L , ECVc , and ECVnL (derived from myocardium T1* and blood T1*), and to explore the diagnostic accuracy of these factors for discriminating between controls and patients. The Modified Look-Locker Inversion Recovery sequence was performed in 42 subjects to generate both T1 and T1* maps. Native and post-contrast T1 values for myocardium and blood pool were obtained, and ECVL, ECVc, and ECVnL were then calculated. The global ECVc values were smaller than the ECVL values  and larger than the ECVnL values  in all participants. The ECVc led to a 4–6% increase in the AUC value and a 24–32% reduction in the sample size to differentiate between the controls and other patients when compared with the ECVL. Blood T1* correction can improve the precision of blood T1 values and can consequently increase the accuracy of the extracellular volume fraction measurement. The ECVc can be used to improve diagnostic accuracy and reduce the sample size required for a clinical study.The goals were to compare the differences between ECV The extracellular volume fraction (ECV), derived from native and post-contrast T1 mapping, reflects the size of the extracellular space in the myocardium and can be used as an important diagnostic biomarker of disease2, as well as for observation of disease progression3 and prognosis5. T1 mapping, together with the ECV, introduced a new frontier in radiology and cardiology, enabling the quantification of important tissue properties of both local and global myocardium, independent of function6.Cardiac T1 mapping allows the quantitative measurement of myocardial and blood longitudinal relaxation T17, saturation pulse prepared heart-rate-independent inversion recovery (SAPPHIRE)8, and a widely used ECG-triggered method 10. Although the effects of T2 sensitivity, magnetization transfer, and inversion efficiency lead to an underestimation of myocardial T1 values11, the higher signal-to-noise ratio (SNR), which is due to IR preparation and a large number of images, permits MOLLI to more precisely measure T1 values than SASHA. Compared with SASHA and its modified version (SAPPHIRE), MOLLI and the shortened MOLLI (ShMOLLI)12 yield higher precision and lower accuracy13. Modifications of MOLLI sampling schemes (such as 5(3)3 and 4(1)3(1)2 for native and post-contrast T1 mapping14) have been proposed to reduce breath-hold duration and reduce heart rate sensitivity, which incrementally increase the precision of T1 measurements. To summarize, MOLLI has been widely accepted and used for the precise measurement of myocardial T1.T1 mapping can be performed utilizing several techniques, such as Saturation recovery Single-sHot Acquisition (SASHA)15. In previous studies, the ECV was obtained by manually drawing regions of interest (ROIs) on T1 maps. The application of the motion correction (MOCO) technique can eliminate the effect of respiratory and heart motion to allow the calculation of a more accurate myocardial T1 value and permit the generation of fully automated calculated pixel-wise ECV maps17. However, due to the inflow effect of the blood pool, the T1 values of the blood pool and the myocardium differ in the measurement. More specifically, for the measurement of blood T1, because there is inflow or replacement of fresh blood with each heartbeat, the Look-Locker (LL) correction should be eliminated to provide a more realistic estimation of the blood T1.Calculation of the ECV is based on the measurement of both native and post-contrast T1 of the myocardium and the blood pool and is calibrated using the hematocrit (HCT) value18, Zhao et al. described the LV ECV calculated from myocardial T1 and blood T1* in patients with atrial fibrillation but did not compare this measurement method with others. Nickander et al. reported that blood T1 and T1* correction reduced the variability in native myocardial T1 values19. They did not calculate ECV, but their results placed much importance on the effects of blood values in the myocardium. Considered together, blood T1* values should be prioritized to obtain more accurate measurements of the ECV.ECV measurements based on the blood T1 values from LL-generated maps may lead to misestimation of their true values, which will likely limit the clinical implications of ECV in disease diagnosis, observation of disease progression, and prognosis. Theoretically, T1* maps, based on image registration without the LL correction, can therefore be used for more accurate measurement of blood T1 values, and thus, a more accurate ECV.In a previous studyTherefore, we hypothesized the following: 1) There may be differences in blood T1 values obtained from T1 and T1* mapping; 2) ECV can be more accurately calculated