Athletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness.2max).Thirty five endurance athletes and 35 age and sex matched controls underwent CMR at 3.0 T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇OP = 0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate  had a significant association with V̇O2max.LV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta = −0.37, This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs. It is well recognised that athletic training leads to ventricular remodelling, specifically increases in left and right ventricular end diastolic volume (LVEDV & RVEDV) and left ventricular mass (LVM) , 2. ThesAlthough less well established, there is also evidence for changes in functional parameters in the hearts of trained athletes. Endurance athletes have reduced ejection fraction, circumferential and longitudinal strain of both the left and right ventricles compared to healthy controls –6. The hBoth strain and torsion parameters can be measured using cardiovascular magnetic resonance (CMR) tissue tagging techniques . CMR tag2max) [2max in endurance athletes [Cardiopulmonary exercise testing (CPX) with breath-by-breath measurement of gas exchange responses is an established method for assessment of whole-body exercise tolerance, and key parameters of aerobic function: the lactate threshold (LT) and the maximal pulmonary oxygen uptake (V̇O2max) . This in2max) . Previouathletes –16.2max. We also planned to specifically investigate if any strain parameters were associated with LT.In this study we investigated the relationship between strain-derived parameters of cardiac function and CPX-derived performance parameters that has not previously been investigated. We hypothesised that strain parameters measured at rest would be lower in athletes than in controls and lowest in athletes with the highest V̇OThirty five endurance athletes were recruited from local sporting clubs. They all trained more than 6 h a week and competed regularly at local, national or international level. Exclusion criteria were any medical illness or contraindication to CMR. Thirty five controls who exercised less than 3 h a week were also recruited and prospectively matched to the athletes for age and gender. No athletes or controls had any medical condition or took any regular medication.CMR was performed on a dedicated cardiovascular 3 Tesla Philips Achieva system equipped with a 32 channel coil and MultiTransmit® technology. Data was acquired during breath-holding at end expiration. From scout CMR images, the left ventricular long and short axes were determined.3, 30 cardiac phases TR/TE 2.6/1.3 ms, flip angle 40°, field of view 300–420 mm, typical temporal resolution 39 ms) and in orthogonal long-axis planes. Then axial cine images planned to cover the right ventricle were acquired .Cine images covering the entire heart in the LV short axis plane were acquired , spatial resolution 1.2×1.2×10mm3, tag separation 7 mm, ≥18 phases, typical TR/TE 5.8/3.5 ms, flip angle 10°, typical temporal resolution 55 ms) was acquired in the three short axis slices acquired at the apex, mid-ventricle, and base. Slices were positioned using the highly reproducible “3 of 5 technique” [Tissue tagging by spatial modulation of magnetization (SPAMM) . Epicardial and endocardial borders were traced on the LV and RV cine stack at end-diastole and end-systole to calculate end diastolic volume (LVEDV), end systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass. Volumes were indexed to body surface area (BSA) calculated using the Mosteller equation.For tagging analysis endocardial and epicardial contours were drawn on the short axis SPAMM sequences using a semi-automated process. Peak circumferential LV strain was measured for the three slices at apex, mid-ventricle, and base. Peak systolic and both early and late diastolic LV strain rates were measured from the mid-ventricular slice. Strain was measured in the mid-myocardial layer which has previously been reported to be the most reproducible . LV twisFor feature tracking analysis endocardial and epicardial contours were drawn on a long axis 4 chamber cine using a semi-automated process. Peak longitudinal strain, systolic strain rate (SSR), early and late diastolic strain rates (EDSR and LDSR) were measured for both the LV & RV. LDSR was defined as peak rate during atrial contraction. We have used feature tracking rather than SPAMM for the analysis of longitudinal strain. However, tissue tagging is hampered by a lower temporal resolution than cine imaging and tag fading during diastole. As we specifically wanted to examine longitudinal strain rates in diastole we therefore chose to use feature tracking for this while using SPAMM tagging for assessment of circumferential strain parameters.2max determined as the highest 12-breath mean. An additional step-exercise test performed to the limit of tolerance confirmed that V̇O2max was attained in all participants [A ramp-incremental test (20–30 W/min) to the limit of tolerance was performed on a cycle ergometer , with breath-by-breath pulmonary gas exchange measured throughout . A 12-lead ECG was also monitored throughout this test, with heart rate determined from the R-R interval. LT was estimated using standard ventilatory and pulmonary gas-exchange criteria (REF), and V̇Oicipants .N (%). Shapiro-Wilk test was used to test normality and unpaired t-tests and Mann Whitney U test used to compare athletes and controls. Pearson’s coefficient was used to measure correlation between exercise and CMR parameters. Univariable analyses were performed to identify predictors of LT and V̇O2max. Variables with a probability value <0.1 in the univariable analysis were included in a multivariable linear regression analysis. The standardised coefficient (beta) is reported. P < 0.05 was considered statistically significant.Statistical analysis was performed using IBM SPSS® Statistics 20.0 . Continuous variables were expressed as means ± SD. Categorical variables were expressed as 2max. Mean V̇O2max was 4.2 ± 0.80 l/min, 58.9 ± 8.2 ml/min/kg or 160.0 ± 18.8 % of predicted V̇O2max [Of 35 athletes 7 were runners, 15 cyclists and 13 triathletes. The athletes trained 11.5 ± 3.7 h per week and all had trained >6 h per week for 8.4 ± 6.0 years. Mean ramp duration was 772 ± 93 s reaching a peak work rate of 370 ± 64 W. HR rose from 55 ± 7 beats/min at rest to 182 ± 10 beats/min at peak exercise. Mean LT was 2.60 ± 0.57 l/min, 36.5 ± 6.7 ml/min/kg  or 62.1 ± 8.0 % V̇O V̇O2max .P = 0.001 and P < 0.001 respectively).Athletes and controls were prospectively matched for age and gender Table . BMI andP = 0.04) but there was no difference in RVEF (P = 0.27). Strain parameters are shown in Table LV volumes for athletes and controls are shown in Table P = 0.20, 0.85 and 0.21 respectively). LV torsion had a trend to correlation with LVMI  but there were no significant associations with LVEDVI or LVM/EDV (P = 0.61 and 0.08 respectively).In athletes, there were no significant correlations between left ventricle mass indexed to BSA (LVMI), left ventricle end diastolic volume indexed to BSA (LVEDVI) and LVM/EDV and LV twist (2max) were with torsion parameters. Peak twist , peak torsion  and twist rate  all had a significant correlation with LT. There was no significant correlation between LT and any demographic, volumetric measurement  and both LVMI  and LVEDVI  [2max . No LV strain parameters had a significant correlation with V̇O2max. RV longitudinal SSR  and RV LDSR  both correlated with V̇O2max.There was a correlation between V̇O = 0.01) , 21. TheP = 0.03) had a significant association with LT.On univariable linear regression of the parameters shown in Table 2max. On multivariable linear regression only RV longitudinal LDSR  had a significant association with V̇O2max.On univariable linear regression of the parameters shown in Table 2max). This diverse, but well characterised group has allowed us to investigate specifically the ventricular strain parameters that have a relationship with key parameters of aerobic function and exercise capacity, namely LT and V̇O2max [We have carried out comprehensive cardiac functional assessment of 35 endurance athletes from a broad spectrum of event type, age and athletic ability  has been reported. Furthermore we have found that in athletes with the highest LT the decrease in torsion is secondary to decreased apical rotation.We have reported with high statistical significance that LV torsion was lower in endurance athletes than controls. Previous CMR tagging studies have been small and insufficiently powered and therefore unable to report a difference in baseline torsion parameters between endurance athletes and controls , 24.Several echocardiography studies using techniques including tissue Doppler imaging and speckle tracking have been used to investigate left ventricular torsion in athletes. Some have reported similar findings to ours of decreased apical rotation and LV torsion in athletes with high levels of aerobic fitness  whereas It has previously been suggested that decreased torsion in athletes is mediated by eccentric hypertrophy of the LV with decreased lever arm forces from epicardial fibres . AthleteThe trend to correlation between LVMI and LV torsion may reflect that as athletes train they increase both V̇O2max and LT . The training done to increase V̇O2max tends to be associated with an increase in LV mass –16 and w2max is a key determinant of performance in endurance sport [An alternative mechanism for decreased torsion in athletes with high LT is cellular changes within the heart as a consequence of high-intensity training. It is well recognised that LT particularly as a proportion of V̇Oce sport  and enduce sport  and imprce sport  within tce sport .In diffuse myocardial diseases , 33 incr2max. Although this result is less striking, to our knowledge it is the first time that CMR strain techniques have been used to compare longitudinal functional changes in athletes and controls. Conflicting findings have been reported when echocardiographic assessment of diastolic function has been used with some studies reporting augmented relaxation of both ventricles in endurance athletes [2max can be attributed to reduced active atrial contraction late in diastole. In athletes the atrial contribution to ventricular filling is not required at rest but of course can then be utilised to maximise cardiac output during exercise.We have also reported lower RV peak longitudinal strain, LV LDSR, RV EDSR and LDSR in athletes versus controls. On multivariable linear regression only increasing RV LDSR was associated with lower V̇Oathletes , 34 and athletes . Our finOur study was carried out on a cross sectional cohort and it is important in the future to demonstrate that these findings can be replicated in a longitudinal study. The cohort in the study also has a wide range of age and athletic ability; although this was deliberate to allow study of athletes with a range of aerobic fitness. We have only studied the contribution of cardiac performance, and not ventilatory or neuromuscular function, to measures of aerobic fitness. All of the cardiac changes reported are during rest. Many of the strain parameters measured may not be independent and analysis of their individual interactions with aerobic fitness requires more complex modelling. We have not performed this in our study as very few strain parameters were associated with aerobic fitness.This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs.CMR, cardiovascular magnetic resonance; CPX, cardiopulmonary exercise testing; EDV, end diastolic volume; EDVI, end diastolic volume indexed to body surface area; ESV, end systolic volume; LT, lactate threshold; LV, left ventricle; LVM, left ventricle mass; LVMI, left ventricle mass indexed to body surface area; RV, right ventricle; SPAMM, spatial modulation of magnetization; SSFP, steady state free procession; V̇O2max, maximal oxygen uptake (ml/min/kg)


