min−1 of dobutamine.−1·min−1 of dobutamine except there was no significant difference of subepicardial torsion (p = 0.33) and global torsion (p = 0.06) between rest and 10 µg·kg−1·min−1 of dobutamine (Model 1 (25–75%) was the only approach that revealed significantly increased torsion and recoil rate  between rest and both levels of dobutamine as well as between 10 and 20 µg·kgbutamine Figure 4Bland Altman analysis, ICC and CoV are displayed in Myocardial twisting and untwisting represent fundamental mechanisms of LV systolic and diastolic function. It has been suggested that even up to 40% of stroke volume is produced from systolic twisting forces The presented approach used a complete LV rotational model to define exact apical and basal slice positions by assessing rotational profiles of all short-axis slices of a short-axis stack with subsequent linear interpolation of inter-slice rotation between adjacent slices. This approach appears suitable since several studies revealed strict linear progression of rotation from base to apex CMR-FT represents a relatively novel approach to quantify myocardial deformation. Previous CMR-FT studies primarily focused on ventricular strain measurements. The reported amount of reproducibility and repeatability varies between studies with most studies reporting reasonable reproducibility of global strain levels Previous studies investigated the effect of inotropic stimulation with dobutamine on LV torsion in a canine model and found increased torsion paralleled by accelerated recoil rate Previously described CMR based modalities for the study of myocardial twisting and untwisting motion include myocardial tagging Regarding longitudinal assessments, previous studies applied myocardial tagging to investigate the inter-study reproducibility for quantitative analysis of torsion and recoil rate and found good reproducibility for torsion whilst peak recoil rate was only poorly reproducible The sample size of this feasibility study was relatively small. Notwithstanding this fact the results demonstrate feasibility and good reproducibility for torsion and diastolic recoil quantification with CMR-FT from routine cine images. Ideally we would have compared our results to myocardial tagging representing the reference standard for such acquisitions. However, given the necessity to obtain a whole SSFP short-axis stack at rest and with different levels of dobutamine we felt that the acquisition of an equal number of tagged images would have resulted in scanning times difficult to tolerate during dobutamine stimulation.A general limitation of CMR based quantification of myocardial twisting motion is the current lack of standardized methods. Future studies will need to compare CMR-FT derived torsion and recoil rate with parameters from myocardial tagging using equal computation (twist per length) The clinical applicability of CMR-FT derived torsion and diastolic recoil assessment will depend on the speed of the analysis. At the present time the result files originating from CMR-FT are analysed using an in-house module for MATLAB. Future software developments will need to incorporate both post-processing steps in a single application to further minimize post-processing time.Finally the current work aimed to determine the feasibility and reproducibility to quantify torsion and recoil rate from CMR-FT in a collective of healthy volunteers at rest and during dobutamine stress. Future research needs to prospectively validate this novel technique in pathologies such as coronary artery disease, heart failure or valvular disease.CMR-FT allows derivation of myocardial torsion directly from standard SSFP cine images. Torsion and recoil rate calculated from apical and basal slices with 25–75% distance consistently discriminated between rest and increasing levels of dobutamine. Reproducibility was good to excellent for all torsion and recoil rate parameters, but was especially high when using an apical level at 25% LV distance instead of the most apical slice. When using CMR-FT to quantify myocardial torsion, it is therefore suggested to select apical and basal slices at standardized 25% and 75% levels. The analysis of myocardial torsion and recoil motion based on CMR-FT may have potential clinical and research applications when exact quantification of systolic and diastolic function is required. Future validation studies in larger cohorts should follow to establish the clinical utility and the prognostic implications of this technique.


Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH.Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: ΔmPAP > 5 mm Hg and 2: ΔmPAP ≤ 5 mm Hg. Cardiovascular reserve was estimated as the change  during DST compared with rest, including ΔmPAP with respect to ΔCO (ΔmPAP/ΔCO). All patients were prospectively followed up for 2 years.PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher ΔmPAP/ΔCO (p < 0.05). Neither hemodynamic, IVUS and echocardiographic data were different between both PAH groups at rest. In group 1, DST caused a higher ΔEM, ΔmPAP/ΔCO, ΔPVR, and ΔTAPSE than group 2, with a lower IVA increase and a negative ΔSV (p < 0.05). TAPSE correlated with mPAP and RVP (p < 0.05) and, IVA and Sm correlated with CO (p < 0.05). ΔEM correlated with ΔmPAP and ΔIVA with ΔCO (p < 0.05). There were two deaths/pulmonary transplantations in group 1 and one death in group 2 during the follow-up (p > 0.05).Pulmonary vascular reserve and RV systolic reserve are significantly impaired in patients with PAH. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome. Normal pulmonary circulation is characterized by low pressure and low vascular resistance. Mean pulmonary arterial pressure (mPAP) at rest is virtually independent of age and rarely exceeds 20 mm Hg 14 ± 3.3 mm Hg). In healthy individuals, passive distension of compliant pulmonary circulation and active flow-mediated vasodilation allows the pulmonary vasculature to accommodate increased cardiac output (CO) with only a modest increase in mPAP and a fall in pulmonary vascular resistance (PVR) .3 mm Hg. and a reExercise echo-Doppler is being used with increased frequency in the assessment of patients with known or suspected pulmonary vascular disease, focusing on the change in Doppler-estimated PAP with exercise. However, there are surprisingly few data about RV function at exercise, especially considering that the impaired RV functional reserve could get involved in the mechanism of exercise limitation in PAH and other forms of pulmonary vascular diseases . RecentlWe hypothesized that abnormalities in cardiovascular reserve would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH. Therefore, the first aim of the present study was to perform RV systolic function assessment (echocardiography) and hemodynamic monitoring (right heart catheterization) including local elastic properties of proximal PA wall  during dobutamine stress in patients with PAH. The second aim was to evaluate the association between the cardiovascular reserve and the outcome during two years follow-up.The investigation conforms with the principles outlined in the Declaration of Helsinki. The study protocol was approved by the Institutional Ethics Committee of the Hospital Universitari Vall d’Hebron (Barcelona), and all patients gave written informed consent.Eighteen consecutive patients with PAH (Dana Point group 1) under specific drug therapy who underwent a follow-up cardiac catheterization at our institution were included in the study from January 2007 to September 2009. The patients were in NYHA function class II-III, with no clinical and pharmacological changes in the last 4–6 months. Exclusion criteria were: refusal to participate in the study or being in NYHA function class IV. The diagnosis of PAH was made according to the standard algorithm including a right heart catheterization . Causes All subjects underwent a routine right heart catheterization and simultaneous inferior lobe medium-sized elastic pulmonary artery IVUS in the supine position and breathing room air. A transthoracic echocardiographic study was performed concomitantly in PAH patients by a single experienced examiner. All variables were obtained at rest and during dobutamine stress test with simultaneous Trendelenburg (DST). DST consisted of low-dose dobutamine infusion (10 mcg/kg/min) in order to increase myocardial contractility and heart rate, and 30° Trendelenburg position in order to increase venous return (preload), both during 10 minutes, unless symptoms  were observed. These three variables  are the leading factors responsible for the increase in CO during exercise .PAH patients were prospectively followed up for 2 years. Physicians who carried out the clinical follow-up were blinded to the hemodynamic, IVUS and echocardiographic results.A 7 F Swan-Ganz catheter  was inserted into a brachial vein and a 5 F end-hole catheter was inserted into the right radial artery to monitor systemic arterial pressure. Both catheters were connected to fluid-filled transducers, which were positioned at the anterior axillary line level and zeroed at atmospheric pressure. Right atrial, PAP and pulmonary capillary wedge pressures were all measured at end-expiration. CO was calculated