We proposed that the severity of ST-segment elevation myocardial infarction (STEMI) could be classified based on pathophysiological changes.First-STEMI patients were classified within hospitalization. Grade 0: no detectable myocardial necrosis; Grade 1: myocardial necrosis without functional and morphological abnormalities; Grade 2: myocardial necrosis with reduced LVEF; Grade 3: reduced LVEF on the basis of cardiac remodeling; Grade 4: mitral regurgitation additional to the Grade-3 criteria.Of 180 patients, 1.7, 43.9, 26.1, 23.9 and 4.4% patients were classified as Grade 0 to 4, respectively. The classification is an independent predicator of 90-day MACEs : the rate was 0, 5.1, 8.5, 48.8 and 75% from Grade 0 to 4 (p<0.001), respectively. The Grade-2 patients were more likely to have recovered left ventricular ejection fraction than the Grade-3/4 patients did after 90 days . Avoiding complicated quantification, the classification served as a good reflection of infarction size as measured by cardiac magnetic resonance imaging , and with a comparable prognostic value  for MACEs.The new classification represents an easy and objective method to scale the cardiac detriments for STEMI patients. Thanks for the worldwide highlight and availability of therapeutic innovations for ST-segment Elevation Myocardial Infarction (STEMI), myocardial injury following STEMI tends to polarize,2: the pNevertheless, current evaluations are still discretely based on functional  ,5, symptTo achieve satisfactory reproducibility and validity, the ideal evaluation may follow the progressive pathophysiological changes after STEMI. Such a process is composed of several advancing stages that are predictable in each patient according to the severity of cardiac detriments–11: i.e.To validate the hypothesis, we stratified a cohort of STEMI patients into five groups: those without detectable myocardial necrosis, those with clear myocardial necrosis but are absent of functional and morphological abnormities, those with necrosis and demonstrating reduced LVEF, those with LVEF reduction on the basis of significant cardiac remodeling, and those with remarkable mitral regurgitation in addition to morphological and functional detriments . Our resFrom May 2012 to March 2014, first-time-STEMI patients who received reperfusion therapy within 12h of symptom onset were included. The only exclusion criterion is a missing of CMR data within hospitalization.STEMI was defined as a chest pain lasting ≧ 30 minutes together with an ST-segment elevation in ≧ 2 contiguous leads on a standard 12-lead electrocardiogram .All patients received reperfusion therapy by either a primary PCI (PPCI) or a pharmacoinvasive strategy . Standard therapeutic regimes were applied to every patient according to the 2013 ACCF/AHA Guideline for the management of STEMI[Patients were classified by the following criteria: Grade 0: no detectable myocardial necrosis; Grade 1: presence of myocardial necrosis but without functional and morphological abnormalities; Grade 2: myocardial necrosis accompanied with reduced LVEF (LVEF<55%); Grade 3: with reduced LVEF on the basis of cardiac remodeling (≧15% increase of left ventricular end-diastolic volume (LVEDV) compared to normal limitation); Grade CMR was performed at a median of 5.5 days after reperfusion. Images were acquired using an EKG-gated 3.0 Tesla scanner .3). Myocardial edema was detected using a black blood T2 short tau inversion-recovery sequence . Myocardial necrosis was detected by late gadolinium enhancement (LGE) using a 3D inversion recovery segmented gradient echo sequence  10 minutes after contrast injection . Individual optimized inversion time was carefully chosen in a Looklock sequence in order to null the signal of normal myocardium.The scanning protocol was described previously . In brieCMR data were inspected using commercial software . Left ventricular (LV) geometric and functional parameters were calculated on short-axis-view cine images. Myocardial edema and necrosis were determined as high-signal areas compared with remote non-infarcted myocardium on T2W-STIR and LGE images, respectively (≧2 SDs for edema and ≧5 SDs for necrosis). Infarction sizes were quantified and expressed as percentages of LV myocardial volume.Echocardiography was performed on the same day of CMR and 90 days later , respectively, using a Vivid E9 scanner .Images were analyzed using commercial software . LVEF was calculated on short-axis-view images by the Simpson method; the degree of mitral regurgitation was categorized as mild, medium or severe according to the area ratio between regurgitation jet and left atrium . A mediuMajor cardiovascular adverse events (MACEs) were defined as a composite of any death, resuscitated cardiac arrest, acute heart failure , and stroke. In-hospital events were immediately recorded while the 90-day events were determined by telephone follow up with a pre-designed questionnaire.The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Human Research Ethic Committee of Renji Hospital, Shanghai Jiaotong University School of Medicine. All patients signed a written informed consent before inclusion.Continuous variables are expressed as mean ± standard deviation (SD). Categorical variables are expressed as the number and percentage of patients. Comparisons between two groups were performed by Student’s t-test in terms of continuous variables or by Chi-square/Fisher’s exact test for categorical variables. Continuous variables among several groups were compared by one-way ANOVA. Correlations between variables were assessed by Spearman’s correlation coefficients. To adjust the impact of baseline characteristics on prediction of MACEs, a logistic regression analysis with stepwise inclusion was performed including all possible influential factors. To do so, a univariable analysis was performed in advance, and all variables with a p value <0.1 qualified for the multivariable model. Finally, C-statistics were performed to compare between the proposed classification and the infarction size regarding the predictive value for MACEs. All statistical analyses were performed using the SPSS software, version 22.0 .A total of 190 patients were hospitalized during the study period. Among them, CMR data were unavailable in 10 patients .Of the enrolled 180 patients, 3 were classified as Grade 0 (1.7%), 79 as Grade 1 (43.9%), 45 as Grade 2 (25.%), 43 as Grade 3 (23.9%) and 8 as Grade 4 (4.4%). There were 2 patients exhibiting LV expansion but without LVEF reduction, who were assigned to Grade 2, expanding this group to 47 patients (26.1%). Baseline characteristics are listed in To demonstrate the general relationship between the new classification and prognosis, the rates of 90-day MACEs were compared across differently graded patients. As shown in Subtracting the 4 deaths, all 176 patients underwent the second echocardiography after 90 days. Among the patients with reduced LVEF, 23 of the 47 (48.9%) Grade-2 patients had a recovered LVEF (≥55%). On the contrary, only 8 Grade-3 and 1 Grade-4 patient (19.1% of the 47 surviving patients in both groups) exhibited normal LVEF  were remarkably evoked by larger infarction sizes , and patients with mitral regurgitation on the basis of severe morphological and functional deteriorations (Grade-4 patients). Mitral regurgitation did not manifest notable influence on MACEs when the normal shape of LV was persevered . On the opposite, mitral regurgitation concomitant with apparent cardiac remodeling was shown to correlate with significantly higher MACEs rates .To further validate the prognostic value of the pathophysiological classification, potential influential factors of prognosis were adjusted by logistic regression. Only the infarction size and patient’s grade remained to be independent predictors of 90-day MACEs . Nevertheless, extensive infarction often results in significant and quick morphological compensation, known as cardiac remodeling. In this regard, the worsening of LVEF seen in Grade-3 and Grade-4 patients is a reflect of both large necrosis and geometric deconstruction. In the Finally, mitral regurgitation additional to functional and morphological ventricular deteriorations has been proved an explicit mark of cardiac decompensation ,27 and tThe value of the proposed classification is proved by its close relationship with the prognosis of current cohort. On one hand, the ascending grade is a strong indicator of higher rates of 90-day MACEs after adjusting other influential factors. This can be explained by the results of previous studies, that the presence of detectable myocardial necrosis, LVEF reOne important trait of the classification is its close relationship with infarction extent. This can be explained by our results that the occurrences of functional and morphological detriments are largely evoked by extended infarction. It is notable that, in terms of the prediction of 90-day MACEs, the classification has a comparable value as that of the infarction size itself, thus providing the classification an important advantage–namely, being a good surrogate of infarction extent but avoiding the requirements of complicated and facility-reliant quantification.To be noted, the usage of CMR in this study was only to guarantee the equal criteria and comparison. In clinical practice, recognition of myocardial necrosis can be based on other methods according to the time point and facility availability, in the meanwhile, functional and morphological parameters can be acquired through multiple cardiac imaging technologies.Due to the high cost of CMR, the sample size of the study was limited. Moreover, the criteria may be further refined to achieve a more precise stratification.Based on different pathophysiological stages, the severity of STEMI can be objectively stratified while patient’s prognosis can be well indicated.