It is not clear whether patients with sinus rhythm and reduced left ventricular function should be treated with anticoagulation therapy during or after treatment for heart failure.A 67-year-old Japanese man was hospitalized at our institution with heart failure due to dilated cardiomyopathy. On day after discharge, he developed cerebral infarction and showed persistence of multiple left ventricular thrombi. His paralysis completely improved at 2 days after edaravone and heparin administration; however, his left visual field defect persisted.Patients in sinus rhythm with reduced left ventricular function might benefit from anticoagulation therapy during treatment for heart failure. We occasionally encounter patients who develop cerebral infarction during treatment for heart failure. Embolic events are estimated to occur in 4% of patients with dilated cardiomyopathy who have a left ventricular ejection fraction (LVEF) ≤35% . FurtherA 67-year-old Japanese man was hospitalized at our institution with heart failure due to dilated cardiomyopathy. He was not taking any medications and had a history of mild diabetes mellitus. He was discharged after 1 week of treatment with vasodilators and diuretics. Electrocardiographic monitoring during his hospitalization showed sinus rhythm.On the day after discharge, the patient presented to our emergency unit with left-limb paresis and left visual field defect. His medications at that time consisted of bisoprolol, enalapril, digoxin and metformin. A physical examination showed that his blood pressure was 119/67mmHg, heart rate was 60 beats/min and his respiratory rate was 10 breaths/min. He was alert, and an electrocardiogram obtained upon admission showed LV hypertrophy, premature ventricular contractions and sinus rhythm with a heart rate of 57 beats/min Figure . EchocarHis paralysis improved at 2 days after edaravone and heparin administration; however, his left visual field defect persisted. After 6 days of heparin therapy, the patient was initiated on warfarin, which led to disappearance of the two mobile left ventricle clots. No evidence of embolism was seen during treatment. We conclude that this patient had multiple cerebral infarctions due to LV thrombi immediately after treatment for heart failure. These observations highlight that LV thrombi can occur in patients in sinus rhythm who have reduced LV function and are undergoing treatment for heart failure. Fortunately for our patient, his thrombi disappeared after initiation of anticoagulation therapy.There are several reports of multiple LV thrombi in patients with LV noncompaction , arrhythAnticoagulant therapy  is used for the treatment of intracardiac thrombi ; howeverIn this report, we describe a case of a patient with dilated cardiomyopathy who had persistent multiple LV thrombi after experiencing a stroke. This finding suggests patients in sinus rhythm with reduced LV function might benefit from anticoagulation therapy during treatment for heart failure, but review of additional cases is needed to validate this conclusion.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.LVEF: Left ventricular ejection fraction.The authors declare that they have no competing interests.TM drafted the manuscript and contributed important intellectual content. TM, IS and HM made substantial editorial revisions to the manuscript. HM made major contributions to the conception and design of the report. All authors read and approved the final manuscript.Video of echocardiogram shows two mobile thrombi in the left ventricle.Click here for file


Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF.kt perfusion and voxel-wise Fermi deconvolution.A group of 58 patients with heart failure  and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T 30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group . In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments . No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups.Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF. Despite recent advances in diagnosis and management, heart failure (HF) remains a common cause of death and morbidity -3. Myocakt CMR perfusion enables high spatial resolution perfusion assessment and provides data suitable for voxel-wise quantitative analysis [kt high-resolution and voxel-wise quantitative perfusion CMR in this subgroup of patients.In recent years, cardiovascular magnetic resonance (CMR) has established itself as an important component to the assessment and management of patients with coronary artery disease (CAD) and HF ,8. CMR ianalysis ,15. The We identified patients referred for perfusion CMR to assess HF aetiology. Patients were then retrospectively classified on the basis of the aetiology of HF as ischaemic  or non-ischaemic  . A groupAll patients studied provided written consent (09/H0802/78) and the study was conducted in accordance with the Declaration of Helsinki.kt turbo-gradient echo sequence (imaging parameters: shortest echo time (range 1.35 to 1.54 ms), shortest repetition time (range 2.64 to 3.12 ms), 18° flip angle, 90° saturation prepulse, 120 ms prepulse delay, typical TR 2.6 ms, typical TE 0.9 ms, typical spatial resolution 1.2×1.2×10mm. Three short-axis slices  were acquired over every heartbeat covering 16 of the standard myocardial segments (segment 17 was excluded). Stress imaging preceded rest imaging by 14 ± 2 min (range 10 to 19 min). For stress imaging, 140 μg/kg/min of adenosine was administered intravenously for 4 min. Imaging commenced 3 min into the infusion and continued for 1 min during the acquisition of the images. All subjects were asked to abstain from caffeine and caffeine-containing food and drink for at least 24 hours before the scan, according to institutional practice.Images were acquired on a Philips Achieva 3 T (TX) system, equipped with a 32-channel cardiac phased array receiver coil . First pass perfusion imaging consisted of a high-resolution Perfusion data were acquired during first pass injection of 0.075 mmol/kg Gadobutrol  at 4 ml/minute followed by a 20 ml saline flush. A dual bolus contrast agent scheme was used to correct for signal saturation of the arterial input function as previously described ,17. A coThe studies were analyzed visually by two independent experts blinded to all other data. CMR scans were classified visually positive for ischemia in the presence of a perfusion defect  which was transmural, or involving ≥2 adjacent myocardial segments according to the criteria by Hussain et al. . In the An experienced operator, blinded to visual assessment and other clinical data, performed quantitative analysis using software and methods developed and previously validated against phantom and PET data ,20. The h(t), were fitted to the Fermi function with the following analytical expression:Quantitative perfusion analysis was performed by Fermi deconvolution according to the methods described by Wilke et al.  and Jerok, R and τ0 vary and keeping τd fixed. In the above equation, u(t–τd) is the unit step function. The τd accounts for the delay time between the appearance of the signal in the LV blood pool and myocardial region of interest (ROI) [τ0 characterizes the width of the shoulder of the Fermi function during which little or no contrast agent had left the ROI. R is the index of contrast agent influx parameter and k represents the decay rate of h(t) due to contrast agent washout. Using the above equation, myocardial blood flow (MBF) estimates are calculated as h(t) at t=0 [using a Marquardt-Levenberg nonlinear least square algorithm by letting st (ROI) . τ0 char) at t=0 . MyocardIn addition, voxel-wise MPR results from the epicardial half  and from the endocardial half of each segment  were averaged and the endocardial to epicardial MPR ratio  was calculated.Invasive coronary angiogram was performed on all patients with ischaemic cardiomyopathy or normal LV function within 6 months of the CMR scan.A visual score was given for image quality of each dataset using a four-point scale: 1—poor, 2—fair, 3—good, and 4— excellent. The severity of respiratory artefacts and dark rim artefacts were also scored on a four-point and three-point scale respectively. For respiratory artefacts: 1 – non-diagnostic; 2 – severe artefacts but diagnostic; 3 – mild artefacts; 4 – no artefacts. For dark rim artefacts: 1- circumferential; 2- segmental; 3- absent.t test and 1-way ANOVA as appropriate. The statistical analyses were performed using PASW software for Macintosh . Agreement between perfusion CMR and coronary angiography for the diagnosis of CAD was evaluated using a Kappa agreement test. Mann-Whitney and Chi-squared tests were used to test the qualitative measurements for statistical significance, with a p value threshold of 0.05.Data are presented as mean and standard deviation. Group means were compared using paired and unpaired Student A total of 91 subjects were studied. This included 58 patients with HF (LVEF 39 ± 10%) and 33 patients with normal LV function  (LVEF 64 ± 5%). In the HF group, 30 patients (51.7%) had a final diagnosis of ischaemic cardiomyopathy (ICM) and the remaining 28 subjects had a final diagnosis of non-ischaemic cardiomyopathy (NICM). Demographics, CMR structural findings and haemodynamic parameters are given in Table In the ICM group, 25/30 (83%) patients showed evidence of a perfusion abnormality. Of these 19/25 (76%) patients showed stress-induced perfusion abnormalities, either extending beyond an area of scar or in an area served by a separate coronary territory. On segmental analysis, there were 73 segments showing stress-induced perfusion abnormalities (4.06 ± 2.05/patient). 90 segments showed scar-related perfusion abnormalities (4.29 ± 2.13/patient).In the NICM group, no visual perfusion abnormalities were reported and 7/28 patients  showed late enhancement with a non-ischaemic-pattern .15/33 (46%) patients in the Normal LV group showed stress-induced perfusion abnormalities, with a total number of 105 positive segments (6.4 ± 4.5/patient). No patients from the Normal LV group showed scar on late gadolinium enhancement images.Detailed results of stress and rest quantitative analysis are reported in Table No significant difference in visually normal segments was observed between groups, with an average stress perfusion rate of 2.2 ± 1.0 ml/g/min in the ICM group, 1.9 ± 0.8 ml/g/min in the NICM group and 2.3 ± 1.3 ml/g/min in the Normal LV group (p = 0.18).In the ICM group, there was a significant difference in stress perfusion rate between visually normal and abnormal segments . The presence of ischaemic scar was associated with significantly reduced perfusion rate compared to visually normal segments .Within the Normal LV group, the difference in stress perfusion rate between visually normal and abnormal segments was less pronounced and not statistically significant .There was no significance difference in stress perfusion values between the ICM and Normal LV groups in visually abnormal segments (p = 0.47).Examples of high-resolution, voxel-wise perfusion maps are given in Figures Detailed results of MPR analysis are also reported in Table No significant difference in visually normal segments was observed between groups, with an average MPR of 2.3 ± 0.8 in the ICM group, 2.2 ± 0.9 in the NICM group and 2.6 ± 1.1 in the Normal LV group (p = 0.19).In the ICM group, there was a significant difference in MPR between visually normal and abnormal segments . The presence of ischaemic scar was associated with significantly reduced perfusion rate compared to visually normal segments .Similarly, within the Normal LV group, the difference in MPR between visually normal and abnormal segments was statistically significant .There was no significance difference in MPR values between the ICM and Normal LV groups in visually abnormal segments (p = 0.62).There was no significant difference in the endo-epi MPR ratio in