using the Fick method. In patients with tricuspid regurgitation and low CO, such as those with PAH, the thermodilution method has not been reported to be more accurate than the Fick method , howeverIVUS examination was performed with an Eagle Eye Gold catheter 20 MHz, 3.5 F  with an axial resolution of 200 μm and an automatic pullback of 0.5 mm/s. The images were obtained from a segmental PA of the inferior lobe (elastic PA between 2–3 mm) -18 and sBaseline and stress echocardiography was performed using commercially available equipment  with a standard 2D broad-band phased array M4S transducer and tissue Doppler imaging software. The transducer was maximally aligned to optimize endocardial visualization and spectral displays of Doppler profiles. Real-time 2-D and colour Doppler myocardial imaging were performed in the apical 4-chamber view as well as the parasternal short-axis and subcostal views. The predominantly longitudinal contractile pattern of the RV can be exploited to assess RV systolic function . We estiCardiovascular reserve was expressed as the change (increase or decrease) in heart rate , RV systolic function  and pulmonary vascular function  during DST when compared with rest .Continuous variables are expressed as mean ± SEM. Based on the rounded mean + 2SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH patients were divided, prior to analysis, into two groups according to their hemodynamic response to pharmacological stress: group 1 included those patients whose mPAP during stress increased > 5 mm Hg with respect to the resting value, and group 2 comprised those patients with a mPAP increase ≤ 5 mm Hg. Independent sample t-tests were used to compare differences between the control and PAH groups; and paired t-tests were used to compare the effects of stress maneuver within each group. Chi-squared was used for comparing proportions of patients. Intergroup variation was analyzed using one-way ANOVA.P value < 0.05 was regarded as significant. Data analysis were carried out using SPSS 17.0 for Windows 7 software.The association between hemodynamic response  and cardiovascular reserve  were explored using linear regression analysis (Pearson coefficient). A two-sided P < 0.05). There were no significant difference in heart rate, SV, CO, right atrial pressure and pulmonary capillary wedge pressure between both groups.The age and gender of PAH subjects and control subjects were well matched Table . Table 2P < 0.05) with a significant reduction in PVR and TPR, and improvement of IVUSp and EM (P < 0.05) (Table P < 0.05). None of control subjects exceeded 20 mm Hg of mPAP at rest and 30 mm Hg during stress.During DST healthy controls showed an increase of CO, SV and heart rate (5) Table . These cP = 0.034), therefore the CO increment was mainly dependent on heart rate increase. mPAP, pPAP and EM increased significantly and PC significantly decreased during stress . The CO increase was less marked than in healthy controls (P < 0.05), and consequently, ΔmPAP/ΔCO was higher  in PAH patients than in controls , and there were no relevant changes in its severity during the complete protocol. Only six of 18 PAH patients increased SV, and the heart rate increase was significantly lower than control subjects  and nine patients changed mPAP ≤ 5 mm Hg (group 2) during stress. Etiology of group 1 was 5 IPAH, 2 scleroderma-associated PAH, 1 congenital cardiac shunt and 1 HIV PH. Etiology of group 2 was 7 IPAH, 1 scleroderma-associated PAH and 1 porto-pulmonary hypertension. Neither demographic nor clinical differences between PAH group 1 and PAH group 2 were found (Table  and nineP < 0.05), although without significant differences between them . Only PAH group 1 showed a significant increase in mPAP, decreasing PC and increasing EM significantly, with no change in PVR and TPR. PAH group 2 decreased PVR and TPR without significant change in PC, IVUSp and EM (Table P < 0.05). PC decreased in 9/9 patients in group 1 and in only 4/9 in group 2 (P = 0.08). Starting from a similar EM at rest, the EM of PAH group 1 was significantly higher than PAH group 2  (Table P < 0.05) in PAH group 1 during stress.RV systolic function indexes were similar between both PAH patients groups at rest. DST unmasked a significant lower increase of IVA of PAH group 1 with respect to PAH group 2 (5.9 ± 0.7 vs. 9.9 ± 1.5 m ⋅ s2) Table . ConcomiP < 0.05). The negative change in ΔEM and ΔPVR during stress revealed an increased vascular reserve associated with a low ΔmPAP/ΔCO ratio (Table Control subjects showed a higher chronotropic (Δheart rate) and systolic reserve (measured by ΔSV) than PAH patients (io Table .P < 0.005) and ΔCO .Considering all PAH patients, resting EM, but neither PVR nor PC, was