from myocardial T1 and blood T1*; and 3) The more precise ECV can improve the accuracy of disease diagnosis and reduce the sample size needed to identify the difference in the ECV between the controls and patients.The demographic and left ventricular functional parameters of all the participants are shown in Table Both the native and post-contrast T1 values of the sixteen segments of the LV myocardium and blood pools in the three slices are presented in Fig. The sixteen segments and the ECVL  and ECVc  of the global LV myocardium in all the participants are shown in Fig. The ECVc and ECVnL (derived from myocardium T1* and blood T1*)of the global LV myocardium and sixteen segments in all the participants are shown in Fig. Regarding the comparison between the ECVL and ECVnL, all the data are summarized in Supplementary Table The mean and standard deviation (SD) of the ECVL and ECVc are summarized in Table To differentiate between the controls and T2DM without HT, the AUC values for the ECVL and ECVc were 0.677 and 0.707, respectively, and the difference between the two AUC values was statistically significant  was 0.00064 ± 0.00004 ms-1 and mean blood R1* (1/T1*) was 0.00061 ± 0.00005 ms-1 at 1.5 T CMR. Although the differences were not compared, those data showed a trend suggesting that the blood T1* value was larger than the blood T1 value. In MOLLI, due to the recurrent signal readout after a single inversion, the magnetization returns to steady state more rapidly than in free relaxation, and this is addressed by the Look-Locker correction. In this study, a true Look-Locker experiment with MOLLI was not performed, as there were long episodes of free relaxation disturbed by a few readout trains. Nevertheless, there was an “enforced” decay that could have been addressed by correction, as proposed for the original Look-Locker method. As the blood did not see the repeated readout pulse trains, it should not require this type of correction. Therefore, blood T1 value measurements are not sufficiently accurate on the T1 maps generated by the LL technique or its derived MOLLI prototype. T1*, as one of the three parameters in a three-parameter model to obtain T1 maps, is initialized as the linearly interpolated zero-crossing time generated from the “polarity” corrected signal intensity curve20. The pixel-wise T1* parametric maps, which have not undergone the LL correction, should be used for more accurate measurements of the blood T1 values18. Therefore, there is theoretically a significant difference in the blood T1 obtained from the T1 and T1* maps. Of note, our in vivo study results corroborate this theory. In future studies, T1* maps should be used for more accurately measuring the blood T1.We found that the blood T1* values were higher compared to the blood T1 values for the native T1 acquisitions and were mirrored by inverse effects in post-contrast acquisition in all the participants. Our results are consistent with those in a study conducted by Nickander22 indicated that the inversion factor can be applied to correct T1 (T1corrected = T1/ inversion factor) to improve MOLLI T1 estimation accuracy. Although it can be estimated by simulating the adiabatic inversion pulse21 for a certain tissue, the actual in vivo inversion factor can be significantly different from the theoretical value. Further study23 showed that the actual in vivo inversion factor may be dependent on the MRI hardware and may need to be measured in vivo for each MRI scanner. Our present study focused on T1*, so the influence of inversion factor on T1 estimation was not explored. In view of its importance, inversion factor shall be attached to more attention in the future studies.The inversion efficiency is another important factor that can influence the accuracy of MOLLI-based T1 estimation to a certain extent. Recent studies24, the inversion group (IG) fit25 and the Instantaneous Signal Loss simulation (InSiL) T1 estimation23. Shao et al.22 compared four T1 estimation algorithms for MOLLI with inversion factor correction and indicated that BLESSPC has superior accuracy and is the least sensitive to the flip angle, the heart rate and the acquisition scheme variations than the original fit, IG fit and InSiL, but the original fit has superior precision than the other three methods for T1 > 400 ms. Due to the absence of in vivo inversion factor, diagnostic accuracy for ECV of the “no correction” T1* approach was not compared with BLESSPC, IG fit and InSiL in the present study. It is interesting to see which method can provide better diagnostic accuracy for ECV in the future.Besides the original three-parameter exponential curve fitting T1 estimation algorithm, several