visually normal segments across groups with an endo-epi MPR ratio of 1.05 ± 0.16 in ICM patients, 1.02 ± 0.04 in NICM patients and 1.00 ± 0.06 in Normal LV patients (p = 0.57).There was a significant difference in endo-epi MPR ratio between visually normal and visually abnormal non-scarred segments in both the ICM and Normal LV groups .The results of invasive coronary angiography and perfusion CMR in relation to coronary artery territories, including Kappa results are detailed in Table Detailed results of overall image qualitative assessment, respiratory artefacts and dark rim artefacts are presented in Table kt 3 T acquisition methods and high-resolution voxel-wise quantification. There were significant differences of MPR between visually normal and abnormal segments in both ICM and Normal LV groups. In the ICM group stress perfusion values were also statistically significant between visually normal and abnormal segments. However, this was not the case in the Normal LV group. This could be explained by the relatively low number of subjects positive for ischemia included in the study and is in keeping with previous validation studies that compared CMR perfusion and PET, showing good correlation for MPR values and weaker correlation for absolute stress perfusion values. This may relate to differences in the methods used for quantification such as the tracer properties, model assumptions, fitting methods and parameter constraints. MPR cancels out a degree of variability and this may help explain our results [This study has several novel findings. Most importantly, it demonstrates the feasibility of quantitative first-pass perfusion analysis in patients with heart failure using a combination of high-resolution  results .CMR is now well established for the evaluation of patients with coronary disease and heart failure. Perfusion CMR is increasingly used to determine aetiology of heart failure and to plan patient management. At the same time, CMR is now well established for the evaluation of patients with CAD and ischemia detection is rapidly becoming one of the main indications for CMR examination . StudiesPerfusion CMR has been previously shown to be at least as accurate as nuclear perfusion imaging in patients with angina ,29,30 ankt sensitivity encoding allows considerable improvement in spatial resolution with improved image quality, signal-to-noise, contrast-to-noise and reduction in the transmural extent of dark-rim artefacts, particularly at 3 T [kt sequence in comparison with standard perfusion CMR sequences when using visual assessment has been demonstrated in patients with normal LV function [Within the field of perfusion CMR, several technical developments have refined the sequences. The use of an advanced sequence such as y at 3 T . The advfunction ,35.To our knowledge, there are no previous studies focusing on perfusion in patients with heart failure using CMR. Only a few studies, using PET, have been performed specifically exploring perfusion abnormalities in patients with HF and have produced conflicting results -38. Van Non-invasive assessment of myocardial perfusion in patients with HF can be challenging for a number of reasons. Foremost, in cases of advanced HF the LV wall is often thinner and remodeled, requiring higher spatial resolution to reliably identify subendocardial areas of stress-induced ischemia or areas of peri-infarct ischemia. PET is considered the reference standard for in-vivo quantitative perfusion assessment. However, it is limited by the intrinsically lower spatial resolution and this might become an important limiting factor for the assessment of dilated and remodelled ventricles.Perfusion CMR, and in particular 3 T kt, offers higher spatial resolution and arguably is best placed to identify areas of ischemia in these patients. In addition, the advantage of CMR over other techniques to directly visualise scar enables more precise assessment of peri-infarct ischemia. This reduces the risk of including scarred areas in segmental averages of perfusion. Perfusion rate in areas of scar was found to be reduced which, if included in the analysis, could result in false positive ischemia results.We observed a non-significant trend towards lower perfusion rates in visually normal segments of patients with NICM, which would be in keeping with the results previously obtained by PET. However, this comparison is beyond the scope of the study and would need to be addressed in future work.Importantly, our results demonstrate a significant endocardial-epicardial MPR ratio in ischaemic segments, even in patients with HF who have thinned and remodelled ventricles. This is in keeping with findings of a study by Parodi et al. where microspheres were injected into hearts of patients at time of transplantation, demonstrating the presence of a perfusion gradient in the presence of extensive LV remodelling . To our kt sequences, used in this study, more significantly than other perfusion sequences. We did not observe this effect in our study, which may be a reflection of good patient coaching and careful selection of the time for the breath hold command.Perfusion assessment in patients with HF can be further complicated by a well-recognised irregularity in respiratory motion and reduced tolerance to breath-holding which can result in a reduction in image quality -43. ThesThis is a feasibility study. No reference standard except for visual assessment was used. However, visual assessment is considered the clinical diagnostic standard for perfusion CMR evaluation and extensive validation is available against Fractional Flow Reserve (FFR), invasive angiography, Single Positron Emission Computed Tomography (SPECT) and PET.Though we were able to compare our findings with invasive coronary angiography, this serves as a limited reference method in the absence of invasive functional assessment of coronary flow reserve. Furthermore, the variability in coronary anatomy in terms of territory supplied, may underestimate the degree of correlation between the two techniques.Results might not be easy to generalise to other CMR sequences and field-strengths, or to standard  quantitative analysis methods. The quantification process may need to be adjusted for other field strengths and perfusion sequences and this could form part of future work.kt high-resolution perfusion CMR with high-resolution voxel-wise quantitative analysis appears feasible in this group of heart failure patients. This approach allows additional information gained from improved spatial resolution to be preserved, a feature that is of crucial importance in thinned and remodeled ventricles.This study demonstrates that the combination of 3 T


The atrium has been considered for too many years a neglected chamber and because of this the assessment of atrial function is still a challenge.More recently, new noninvasive diagnostic modalities have shed new light on atrial role in several diseases.The assessment of atrial function may have particular relevance for the growing epidemic of atrial fibrillation which currently affects nearly 2% of the general population, with prevalence expected to double by 2050.A better knowledge and understanding of atrial function in different cardiac diseases  may have a significant clinical impact in the management and in the prognostic evaluation of our patients.This special issue focuses on original research articles and review papers that address a broad range of mechanisms associated with atrial dysfunction, with possible prognostic and therapeutic interventions.In this dedicated issue, R. Leischik et al. reviewed in detail the importance and pitfalls of advanced echo modalities such as strain technology and 3D echocardiography for the analysis of left atrial mechanics.Strain imaging  seems toP. Kuchynka et al. reviewed the role of cardiac magnetic resonance and computed tomography in assessment of left atrial size and function, especially before and after atrial fibrillation ablation.Cardiac magnetic resonance is considered to be the gold standard for volumetric assessment of left atrial size. However, the cost and the availability of the technique do not seem to justify the potential added role when compared to 2D and 3D echo. Late gadolinium enhancement has the ability to tissue-characterize the atria and this may be used for optimizing the treatment of patients suffering from atrial fibrillation. However, the very promising results obtained by strain imaging in detecting atrial fibrosis may represent a valid alternative. Cardiac CT is considered the method of choice for evaluation of pulmonary vein and left atrial anatomy before catheter ablation procedures for atrial fibrillation and for detection of pulmonary vein stenosis after ablation. However, the exposition to ionizing radiations should be carefully taken into account.D. Regazzoli et al. presented a comprehensive analysis of the potential role of left atrial appendage occlusion in stroke prevention. The left atrial appendage is considered the “most lethal human appendage” as it may cause significant mortality and morbidity in AF patients. In this regard, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in atrial fibrillation especially in certain categories of patients.It is of note that G. de Maat et al. in the present issue demonstrated the effect of left atrial appendage amputation on atrial mechanics.Finally, C. Santosa et al. presented data on the potential utility of combined 3D left atrial volume measurement and peak E wave mitral flow velocity as echocardiographic guides for acute volume resuscitation.Taken together, the papers in this special issue present the recent developments and future perspectives in the morphological and functional evaluation of the atria and new possible therapeutic approaches. Importantly, these papers also unmask many challenging issues that should be overcome to improve the evaluation of atrial function as well as the new proposed therapeutical approaches.Giovanni Di Salvo


Impaired microvascular reperfusion (no-reflow) and unsuccessful infarct-related artery (IRA) revascularization are associated with a worse clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Reperfusion can be identified by epicardial or microvascular flow determined by angiography as Thrombolysis in Myocardial Infarction (TIMI) flow grade and a myocardial blush grade (MBG), respectively. Moreover, microvascular obstruction (MVO) determined by CMR is also a well-known predictor of an unfavorable clinical outcome after STEMI.The aim of the study was to determine the effect of impaired reperfusion estimated by angiography on microvascular obstruction and infarct size (IS) measured by CMR.We examined 85 patients  with first STEMI treated with pPCI within 12 hours from symptoms onset. Infarct related artery TIMI flow and MBG were estimated after pPCI. CMR was performed on the 1.5T system within 96 hours after pPCI. Morphology and function of myocardium was estimated by a steady-state free precession (SSFP) sequence. To evaluate the infarct size and MVO, a late gadolinium enhancement (LGE) technique was performed (10-15 min after the administration of Gd-DTPA). Infarct size was defined as an area greater than 50% of the maximal signal intensity within LGE . MVO was defined as an area of the absence or hypoenhancement of contrast surrounded by LGE. IS and MVO were determined by planimetry and a summation of discs method.Revascularization was successful in 41 patients (MBG 3 and TIMI 3) with preserved ejection fraction (EF=56.3±7.8%), IS of 16.92±11.35g and MVO 0.53±1.28g. Patients with suboptimal reperfusion (TIMI<3 and/or MBG<3) had similar EF  but larger IS (31.7±24.83g) and MVO (3.42±6.13g); (p=0.0008 and p=0.004 respectively).Infarct size and microvascular obstruction evaluated by CMR in patients with STEMI are associated with impaired reperfusion. Small IS and MVO results are related to a successful reperfusion after pPCI.N/A.


Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia.+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts .CrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates . Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia . The cardioprotective effect of hypothermic high KThese observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury. This was attributed to increased phosphocreatine (PCr) buffer capacity, elevated myocardial glycogen, improved ‘energy reserve’ and the ability of creatine to reduce the open probability of the mitochondrial permeability transition pore . CardiopRapid revascularization of ischaemic regions within the heart by thrombolysis or primary percutaneous coronary intervention remains at the clinical forefront to effectively treat AMI ,19. Pre-It should be noted that previous work from our laboratory has shown that very high myocardial [Cr] may itself cause LV hypertrophy and dysfunction , and defWe also performed experiments in mice aged 18 months since the ageing heart is known to have altered cardiac substrate metabolism , is more+ and Mg2+ ions to reduce metabolic demand and prolong ischaemic tolerance [ex vivo rat hearts [Cold, cardioplegic arrest of the heart remains the gold standard for effective myocardial protection during cardiac surgery  and hearolerance . In thisolerance  and in polerance  undergoit hearts . Howevert hearts . These bt hearts  and not ex vivo not in vivo experimental approaches and ideally we would have both. This reflects the limitations of having sufficient numbers of aged animals and the welfare implications of combining TAC surgery with ischaemia-reperfusion surgery. Furthermore, we did not perform tetrazolium staining in our ex vivo hearts since the period of reperfusion was insufficient for complete washout of NADH from necrotic tissue, which would lead to under-estimation of infarct sizes [During ischaemia, the heart undergoes many metabolic changes including a reduction in intracellular PCr . We did ct sizes . It is tct sizes .We have shown that elevating creatine levels in the mouse heart improves functional recovery following ischaemia-reperfusion even in the presence of old age or LVH. Both conditions previously associated with loss of cardioprotective efficacy. Furthermore, elevating intracellular creatine is additive to standard hypothermic cardioplegia for recovery from prolonged ischaemia. Together these findings support the development of small molecule activators that increase intracellular Cr , which wS1 File(DOC)Click here for additional data file.


Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM).In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)—one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments.In study 1, the HHC (compared with control) increased glucose  and insulin  concentrations, and reduced FFA levels , but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global  and regional  myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia.In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM.http://www.isrctn.org. Unique identifier ISRCTN69686930Trial Registration:  Hyperglycemia is common in patients presenting with acute coronary syndromes (ACS) and a powerful predictor of morbidity and mortality . AlthougGlucagon-like peptide-1 (GLP-1) is an incretin hormone which regulates glucose metabolism by stimulating insulin secretion, suppressing glucagon and promoting glucose uptake into muscle and adipose tissue. These effects are dependent on the prevailing glucose concentration so that the risk of hypoglycemia is minimized . As a reWe have previously used a model of hyperinsulinemic euglycemic clamping (HEC) during dobutamine stress echocardiography (DSE) to demonstrate that alteration of the myocardial metabolic environment in patients with obstructive coronary artery disease (CAD) can attenuate left ventricular (LV) ischemic dysfunction, especially in those with insulin resistance . HoweverPatients with obstructive CAD  and preserved resting LV systolic function were invited to participate. All patients had undergone recent coronary angiography before enrolment in the study. Exclusion criteria included LV ejection fraction (EF) <40% (either on echocardiography or LV angiography), regional wall motion abnormalities at rest, a history of previous myocardial infarction within the preceding 3 months, conduction abnormalities, valvular heart disease, patients taking insulin, dipeptidyl peptidase-4 (DPP4) inhibitors or GLP-1 receptor agonists, and those with permanent pacemakers. The study protocol was approved by the local ethics committee (REC number 08/H0304/68), and conformed with the guidelines set out in the Declaration of Helsinki. All participants gave written informed consent. The trial number was ISRCTN69686930Study 1: effects of hyperglycemia on myocardial performance during dobutamine stressTwo separate studies were undertaken:Each subject underwent two DSEs, performed approximately one week apart. One DSE, determined randomly, was performed during the steady-state phase of a hyperinsulinemic hyperglycemic clamp (HHC) and the other DSE acted as a control Fig. .Fig. 1FlStudy 2: effects of GLP-1 (7-36) on myocardial performance during dobutamine stress in the setting of hyperglycemiaConsecutive patients with T2DM underwent DSE during the steady-state phase of a HHC on two separate occasions, approximately one week apart. One DSE, determined randomly, was performed during an intravenous infusion of GLP-1 (7-36) amide  at a dose of 1.2 pmol/kg/min, and the other DSE (control HHC) during an intravenous infusion of normal saline  and if necessary, up to 2 mg of atropine was given to achieve the target heart rate. Subjects underwent continuous 12-lead ECG monitoring, with blood pressure being recorded at baseline and at the end of each stage of dobutamine. Criteria for stopping the test were achievement of target heart rate of (220-age) × 0.85 bpm, ischemic ECG changes (>2 mm ST depression), angina, systolic blood pressure increase to >240 mmHg or decrease to <100 mmHg, and severe arrhythmias. Two-dimensional echocardiography  was performed with the patient in the left recumbent position, and images were recorded at rest, peak stress and in recovery. Three cardiac cycles of the apical 4-, 3-, and 2-chamber views were captured with tissue Doppler imaging (TDI). The image sector width was kept as narrow as possible to maximize the frame rate. All recordings were made in gently held mid-expiration to minimize beat-to-beat variability, and the data were stored for subsequent off-line analysis .In addition to blood glucose sampling, blood samples were taken in the fasted state to measure insulin, FFA, and GLP-1(7-36) concentrations at baseline, at the steady state stage of the HHC immediately prior to commencement of the DSE (pre-DSE), during peak dobutamine stress and in the recovery phase at 30 min after cessation of dobutamine. The syringes for the collection of GLP-1 samples were pre-prepared with DPP-4 inhibitor (Millipore) to prevent GLP-1 degradation. Plasma GLP-1 levels were measured using a commercially available assay .The scans were analyzed off-line by a reviewer who was blinded to the treatment strategy. Regional wall LV motion was assessed using a 12-segment model comprising the base and mid level of six regional walls  obtained from the three apical views. LV volumes and EF were calculated using the Simpson biplane method according to the guidelines of the American Society of Echocardiography. Global LV function was also assessed by mitral annular systolic velocity (MASV) averaged from six sites . Peak syA diameter stenosis of >70% stenosis on coronary angiography was considered hemodynamically significant. Myocardial segments were assigned to the perfusion territories of stenosed vessels, considering the left anterior descending coronary artery to supply the anterior and anteroseptal segments, the right coronary artery (when dominant) to supply the inferior and inferoseptal segments, and the circumflex artery to supply the anterolateral and inferolateral segments.t test, α = 0.05, β = 0.10). Interim analysis was conducted after the first seven participants to make adjustments to the sample size if required and therefore avoid patients undergoing DSE unnecessarily. Comparisons were made between HHC and control scans (study 1), or GLP-1 HHC and control HHC scans (study 2), with each patient acting as their own control. Continuous and discrete variables are expressed as mean ± standard deviation (SD) and compared by use of the paired Student’s t test  or the Wilcoxon signed-rank test where appropriate after testing for normality of distribution using the Shapiro–Wilk test. Categorical data are expressed as numbers (percentages) and compared by use of McNemar’s test. Two-tailed tests were used on all occasions, and a probability value of <0.05 was considered statistically significant. Intra- and inter-observer variations were calculated using the Bland–Altman method and expressed as the coefficient of variation  ± the 95% limits of agreement.The number of subjects had been calculated on the basis of previous work in our laboratory in patients with CAD, where EF increased from 70.8 ± 5.0% to 77.0 ± 4.4% when dobutamine stress was performed during an intravenous infusion of GLP-1 (7-36). To detect a change in global LVEF of 5% after dobutamine stress (standardized effect size of 1), 12 patients were required , insulin  or FFA  between the HHC and control studies  and insulin  concentrations, and reduced FFA levels , in the clamp study compared with control. In the recovery phase at 30 min after cessation of dobutamine (15 min after cessation of the glucose infusion), glucose  and insulin  concentrations remained higher and FFA concentrations lower  in the HHC study, although the magnitude of the differences was not as great.There were no differences in EF between the clamped and control studies at any stage . Assessment of global LV function by MASV confirmed these findings. The HHC was not observed to have any net effect on this parameter before, during or after dobutamine stress  , insulin , FFA  or GLP-1(7-36)  between the GLP-1 and control studies  amide approximately 50 times above the levels in control , and the HHC elevated plasma glucose concentrations during both visits to a similar level . However, endogenous insulin production was greater  and FFA concentrations lower  after GLP-1 than in the control studies.In the recovery phase at 30 min after cessation of dobutamine (15 min after cessation of the GLP-1 and glucose infusions), the GLP-1(7-36) amide concentration remained higher than in control  resulting in a lower glucose concentration . Insulin concentrations remained higher  and FFA concentrations lower  in the GLP-1 study.There was no difference in resting EF between the GLP-1 and control studies . At peak stress, there was a greater increase in LV function after GLP-1 infusion during hyperglycemia , and this improved performance persisted into recovery . Assessment of global LV function by MASV confirmed these findings. LV function was similar before both scans . However, after GLP-1 infusion during hyperglycemia, myocardial performance was enhanced both at peak stress  and at 30 min after dobutamine stress   HH has a neutral effect on LV function during dobutamine stress; and (2) in patients with T2DM, an intravenous infusion of GLP-1(7-36) amide at the time of hyperglycemia enhances