correlated with ΔmPAP , whereas, IVA and Sm were correlated with CO  (Table P < 0.05) and ΔIVA was correlated with ΔCO  .In the 2-year clinical follow-up there were two deaths/pulmonary transplantations in PAH group 1 and one death in PAH group 2  . AccordiIn the control group, the marked increase in CO during DST did not cause any significant change in mPAP and determined a low ΔmPAP/ΔCO ratio (0.7 ± 0.2 mm Hg/L/min). This value corresponds well to the cohort of Kovacs et al. which reported a ΔmPAP/ΔCO ~1.06 mm Hg/L/min .The modest increment in mPAP relative to CO during pharmacological stress is attributable to passive recruitment and distension of a normally compliant pulmonary circulation with active flow-mediated vasodilation, decreasing PVR and TPR . StudiesAlthough, both controls and PAH patients had similar heart rate at rest, PAH cohort showed an impaired chronotropic response during stress maneuver. This chronotropic incompetence has been previously documented by Provencher et al. and may reflect the loss of normal physiological reserve secondary to significant autonomic nervous system abnormalities and probably as a result of down-regulation of β-adrenoreceptors ,29.Both PAH patient groups had similar resting hemodynamics and chronotropic reserve. However, the higher increase in mPAP and pPAP with similar increase of CO during stress in PAH group 1 with respect to PAH group 2, would be related to the reduced recruitability and distensibility of more highly remodeled pulmonary vessels. This illustrates a lack of physiological adaptation of the PA wall to increased flow in relation with a lower vasodilation reserve (positive ΔPVR), a higher PA wall remodeling (higher resting EM) and a concomitantly lower buffering function (higher ΔEM). By contrast, PAH group 2 preserved some extent of vascular reserve secondary to a vasodilation response (negative ΔPVR) and a lower impairment of buffering function (lower positive ΔEM). This would explained the significant lower ΔmPAP/ΔCO ratio than group 1. Accordingly, we have previously reported that PAH patients with higher IVUSp and lesser EM displayed an absolute PA vasodilation during acute vasoreactivity testing . We cannIn accordance with previous data, resting hemodynamic measurements are poorly correlated with the response to pharmacological stress . However-1 (10–19) and IVA 3.7 m ⋅ s-2 (2.2-5.2) [In the context of PAH, evidence of RV dysfunction and clinical right-sided heart failure at rest have been shown to be the most important determinants of morbidity and mortality, independently of PAP values. We used three measures of longitudinal RV shortening in an effort to characterize simple and reproducible measurements of global RV systolic function . The mea-1 10– and IVA 2.2-5.2) . Prelimi2.2-5.2) . However2.2-5.2) . This ma-1 10– and IVA 2.2-5.2) . IVA app2.2-5.2) ,36.Recently, Blumberg et al. correlated exercise hemodynamics with peak oxygen uptake and determined their prognostic significance in PAH patients. Among hemodynamic variables, only exercise cardiac index and the slope of the pulmonary pressure/flow relationship were significant prognostic indicators . TherefoAlthough care must be taken when comparing hemodynamic response induced by physical exercise with pharmacological stress produced by low-dose dobutamine infusion, the similar response to exercise and to dobutamine infusion at 10 mcg/kg/min in patients with PH following the Mustard operation is compelling .In addition, our pharmacological stress was a step closer to real exercise, since increased preload was achieved with the addition of 30° Trendelenburg. In fact, our stress maneuver doubled the CO in the control population. The stress with dobutamine and Trendelenburg works by a purely passive effect on PVR and PC, mimicking the CO response to moderate exercise without interfere with PA vascular tone. Invasive recordings of exercise hemodynamics in PAH require an intensive protocol, best performed by an experienced team, and thus it does not belong in the routine evaluation of PAH patients ,24. Our The relative contributions of longitudinal and transverse shortening to overall RV function have been quantified recently. Although, we only assess RV systolic reserve by longitudinal shortening indices, Brown et al. showed that improved RV function following pulmonary vasodilator therapy occurs solely from improvements in longitudinal contraction, suggesting that longitudinal shortening may represent the afterload-responsive element of RV functional recovery . FinallyPulmonary vascular reserve and RV systolic reserve are impaired in PAH patients. The PA wall remodeling, pulmonary buffering function and RV contractility appeared as the main factors of the cardiovascular reserve dysfunction in PAH patients. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome. Further study is needed to elucidate whether cardiovascular reserve dysfunction adds independent prognostic information in a multivariate analysis. In addition, further studies needs to assess whether improvement of cardiovascular reserve could be a therapeutic target in patients with established pulmonary hypertension.CO: Cardiac output; DST: Dobutamine stress test with simultaneous 30° Trendelenburg; EM: Elastic modulus; IVA: Myocardial acceleration during isovolumic contraction; IVUS: Intravascular ultrasound; IVUSp: IVUS pulsatility; mPAP: Mean pulmonary arterial pressure; PA: Pulmonary artery; PAH: Pulmonary arterial hypertension; PC: Pulmonary capacitance; pPAP: Pulse PAP; PVR: Pulmonary vascular resistance; RV: Right ventricle; Sm: Myocardial peak velocity during ejection phase; TAPSE: Tricuspid annular plane systolic excursion; TPR: Total pulmonary resistance.The authors declare that they have no competing interests.ED and JCG conceived of the study, participated in its design, conducted the study, analyze the data, and wrote the manuscript. RA participated in the design of the study, conducted the study and helped write the manuscript. CA and NB conducted the study and analyze the data. MLM conceived of the study and participated in its design. AR conceived of the study, participated in its design, and wrote 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/1471-2466/14/69/prepub


Background: Chronic renal failure and hemodialysis affect many ECG parameters which can affect cardiac repolarization.Objective: To investigate the change in ventricular repolarization before and after kidney transplantation in children.Methods: A total of 45 children with end-stage renal disease, 45 children at least 6 months after successful renal transplantation, and 45 normal age-matched subjects were enrolled into this study. A 12-lead ECG was recorded in the 3 groups. QT dispersion, QTc dispersion, and T peak to T end (TPE) dispersion were measured.Results: In the patients before and after renal transplantation and the normal children, respectively, the mean±SD QT dispersion was 0.083±0.033, 0.056±0.029, and 0.033±0.016 (p<0.01); the mean±SD QTc dispersion was 0.104±0.038, 0.066±0.033, and 0.039±0.020 (p<0.01); the mean±SD TPE interval dispersion was 0.060±0.021, 0.045±0.021, and 0.034±0.019 (p<0.01). There was a significant correlation between left intra-ventricular diastolic diameter and QT dispersion, QTc dispersion, and TPE dispersion. The systolic velocity of the mitral valve also correlated with TPE dispersion .Conclusion: In children with chronic renal failure, indices of ventricular repolarization improve after transplantation, though they still remain longer than the normal values. The leading cause of death in patients with chronic renal failure is premature cardiovascular disease. Although the adult patients have many risk factors such as hypertension and hypercholesterolemia, pediatric patients are less likely to develop these risk factors -4.The pattern of cardiovascular involvement in patients with chronic kidney disease differs from that in the general population; these patients have increased chance of sudden death rather than myocardial infarction. The increased QT interval in ECG in these patients, is associated with the development of arrhythmia and sudden cardiac death . AlthougQTc, QTc dispersion, and QT dispersion are risk factor for the development of arrhythmia in the patients under chronic hemodialysis . QT dispOther indices of ventricular repolarization are “T peak to T end” (TPE) interval and dispersion. TPE interval provides an index of maximum dispersion of repolarization and reflects the transmural dispersion of the repolarization vector among different regions of the ventricle . The shaWe conducted this study to determine the effect of renal transplantation on the QT dispersion, QTc dispersion, and TPE dispersion in pediatric patients with chronic renal failure.This study was conducted from September 2009 to May 2011, in Namazi Hospital, Shiraz, Iran, on a group of patients aged <18 years. The study was performed on 45 pediatric patients with ESRD who were candidate for renal transplantation, none of whom had any signs of heart failure or electrolyte abnormalities; 45 consecutive kidney transplant recipients with functioning graft patients at least six months after a successful renal transplantation; and 45 healthy children <18 years old, who had no cardiac or other organic diseases. For each patient, serum level of sodium, potassium, and calcium was checked; a 12-lead digital ECG was recorded by one nurse, and echocardiography was