T1 estimation algorithms have recently been proposed for the MOLLI sequence, including the Bloch equation simulation with slice profile correction (BLESSPC) T1 estimation26, injection scheme27, or time point post-contrast image acquisition28, among other factors. The ECV is not sensitive to these effects, accounting for the blood T1 values and variation in the HCT1. Therefore, besides the myocardial issue, blood T1 values should also be seriously considered. We found that for the native T1 value of blood, T1* was higher than T1; for the post-contrast T1 value of blood, T1* was lower than T1. Thus, the ECVc is consequently lower than the ECVL.ECV was introduced to overcome the limitations of post-contrast T1 values in assessing diffuse abnormalities, one of which is the type and dose of contrast agent30 has demonstrated that the synthetic ECV strongly correlates with the conventionally calculated ECV  and can be an alternative to it without blood sampling. However, Raucci et al.31 reported that although it strongly correlates with conventionally calculated ECV (0.80 < R2 < 0.90 at 1.5 T MR), synthetic ECV can result in miscategorization of individual patients, especially in pediatric and young adult patients. Although the clinical value of synthetic ECV is still on the line, the accuracy of blood T1 values is being embraced as a very important factor in ECV calculation. The present study did not focus on estimating the synthetic ECV, but more attention will be attached to it in our future study.Recently, much effort has been put to explore the feasibility of the synthetic ECV which derived from the blood T1 value and to validate its clinical value. Some studies32. In Wong’s study5, which comprised 231 patients with diabetes and 945 participants without diabetes, the median ECV of the participants with and without diabetes were 0.302 and 0.281, respectively. The difference between the two groups was about 0.021 (7%). Although the difference in the ECV of the two groups was significant, there was a marked overlap of the ECV between the two groups. Nevertheless, the ECV was determined to be an important prognostic index for predicting mortality and/or incident hospitalization for heart failure in diabetes. Therefore, even small differences between the values calculated from unstandardized sequences or post-processing procedures may limit the clinical utility of the ECV. Notably, the accuracy and precision of the ECV measurements are thus far unclear because of the difficulty in obtaining in vivo reference values for ECV measurements. Previous studies have demonstrated that different reference values for the ECV were acquired in studies with different field strengths and sequences33. Regarding our results in the present study, there was a minor but statistically significant difference between the ECVL and ECVc measurements, which indicated an incremental role of blood T1 measurements accuracy in ECV values. Further studies are needed to confirm the reference values for the ECVc measurements in the normal controls and patients.Our results highlight the complexity of performing ECV measurements, but they also stress the importance of post-processing methods aimed at increasing accuracy and enhancing clinical diagnostic use. While some diseases such as MI or CAL show a significant increase in the ECV, more subtle differences are obtained in conditions with less myocardial damage, such as T2DM, HT, or HCM without LGEOur results indicate that the ECVc led to an increase in diagnostic accuracy compared with ECVL, which may be attributed to the ECVc-associated larger mean difference between the groups and smaller SD in each group. This might have significant clinical implications for diseases that are characterized by an alteration in the ECV, such as amyloidosis, cardiomyopathies, HT, and/or T2DM-related cardiac diseases. With increased diagnostic accuracy, these diseases could potentially be detected earlier when only subtle differences in the ECV may be present. In addition, the 4–6% increase in diagnostic accuracy means that 4–6% subjects can be clearly diagnosed and treated in time, which is very important for patients.This study has several limitations. First, the sample size of this study was relatively small, more specifically the proportion of patients with serious myocardial damage . Because the complexity of enrolled patients can test the robustness and efficiency of the ECV calculation method, more patients should be included in future studies. Second, considering that the ECVc measurements were derived from myocardium T1 maps and blood T1* maps, T1* maps cannot be generated using cvi42. Thus, although the ECV values