myocardial performance during dobutamine stress.It is well recognised that acute hyperglycemia may have a direct detrimental effect on ischemic myocardium. Although a large number of potential mechanisms have been postulated, those relevant to demand ischemia include increased oxidative stress and reduced nitric oxide production  leading In our study, the HHC stimulated endogenous insulin production and resulted in inhibition of lipolysis with an associated reduction in FFA concentration. At peak stress, the combination of pancreatic β1-stimulation from dobutamine and hyperglycemia led to a marked potentiation of insulin release, increasing further the differences between insulin and FFA. These metabolic differences persisted (but to a lesser degree) in the recovery phase at 30 min after cessation of dobutamine. However, despite these metabolic alterations, there was no significant net effect observed on either global or regional LV function during dobutamine stress or in recovery.These findings are in contrast to the results of our previous work where we observed improved myocardial performance in patients with CAD undergoing DSE during the steady state stage of a HEC . Whilst Insulin resistance refers to the reduced response of glucose uptake to the stimulatory effect of insulin. In the myocardium, insulin resistance suppresses oxidation of glucose, improves fatty acid metabolism and alters intracellular signalling, leading to numerous impairments of excitation–contraction coupling, less efficient energy production and increased susceptibility to ischemia/reperfusion injury . AlthougTo the best of our knowledge, our study is the first to investigate the effect of GLP-1 modulation on LV function during myocardial ischemia in the setting of hyperglycemia in patients with T2DM and CAD. In study 2, there were no differences in GLP-1 levels or LV function between the two scans at baseline. Infusion of GLP-1 during HHC increased the plasma concentration of active GLP-17-36) amide approximately 50 times above the levels in control, resulting in increased insulin and suppressed FFA concentrations. Compared with control, GLP-1 was associated with improved parameters of both global and regional LV performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. Glucose levels were similarly elevated in both scans, suggesting that the favorable cardiovascular effects were due to GLP-1 itself and not to euglycemia. Although insulin concentrations were higher during the GLP-1 scan, numerous studies have demonstrated that incretin-related cardioprotection occurs independent of an effect on insulin , 16, 36. amide apOver the last decade, there has been an increasing body of evidence highlighting the favorable cardiovascular properties of GLP-1 –39. In aHyperglycaemia is known to be associated with an adverse prognosis in patients presenting with ACS . HoweverThis study has a number of important limitations. Firstly, we have used tissue Doppler-derived indices of myocardial deformation to assess regional LV function, which has a number of potential pitfalls compared with two-dimensional speckle tracking echocardiography (STE). These include a high dependence on a favorable angle of incidence during image acquisition, an inability to accurately assess apical segments, and potentially high inter-and intra-observer variations. However, since TDI allows for measurements of strain and strain rate with excellent temporal resolution, this technique may be advantageous to STE at times of higher heart rates (e.g. during dobutamine stress). Secondly, whilst all attempts were made to conduct the two DSE scans for each patient in identical fashion and to obtain the peak stress images at the same degree of dobutamine stress, we cannot exclude the possibility of a degree of variation in the response of individual patients to dobutamine on the two separate study days. Thirdly, the potential cardioprotective effects of GLP-1 have been assessed using echocardiographic  endpoints in only a small number of patients. Further work, in the form of adequately powered randomized controlled trials, is required to ascertain if these favorable cardiovascular effects at the time of demand ischemia translate into an improvement in clinical outcomes.In patients with obstructive CAD, hyperglycemic hyperinsulinemia has a neutral effect on LV function during dobutamine stress. However, an infusion of GLP-1(7-36) at the time of hyperglycemia protects the heart against demand ischemic LV systolic dysfunction in patients with T2DM and IHD.


Background: Echocardiographic evaluations of the longitudinal axis of the left ventricular (LV) function have been used in the diagnosis and assessment of heart failure with normal ejection fraction (HFNEF). The evaluation of the global and segmental peak systolic longitudinal strains (PSLSs) by two-dimensional speckle tracking echocardiography (STE) may correlate with conventional echocardiography findings. We aimed to use STE to evaluate the longitudinal function of the LV in patients with HFNEF.Methods: In this study, 126 patients with HFNEF and diastolic dysfunction and 60 normal subjects on conventional echocardiography underwent STE evaluations, including LV end-diastolic and end-systolic dimensions; interventricular septal thickness; posterior wall thickness; LV volume; LV ejection fraction; left atrial volume index; early diastolic peak flow velocity (𝐸); late diastolic peak flow velocity (𝐴); 𝐸/𝐴 ratio; deceleration time of 𝐸; early diastolic myocardial velocity (e′); late diastolic myocardial velocity (A′); systolic myocardial velocity (S); and global, basal, mid, and apical PSLSs. The correlations between these methods were assessed. Results: The mean age was 57.50 ± 10.07 years in the HFNEF patients and 54.90 ± 7.17 years in the control group. The HFNEF group comprised 69.8% males and 30.2% females, and the normal group consisted of 70% males and 30% females. The global, basal, mid, and apical PSLSs were significantly lower in the HFNEF group . There was a significant positive correlation between the global PSLS and the septal e' . There was a negative correlation between the global PSLS and the E/e' ratio . There was a significant negative correlation between the E/e' ratio and the mid PSLS  and the basal PSLS . There was a weak positive correlation between the septal e' and the mid PSLS  and the basal PSLS . There were also weak negative correlations between the isovolumic relaxation time and the global PSLS  and the mid PSLS  and also between the New York Heart Association functional class and the mid PSLS  and the basal PSLS . Conclusion: Our HFNEF patients on conventional echocardiography had different STE findings compared to our normal subjects, which is indicative of diastolic dysfunction. The longitudinal systolic function of the LV, which was measured by STE, was reduced in all the segments, denoting some degree of subclinical systolic dysfunction in these patients. This entity represents almost half of the HF population, especially among females and older subjects,9 The systolic function of the left ventricle (LV) is usually measured using conventional echocardiography along with tissue Doppler. Two-dimensional (2D) speckle tracking echocardiography (STE) could be beneficial in the evaluation of the LV diastolic and systolic functions. Tissue Doppler is affected by different factors such as angle dependency, preload, and afterload and, as such, may have some limitations in the accurate assessment of the LV function.10-15 STE has overcome some of these shortcomings, and previous studies have assessed its accuracy and clinical utility. STE uses 2D standard images and affords an offline analysis of the previously recorded data. Considering these factors, STE has emerged as an acceptable method in echocardiographic evaluations.16-19HFNEF patients have few differences with HFREF patients in terms of clinical signs and symptoms and radiographic findings, and echocardiography is the only accurate method for differentiating these patients.10, 14, 20 It has been reported that HFNEF patients have reduced LV systolic longitudinal function, which is indicative of the subclinical impairment of the systolic function.21-24 The use of STE seems to be useful in understanding HFNEF and making early diagnosis. In this study, we aimed to assess the utility of STE in the evaluation of the systolic longitudinal function of the LV in HFNEF patients.The echocardiographic evaluation of the longitudinal function of the LV has been helpful in the understanding of HFNEF.25-27 Patients with non-sinus rhythm ; extensive regional wall motion abnormality at rest; LVEF < 50%; unstable vital signs; moderate to severe valvular heart disease; primary or secondary increase in pulmonary pressure not related to HFNEF or diastolic dysfunction; severe systemic disease, including pulmonary, renal, and hepatic disease; pericardial disease; cardiomyopathy; or congenital heart disease were excluded. Normal subjects without symptoms or history of cardiovascular disease, high blood pressure, and diabetes mellitus as well as normal electrocardiography and echocardiography were included as the control group. The study protocol was approved by the Ethics Committee of Tabriz University of Medical Sciences, and all the subjects gave written informed consent.In this cross-sectional study, 126 patients with confirmed HFNEF and 60 normal subjects were enrolled. The two groups were matched for age and sex. Patients were considered to have HFNEF if they had HF symptoms and LV diastolic dysfunction with a preserved LVEF (LVEF ≥ 50%) diagnosed by conventional echocardiography according to the guidelines of the American Society of Echocardiography (ASE) and the European Association of Echocardiography (EAE).25 The LV volumes and the LVEF were measured using the modified biplane Simpson method as recommended by the ASE and the EAE.26, 27 The left atrial volume index (LAVI) values were calculated using the area length method.28All the subjects underwent conventional echocardiography and then STE (2D strain) using the Automated Function Imaging (AFI) software on a commercially available machine . All the images were obtained from the standard parasternal and apical positions using 2D, M-mode, and Doppler echocardiographic techniques. The LV end-diastolic and end-systolic dimensions as well as the interventricular septal thickness (IVST) and the posterior wall thicknesses (PWT) were obtained via M-mode echocardiography.27The pulse Doppler sample volume was placed at the tips of the mitral valve leaflets in the apical four-chamber view to record the LV inflow velocity. From the LV inflow velocity, the early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), E/A ratio, and deceleration time of the E wave velocity were measured. Additionally, the early diastolic myocardial velocity (e′), late diastolic myocardial velocity (A′), and systolic myocardial velocity (S) were obtained using STE as the average of the septal lateral corner of the mitral valve. The isovolumic relaxation times were also calculated using STE.The STE images of the LV were acquired in the apical four-chamber, two-chamber, and apical three-chamber views with the same ultrasound machine . Three ct-test was used in those with normal distribution and the Mann–Whitney U test if the distribution was not normal. The association between the qualitative variables was studied using the chi-square test or the Fisher exact