performed.Measurement of QT was made in all possible leads, by one observer. Recordings were made by a digital ECG machine . The digitally recorded ECG tracings were evaluated using a digital clipper in Corel Photo Paint ver 13 software . Magnification of the ECG made it possible to determine the measurement points more precisely. The QT interval was measured from the beginning of the QRS complex to the termination of the T wave (defined as the return to the isoelectric line) in 12-lead ECG. Bazett’s formula was used to calculate the QTcThe QT and QTc wave dispersion were then calculated according to the definition of dispersion—the difference between maximum and minimum duration values in 12-lead ECG. TPE interval was measured in each precordial lead. It obtained from the difference between QT interval and QT peak interval, measured from the beginning of the QRS to the peak of the T-wave. TPE dispersion was also calculated as the difference between the maximum and minimum TPE interval in precordial leads during a single beat.Echocardiography was performed by a GE Vivid 3 echocardiographic machine  using a 3-MHz probe with pulsed Doppler tissue imaging software. All M-mode, two-dimensional, Doppler, and pulsed tissue Doppler echocardiographic studies were conducted with the patients in left lateral decubitus position by a one qualified cardiologist. The ejection fraction, shortening fraction, and septal and posterior wall thickness during systole and diastole were measured in the left parasternal long axis view. The pulsed Doppler sample volume was placed at the mitral valve and tricuspid tips, and three cardiac cycles were recorded from the apical window. Early (E) and late (A) peak velocities and their ratio were measured to assess the diastolic function. Pulsed tissue Doppler tissue images were obtained with the sample volume placed at the lateral corner of the mitral annulus, then at the medial  and tricuspid corner in the apical four-chamber view, and finally at the anterior wall and posterior wall in the parasternal short-axis view. In each region, systolic (S) wave, early diastolic (Ea), and late diastolic (Aa) wave velocities were recorded. The average of three consequtive waves was recorded, as well. Statistical analysis® for Windows® ver 16.0  was used for data analyses. Continuous variables are expressed as mean±SD. The mean of normally distributed variables were compared among the study groups by one-way ANOVA. Pearson’s correlation coefficient was used to assess the level of correlation between serum electrolyte levels, echocardiographic indices recorded, and ECG parameters. A p value <0.05 was considered statistically significant.SPSSThe mean±SD age of patients before transplantation, patients after transplantation, and normal age-matched children was 13.8±4.3, 13.2±4.8, 12.8±4.5 years, respectively. All the participants had a normal serum calcium, potassium, and sodium level. The mean±SD duration passed after the transplantation was 4.2±2.9 years. The post-transplantation patients were on tacrolimus or cyclosporine in addition to corticosteroids, mycophenolate mofetil, and azathioprine. The demographic data of study participants are presented in A statistically significant difference was observed in the mean QT dispersion, QTc dispersion, and TPE dispersion among the three groups .Left ventricular end-diastolic diameter was significantly correlated with QT dispersion , QTC dispersion , and TPE dispersion . There was also a significant correlation between the systolic velocity of the lateral mitral annulus, which was measured by tissue Doppler, and TPE dispersion . No significant correlation was observed between the ejection fraction; diameter of inter-ventricular septum; diameter of the left ventricular posterior wall; the mitral valve E wave and A wave velocities; E/A ratio; the tricuspid E wave and A wave velocities; S wave velocity of the lateral tricuspid valve annulus; Ea wave and Aa wave velocities of the lateral mitral valve annulus; Ea wave and Aa wave velocities of the lateral tricuspid valve annulus; E/Ea ratio of the mitral valve; and QT dispersion, QTc dispersion, and TPE dispersion.Cardiovascular events contribute to a significant proportion of all deaths in children with chronic renal disease. The European Dialysis and Transplant Association reported that 41% of all deaths in the children with ESRD were attributed to cardiovascular causes. In addition, the majority of the deaths were sudden and unexpected . This moeg, torsade-de-pointes) is closely related to the enhancement of the normally existing transmural dispersion of repolarization rather than prolongation of the ventricular repolarization [A non-invasive way for assessing ventricular