can be directly obtained from ECV maps, ECVc values cannot be directly obtained from T1* maps. In this study, we acquired the T1 and T1* values of the myocardium and blood on native and post-contrast T1 and T1* maps and subsequently calculated the ECVL and ECVc. Although this was time-consuming and relatively complicated, the process can reduce errors substantially. In the future, the importance of ECVc values should be further investigated to directly generate T1* maps.Blood native T1* is longer than native T1 and post-contrast T1* is shorter than post-contrast T1. The ECVc is smaller than the ECVL and larger than the ECVnL. In general, blood T1* correction can improve the accuracy of blood T1 values and can consequently increase the accuracy of extracellular volume fraction measurement. The ECVc can be used to improve diagnostic accuracy and reduce the sample size required for clinical study.All the recruited participants were scanned with cardiac magnetic resonance (CMR) between January and March 2017, in our hospital. Three patients who did not receive gadolinium injections were excluded, and therefore a total of 42 participants were included, comprising nineteen patients with type 2 diabetes mellitus (T2DMs) without hypertension (HT), five with T2DMs with HT, two patients with HT, four with hypertrophic cardiomyopathy (HCM), and one each with cardiac amyloidosis (CAL), chronic myocardial infarction (MI), left ventricular noncompaction (LVNC), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Seven healthy volunteers, who were not referred as patients for normal manifestation on clinical CMR and without risk factors or evidence of cardiovascular disease, were also recruited. The study was approved by the Southwest Hospital Ethics Committee  and was performed in accordance with the Declaration of Helsink and all the participants provided written informed consent.All CMR was performed using a 3 T MAGNETOM Trio a Tim System  with a 6-channel body matrix coil plus 2 rows of the spine array coil. A prototype for patient-specific, localized shimming in the heart was used to improve field uniformity. Blood samples were collected about 30 minutes before scanning and were immediately sent to the Department of Clinical Laboratory to obtain the HCT.L , ECVc , and ECVnL (derived from non-LL-corrected myocardium T1* and blood T1*); calculated the sample size using the ECVL and ECVc for identifying differences in the ECV between the controls and patients; and compared the differences in the diagnostic accuracy of the ECVL and ECVc to discriminate between the controls and patients.We compared the differences in T1 values of the myocardium and blood acquired from both T1 and T1* mapping; compared the differences in ECVElectrographic-gated, breath-hold steady-state free-precession (SSFP) short-axis retro-gated cine images covering the entire left ventricle (LV) were taken at 6 mm slice thickness, 1.5 mm slice gap, field of view (FOV) 325 × 400 mm², matrix 179 × 256, repetition time (TR) 59.22 ms, and echo time (TE) 1.45 ms, and at 25 phases per cardiac cycle. All the cine images were analyzed offline on a workstation with Argus software . Endo- and epicardial contours were manually traced to measure the LV cavity at end-diastole and end-systole. The papillary muscles were included in the LV volume. The LV end-diastolic volume index (EDVi), end-systolic volume index (ESVi), stroke volume index (SVi), ejection fraction (EF), cardiac index (CI), and myocardial mass index (MMi) were obtained.Segmented LGE images covering the entire LV were performed using the Phase Sensitive Inversion Recovery (PSIR) sequence  approximately 10 min after a bolus administration of 0.2 mmol/kg gadodiamide .A breath-hold ECG-gated, MOLLI prototype with a 5(3)3 and 4(1)3(1)2 sampling pattern was performed for native and post-contrast T1 mapping, respectively, with FOV 400 × 300 mm², matrix 256 × 166, and 6 mm thickness. Basal, mid-ventricular, and apical short-axis images were acquired before and approximately 15 min after the administration of gadodiamide. T1 maps were generated inline from the MOLLI images with MOCO and T1* maps were generated from the images without the Look-Locker correction. All the T1 and T1* maps were transferred to the cvi42 software  for offline analysis.The LV endo- and epicardial borders were manually delineated with attention paid to avoiding partial-volume effects from the blood pool and epicardial fat. Sixteen myocardial segments  and global native and post-contrast T1 and T1* values were obtained. The regions of interest (ROIs) were manually drawn with care in the LV cavity to avoid the papillary muscles and myocardium. Global and