Coronary microvascular dysfunction is highly prevalent in patients with amyloid light-chain (AL) cardiac amyloidosis (AL-CA). The aim of this study was to clarify the feasibility of first-pass perfusion imaging using 3 T cardiovascular magnetic resonance (CMR) for evaluating the difference in left ventricular (LV) regional myocardial microvascular function among normal subjects and in patients with AL-CA. The amyloidosis patients were classified into those with impaired systolic function [LV ejection fraction (LVEF) < 50 %] and those with preserved systolic function.In total, 32 patients with biopsy-proven AL-CA, including 11 AL-CA patients with systolic dysfunction, 21 AL-CA patients with preserved systolic function, and 25 healthy subjects, underwent CMR examination. LV regional myocardial perfusion parameters included upslope, time to maximum signal intensity (TTM) and max signal intensity (MaxSI) were compared among the three patient groups. Receiver operating characteristic analysis was performed to determine whether perfusion parameters could be used in discriminating regional myocardial microvascularity between AL-CA patients and normal subjects.P < 0.01). Compared with the patients with AL-CA and preserved LVEF, the patients with AL-CA and impaired systolic function had a longer TTM in the basal  and mid-ventricular  segments; lower upslope in the basal , mid-ventricular , and apical  segments; and lower MaxSI  in the basal segment. The ROC curve analysis revealed that the first-pass upslope, TTM, and MaxSI may be used as indicators for differentiating microcirculation between AL-CA patients with preserved or impaired systolic function and normal subjects.The patients with AL-CA had significantly reduced first-pass perfusion upslope and MaxSI, and increased TTM compared with the normal subjects (all The differences in LV regional myocardial microvascular function among normal subjects, AL-CA patients with systolic dysfunction, and AL-CA patients with preserved systolic function can be monitored using first-pass perfusion CMR. Amyloidosis is a rare disorder characterized by the extracellular deposition of pathological insoluble proteins in multiple organs, including the heart , 2. AmylNecroscopy examinations have confirmed that amyloid infiltration in the microvascular system may cause coronary microcirculation disorder, with patients presenting with symptoms of angina and signs of ischemia –8. In adAs amyloid infiltration in the cardiac microvascular system is prevalent in patients with CA and is potentially associated with LV systolic function and wall thickening , 9, it in = 6; 18.8 %), bone marrow , liver , fat , rectum , skin , and tongue  and typical echocardiographic findings, including a mean wall thickness of the ventricular wall and/or interventricular septum measuring >12 mm in diastole [The institutional ethics committee of our hospital approved this study, and written informed consent was obtained from each participant prior to the investigation. Between September 2013 and March 2015, 38 patients with biopsy-proven AL amyloidosis were enrolled in the study, according to the following inclusion criteria: (a) AL amyloidosis, initially diagnosed in extracardiac tissue using congo red and immunohistochemical staining and (b) cardiac involvement, confirmed according to echocardiographic criteria . The excdiastole .All patients were examined in the supine position using a 3 T whole-body scanner  at least 3 days following ECG examination. A dedicated two-element cardiac-phased array coil was used for signal detection. The manufacturer’s standard ECG-triggering device and the breath-hold technique were used to monitor the individuals’ ECG values and breathing, respectively. Following a survey scan, cine images were acquired in 2-chamber, 3-chamber, and 4-chamber views using a TrueFISP sequence . Subsequently, gadobenate dimeglumine  was intravenously injected using an automated injector  at a dose of 0.1 ml/kg body weight and a flow rate of 2.5–3.0 ml/s. In addition, a 20 ml saline flush was injected immediately following contrast at a rate of 3.0 ml/s. Rest regional perfusion images were acquired in three standard short-axis slices  and in one slice of the 4-chamber view using an inversion-recovery prepared echo-planar imaging sequence . Each set of first-pass perfusion images was completed in 80 cardiac cycles.42; Circle Cardiovascular Imaging, Inc., Calgary, Canada). Endocardial and epicardial traces were performed manually by two experienced observers (Wen LY and Li R) in the serial short-axis slices at the end-diastolic and end-systolic phases. The global cardiac function, including LV end-diastolic volume (EDV), end-systolic volume (ESV), and LV ejection fraction (LVEF) were computed using a modified Simpson’s rule. For regional analysis, a 16-segment mode (Bull’s eye plot), according to AHA standard segmentation, was constructed on the basis of analysis of the long- and short-axis slices . A Mann–Whitney U test was used to compare the regional myocardial perfusion and functional parameters among the normal subjects and the AL-CA patients with or without systolic dysfunction using Bonferroni’s correction for multi-group comparisons. If a significant difference was confirmed, receiver operating characteristic (ROC) analysis was performed to determine whether the cut-off values of regional cardiac perfusion can be used to differentiate myocardial microvascular function between AL-CA patients and normal subjects. Spearman’s rank correlations analysis was performed to examine the correlation between regional myocardial perfusion, wall thickness, and wall thickening. P < 0.05 was considered to indicate a statistically significant difference.All statistical analyses were performed using SPSS software . The results are expressed as the mean ± standard deviation (SD). Continuous variables were compared using independent Student’s P = 0.013). The AL-CA patients with impaired LVEF had a significantly higher LVESV and lower SV than that of the normal subjects and the AL-CA patients with preserved LVEF . However, no statistically significant differences were observed between the patients with preserved LVEF and the normal subjects in LVESV  or LVEF . The LV mass in the AL-CA patients were markedly increased as compared with that in the normal subjects (both P < 0.0001); however, there was no significant difference between the AL-CA patients with LV systolic dysfunction and those without LV systolic dysfunction . After CMR and echocardiography, fifteen (46.9 %) patients received chemotherapy whereas seventeen (53.1 %) did not, and the chemotherapy regimen was listed in Table The baseline characteristics the AL-CA patients and normal subjects are presented in Table P < 0.05; Table P < 0.0001) and increased EDWT (P = 0.014). However, there was no significant difference in ESWT between the AL-CA patients with LV systolic dysfunction and those without LV systolic dysfunction. Using the Bull’s eye plot, baso-apical gradients of decreased EDWT and ESWT and increased Wth were observed in the AL-CA patients. The average differences in EDWT, ESWT, and Wth in the basal, mid-ventricular, and apical segments between the AL-CA patients with or without LV systolic dysfunction were compared  and thicker EDWT in the basal segment . However, no significant differences in ESWT were observed between the AL-CA patients with or without LV systolic dysfunction in any of the three segments.The AL-CA patients had significantly thicker EDWT and ESWT and reduced Wth compared with the normal controls . The AL-CA patients with LV systolic dysfunction exhibited a shorter upslope in the three segments , reduced MaxSI in the basal segment, and longer TTM in the basal and mid-ventricular segments  as compared with the AL-CA patients without LV systolic dysfunction.The first-pass perfusion parameters of all subjects are shown in Table P < 0.0001) and between the MaxSI and Wth . A negative correlation was found between the first-pass perfusion upslope and EDWT  and ESWT  and between the MaxSI and EDWT  and ESWT .A significant and positive correlation was demonstrated between the first-pass upslope and Wth  area at the base compared with the apex segments, and echocardiographic studies using strain analysis, which reported reduced basal systolic longitudinal and radial strain in CA –32.Another finding in our study was that the AL-CA patients with impaired LVEF were associated with more marked regional LV microvascular disorder as compared with the AL-CA patients with preserved LVEF. As an independent predictor of cardiac mortality in AL amyloidosis patients, systolic dysfunction tends to occur in advanced stages of the disease and is often associated with poor outcome , 33, 34.As significant differences in first by-pass perfusion parameters were observed between the AL-CA patients with impaired or preserved systolic function and the normal controls, these perfusion data may assist in discriminating between the microvascular dysfunction AL-CA patients and normal controls. The data obtained from the ROC analysis supported the use of the upslope, TTM, and MaxSI as criteria to enable the differentiation of the microcirculation of AL-CA patients, regardless of LVEF, from that of normal control individuals. Besides, precise identification of amyloisosis type is also crucial in clinical setting due to the prognosis and the treatment depends on the type of this disease. CMR LGE could help differentiate noninvasively between cardiac light chain amyloid and transthyretin-related amyloidosis (ATTR), and among different ATTR pathogenic mutation groups , 38. As Our study had several limitations. Firstly, a larger sample size of AL-CA patients is required for further investigation, with an emphasis on myocardial perfusion. Secondly, our present study did not evaluate whether the interstitial myocardial fibrosis detected by LGE or quantified by T1 blood-pool gadolinium kinetics or T1 mapping on CMR could affect coronary microvascular dysfunction, which are valuable for differential diagnosis and the prediction of outcomes in CA patients –41. The The difference of LV regional myocardial microvascular function among AL-CA patients with or without LV systolic dysfunction, and normal subjects can be monitored by first-pass perfusion CMR imaging, and the threshold values of LV regional myocardial perfusion parameters may be used as indicators for differentiating myocardial microvascular dysfunction between AL-CA patients with preserved or impaired systolic function and normal subjects.


The relationship of right ventricular (RV) regional and global systolic function to right heart hemodynamics is not well understood. In this study we used MRI feature tracking to assess regional RV wall motion, cine MR to evaluate global RV function and examined the relationship of regional wall motion and global RV function to right heart hemodynamics.feature tracking software . Right heart hemodynamics was assessed during catheterization.Fifty patients undergoing clinically indicated right heart catheterization were prospectively recruited to a research CMR within 5 hours of catheterization. Majority of the heart failure cases were due to left heart failure. SSFP cine images were acquired to evaluate RV regional and global function. RV longitudinal and long axis radial strains were derived from the 4-chamber cine, and mid wall septal circumferential and radial strains from the short-axis plane in mid ventricle using CIM Mean age was 64±13 years, mean RV ejection fraction (EF) 51±13%. Reduced longitudinal and radial displacement in 4 chamber view was significantly associated with reduced RVEF, r=-0.621 (p<0.001) and r=0.346 (p=0.014), respectively. Similarly, in short axis plane reduced septal circumferential and radial strain were also significantly correlated with RVEF, r=-0.488 (p=0.001) and r=0.527 (p<0.001) respectively. In regression analysis reduced RVEF had strongest association with increased pulmonary wedge pressure  in univariate analysis and in multivariate analysis (p<0.001) after adjusting for all the right heart hemodynamic parameters. Pulmonary wedge pressure contributed to 41% of RVEF variation in this cohort with predominant left heart failure. While also significantly correlated with pulmonary wedge pressure, regional wall motion including longitudinal strain, septal circumferential and radial strain had strongest association with mean pulmonary arterial pressure, r=0.577 (p<0.001), r=0.440 (p=0.002) and r=-0.451 (p=0.001), respectively.It is feasible to use MR feature tracking to characterize RV regional wall motion. Reduced global and regional RV systolic functions are associated with right heart hemodynamic abnormalities. In patients with predominant left heart failure, pulmonary wedge pressure contributes importantly to RVEF variation.None.