test. The correlation between the STE and conventional variables was evaluated using the Pearson correlation. A p value ≤ 0.05 was considered significant. The data were analyzed using Statistical Package for Social Sciences, version 17.0 . The baseline data are reported as mean ± standard deviation (continuous data) or percentages , depending on the data level. In order to analyze the differences between the groups in the quantitative variables, the Student In this study, 126 patients with HFNEF and 60 normal subjects were evaluated. The demographic findings of the groups are demonstrated in The conventional echocardiography findings are depicted in According to the STE findings, the HFNEF group also had significantly lower global, apical, mid, and basal PSLSs than the normal subjects . The correlation between the STE and conventional echocardiography findings was evaluated in the HFNEF group. There was a significant positive correlation between the global PSLS and the septal e'  and a negative correlation between the global PSLS and the E/e' ratio . There were also significant negative correlations between the mid PSLS and the E/e' ratio  and between the basal PSLS and the E/e' ratio . There were weak positive correlations between the septal e' and the mid PSLS  and the basal PSLS . Our results also revealed negative correlations between the IVRT and the global PSLS  and the mid PSLS . The New York Heart Association (NYHA) functional class also had a weak negative correlation with the mid PSLS  and the basal PSLS . The correlation analysis was performed in the control group, but no significant correlation was observed.6, 7 The longitudinal function of the LV is a sensitive index in detecting early changes in the LV function with pathologic processes or aging. Recent studies have recommended the global PSLS as an early marker of the subclinical dysfunction of the LV.29-31Diastolic dysfunction with no signs and symptoms is usually present in 40%-60% of patients with coronary artery disease, hypertension, valvular heart disease, diabetes mellitus, hypertrophic cardiomyopathy, or cardiac amyloidosis and can progress to symptomatic HF.32, 33 In the present study, we evaluated systolic function by STE in HFNEF patients with diastolic dysfunction. Diastolic dysfunction was grade I in 120 patients and grade II in 6 patients. We observed that the E/e' ratio and the deceleration time, as the indicators of diastolic dysfunction, were significantly higher in the HFNEF patients with diastolic dysfunction than the normal subjects without diastolic dysfunction. Previous studies have demonstrated that some degree of systolic dysfunction is present in HFNEF patients with diastolic dysfunction.34-39 Similar results were observed in the present study. Diastolic dysfunction is a known predictor of the clinical outcome in many situations such as HFNEF and HFREF.40Our results demonstrated that most of the HFNEF patients had a high LAVI with grade I diastolic dysfunction: this is considered as grade Ia diastolic dysfunction. In most patients with diastolic dysfunction grade I, the diastolic filling pressure is not increased and the E/e' ratio is 8 or higher. However, in a subgroup of patients, the E/e' ratio is > 15, with an E/A ratio < 1. This pattern has been designated grade Ia diastolic dysfunction to emphasize the fact that the filling pressure is increased, while there is a typical grade 1 mitral inflow velocity pattern. Also in this pattern, the LAVI is elevated.36 observed that their HFNEF patients with impaired systolic and diastolic functions of the LV myocardium had significantly increased LV filling pressures and decreased cardiac outputs. Similarly, we found significant differences in the LV filling pressure between the HFNEF patients and the normal subjects. Morris et al.41 reported that the global longitudinal strain findings were significantly lower in the HFNEF group than in the normal group. Kraigher-Krainer et al.34 also noted lower longitudinal strain values for the HFNEF patients compared to the normal subjects in their investigation. In another study, Choi et al.37 observed that the mid and basal PSLSs in the patients with diastolic dysfunction grade I and II were significantly lower than those of the normal subjects. We observed that the HFNEF patients had significantly lower global, apical, mid, and basal PSLSs than the normal subjects. Likewise, Saha et al.In the current study, a comparison of the correlation between the PSLSs and the markers of diastolic dysfunction demonstrated significant positive correlations between the global, mid, and basal PSLSs and the septal e' and negative correlations with the E/e' ratio. There were also negative correlations between the IVRT and the global and mid PSLSs and negative correlations between the NYHA functional class and the basal and mid PSLSs. It should be noted that most of the patients in our study had grade I diastolic dysfunction, which could be an important cause for the negative correlation observed between the STE findings. 34 found no correlation between the longitudinal strain and the echocardiographic findings of diastolic function (e' or E/e'). In another study, Choi et al.37 observed that the mid and basal PSLSs had a significant correlation with the early diastolic mitral annular velocity, LAVI, e', and IVST, which had a close correlation with the diastolic function of the LV. In contrast to our findings, Kraigher-Krainer et al.The important finding in all these studies is that strain imaging using STE can determine some degree of systolic dysfunction despite a preserved LVEF detected by conventional echocardiography in HFNEF cases. The present study has some limitations. The study population is small and the percentage of the patients with higher grades of diastolic dysfunction is limited, with most cases having grade I diastolic dysfunction. Another weak point is that the patients’ drug history was not taken into consideration, which may have had some influence on the observed findings since many drug classes exert a significant impact on the systolic and diastolic functions of the LV, especially in ischemic and hypertensive patients. Enrolling more subjects with higher grades of diastolic dysfunction would be helpful. The results of the present study showed that the HFNEF patients on conventional echocardiography had different STE findings compared to the normal subjects. The longitudinal systolic function of the LV, which was measured by STE, was reduced in all the segments, which was indicative of some degree of subclinical systolic dysfunction in these patients, although the global LVEF was preserved.


Pulmonary hypertension (PH) is a severe disorder defined as a mean pulmonary artery pressure (mPAP) ≥ 25mmHg at right heart catheterization. Previous research indicates the mPAP of healthy volunteers is 14mmHg (±3.3mmHg) at rest, and patients with mPAP of 21 to 24mmHg are considered as borderline PH.This study investigates demographic, co-morbidities, invasive haemodynamics and cardiac magnetic resonance (CMR) imaging characteristics of patients with borderline PH.Consecutive patients who underwent CMR at 1.5T at a large volume pulmonary hypertension centre were identified. CMR imaging was performed on a whole body scanner GE HDx at 1.5T  with an 8 channel cardiac coil. Exclusion criteria were non-diagnostic imaging or right heart catheterisation (RHC) >24 hours from time of CMR. Biventricular volume, mass and function, pulmonary artery form and function, left atrial (LA) volume and inter-ventricular septal (IVS) angle were assessed. All demographic, invasive haemodynamic and CMR and haemodynamic variables were compared between patients with normal pulmonary artery pressure (mPAP ≤ 20mmHg) and a borderline group (20 ≤ mPAP ≤ 24 mmHg) using an independent samples t-test, and bilogistic regression.797 consecutive patients with suspected PH referred for CMR between April 2012 and March 2014 were identified. 83 patients had mPAP of less than 25, and 72 were included in this study having CMR within 24 hours of RHC. There was no significant difference between the age, sex distribution, body surface area, heart rate or cardiac output of the two groups. MRAP, PCWP and as expected PVR were significantly elevated in the borderline PH group. RVEDVI (p=0.025), IVS angle in systole (p=0.024) and LA volume (p=0.047) are all significantly higher in patients with borderline PH than those with mPAP<20mmHg. RV functional measurements were not elevated in patients with borderline PH. At bilogistic regression borderline PH was independently associated with elevated IVS angle. MPAP correlated significantly with RVEDVI (p=0.040) and IVS angle (p=0.046), and PVR correlated strongly with PA relative area change (p=0.001).Patients with borderline PH have higher indexed RV end-diastolic volume and greater septal deviation but preserved RV functional metrics when compared to patients with normal pulmonary artery pressure. Elevated PCWP and LA volume likely relates to the higher proportion of patients with underlying left heart disease in the borderline PH group. This is the first study to demonstrate changes in CMR cardiac morphology in patients with borderline pulmonary hypertension, these findings challenge the current definition of PH.AJS and JMW have received funding from the National Institute for Health Research (NIHR). JMW is also funded by the Engineering and Physical Sciences Research Council (EPSRC). DC receives funding from Bayer Schering.


Elevated high sensitivity cardiac troponin (cTnT) levels, LVEF, and the degree of myocardial replacement fibrosis (RF) have been shown to be significantly associated with cardiovascular outcomes. However, the relationship amongst them has yet to be studied. Cardiac magnetic resonance (CMR) has become the gold standard for viability imaging and accurately characterizing RF. Recently, a new technique has been employed to quantify diffuse myocardial fibrosis via assessment of myocardial extracellular volume (ECV). The current study sought to investigate the association between ECV, RF, LVEF, LV mass (LVM) and cTnT levels.We enrolled 192 patients who underwent cine CMR for assessment of LVM and LVEF, delay enhancement CMR (DE-CMR) for assessment of RF, and T1 mapping for assessment of diffuse interstitial fibrosis (ECV). Patients with hypertrophic cardiomyopathy were excluded. Serum samples collected at time of scan were assayed for cTnT levels. The extent of RF was determined by visual inspection. ECV was estimated from the concentration of extracellular contrast agent in the myocardium relative to the blood in the dynamic steady state. Care was taken to avoid measuring ECV in regions with RF detected on DE-CMR.2= 3.0). With the same statistical test, the following parameters showed a very significant relationship: RF , LVEF , LV end diastolic volume , LV mass .Mean age of enrolled patients was 62±14 years  with an average LVEF of 58±16%. RF in the LV myocardium was present in 84 patients (41%). The mean cTnT value was 27ng/L and the median  was 11 ng/L . Using Kruskal-Wallis test with TnT quartiles as cuttoffs, ECV showed a non-significant positive relationship with increased levels of Troponin (ΧThis study demonstrates a significant mean rank between RF, LVEF, and LVM with cTnT levels. It also shows a positive relationship between ECV and cTnT. However, a larger study is needed to elucidate the true relationship between ECV and cTnT.N/A.