three-slices blood native and post-contrast T1 and T1* values were measured Fig. . The glo34. The relationships between bivariates were analyzed using Pearson’s method. For inter-observer reproducibility, images of ten randomly selected participants were independently analyzed by two radiologists . For intra-observer reproducibility, one radiologist (Shang Y) reanalyzed images of ten participants after one month. The intra- and inter-observer variabilities for the ECV were visualized as Bland-Altman plots and analyzed by determining the intra-class correlation coefficient (ICC). The values for the area under the receiver operating characteristic (ROC) curves (AUC) were calculated to compare the capacity of the ECVL and ECVc to discriminate between the controls and others. The sample size was also calculated. Statistical tests were two-tailed, and the statistical significance was defined as P < 0.05. Statistical analysis was performed using SPSS , GraphPad Prism , and MedCalc .The data were expressed as mean and standard deviation. Differences between the means for all the participants were compared using the paired t-test and the Bland-Altman methodThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.Supplementary information


Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR.n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods.AR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (p < 0.05). These effects concurred with decreases in indices of LV preload  as well in the aortic pre-ejection period / left ventricular ejection time ratio . The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters.OM increased indices of global cardiac function , and increased systolic performance  (all The cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR. Aortic regurgitation (AR) is a valvular disease that affects men more than women, and whose incidence increases with age . Severe In chronic AR, indices of systolic function such as left ventricular ejection fraction (LVEF) are better prognostic indicators than indices of cardiac overload . MoreoveIn two different canine models of pacing-induced systolic heart failure  or to AR creation (n = 20). Rats that survived the acute phase (n = 12) were randomized into an OM group (n = 7) or a placebo group (n = 5). The 4 rats (two in the OM group and two in the placebo group) who underwent a sham operation served as controls for the effect of time and measurement repetition on the parameters investigated in the study.Experiments were approved by the Institutional Animal Care and Use Committee of the Free University of Brussels. Studies were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health . Twenty-four male adult Wistar rats (401 ± 90 g body weight) were randomized to a sham intervention 3]} + 0.6 g. Aortic diameter was measured from the right long axis parasternal view. Aortic flow was measured from the left apical view to calculate forward stroke volume (SV) and cardiac output and to measure pre-ejection period , LV ejection time , and inter-beat interval (RR). Systolic time was determined as PEP + LVET (ms). Diastolic time (ms) consists in RR interval (ms) - systolic time (ms). PEP/LVET ratio was also calculated. PEP/LVET is a more useful index of overall LV performance [Transthoracic 2D, M-mode and Doppler echocardiography were performed under general anesthesia with an ultrasound unit  equipped with a 10Mhz surgical transducer. Rats were placed in the right and left lateral recumbent positions and their electrocardiogram was monitored via limb leads throughout the procedure. All measurements were made according to the recommendations of the American Society of Echocardiography currently applied to humans . Standarformance . This raformance . SeveritDoppler-echocardiography was performed before AR creation, during surgery to confirm the presence and the severity of AR, and 2 months thereafter, both before and after OM (1.2 mg/kg/hour) or placebo (NaCl 0.9%) infusion for 30 min, by means of a femoral vein perfusion. All animals received equal volumes (12 ml/kg) of placebo or OM. This achieved plasma concentration of nearly 400 ng of OM/ml in a previous study . Dopplerp value less than 0.05. .Results are expressed as means ± SD. A 2-factor ANOVA for repeated measures followed by post-hoc Bonferroni corrections for multiple comparisons was used to assess the effects of OM versus placebo, and any interaction between them, after 2 months of AR on the 16 animals. All other statistical analysis consisted of paired-t tests between variables. Significance was set at a n = 12, all p < 0.05, paired t tests). Load dependent indices of LV systolic function (FS and EF) were