Diastolic heart failure is a common and deadly complication of diabetes mellitus, with the development of diabetic cardiomyopathy as one of the key determinants of the disease’s complex pathology. The cause of the association is unknown and has no approved therapy strategies as of yet. However significant advances in this area may come from studies on suitable animal models.A total of 25 male rhesus monkeys  were enrolled. Fifteen of them were diagnosed as spontaneous type 2 diabetes mellitus . The other 10 monkeys were non-diabetic . Echocardiography and cardiac magnetic resonance were used for evaluating the cardiac structure and function. One T2DM monkey with impaired diastolic function and another ND monkey were both sacrificed to gain the necessary pathology and protein expression studies displayed here.Six out of 15 T2DM rhesus monkeys were diagnosed with diastolic dysfunction (DD) by echocardiography. Additionally, no abnormalities were found in the group which we determined as the ND monkeys. The six DD monkeys all showed low e’ velocity and decreased e’/a’ ratio, among which three of them showing decreased E/A ratio and the other 3 having elevated E/A ratio, this appears to be similar to the impaired relaxation pattern and pseudonormal pattern found in human patients respectively. The EF and FS of monkeys with pseudonormal pattern decreased significantly compared with ND subjects. A CMR study showed that LVID at end systole of 5 DD monkeys is significantly longer than that of 3 ND monkeys. Of great interest, myocardium lesions and mitochondria impairments and increased expression of AGEs and caspase-3 were found in a sacrificed DD subject.The changes in the imaging and physiological markers of spontaneous T2DM rhesus monkeys are similar to those key markers found in human type 2 diabetes and diastolic dysfunction. This monkey model could help the medical community and us to understand the pathology of this debilitating disease and serve as a beginning to explore important measures to prevent and treat diabetic cardiomyopathy. Cardiovascular diseases (CVD) are the leading causes of death and disability among people with diabetes. At least 65 % of people with diabetes die from certain forms of cardiovascular diseases . As a maDCM has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause, such as coronary artery disease (CAD) or hypertension . AdditioAlterations of certain biomarkers have also been reported to play key roles in the development of cardiac dysfunction and are therefore important to monitor. For example, advanced glycosylation end products (AGEs) can covalently crosslink and biochemically modify collagen structures in diabetes induced myocardial stiffness . AnotherSignificant advances in diabetic-related diseases may come from the studies on suitable animal models. Abnormalities in cardiac functionality and structure in diabetic subjects have been demonstrated in a variety of type 1 and type 2 diabetic rodent models –18. In mMacaca mulatta) are more similar to humans in physiology and to the susceptibility of known metabolic diseases in human patients [Compared with other animal models, rhesus monkeys  at a dosage of 10 mg/kg i.m. and the coat of monkey was bilaterally shaved from the cervical part to the navel, and rinsed copiously with water in order that acoustic coupling was obtained using ultrasound gel. Transthoracic echocardiography was performed by using a commercially available ultrasound system (Mindray M7vet) with the same investigator taking the measurements with the monkeys placed in a dorsal decubitus position while in a stable sedation state. All measurements were performed around the midday to avoid the influence of circadian rhythm on the left ventricular diastolic function . All echPulsed-wave Doppler measurements: Blood flow velocity was recorded at the mitral diastolic inflow at the level of the mitral leaflet tips from the apical 4-chamber view. The following velocities were observed and recorded according to the current standards of the practice of echocardiography: E wave, A wave and E/A ratio. Early filling deceleration time (EDT) and isovolumic relaxation time (IVRT) were measured and averaged from 3 consecutive beats. Pulmonary venous flow (PVF) was recorded from the same acoustic window, placing a sampling volume 1 cm into the right upper pulmonary vein. Peak systolic (S), diastolic (D), and atrial reversal (AR) velocities were measured and averaged from 3 consecutive beats.Conventional M-mode Doppler ultrasound: Real-time two-dimensional targeted M-mode echocardiograms of the LV minor axis was taken at the papillary muscle level to measure the EF and FS. EF = (EDV-ESV)/EDV. In this study, the values of EDV and ESV were measured by using the Teichholz-corrected formula in standard software included in the ultrasound equipment. EF and FS were calculated automatically by the system when relative cardiac borders were set.Tissue Doppler imaging: to perform this, the ultrasound equipment was switched into tissue Doppler imaging mode, sample volume was located at the septal side of the mitral annulus from the apical 4-chamber view. Early (e’) and late (a’) diastolic mitral annulus velocities and the ratio of early to late peak velocities (e’/a’) were obtained.In one week after echocardiography examination, CMR imaging was performed with a 3.0-T whole-body MR system  on four ND monkeys and only five DD monkeys (anesthesia failure happened to one monkey with moderate DD). Intravenous propofol were used for anesthesia induction, and inhalation isoflurane were used for anesthesia maintenance. Data were acquired during end-inspiratory breath holding. After scout images, TrueFISP cine sequence  = 20 cm x 20 cm, NEX = 2; matrix = 256 x 256; flip angle, 50°; slice thickness = 2 mm; slice gap = 2 mm) with retrospective ECG-gating was used to acquire dynamic cine loops of the LV for function analysis. The LV was imaged in its entirety from the base to the apex in 9–12 short-axis cine images without inter-slice gaps or overlaps.Cine function analysis was performed off-line with commercial software . At the same mid-ventricular level, endocardial and epicardial boundaries were traced semi-automatically during the end-diastolic and end-systolic phases in order to obtain the dimensional parameters: LVIDd, LVIDs, SWTd, SWTs, AWTd, AWTs, PWTd, and PWTs. Left ventricular cine images were analyzed by an experienced radiologist who was blinded to the echocardiographic results.Extracted heart, liver, kidney and pancreas of a DD monkey were processed for H & E staining. The ultrastructure of myocardial mitochondria were observed by transmission electron microscope (TEM) as we previously did . Fresh t2O2 in methanol for 15 min. The sections were subjected to antigen retrieval procedure by microwaving in 0.01 M pH 6.0 sodium citrate buffer. Additional washing in PBS was performed before the next 30 min of incubation at 37 °C in 10 % normal goat serum. The sections were incubated overnight at 4 °C with diluted (1:100) primary antibodies. The antibodies used were polyclonal goat anti-rabbit AGEs antibodies, goat anti-rabbit caspase-3 antibody and goat anti-rabbit phosphorylated cMyBP-C antibody . For negative controls, the sections received PBS in place of the primary antibody. After washing in PBS, the sections were exposed to a 1 % biotinylated secondary antibody goat and anti-rabbit IgG  for 1 h at 37 °C. The sections were then incubated with the HRP-streptavidin  for 30 min at 37 °C. To visualize the immunoreaction, the sections were immersed in blue diaminobenzidine hydrochloride (DAB). The reaction was monitored microscopically and stopped by the immersion into distilled water as soon as a brown color staining was clearly visualized.Five-micron serial paraffin sections of LV were used to stain for AGEs, caspase-3 and phosphorylated cMyBP-C. Sections were dewaxed in xylene, rehydrated through a graded series of ethanol, washed in distilled water and phosphate-buffered saline (PBS), and then blocked for endogenous peroxidase by incubation with 3 % HStatistical analysis was performed using SPSS 19.0 software. The data is presented as the mean ± SD unless otherwise specified. Comparison among the two groups of subjects for various parameters was carried out by one-way analysis of variance. When normality and/or equal variance testing conditions were not met, the Kruskal-Wallis rank test and/or the Dunn's test for multiple comparisons were used, respectively. A p value less than 0.05 was considered statistically significant.vs 98.1 ± 16.4 mg/dL for 2hPPG, p < 0.05; 5.1 ± 0.2 vs 4.2 ± 0.4, %, for HbA1c, p < 0.05). Obesity was observed in all T2DM monkeys, whose BMI average body weight was larger than that of ND group , while there was no significance in body weight . There were no significant differences between groups in their lipid profiles. Average systolic blood pressure of the diabetic monkeys was found to be higher than that of the ND monkeys .Hyperglycemia and elevated HbA1c percentage were confirmed in all spontaneous T2DM monkeys enrolled  and T2DM with preserved diastolic function (n = 9) subjects averaged E/A ratio for both groups were slightly greater than 1 . However, the difference between mild DD group and the moderate DD group was not significant. As for the IVRT, no significances were found among any of the groups.The mild DD group had the longest average EDT  for these two parameters, whether they were still within normal physical limits still needs to be further studied.M-mode Doppler ultrasound was used for the measurement of left ventricular contractile capacity. Left ventricular systolic function related parameters EF and FS share similar characteristics Fig. . They shvs 17.5 ± 0.1, mm, p < 0.05). As for LV wall thickness parameters , they all showed a tendency to be thinner in the DD group than those in the ND group but still without statistical significance.Left ventricular cine images at the mid-ventricular level were obtained from 5 DD monkeys and 4 ND monkeys who have been through the echocardiographic examination . Increased expression of AGEs, caspase-3 and decreased cMyBP-C phosphorylation in myocardium were observed by light-microscopic examination Fig. , which wEchocardiography and CMR have been used for invasive cardiac phenotype assessment in diabetic animal models , 18, 29 Echocardiography is an invasive and inexpensive tool that allows sonographers to evaluate changes in heart structure/function that are echogenic. This technique has been already used to assess the cardiac structure and function in non-human primates –39, all Mitral valve blood inflow measured by pulsed-wave Doppler and tissue Doppler imaging were combined to assess diastolic function in the hearts of monkeys. Normal pattern for diastolic function under pulsed-wave Doppler were defined as E/A > 1 in human. However, this value may also be observed at early stages of ischemia and hypertrophy. Doppler pattern of impaired LV relaxation, characterized by reduced early and increased late diastolic flow, is an early sign of DD (mild diastolic dysfunction) which shows E/A < 1 . More adImpairment of LV relaxation results in prolongation of the IVRT and EDT. In contrast, increasing filling pressure shortens IVRT and reduces EDT . In thisPulmonary venous flow pattern has also been used to distinguish normal from pseudonormal transmitral Doppler filling. Impairment of LV relaxation results in increased systolic (S) pulmonary venous flow, in contrast increasing filling pressure reduces PV systolic flow . It has Decreased EF and FS were only seen in moderate DD subjects. It is still under debate as to which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy. More studies stated that diastolic function is more commonly impaired than systolic and that diastolic dysfunction might be the initial abnormality in patients with the onset of diabetes , 44, 45.MRI provides accurate, reproducible, noninvasive representations of cardiac structure and function and measurements of