Objectives and Background: Serum biomarkers have been proposed to reflect fibrosis of several human tissues, but their specific role in the detection of myocardial fibrosis has not been well-established. We studied the association between N-terminal propeptide of type I and III procollagen , galectin-3 , soluble ST2 (ST2), and myocardial fibrosis measured by late gadolinium enhanced cardiac magnetic resonance imaging (LGE CMR) and their relation to left ventricular diastolic filling properties measured by tissue Doppler echocardiography (E/e') in patients with stable coronary artery disease (CAD).Methods and Results: We determined the PINP, PIIINP, gal-3, and ST2 serum levels and performed LGE CMR and echocardiography on 63 patients with stable CAD without a history of prior myocardial infarction. Myocardial late gadolinium enhancement T1 relaxation time was defined as a specific marker of myocardial fibrosis. ST2, PINP, and PIIINP did not have a significant correlation with the post-LGE T1 relaxation time tertiles , but the lowest post-LGE T1 relaxation time tertile had significantly higher gal-3 values than the other two tertiles (p = 0.002 and 0.002) and higher E/é-values (p = 0.009) compared to the highest T1 relaxation time tertile. ST2 (p = 0.025 and 0.029), gal-3 (p = 0.003 and < 0.001) and PIIINP (p = 0.001 and 0.007) levels were also significantly higher in the highest E/é tertile, compared to the other two tertiles.Conclusions: Elevated serum levels of gal-3 reflect the degree of myocardial fibrosis assessed by LGE CMR. Gal-3, ST2, and PIIINP are also elevated in patients with impaired LV diastolic function, suggesting that these biomarkers are useful surrogates of structural and functional abnormality of the myocardium. Impaired left ventricular (LV) diastolic filling in subjects with preserved LV function has been associated with worse outcome among coronary artery disease (CAD) patients and patients with heart failure with preserved LV function .Sixty-three consecutive patients with angiographically documented stable CAD were prospectively recruited from the ARTEMIS-Oulu database . The exclusion criteria included rhythm other than sinus rhythm, reduced left ventricular ejection fraction, greater than mild valvular disease or previous valve surgery, clinical history of myocardial infarction , permanent pacemaker, significant renal disease, and claustrophobia. The study was approved by the local institutional ethics committee. Written informed consent was obtained from all the patients.The concentrations of gal-3 and ST2 were determined from serum samples. Serum was prepared by allowing the blood to clot for 30 min followed by centrifugation at 2000 ×g for 10 min. The serum was stored at -20°C until analyzed. ST2 levels were analyzed using a sandwich, enzyme-linked immunosorbent assay (ELISA)  with a sensitivity of 5.1 pg/mL. Gal-3 levels in serum were determined by an enzyme-linked immunosorbent assay (ELISA) from BG Medicine . The limit of detection (LoD) for the assay was 1.13 ng/mL  diameters and wall thickness. LV mass was derived from the ASE equation. LV ejection fraction was measured from the apical view by the biplane method from the 2- and 4-chamber views. Left ventricular diastolic filling was assessed by end-expiration ratio of peak early diastolic mitral velocity to tissue Doppler-derived peak early diastolic mitral annular velocity measured in the septal mitral annulus (E/é).CMR with the same 1.5T scanner  and 32-channel cardiac coil was performed on all the patients. Mid-ventricular short axis images were obtained. T1 was measured i.e., T1 mapping was performed with a ECG-triggered Look-Locker sequence . The images were acquired during breath holds. MRI images were analyzed off-line using an in-house MATLAB application . Regions of interest were segmented manually. The segments with visible LGE i.e., replacement fibrosis were excluded from the analysis. The possible position differences between images with different TI's were taken into account by segmenting each image separately and calculating ROI-wise T1 using the mean intensities of each image. T1 relaxation time was measured 10–15 min after contrast agent injection .p < 0.05 were considered statistically significant.All continuous data are presented as mean ± standard deviation. IBM® SPSS® Statistics v. 21  was used to analyze all statistics. Because of the skewed distribution of the variables, no correlation co-efficient were analyzed. For the same reason and due to the small study population we tested differences between tertiles divided according to LGE T1 relaxation time and E/é. Oneway analysis of variance was used followed by post hoc Bonferroni test in comparisons between the tertiles. All results with The mean T1 relaxation time was 365 (±43.9) ms, the mean value of E/é 9.77 (±4.92) and the concentration of ST2 was 20.37 (±6.62) ng/mL, of gal-3 12.13 (±4.93) ng/mL, of PINP 36.27 (±16.29) ng/mL, and that of PIIINP 3.81 μg/L (±1.13).Age, gender, BMI, diabetes, history of smoking, medication, blood pressure, left ventricular ejection fraction, LV mass, and LV mass index, Syntax score, renal function, HbA1c levels, serum cholesterol levels, high sensitive CRP, and BNP levels did not differ significantly between the T1 relaxation time tertiles . However, there was no significant difference in ST2 , PIIINP , or PINP  between the LGE T1 tertiles  , ST2 , and PIIINP  , or any metabolic risk variable.CMR has emerged as a non-invasive imaging method for focal fibrosis but it also allows the assessment of diffuse interstitial fibrosis. Isolated post-contrast T1 relaxation time has been shown to have a strong correlation with histologically confirmed myocardial fibrosis in small studies involving patients with heart failure (Iles et al., Previous studies using T1 relaxation time analysis to estimate the amount of fibrosis have excluded patients with stable uncomplicated CAD. In our study we were able to show that also in patients with CAD, isolated post-contrast T1 relaxation time correlates with diastolic filling properties, even when areas of visible LGE where excluded from analysis. In post hoc analysis we could show that the patients in the tertile with the highest amount of interstitial fibrosis in CMR had significantly higher E/é-values than the tertile with least fibrosis.Myocardial collagen tissue consists mostly of collagen type I and III. Procollagen N-terminal peptides, which can be measured from blood samples, have been used as surrogates of myocardial fibrosis. Nevertheless there has been some controversial evidence of PINP and PIIINP as biomarkers of collagen biosynthesis and as predictors of outcome of heart failure patients. Gal-3 and ST2 are more novel biomarkers of fibrosis. Gal-3 is an important mediator that induces fibroblasts to proliferate and deposit collagen, which contributes to myocardial fibrosis and remodeling. ST2 is a member of the interleukin receptor family and the gene expression of ST2 is upregulated in fibroblasts and cardiomyocytes subjected to mechanical stress. ST2 also prevents the IL-33 effects in reducing fibrosis and hypertrophy. GAL-3 (Lok et al., In this study we found a correlation between the LGE T1 relaxation time and GAL-3, but the other biomarkers of fibrosis did not have a significant correlation to myocardial fibrosis measured by LGE CMR. One of the reasons for these observations might be that ST2 concentrations are thought to raise as a result of increased myocardial strain whereas gal-3 can be seen as an initiator of collagen deposition and therefore as a better surrogate of incipient or existing interstitial fibrosis even without systolic or diastolic impairment.In the tertile analysis divided according to diastolic function i.e., E/é-values, we were able to show significant differences in the biomarker levels of Gal-3, ST2, and PIIINP between the most marked diastolic impairment tertile compared to the other two tertiles. These data provide evidence of the utility of these serum biomarkers in the rapid diagnosis of cardiac diastolic dysfunction, but these findings need confirmation in larger patient samples.The relatively small sample size of the study prevents definite conclusions regarding the lack of correlation between some of the biomarkers, such ST2 and PIIINP, and myocardial fibrosis measured by CMR. Measurement of relaxation time T1 by the LGE method may also have some limitations in terms of reliable quantification of diffuse myocardial fibrosis. Despite these limitations, we feel that the present findings provide some useful information about the value of serum biomarkers as predictors of both myocardial fibrosis and cardiac diastolic properties.In patients with uncomplicated CAD, serum biomarkers, especially gal-3, are associated with diffuse interstitial fibrosis imaged with cardiac MRI. Additionally, these biomarkers are associated with echocardiographically measured impaired LV diastolic filling properties. These results suggest that LV interstitial fibrosis plays an important role in impaired diastolic function among CAD patients and the level of cardiac diastolic dysfunction can be assessed with serum biomarkers of fibrosis.