repolarization is the measurement of the QT interval. QT and QTc dispersion are useful indices for assessing depolarization changes and prediction of arrhythmias in ECG. When QT dispersion increases with heterogeneity in ventricular recovery time, it can be assumed that an increased QT dispersion would be an indicator of the disparity of the ventricular recovery time . Some strization -17. Theset al, indicated that the advantages of QT dispersion, as a non-invasive and useful method for evaluation of myocardial repolarization, cannot be over-emphasized [et al, suggested that the increase in QT, QTc, and QT dispersion in patients with chronic renal failure might be non-invasive methods for detection of ventricular arrhythmias [et al, showed that QT dispersion was a powerful way for predicting ventricular arrhythmias and sudden death in patients with ESRD under chronic hemodialysis [Familoni, phasized . The curphasized -22. Morrhythmias . Brunnerdialysis .et al, who showed that the QT dispersion in renal transplant recipients was similar to that of the healthy control subjects [The effects of renal transplantation on these two ECG indices were evaluated by Koc, subjects . On the et al, described similar effect of ESRD on TPE dispersion as a trans-myocardial dispersion indicator in pre-dialysis patients with ESRD [TPE interval is also another predictor of ventricular arrhythmia though it has been mentioned less often in previous studies. Nevertheless, the role of increased TPE dispersion in ventricular arrhythmias has been confirmed by multiple studies , 27. Tunith ESRD .et al, showed a relationship between the left ventricular hypertrophy and the longest QTc dispersion [In the present study, only a significant correlation was observed between the left ventricular end-diastolic dimension and QT dispersion, QTc dispersion, and TPE dispersion. Tissue Doppler-derived systolic velocity of the lateral mitral valve annulus was also positively correlated with TPE dispersion. So far, a limited number of studies have addressed the correlation between echocardiographic parameters and ECG findings in transplanted children. Familoni, spersion . HoweverIn conclusion we found that ESRD increases QT dispersion, QTc dispersion, and TPE dispersion in children. Renal transplantation improves these changes; however it does not return the indices to their normal values. The left ventricular internal dimension during the diastole also has a significant correlation with repolarization indices.


Left ventricular hypertrophy (LVH) after heart transplant (HTx) is multifactorial, associations include hypertension, chronic immune injury and the intrinsic effects of immunosuppression. Its consequences are significant and potentially provide an explanation for the development of diastolic dysfunction and exercise intolerance, as well as the limited life expectancy after HTx. Both expansion of myocardial extracellular volume (ECV) and myocyte hypertrophy (MH) coexist in this setting. Cardiac biopsies have limitations and may be non-representative to assess global myocardial remodeling. The goal of this pilot study was to characterize both ECV and MH by CMR in cohort of HTx recipients without active rejection.τic), a cell size-dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange.T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water  without acute rejection and 20 age matched health volunteers (mean age 51±14) underwent CMR (1.5T) includingmeasurement of LV function, T2, T1 mapping pre- and post-gadolinium and LGE, and a echocardiogram for measurement of diastolic function. HTx recipients demonstrated normal LVEF (68±11%) with a significant increased in LVMass in comparison with age-matched volunteers . Both groups (HTx and controls) did not show LGE or abnormal signal intensity in T2 images. ECV was substantially higher in HTx patients  compared with volunteers . Both ECV, a marker of interstitial fibrosis, and τic, a new validated maker of myocyte hypertrophy, were significantly associated with LV mass . ECV and τic also demonstrated a strong association with E wave deceleration time (EDT) by TTE . ECV maintained the positive association with EDT indexed to E wave. . by ROC curve analysis, the ECV was able to predict diastolic dysfunction using EDT by ETT with AUC 0.97 .Nineteen HTx recipients (mean age 50±0, 6 female, BSA 1,70±0,16mτic were associated with markers of diastolic of dysfunction after HTx. Non invasive assessment of ECV and Tau by CMR may be useful to follow HTx recipients.By CMR, the ECV quantification characterized expansion of extracellular volume in HTx recipients with increased LV Mass and normal LVEF. Both ECV and Departamental funding - State University of Campinas – UNICAMP.