regional myocardial wall thickening . This noHistological abnormalities of myocardium were reported both in diabetic rodent models and human patients –53. CharAssisted by immunohistochemistry stain, positive products were observed to be abnormally expressed in the DCM monkey myocardium compared with the ND monkey. The formation of AGEs on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to the myocardial stiffness in diabetes . ApoptotThe spontaneously diabetic monkeys are of great importance in both biomedical investigation and for pharmaceutical studies. Literatures and our previous work demonstrated that the clinical manifestations of T2DM monkeys were highly similar to those of human beings. Results show that some if not most of our middle-aged rhesus monkeys were confirmed to have obesity, β-cell impairment, insulin level decline and persistent hyperglycemia verifying the development of spontaneous T2DM. The FPG of healthy monkeys in our monkey model is only approximately 10 %-15 % lower than that of humans. As for DD in monkeys diagnosed by echocardiography, relative parameters exhibit humanlike echo patterns with diastolic dysfunction progression, which has not been reported in rodent models. As for other features like MRI parameters, cardiac structure and biomarkers in cardiomyopathy, the monkeys share the same features as reported in human and rodents. Moreover, the development of spontaneous diabetes and its complications is a multifactorial slow progression. Of note, monkeys have a long enough life span that allows both disease progression and thorough longitudinal studies, which may shed light on the origins, pathways and pathogenesis of these pathologic changes. Meanwhile, these monkeys live in a highly controlled and stable environment with their metabolic history well documented. Thus long-term relationships between cardiovascular pathology changes and diabetic status can now be studied without the confounding lifestyle factors encountered in humans.p obtained by color M-mode Doppler also change with cardiac dysfunction in a diabetic heart. Secondly, CMR can provide more information about cardiomyopathy by using late gadolinium enhancement (LGE), MR tagging and T1 mapping, which we unfortunately failed to obtain in the present study. We are planning to further investigate DCM in rhesus monkeys by CMR in the near future. In consideration of the maintenance of the model, we only sacrificed 2 monkeys for invasive measurements. Luckily, certain myocardial impairments were observed on both microstructure and ultrastructure levels. However, quantified measurements of these biomarkers need to be done on a larger scale for these animals to determine reliability. We are also preparing non-invasive assessments for a better understanding of the mechanisms of these biomarkers and more, hoping to provide evidence for the hypotheses proposed regarding the pathogenesis of DCM.The present study primarily demonstrated diastolic dysfunction and related myocardial impairments in spontaneous T2DM rhesus monkeys. Nevertheless, there are several limitations need to be addressed. Firstly, the echocardiographic parameters we examined in this study were not so sufficient as to allow us to draw a full picture of the dimension and function of the ventricle. It has been reported that EDV, ESV, and VThe present study primarily demonstrated cardiomyopathy in spontaneous T2DM rhesus monkeys. Left ventricular diastolic dysfunction was diagnosed in six out of 15 T2DM monkeys, accompanied with structural abnormalities such as significantly increased LVID at end systole. Systolic related parameters, EF and FS, decreased with DD progression, however significance was found only between the moderate DD group and the ND group. Myocardial microstructure and ultrastructure damages were observed in a DD monkey. Meanwhile, the expression of DCM related proteins altered in a DD monkey. Characteristics of cardiomyopathy in spontaneous T2DM monkeys with DD are similar to those in DCM human patients. We will not only conduct more studies in these subjects for further investigations, but we will also screen for more diseased animals in the future to create a more effective drug testing platform.The protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of Sichuan PriMed Bio-Tech Group Co., Ltd.


The objective of this study is to evaluate left atrial(LA) function and its prognostic value by two-dimensional speckle tracking echocardiography (STE) in patients with non-ST-segment-elevation acute myocardial infarction (NSTEAMI).Global longitudinal LA S/SR data obtained by 2D speckle imaging with automated software .p = 0.001) and baseline mean global left atrial SRe  were the only predictive variables.Clinical variables and angiographic, echocardiographic, and STE parameters were studied in 65 patients with NSTEAMI  who underwent elective PCI. The final study population consisted of 51 individuals  and a 12 ± 3 months follow-up was performed. A total of 22 combined cardiovascular events(20 patients) occurred. With the use of Univariable Cox regression, all parameters were evaluated in the prediction of cardiac events, ischemic events, and/or cardiac death. According to ROC analysis, baseline mean global left atrial SRs (ROC area 0.82, In patients with NSTEAMI, we found that the novel global strain parameter of left atrial function is a valuable predictor of combined cardiovascular events over conventional echocardiography and may therefore be an important clinical tool for risk stratification in the acute phase of NSTEAMI. Coronary artery diseases (CAD) are the most common cardiac disease, which affect more than twenty million adults in China. Acute myocardial infarction (AMI), acting as a canonical component of CAD, contributes to approximately one million identified cardiac events every year. When ST elevation of AMI patient is present, treatment is aimed at reperfusion by opening the occluded coronary artery, either by thrombolysis or by percutaneous coronary intervention (PCI). Due to presence of more sensitive biochemical markers of myocardial necrosis, an increasing number of patients with non-ST-segment-elevation acute myocardial infarction(NSTEAMI) are diagnosed . These pAccording to previous studies, LA function index is a powerful predictor of mortality in AMI patients and provides prognostic information incremental to clinical data as well as reduced left ventricular ejection fraction (LVEF) . RecentlA total of 65 patients  with a diagnosis of NSTEAMI confirmed at the referring hospital by elevated troponin I above the 99 % percentile and positive ECG  were enrolled from March 2012 to March 2013. All patients were considered clinically and hemodynamically stable during index admission, and none were referred for urgent coronary intervention. Time from hospital admission to elective PCI was 5.2 ± 0.8 days . Patients with atrial fibrillation or flutter, valvular heart disease (of mild or greater severity), or a history of previous myocardial infarction were excluded.All the patients had received optimized anti-ischemic , dual antiplatelet and antithrombotic therapy . The study protocol was approved by the Ethics Committee of The Second Affiliated Hospital of Soochow University . Each participant provided written informed consent to be included in the study.Coronary angiography was performed on clinical indication by standard (Judkins) technique using digital imaging acquisition and storage. Direct stenting was allowed and various kinds of pre-dilatation devices and manual aspiration devices were allowed in case of acute myocardial infarction with severe thrombus in target artery.The patients were investigated by transthoracic echocardiography immediately prior to coronary angiography and after 6 months of follow-up on a Vivid7 ultrasound system  equipped with a phased array transducer (frequency range of 1.7–3.4 MHz). M-mode echocardiography was used to measure LA diameter and LV end-diastolic and end-systolic diameters. LV ejection fraction (LVEF) was calculated from 4-chamber and 2-chamber view, using the modified Simpson rule. Three separate LA volumes were computed following American Society of Echocardiography guidelines using biplane modified Simpson’s method . Left atLV diastolic function was explored by pulsed Tissue Doppler imaging, placing the sample volume at the level of mitral lateral and septal annulus from the apical four chamber view. Mean peak systolic (S), early diastolic (E’), and late diastolic (A’) annular velocities were obtained by averaging respective values measured at the septal and lateral sides of the mitral annulus. Mean Em and the derived mean E’/A’ ratio were used as load-independent markers of ventricular diastolic relaxation. Mean E/E’ ratio was also calculated.n = 8), LA foreshortening or inadequate acoustic windows (n = 6). The final study population consisted of 51 individuals .In the setting of 2D-STE analysis, three consecutive heart cycles were recorded and averaged. The frame rate was set between 60 and 90 frames per second. Echocardiograms were digitally stored and later analyzed off-line using acoustic-tracking software . LA endocardial surface was manually traced in each view with a point-and-click approach. An epicardial surface tracing was then automatically generated by the software, creating a region of interest (ROI). Afterwards, The ROI was divided into three segments: annular, mid and roof, whereas the resultant tracking quality for each segment is automatically scored for evaluation as either acceptable or non-acceptable. Finally, the software generated strain and strain rate curves for each atrial segment . We acquFifty one NSTEAMI patients were followed from March 2011 to March 2013 with follow-up telephone conversations or review of medical records. Patients were monitored regularly for the occurrence of cardiac mortality and adverse cardiac events. The primary end point of this study was combined cardiac events, which were defined as combined cardiac-cause mortality and re-hospitalization due to adverse cardiac events such as exacerbation of heart failure or acute myocardial ischemia. Cardiac death was defined by clinical data of acute myocardial infarction and/or fatal cardiac arrhythmias and/or refractory congestive heart failure. The date of the last interview or review was used to calculate the follow-up duration.t-test. Categorical parameters are presented as numbers (%), and were analyzed by χ2 test. Univariable Cox proportional-hazards regression models were used to identify independent predictors of late cardiac events. The risk of a given variable was expressed by a hazard ratio (HR) with corresponding 95 % confidence intervals. Receiver-operating characteristic (ROC) curves were constructed, and areas under curves were measured to determine cutoff values with maximum sensitivity and specificity. A 2-tailed p-value < 0.05 was considered significant for statistical inference.Data was analyzed using the statistical software package . Continuous data were presented as mean ± SD. Differences between the baseline and 6 months groups were compared using the independent n = 20) and without (n = 31) cardiac events.Over an average of 12 months  follow-up, a sum of 22 cardiovascular events(20 patients) have been recorded, including 2 patients death (9.1 %) due to a cardiac cause, 11 progressive heart failure (50.0 %), and 9 recurrent acute coronary syndrome(ACS) (40.9 %) , baseline mean GLASRs, mean Glaser and 6 months mean GLASRs,but increased E/E’ ratio.Conventional and TDI echocardiography parameters of LA and LV function are shown in Table p = 0.003), LA total EF , baseline mean GLSRs  and baseline mean GLSRe . Other clinical variables , angiographic variables , conventional electrocardiographic characteristics  and STE variables  tested were not significant predictors of diagnostic accuracy of cardiac events.Correlations of cardiac events were assessed using multivariable Cox proportional hazards models Table , containp = 0.001) and baseline