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The various prevalence of LVH and abnormal LV geometry have been reported in different populations. So far, only a few reports are available on the prevalence of LV geometric patterns in a large Chinese untreated hypertensive population.OR) and 95% confidence intervals (CI) of the risk factors of left ventricular hypertrophy.A total of 9,286 subjects (5167 men and 4119 women) completed the survey and 1641 untreated hypertensive patients  enrolled in the present study. The LV geometry was classified into four patterns: normal; abnormal,defined as concentric remodeling;concentric or eccentric hypertrophy based on the values of left ventricular mass index (LVMI) and relative wall thickness (RWT). Logistic regression model was applied to determine the odds ratio  than in men (14.2%) (P < 0.01). The prevalence of LV geometrical patterns was 34.9%, 11.1%, 9.1% for concentric remodeling, concentric and eccentric hypertrophy,respectively. After adjustment by using Logistic regression model, the risk factors for LVH and abnormal LV geometry were age, female, systolic blood pressure, and body mass index. And low high density lipoprotein maybe a positive factor.The prevalence of LVH and abnormal LV geometric patterns was higher in women than in men and increased with age. It is crucial to improve the awareness rate of hypertension and control the risk factors of CV complications in untreated hypertensive population. In hypertensive patients, an adaptive myocardial response to increased cardiac afterload results in left ventricular hypertrophy (LVH) . HyperteEchocardiography is more sensitive and specific than electrocardiography in the detection of LVH . ClassifThe various prevalence of LVH and abnormal LV geometry have been reported in different populations , 14. So This community-based cross-sectional study was conducted in the Rizhao City and Hong Xing Long County, in the northern region of China from 2009 to 2010. A multistage cluster sampling method was used. A total of 9,286 subjects (5167 men and 4119 women) completed the survey, yielding a response rate of 97.48%. Among them, 2984 hypertensive patients were identified and thoroughly examined. Hypertension was defined as diastolic blood pressure (DBP) of ≥90 mmHg, and/or systolic blood pressure (SBP) of ≥140 mmHg, physician diagnosis, or current medication for hypertension (as defined by WHO 1999). Untreated hypertension was defined as never receiving any antihypertensive treatment befor the study.Patients were excluded if they had hypertrophic cardiomyopathy, ischemic heart disease, congenital heart disease, or other organic heart disease including valvular disease. Patients with secondary hypertension, either suspected or established, were excluded as well.The study was governed under the most recent (2007–2008) version of the World Medical Association’s Declaration of Helsinki. The study protocol was reviewed and approved by the ethical committees of the Fuwai Hospital and local hospitals. Participation is voluntary; informed consent was obtained from each participant. All investigators were trained at the Cardiovascular Institute, Chinese Academy of Medical Sciences  and qualified for the clinical investigation.We identified eligible individuals according to their age and documents of residence and invited them to a community clinic by telephone. Each participant was interviewed and completed a standardized questionnaire that included a range of demographic factors, medical history, history of medications, and lifestyle.Anthropometric measurements of subjects who wore light clothing and were in bare feet were conducted by experienced research staff. Height was measured once to the nearest 0.1 cm, and weight was measured in the upright position to the nearest 0.1 kg.BP was measured by trained professionals with a standardized mercury sphygmomanometer, and one of three cuff sizes  was chosen on the basis of the circumference of the participant’s right arm. All participants were advised to avoid alcohol, cigarette smoking, coffee/tea, and exercise for at least 30 minutes before their BP measurement. Three BP readings were recorded at least 1 minute apart in the sitting position after at least 5-minute rest and averaged for further analysis.Transthoracic echocardiography was performed according to standard protocol  with M-mLeft ventricular mass (LVM) was calculated using the equation:3–LVIDD3] + 0.6, which yields values closely related (R = 0.90) to necropsy LV weight [LVM = 0.8 × 1.04 × [(IVSd + LVIDD + PWTd)V weight , where I2.7 and body surface area (BSA) to obtain left ventricular mass index (LVMIh2.7 and LVMIBSA). BSA was calculated by using the Du Bois formula [0.4253 × (height (cm))0.725.LVM was divided by height formula : 0.0 071h2.7 more than 49.2 g/m2.7 and 46.7 g/m2.7 for males and females, respectively [LV hypertrophy was diagnosed by using the criteria of the LVMIectively . Relativectively  was calcNormal geometry: LVMI was normal and RWT was < 0.43;Concentric hypertrophy: LVMI was increased and RWT was ≥ 0.43;Eccentric hypertrophy: LVMI was increased and RWT was < 0.43;Concentric remodeling: LVMI was normal and RWT was ≥ 0.43.The LV geometry was classified into four patterns based on LVMI and RWT  values:NData are reported as mean ± standard deviation (SD) for continuous variables and as frequency for categorical variables. Differences in continuous variables between two groups were compared with a Student t-test and differences in categorical variables were measured with a chi-square test. Differences between multiple groups were performed by analysis of variance (ANOVA). Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Potential confounders were adjusted. A 2-tailed value of P < 0.05 was considered significant. Analyses were performed with SPSS 11.0  for Windows . The authors had full access to the data and take full responsibility for its integrity.A total of 1641 untreated hypertensive patients  with integrated clinical and echocardiographic data enrolled in the present study Table .Table 12.7 , and by BSA . Moreover, RWT was higher in women, but this difference did not attain statistical significance.LVIDD as well as PWTd were larger in men than in women, so did LV mass . The trend was opposite after indexed by heightOf 1641 untreated hypertensive patients, 20.2% (n = 332) was found to be LVH, 14.2% in men and 30.8% in women respectively. Sex-specific prevalence of LVH increased with ageing , eccentric hypertrophy (9.1%), concentric remodeling 34.9%) and normal geometric (44.9%). Concentric remodeling was the most common abnormal LV geometric pattern in men (35.9%), also, in women (33.0%). The LV geometric abnormality increased steadily with ageing (from 43.8% to 71.0%)  disease is extremely crucial. To effectively reducing of CV complications, it is of utmost importance that not only weight and BP control but also improving the awareness rate of hypertension in China and the risk factors of CV complications.


This study investigated the safety profile and potential "therapeutic" effect of intravenous ultrasmall superparamagnetic iron-oxide (USPIO)-based iron administration regarding infarct healing in patients with ST-elevation myocardial infarction (STEMI).Seventeen study patients  and 22 matched controls  both with primary reperfused STEMI underwent multi-parametric CMR studies in the first week and three months after acute MI. Only IRON patients received a single intravenous bolus of 510 mg elemental iron as ferumoxytol (FerahemeTM) within four days following acute MI.Three months after study inclusion, all patients were alive and there were no adverse cardiac events. Significant improvement in left ventricular (LV) ejection fraction  as well as shrinkage of infarct size were seen in both groups at follow-up. There was a more pronounced decrease in infarct size in the IRON group  in addition to a significant decrease in both endocardial extent and prevalence of transmural infarctions in IRON but not in CONTROL patients. A significant decrease in LV end systolic volume was only seen in the IRON group .Intravenous iron administration in acute STEMI patients is associated with both improved infarct healing and beneficial global left ventricular remodelling (compared to matched controls). These findings together with the good safety profile make USPIO-based iron administration a promising future candidate as a "diagnostic" and "therapeutic" adjunctive solution in acute MI management.This work was financially supported by a grant from the German Federal Ministry of Education and Research .


Fifty years ago, the focus on the Val30Met type of the disease, in which neurologic manifestations predominate, led to the widespread notion that hereditary transthyretin-related amyloidosis (ATTR) was essentially a neurologic disease. It is now clear that ATTR is extremely heterogeneous on both genotypic and phenotypic grounds. The clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to strictly cardiac manifestations. This heterogeneity is linked to several factors including specific transthyretin mutations, geographic distribution and endemic vs. non-endemic aggregation type. The existence of exclusively or predominantly cardiac phenotypes makes the recognition of the disease very challenging since it can mimic other more common causes of left ventricular “hypertrophy”. Assessment of such patients should include an active search for possible red flags that can indicate the correct final diagnosis. More in general the clinician must be aware that:• Cardiac amyloidosis (CA) should be suspected in any patient with heart failure, unexplained increased LV wall thickness and non-increased end systolic left ventricular volume• In a patient with an initial diagnosis of hypertrophic cardiomyopathy (HCM), look for the infiltrative phenotype hidden beneath the hypertrophic one!• A distinctive sign of CA is the abnormal ratio between left ventricular thickness and QRS voltages rather than low QRS voltages, alone. The absence of low QRS voltages doesn’t rule out a CA if the context is otherwise fitting and up to 20% of subjects with CA can have electrocardiographic evidence of left ventricular hypertrophy.• In an elderly man with unexplained concentric left ventricular hypertrophy, especially in the absence of hypertension, always consider the possibility of wtTTR CA!• Amyloidotic cardiomyopathy in an elderly patient with monoclonal gammopathy is not necessarily related to AL: consider the possibility of wTTR + MGUS• Longitudinal LV function can be severely depressed despite a normal LVEF and the myocardial contraction fraction is often low suggesting reduced global myocardial shortening.• Myocardial deformation is reduced in amyloidotic cardiomiopathy but the apex is generally spared• In CA, Gadolinium distribution at MRI is heterogeneous: subendocardial late gadolinium enhancement (LGE) is not the only diagnostic pattern and the absence of LGE does not exclude CA.• Bilateral carpal tunnel syndrome in a man with HCM-like phenotype on echo is highly suggestive of TTR-related CAThe natural history of ATTR is only partially known, due to the rarity of the disease and its high genotypic heterogeneity. Patients with ATTR cardiomyopathy have a much more indolent course than those with AL etiology. Progression of neurological disease and heart failure are the leading causes of death. As in AL amyloidosis, in ATTR the presence of cardiac involvement is an incremental risk factor for overall and cardiovascular events. Consequently, non-Val30Met mutations, in which cardiac involvement is more frequent and severe, appear to be associated with a particularly poor prognosis, even after successful OLT . Very little is known about the underlying cause and the incidence of sudden death, which has been reported to be associated with the occurrence of advanced atrioventricular blocks, ventricular tachycardia/fibrillation, or, probably more frequently, electromechanical dissociation.