mean GLSRe  displayed a better prognostic value in predicting cardiac events than LAPEF  and LA total EF . The “optimal” cut off values of baseline mean GLSRs and baseline mean Glare for cardiac events were 1.62 (s−1) and −1.16 (s−1), respectively  in patients with NSTEAMI after PCI.The left atrium serves as a blood reservoir during ventricular systole and a conduit for the passage of blood from the pulmonary veins into the left ventricle during early and middle ventricular diastole, as well as a booster pump increasing LV filling during late diastole . Using cStrain rate imaging on the basis of speckle-tracking technique represents the velocity gradient between two spatial points in relation to each other and overcomes noise artifacts associated with Doppler velocity imaging . Quantifp = 0.094) and LA total EF  than STE in baseline mean GLSRs  and mean GLSRe . A cutoff value of baseline mean GLSRs 1.62 s−1 and mean GLSRe −1.16 s−1 predicted cardiac events with a sensitivity of 71.4 and 61.9 %, specificity of 83.3 and 63.3 %, respectively. Nevertheless, LAPEF and LA total EF identified cardiac events with a sensitivity of 52.4 %, 66.7 % and a specificity of 46.7 %, 53.3 %, respectively, which were lower than that of baseline mean GLSRs and mean GLSRe  reflecting the total extent of the whole LA function damage—might provide a better prediction of clinical outcomes after MI. Our study demonstrated that both mean GLSRs and mean GLSRe improved significantly from baseline to 6-month, suggesting that LA reservoir and conduit function were restored to a certain extent in patients with NSTEAMI after PCI.To our perspective, this study provides evidence that noninvasive provides prognostic information about the success of PCI procedure is highly desirable. With the use of this definition, mean GLSRs and mean GLSRe of left atrium, represents an optimal method with high specificity and sensitivity for the prediction of patients with NSTEAMI. In this regard, the value of 2D STE arises from its ability to directly measure atrial myocardium deformation that can be used at the bedside and provide additional information about atrial function of NSTEAMI to what can be obtained from a conventional echocardiographic analysis.2D-STE provides important insights into the mechanism and temporal sequence of left atrial dysfunction after NSTEAMI. As confirmed in our study, mean GLSRs and mean GLSRe, the new LA function parameters, which are measured by 2D-STE, exert better prognostic value in predicting cardiac events over conventional echocardiography and should be the preferred method in patients with NSTEAMI.


Left ventricular assist device placement is an increasingly common treatment for cardiac failure, resulting in cardiac unloading and potentially reversing the remodelling changes seen in heart failure. A popular animal model for human ventricular unloading is the rodent heterotopic non-working heart transplant; the volume loading status of this preparation is important to interpreting the resulting reverse remodelling yet has not been previously investigated. This study was designed to assess the variability of left ventricular volume loading in the rodent transplant model.Heterotopic abdominal heart transplant was performed on syngeneic rats; high resolution cine magnetic resonance imaging was subsequently performed on the heterotopic transplanted hearts in anesthetised rats, after variable post-transplant recovery times, in order to assess ventricular loading status.Highly variable left ventricular volume loading status was demonstrated, with some hearts exhibiting considerable ventricular filling and ejection.in vivo imaging of such hearts to quantify the degree of ventricular loading.These observations call into question the assumption that studies using this model are consistently examining fully unloaded ventricles, and indicate the desirability of  Heart failure is a major cause of mortality in the Western world and this has led to considerable efforts in understanding its pathoetiology and rationalising its treatment. It is characterised by failure to maintain adequate cardiac output, with resulting volume overloading of the cardiac ventricle. Treatment aims to offload the ventricle and decrease ventricular overfilling; in extreme cases cardiac output can be augmented by implantation of a ventricular assist device (VAD) which mechanically pumps blood from the ventricle or pulmonary vein into the aorta. This intervention has the benefit of “unloading” the ventricle, maintaining coronary perfusion whilst decreasing wall tension. Originally conceived as a “bridge” to transplantation, whereby the patient awaited availability of a donor organ, it became apparent in some cases that functional recovery of the ventricle had occurred during unloading with the VAD, permitting removal of the device and preventing the need for transplantation , 2. ThisIn an attempt to understand the changes  occurring in unloading and reverse remodelling, and to model the VAD-unloaded state of treated human heart failure, the rodent heterotopic heart transplant model has been advocated , 11, in Experiments were performed in accordance with the United Kingdom Home Office guidelines under The Animals (Scientific Procedures) Act, 1986. Inbred male Fischer F344 rats (200-250 g) were obtained from a commercial breeder  and maintained on a standard laboratory chow diet with a 12h light: 12h dark cycle and free access to water.Hearts were transplanted by one operator (AB) by the method of Ono & Lindsey ; the proOnline Resource Supplementary Movies). Rats were anaesthetised with 2.0% v:v isoflurane in oxygen and positioned supine in a purpose built cradle. Two ECG signals were obtained, one from the recipient (thoracic) heart and a second, for gating, was obtained from the heterotopic transplanted heart using two subcutaneous needles adjacent to the palpated beat  in a vertical bore 500 MHz, 11.7 T MR system with a Bruker console running Paravision 2.1.1 . Although all hearts could be readily detected by palpation, and were felt to be beating strongly, it was clear from cine MR images that the degree of left ventricular unloading varied substantially between individual hearts . Furthermore, in hearts which remained partially volume loaded with visible left ventricular filling and emptying, blood flow across the aortic valve could be clearly detected in long axis views (Online Resource Supplementary Movies 2a-4a). For comparison, in two additional animals not included in the quantitative analysis, transplantation of the heart was prolonged (ischemic time >100 min), causing ischemic damage to the myocardium and resulting in regional wall motion abnormality and ventricular dilatation; areas of infarcted myocardium were clearly visible . Epicardial and endocardial borders were measured in end-diastolic and end-systolic frames by freehand drawing tool, and summed over the whole heart to estimate LV mass (184-558 mg), end-diastolic volumes  and end-systolic volumes ; calculated stroke volumes (SV=EDV-ESV) varied from 10-56 ml and cardiac outputs (SV × heart rate) from 3-17 ml/min. Hearts were empirically divided into “unloaded” and “partially loaded” groups according to the LV end-diastolic volume (LVEDV): 12 of the 20 transplanted hearts studied (60%) had LVEDV less than 60 ml, whilst 8/20 of the transplanted hearts (40%) had LVEDVs of more than 60 ml (Table P<0.001), suggesting cardiac “hypotrophy”, but there was no correlation between stroke volume and cardiac mass . Ventricular pressures were not measured in this study, and therefore no conclusions regarding workload can be made. There was also no correlation between the length of time post-surgery at which cardiac function was measured (6-24 days) and the observed degree of ventricular unloading (data not shown), so that differences in cardiac function were more probably due to variable surgical anatomy and its consequences.A total of 22 hearts were transplanted. All surgical procedures were performed by a single surgeon (AB) who has extensive experience of rodent  heterotopic heart transplants,  . During Online Resource Supplementary Movie 4a and 4b), was not found. Consistent surgical technique may be predicted to minimise all three putative causes. It was not possible to accurately assess the competency of the mitral valve in these studies. Although LV pressure was not measured in the current study, and hence work could not be quantified, an estimate of cardiac work was attempted by measuring stroke volume; as with volume loading status, there was high degree of variability in ejection, and possibly therefore in workload. It is also likely that the observed partial loading accounts for the untypical pattern of atrophy/hypotrophy observed in such studies . Transplanted hearts may be allogeneic or syngeneic and may be implanted as orthotopic grafts in the thorax or heterotopic grafts in the abdomen, pelvis or neck; in practice, the technical challenges of orthotopic cardiac transplantation in rodents have precluded this approach and therefore in practice heterotopic sites have been used. For immunological studies, a loaded heart is desirable, and many schemes have been described to ensure the “working” heterotopic heart is filling and ejecting ; MRI has studies , althoug studies , 24. It  studies , 25 and  studies  heteroto studies -14, but


Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG) signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave , prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves , spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria. Cardiovascular diseases are the main causes of mortality and an important public health problem. Sudden cardiac death is a major health problem, and most of the cases occur outside the hospital, without warning signs , 2. StruDespite the benefits of physical activity, vigorous exertion may also increase the risk of sudden cardiac death and other acute cardiovascular events . Sudden Physiological cardiovascular adaptation to sustained physical exertion, “athlete's heart,” causes several common ECG changes, not associated with increased cardiovascular risk, such as sinus bradycardia, due to increased parasympathetic tone, first degree atrioventricular block, early repolarization, incomplete right bundle branch block, and increased QRS voltage due to physiologic left ventricular hypertrophy , 9. SeveThe electrocardiogram, the written record of a heartbeat, is used in clinical practice for diagnosis and prognosis, but also in clinical trials, as a valid, reliable, repeatable, quantitative method, inexpensive and unbiased by clinical information .The aim of the present paper was to review ECG signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. Several ECG variables are associated with cardiovascular mortality . Prolonged P wave duration signifies a conduction delay between the left and right atria, called interatrial block, and is related with atrial fibrillation and, lately, with increased all-cause cardiovascular disease and stroke mortality in the general population [The P wave is the expression of atrial depolarization and atrial conduction. P wave indices derived from the standard ECG are P wave duration, morphology, and amplitude and provide information about the atrial electrical activity.pulation –17. Coropulation . Interatpulation , 20.During a follow-up of 18 years in a study including 739 middle-aged type 2 diabetic patients without previous major cardiovascular events, prolonged P wave duration was associated with increased stroke mortality among patients with nonmajor cardiovascular disease, independent of conventional cardiovascular risk factors, proteinuria, duration and treatment of diabetes, glycemic control, heart rate, and left ventricular hypertrophy .Deep terminal negativity of P wave in V1 (DTNPV1), a marker of atrial abnormality, defined as biphasic P wave, with the negative P prime larger than 1 mm, easily detected by simple visual inspection of the resting 12-lead ECG, was associated with an increased risk of death due to all-cause cardiovascular disease and ischemic heart disease in a large study, including 8,146 participants, during a follow-up of 13.8 years [.8 years , 22. DTNTo conclude, the most important atrial ECG predictors of cardiovascular death are prolonged P wave duration, interatrial block, and deep negativity of the P wave in V1.Left and right atrial enlargements are considered minor abnormal findings according to the “Refined Criteria for ECG Interpretation” for elite athletes [athletes  and are athletes . Left atathletes .The QT interval, from the onset of the QRS complex to the end of the T wave, is a reflection of the summed ventricular action potential durations in the heart . The relTorsade de pointes do not appear in some patients with prolonged QT intervals, if the transmural dispersion of repolarization is not increased or if the repolarization reserve is normal . More seA heart rate corrected QT interval of 470 ms or longer is considered a training-unrelated abnormal finding in elite athletes . Not jusQRS duration predicts mortality in patients with left ventricular dysfunction and hypertension  and cardDevelopment of fragmented QRS is related to intraventricular conduction delays due to inhomogeneous activation of the ventricles caused by myocardial scars, myocardial ischemia and fibrosis, impaired signal transduction and ventricular depolarization, and peri-infarction conduction blocks –34. FragVarious types of fragmented QRS were described in the literature, including notches on the R or S wave, RSR′ pattern, additional R waves, fragmented right and left bundle branch block, and fragmented QRS associated with ST segment elevation , 33, 34.The rSr′ pattern in leads V1-V2 can be found in benign or sever life-threatening heart diseases, including the Brugada syndrome or arrhythmogenic right ventricular dysplasia. It was frequently associated with syncope or cardiac arrest, and it also appeared in healthy, asymptomatic young persons and athletes or when leads V1 and V2 were placed higher . A R′ paStrauss et al. , 39 usedNotched QRS in V1 is included in the common, training-related ECG abnormalities in athletes, but Brugada-like early repolarization is a major, training-unrelated ECG abnormality in athletes .In other words, fragmented QRS complexes predict cardiovascular mortality in patients with left ventricular dysfunction, acute coronary syndromes, Brugada syndrome, and arrhythmogenic right ventricular dysplasia, but not in athletes. new left bundle branch block could predict an acute myocardial infarction with a sensitivity of 42% and a specificity of 65% in 182 patients with left bundle branch block  [fragmented left bundle branch block,” a significant sign of myocardial infarction scar and mortality [ Right bundle branch block may represent a myocardial scar located in the right ventricle or inferior wall, with a better prognosis than a left bundle branch block [Aggressive therapy of myocardial infarction using thrombolytic agents and early coronary revascularization reduced the incidence of Q wave myocardial infarction and increased non-Q myocardial infarction, making the diagnosis of an old myocardial infarction in the presence of bundle branch block more difficult , 40. Latortality . Right bch block . A left ch block .Complete left BBB or right BBB are not related to training in elite athletes and are considered abnormal findings . On the To conclude, a left bundle branch block could predict an acute myocardial infarction and right bundle branch block a myocardial scar in the right ventricle. Both complete left and right bundle branch blocks are abnormal ECG findings in athletes.ST segment elevation has been described in many conditions, including acute myocardial infarction, Brugada syndrome, early repolarization, and acute pericarditis [carditis . Elevatecarditis . STJ andcarditis . ST segmcarditis . upsloping ST segment depression and flat or inverted T waves, are common in asymptomatic, older patients and were significantly associated with an increased risk of coronary death and primary arrhythmic death in a more than a decade follow-up study [Isolated minor nonspecific ST segment and T wave abnormalities, such asup study . Nonspecup study –48. It wup study , but in up study . Isolateup study . It seemup study , 49.Regular, intensive exercise is associated with repolarization changes affecting the ST segment and T wave morphology . ST segmIn other words, ST segment depression predicts coronary and arrhythmic death and is an abnormal finding in athletes. Tpeak-Tend interval (TpTe) is an index of transmural dispersion of repolarization, a marker of ventricular arrhythmia vulnerability [There is limited information about the utility of repolarization subintervals. Therability , 52. TheInverted T Wave and T Wave Axes. Abnormally inverted T wave and prolonged QTc, increased heart rate, and hypertension were found to be stronger predictors of sudden cardiac death risk than coronary heart disease in a study enrolling 18,497 participants, initially free of coronary heart disease, after a follow-up of at least 13 years [13 years .According to a recent consensus article, negative T waves are not caused by acute ischemia but appear in chronic or vanishing ischemia, and the negative ischemic T waves are symmetrical, of variable deepness, presenting mirror patterns, and may be accompanied by positive or negative U waves . MyocardT wave inversion on the ECG (in leads V1–V3) may be also due to the persistence of the juvenile pattern of repolarization . In athl positive T waves in lead aVR in 169 consecutive patients, with acute ST segment elevation myocardial infarction, who underwent primary percutaneous coronary intervention, were associated with an increased in-hospital cardiovascular mortality [Not only do negative T waves have prognostic value, but alsoortality .The T wave alternans, a repeating ABABAB variability pattern in the morphology and amplitude of the T wave, reflects heterogeneity of repolarization and arises from beat-to-beat alteration of action potential duration at the level of cardiac myocytes, serves as a mechanism of arrhythmogenesis, and expresses vulnerability to lethal ventricular arrhythmias [hythmias . Despitehythmias .T wave axes were also associated with increased mortality , 62.Inverted T waves, prolonged TpTe intervals, positive T waves in aVR, and T wave axes are predictors of cardiovascular mortality. spatial T axis and the spatial and frontal plane angles between the QRS and T vectors are strong independent predictors of coronary heart disease and total mortality [μV was the strongest mortality predictor in all subgroups [The ECGortality . Severalortality , 64. Theortality . T aVR aubgroups . Other vubgroups .The spatial angle between mean QRS and T vectors is a measure of the overall deviation angle between depolarization and repolarization sequences, and the spatial angle between Tpeak and normal R reference vectors is a measure of deviation of the repolarization direction from the reference direction during regional repolarization of the left ventricular lateral wall . AlteredX, Y, and Z orthogonal leads [The most important limitation of the mentioned indices is the need of programmed analysis of electronic ECG signals and reconstruction of al leads . Notching of the premature ventricular complexes represent myocardial scar [Ventricular arrhythmias are life-threatening arrhythmias, commonly associated with coronary heart disease. Morphology of the premature ventricular beats can have prognostic value.ial scar , and myoial scar . nonsustained ventricular tachycardia may be detected in Holter electrocardiographic monitoring of patients with hypertrophic cardiomyopathy, in patients with a high risk of subsequent sudden cardiac death [Episodes ofac death .Premature ventricular contractions are not infrequent in athletes without any heart disease . Sudden  left ventricular hypertrophy, such as the classical voltage criteria, including the Sokolow-Lyon criteria: sum of the S wave in V1 and of the R wave in V5 or V6 ≥ 35 mm [Several ECG criteria were described for ≥ 35 mm , and com ≥ 35 mm , the Rom ≥ 35 mm , and the ≥ 35 mm .ECG left ventricular hypertrophy criteria, despite low sensitivity, are valuable risk markers in the epidemiology and prevention of cardiovascular disease , especiaThe LIFE study (Losartan Intervention for Endpoint Reduction in Hypertension) showed that ECG LVH defined by Cornell product criteria, Sokolow-Lyon voltage criteria, or ECG strain improved prediction of cardiovascular events and that regression of ECG LVH during antihypertensive treatment was associated with better outcome, independent of blood pressure reduction .Discrepancies between ECG and cardiac magnetic resonance imaging LVH results are related to several electrocardiographic variables, such as prolongation of QRS duration , minor STT abnormalities, or major electrocardiographic abnormalities  .Physiologic left ventricular hypertrophy due to sustained physical exertion increases QRS voltages according to the classical hypothesis on the ECG left ventricular hypertrophy. The type of exercise, isometric or isotonic, is known to influence wall thickness [ right and not left ventricular dysfunction, with apparent complete short-term recovery, yet structural and functional changes of the right ventricle were evident in some athletes [hickness . A decrehickness . Currenthickness , 13. Thehickness . It has athletes . A studyathletes . Consideathletes . Traininathletes . In enduathletes . The rigathletes , 88. Susathletes . Voltageathletes . Patientathletes .ECG LVH is a predictor of sudden cardiac death, myocardial infarction, congestive heart failure and stroke, and regression of LVH due to therapy improves outcomes. Sustained clinical exertion causes physiologic left ventricular hypertrophy, which needs to be differentiated from hypertrophic cardiomyopathy, and impairs right ventricular function. Isolated QRS voltage criteria for left or right ventricular hypertrophy are common, training-related ECG abnormalities in athletes .Simple ECG markers are valuable noninvasive methods in identifying patients at increased risk of poor outcome, suggesting an important role in risk stratification in the general population and routine ECG screening in asymptomatic individuals, identifying patients who could benefit of more intensive management of cardiovascular risk factors and preventive interventions. The main ECG parameters associated with cardiovascular mortality were the P wave , prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, inverted T waves, spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria. Clear cut-off values are still needed for most of the mentioned ECG variables.ECG is also a valuable tool in risk-benefit estimation of physical exercise and preparticipation screening of athletes, considering that sports activity may trigger fatal cardiovascular events, including sudden cardiac death in individuals with predisposing cardiovascular factors. ECG can contribute to screening and early diagnosis of silent cardiovascular diseases, risk stratification and prevention of sudden cardiac death through lifestyle changes, and restriction of competitive sports activity, drugs, and implantable defibrillators. A single tracing is virtually diagnostic in a high proportion of cases, and serial tracings may confirm the diagnosis. Unfortunately, ECG may show no diagnostic feature in several cardiac conditions, especially when the patients do not have any symptoms and many abnormal patterns may be nonspecific, requiring additional testing. Besides false-positive and false-negative results, several pitfalls may result in ECG interpretation.All repolarization related variables require also further attention in the evaluation of possible toxic drug effects. Standard 12-lead ECG merits further larger studies, in order to identify new ECG variables and to evaluate their importance in cardiovascular disease prognosis.


Cardiac magnetic resonance (CMR) is the gold standard to evaluate right ventricular (RV) hemodynamics after repair of Tetralogy of Fallot (TOF). CMR markers, such as severe RV dilation and biventricular dysfunction, are independent predictors of death, sustained VT and heart failure. However, the relationship between patient's age, type and time of corrective surgery, severity of PR and RV/LV dimensions and function has not been fully explained.We enrolled patients who underwent hemodynamic evaluation by CMR late after TOF repair (by either transannular or infundibular RV outflow tract reconstruction) in two pediatric cardiology centers, between March 2008 and March 2013. Surgical data (time and types of repair) and CMR parameters were collected.The study included 208 patients  aged 17.5 ± 6.6 (range 5-38) years, with age at repair 16.3 ± 21.7 months (range 0.2-146 months). RV end-diastolic volume indexed (RVEDVi) was mildly negatively correlated with patient's age . In details the negative correlation between RV dilation was stronger when limiting the analysis to patients older than 20 years (figure). On the contrary, LVEDVi was mildly positively related to patient's age . RVEDVi was also correlated with time interval from corrective surgery, PRF and RVOT obstruction . Eventually, older age at repair and RVEDVi significantly affected RVEF . LVEF was significantly correlated with RVEF (p < 0.001) and the time elapsed from the repair .RV dilation in repaired TOF patients might have an unexpected behavior over time, with older patients showing a progressive reduction in RV volume. Longitudinal follow-up studies are needed to verify our findings and define the role of a hypothetical RV "restrictive physiology" in predicting the adverse outcomes of patients with repaired TOF.No disclosure to make.


Cardiac magnetic resonance (CMR) stress/rest myocardial perfusion is usually assessed in clinical practice by qualitative visual analysis. There might be some added value in analyzing upslope perfusion curves, but those are labor and time consuming. We aimed to evaluate a new inline post processing tool that allows for completely automatic construction of upslope curves with parametric pixelwise construction of perfusion myocardial maps.We included 20 consecutive patients clinically referred for phamacological CMR myocardial stress perfusion with dypiridamol at target dose of 0.84 mcg/kg administered in 6 minutes - images were acquired 2 minutes after drug interruption. Patients were scanned using a 3T system  and images in stress first and 10 minutes later at rest were acquired during first passage of 0.1 mmol/kg of gadoteric acid meglumine . The sequence used for perfusion acquisition was a s-GRE with saturation pre-pulses before every acquisition. Matrix was 160 × 112, TI 90 to 110 ms, TPAT acceleration factor of 3 and 3 slices in total were acquired at the base, mid and apical regions of the left ventricle. Perfusion maps were built automatically by first applying a motion correction algorithm and then by building a map in which every pixel intensity corresponds to the upslope of myocardial signal increase during perfusion, without baseline correction. These slopes were also acquired by careful manual contouring of the myocardium in an offline workstation with dedicated software . Analysis was performed blindly by segment in a total of 16 AHA segments per patient, carefully including most of the myocardium within a segment, but leaving small endocardial and epicardial margins in order to avoid partial volume averaging.A total of 320 myocardial segments were analyzed (no segment was excluded) from 20 patients 12 male), in which 6 (30%) had the clinical diagnosis of myocardial ischemia by an expert CMR reader. All patients completed the stress protocol uneventfully. Median pre-test probability of obstructive coronary disease was 11% . The Pearson's correlation coefficient R was 0.92, with a linear correlation formula y = 0.92x + 0.4, as seen in Figure 2 male, iAutomatic myocardial stress/rest perfusion mapping has excellent correlation with more labor and time intensive manual plotting of the curves, making it more suitable for clinical use.None.


The problem of prosthetic heart valve selection in fertile women with acquired heart defects remains crucial in modern cardiology. Mechanical heart valves require lifelong indirect anticoagulant therapy, which has significant fetal toxicity and is unacceptable for women planning pregnancy. Bioprosthetic heart valves are the best choice for fertile women; however, their durability is limited, and reoperations are required.We describe the clinical case of a 21-year-old Russian woman with infectious endocarditis who underwent heart valve replacement with an epoxy-treated mitral valve prosthesis.Epoxy-treated bioprosthetic heart valves can be used without long-term anticoagulant therapy because of their optimal hemodynamic functional parameters. Moreover, their high thromboresistance and resistance to infection improve patients’ quality of life in their late postoperative period. We recommend these valves both in older persons and in young patients including women who are planning pregnancy. Acquired heart disease (AHD) is currently the most common cardiac disease among young adults in Russia, with infectious and rheumatic valvular lesions predominating . In contHeart valve replacement surgery significantly prolongs life expectancy and improves quality of life in patients with AHD. There are two basic types of prosthetic heart valves used in current clinical practice: mechanical and bioprosthetic. Deciding which valve to use requires careful consideration of the specific advantages and disadvantages of the valve types and integration of this knowledge into the clinical characteristics and personal preferences of the individual patient .European clinics have solved the problem of selecting prosthetic heart valves for patients with AHD by implementing the American College of Cardiology/American Heart Association (AHA) 2006 guidelines and the European Society of Cardiology (ESC) 2007 guidelines . UnfortuYoung women planning pregnancy are considered high risk patients who require careful selection of the optimal prosthetic heart valve. Mechanical heart valve prostheses, which require lifelong indirect anticoagulant therapy , are not appropriate because of the teratogenic potential of indirect anticoagulants , 4. CurrThe main issue with bioprosthetic heart valves is their finite lifespan and high risk of reoperation in the future . The aveA study of pregnant women with prosthetic heart valves in Denmark with a 30-year follow-up confirmed fetal and maternal complications associated with anticoagulant therapy . The truSeveral studies have demonstrated the safety of unfractionated heparin therapy (UFH). Heparin is thought to be an ideal drug in pregnancy, because it does not cross the placenta, and therefore has no effect on the fetus. However, the reliability and efficacy of UFH has not been proven –13.Bioprosthetic heart valves are preferred over mechanical valves in women of childbearing age who are planning pregnancy . Their mThus, the main advantage of bioprosthetic heart valves is that most patients avoid anticoagulation therapy. Their significant disadvantage is a high risk of structural valve deterioration in the late postoperative period. Specific complications that limit bioprosthetic durability and result in reoperations in the second decade after implantation include primary tissue degeneration associated with most xenografts, calcification and prosthetic valve endocarditis. If prosthetic valve endocarditis develops as a consequence of non-compliance with preventive therapy, primary tissue degeneration occurs as a separate issue, associated with poorly investigated biological tissue transformations during prosthesis production and the natural-biological function in the recipient. Despite the fact that the problem of bioprosthesis calcification has existed since the earliest models, the pathogenetic mechanisms of xenograft calcification have not been fully investigated. Extensive clinical experience in the application of bioprosthetic heart valves has accumulated worldwide, including different valve models fabricated from different biological tissues and various methods of valve preservation and anti-calcification treatment. Hundreds of thousands of bioprostheses have been implanted and management strategies for patients in the early and late postoperative periods have been developed, but the problem of bioprosthetic heart valve dysfunction remains far from resolved. There is no consensus on bioprostheses in the literature . Sudden Several Russian clinics now use new-generation diepoxy-treated bioprostheses. The Russian experience in this area appears to be rare, as no other country has treated xenografts with epoxy compounds; most continue to use glutaraldehyde-treated biomaterials. The hypothesis that the biochemical transformations occurring in xenograft implanted prosthetic devices can be affected by conserving agents has resulted in a new conservation method that increases resistance to biodegradation and calcification. Our experience suggests that ethylene glycol diglycidyl ether, a new-generation conserving agent, improves the structural stability and calcification-resistant properties of bioprosthetic heart valves .n=22), and 360 patients were successfully discharged from hospital. By the end of 2014, the completeness of patients’ follow-up was 94.5 % with a mean follow-up period of 8.0±4.4 years and a follow-up scope of 2792 patient-years. The long-term mortality, including the redo procedures, was 29.2 % (n=105) of the total number of discharged patients. Of the total number of discharged patients, 130 patients (36.1 %) underwent redo procedures because of the development of degenerative changes. Bioprosthetic dysfunction was confirmed by morphological studies in 126 cases (96.9 %). Half of the redo cases (n=63) had primary tissue failure with calcification of the xenogenic material, 15.1 % (n=19) reported bioprosthetic dysfunction with no signs of calcification, and 27 % (n=34) had prosthetic endocarditis. One patient (0.8 %) had prosthetic valve thrombosis, associated with infected tissue prosthesis; nine (7.1 %) patients reported a combination of signs of calcification and infection.We have an 18-year single-center experience with mitral valve replacement using xenoaortic (epoxy-treated) bioprostheses. “KemKor” bioprostheses were implanted in the period from 1991 to 2001 and “PeriCor” prostheses from 2001 to 2009. A total of 382 xenoaortic bioprosthetic heart valves were implanted in the mitral position (the mean age of patients at the time of surgery was 48.8±10.2). The surgeries were performed according to the standard procedure for mitral valve replacement under normothermic cardiopulmonary bypass. The in-hospital mortality was 5.8 %  revealed infective endocarditis, mitral valve failure  and mobile vegetation at the posterior leaflet. A healthy baby was delivered by cesarean section at 39 weeks’ gestation. She then received goal-directed therapy in the cardiac surgery unit aimed at suppressing sepsis and compensating for heart failure: initially New York Heart Association (NYHA) class IV. Mitral valve replacement with bioprosthetic heart valve KemKor-30 was performed 6 weeks after delivery. The management of primary infective endocarditis  and subsequent prevention of prosthetic endocarditis was performed in accordance with the existing (at the time of the follow-up period) guidelines. She received ceftriaxone, 2 g/day administered intravenously in a single daily dose. Her postoperative period was without complications (discharge with NYHA class II). The choice of a bioprosthetic heart valve was determined by her desire for future pregnancy.Indirect anticoagulant (phenindione) therapy was discontinued 6 months after surgery, because of the absence of heart failure symptoms and cardiac arrhythmias and satisfactory prosthesis function. She became pregnant again in 2002, 3 years after surgery. In the follow-up period, she did not receive any cardiotropic agents and anticoagulants, her condition was satisfactory. Her pregnancy was not contraindicated, according to clinical assessment and testing. She was supervised by surgeons, cardiologists and obstetricians during her pregnancy. She delivered a healthy baby boy vaginally without complications. Her child was breastfed. Annual examinations were performed to monitor for bioprosthetic valve failure, because breastfeeding is known to increase the risk of calcification.A moderate calcific degeneration of the leaflet was found 12 years after heart valve replacement, a common finding in bioprosthetic heart valves. Dynamic ECHO revealed a moderate decrease in the effective orifice area and an increase in the mean diastolic transprosthetic pressure gradient and mean transprosthetic blood flow velocity. However, these changes still met the criteria for normal prosthetic heart valve function  or signs of heart failure during patient monitoring.Five ECHO examinations revealed the natural physiological changes caused by cardiovascular adaptation to the increased metabolic needs of pregnancy to ensure adequate oxygenated blood delivery to the peripheral tissues and the fetus. The changes included increased circulating blood volume, heart rate, myocardial contractility and systemic blood pressure, which certainly influenced intracardiac hemodynamic parameters . Her lefHer elevated cardiac output and her left ventricular dilatation were caused by increased myocardial contractility. Her left ventricular ejection fraction rose from 63 to 76 % during her pregnancy. The physiological increase in her heart rate in the last trimester was associated with the overestimation of the effective orifice area. Tachycardia affected the Doppler characteristics of the mitral valve and biased the resulting ECHO parameters. Her mean pulmonary artery pressure increased from 10 mmHg at 5 weeks’ gestation to 16 mmHg at 39 weeks’ gestation, contributing to a moderate increase in peripheral resistance and arterial blood pressure after 32 weeks’ gestation.The bioprosthesis, implanted in the mitral position, contributed to the physiological changes in functional and morphological parameters of cardiac remodeling, whereas cardiac reserve was not impaired during her pregnancy.Natural vaginal delivery of a healthy full-term male newborn  occurred in October 2011, at 39 weeks’ gestation. Her postpartum period was uneventful and she was discharged on the sixth day after delivery.ECHO findings included reduction of bioprosthesis regurgitation to grade I, reduction of left ventricular end-diastolic volume to 85 mL and increase in mean pulmonary artery pressure to 12 mmHg, indicating stabilization of her intracardiac hemodynamics  and mean pulmonary artery pressure (13 mmHg) remained stable. Despite grade I regurgitation, the size of her left atrium did not exceed the upper limit of normal (3.9 cm).No significant health problems arose for our patient or her baby during a 2-year follow-up. Her baby was breastfed for 12 months. Our patient did not have any signs of heart failure or clinically significant cardiac arrhythmias. There were no indications for cardiotropic drugs. Dynamic ECHO assessment of the mitral bioprosthesis revealed its functional safety, despite the thickening of its leaflets. Sixteen years after mitral valve replacement, satisfactory left ventricular ejection fraction (64 %), target blood pressure, mean diastolic transprosthetic gradient (4.2 mmHg) and mean transprosthetic flow velocity (96 cm/second) were maintained. The effective orifice area was 2.8 cmThis clinical case demonstrates the use of bioprosthetic heart valves without the need for long-term indirect anticoagulant therapy. Bioprosthetic heart valves are an alternative to mechanical valve prostheses for women of childbearing age. The experience of this young woman with two pregnancies and lactation periods revealed no signs of bioprosthetic valve dysfunction with the diepoxy-treated bioprosthetic valve and supports the use of bioprosthetic heart valves in patients who are planning pregnancies.Our extensive experience with epoxy-treated bioprosthetic heart valves such as KemKor and PeriCor indicates that patients can avoid long-term anticoagulant therapy because of their optimal hemodynamic functional parameters, thromboresistance and high resistance to infection, without worsening quality of life in the late postoperative period. We recommend these valves both in older persons and in young patients with an active lifestyle, including women who are planning pregnancy.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Pectus excavatum can cause right ventricular (RV) dysfunction due to extrinsic compression. Assessment of ventricular function by echocardiography is often suboptimal due to technical limitations. We utilized cardiac magnetic resonance imaging (CMR) to assess pectus severity and RV systolic function in relation to the site of RV compression in a large pediatric pectus cohort.All CMR studies performed for clinical evaluation of pediatric pectus excavatum at our institution were retrospectively reviewed. CMR analysis included evaluation of Haller index, left ventricular (LV) and RV ejection fractions (EF), and indexed LV and RV end-diastolic and end-systolic volumes. The site of maximal compression of the right ventricle  groove, or free wall) was assessed. The relationships of age, BSA, Haller index, and ln to LVEF, RVEF, and indexed RV end-diastolic volume were assessed using linear regression. The relationships of patient gender and RV compression site to LVEF, RVEF, and indexed RV end-diastolic volume were evaluated using ANOVA with post-hoc Tukey comparisons.We analyzed CMR studies from 197 patients with pectus excavatum . 28 patients (14.2%) had RVEF<50%. 75 patients had no RV compression, 104 had compression of the RV free wall, and 18 had compression of the AV groove. The Haller index, ln, and age did not show linear relationships to LVEF, RVEF, or indexed RV end-diastolic volume. The LVEF was significantly lower in patients with RV compression , although still in the normal range. RVEF varied significantly between RV compression groups . The indexed RV end-diastolic volume was increased in patients with RV compression (96.5 mL/m2) compared to those without compression .CMR imaging is a reliable method to measure pectus excavatum severity, associated sternal abnormalities, and cardiac function in pediatric patients in a single imaging study, obviating the need for echocardiography and computed tomography. RV dysfunction is common, even in pediatric pectus patients. The RVEF varies significantly based on the site of RV compression; however, the Haller index does not predict the severity of RV systolic dysfunction.Cincinnati Children's Heart Institute Research Core.


Chemotherapeutically induced myocardial injury continues to pose a major problem. The exact mechanism of drug-related cardiomyopathy (DRC) is still poorly understood. An early diagnosis of cardiotoxicity and the ability to predict patients at risk are important for preventing chronic heart failure. The guidelines for non-invasive cardiac imaging to screen for DRC show limitations in early identification of patients at risk, currently relying on left ventricular (LV) ejection fraction (EF) for establishing high risk. Contrast enhanced cardiac magnetic resonance imaging (ce-CMR) may offer a stronger screening approach, especially since it can assess the right ventricle (RV) and detect early changes in response to chemotherapy.51 patients  with various types of cancer, who underwent chemotherapy with a variety of regimens, were assessed with ce-CMR within 6 months of chemotherapy. Ce-CMR results for both RV and LV were compared with published data  using the 1-sample Student t test. A p value <0.05 was considered significant. Descriptive statistics are described as percentages.In patients, EF was lower in both ventricles: RVEF=54.8% and LVEF= 53.6% vs. controls: RVEF=61% and LVEF= 69%, . Right and left stroke volumes (SV) were also lower: RVSV= 69.1 mL, LVSV= 76.3 mL, vs. controls: RVSV and LVSV=104 mL (p≤ 0.001). Both ventricles demonstrated decreased end diastolic volumes (EDV): RVEDV=132.8 ml, LVEDV=144.4 ml, vs. controls: RVEDV =173 ml and LVEDV=150ml, though only statistically significant in the RV (p<0.001). An elevated end systolic volume (ESV) was also noted: RVESV=70.1 mL, LVESV=67.4 mL vs. controls: RVESV=69 ml and LVESV=47 ml, though only statistically significant in the LV (p<0.001).Interestingly, with respect to wall motion abnormalities, 4 (8%) patients demonstrated segmental abnormalities in the RV. In the LV, 15 patients (29%) demonstrated wall motion abnormalities, involving multiple segments . Only 1 (2%) patient demonstrated delayed enhancement (DE) in the RV, while 10 patients (20%) demonstrated DE in the LV, also involving multiple segments: 10/10 in the basal LV, 8/10 in the mid LV, and 7/10 in the apex.Decreased RVEF, LVEF and ventricular volumes, as well as wall motion abnormalities and presence of DE regions in non-coronary pattern of distribution, may represent early changes secondary to chemotherapy. Earlier detection of DRC may allow for earlier initiation of treatment, and prevent progression of heart failure.None.