unchanged but LVESD were increased. SV and cardiac output were decreased . As expected, no AR was detected in sham operated rats (n = 4) with no modifications of LV function or dimension in the placebo group while only FS and EF increased after injection of OM   was achieved at 3.67 ± 0.44, and echocardiographic signs of volume overload and eccentric hypertrophy were present with increased left atrial diameter, LVEDD, LVEDV and LV mass .Before infusion, there was no difference in echocardiographic results between the 2 groups (placebo versus OM). NaCl infusion affected none of the echocardiographic parameters of global and systolic cardiac function neither the indices of LV preload . These effects concurred with decreases in measures of LV preload , and a decreased PEP/LVET ratio . OM did not affect the severity score of the AR jet.OM increased indices of global cardiac function , decreased HR and increased systolic performance    of sham animals, OM increase EF and FS in sham OM group (n = 2).The central hemodynamic feature of chronic AR is a combined volume and pressure overload of the LV , 23. TheIn our study OM decreased volume overload induced by AR during the whole cardiac cycle, by lowering LVEDD. Moreover, by decreasing LVEDD and LVESD and increasing SWTs, OM decreased wall stress in AR. This is of importance, since an increased wall stress may lead to overt LV systolic dysfunction . ImproviIn our study OM decreased the PEP/LVET ratio, a reliable index of LV performance. Acute reduction in afterload in patients with congestive heart failure improves LV systolic performance and decreases the PEP/LVET ratio, while an increase in preload will shorten PEP, prolong LVET and decrease PEP/LVET . We founIn contrast to our initial hypothesis, we found that OM did not affect the severity of the aortic leakage since the diastolic time-span remained unchanged, as a result of a reduction in HR. In mitigation, however, excessive prolongation the duration of systole might compromise myocardial blood flow, and thereby aggravate ischemia; even if studies with OM in patients with angina and ischemic cardiomyopathy seem reassuring in this regard . This stKetamine is a dissociative anesthetic agent that has cardiovascular effect resembling sympathetic nervous system stimulation,increase heart rate and cardiac output . MedetomDobutamine infusion, in patients with chronic aortic regurgitation and depressed LV ejection fraction, decreased LVEDD, LVEDV, LVESD and LVESV, while FS and EF improved . In consCurrently available inotropes Dobutamin, Dopamin, Milrinone and Levosimendan have demonstrated pro-arrhythmic effects linked to increased mortality that can limit their clinical utility . Most inIn our study we administrated 1.2 mg/kg/h of OM during 30 min. This was expected to raise plasma concentrations of OM to nearly 400 ng/ml . In ratsThe tested animal group was small because many rats did not recover from the acute AR procedure. Another striking limitation of our study resides in the fact that we could not achieve ventricular blood pressure measurement during the study. As such, our assessment of ventricular loading conditions remains incomplete. Several studies suggest however that systemic blood pressure is not affected at the OM concentrations we achieved in our study , 37. OurAnother limitation of the study, the possible fistula with left atrium created during aortic valve leaflets puncture, this fistula can explain the decrease of stroke volume and cardiac output after the creation of the aortic regurgitation.The present placebo-controlled study shows improvements in cardiac function after infusion of OM. Our investigations demonstrate these effects for the first time in the rat-model with chronic severe AR. We observed a decrease in volume overload and an increase in cardiac output and wall thickness. Moreover OM enhanced EF and FS, while coincidently lowering the HR and wall stress. On the other hand, OM did not affect the duration of diastole and the severity of AR.


Adaptation of CMR in clinical setting among non-experts is limited due to the time-consuming and labor-intensive nature of both CMR data acquisition and post-processing. In many clinical instances, e.g., myocardial viability (MV), it is time efficient to acquire LV cine SSFP images after contrast administration. In this study we clinically validate an ultrafast algorithm that computes LVEF as an extension of the data acquisition by using temporal intensity variation (TIV) in cine SSFP images acquired with or without contrast.All imaging for this prospective, IRB approved study, was performed on a 1.5T commercial MR scanner . Study consisted of 16 volunteers yrs) and 44 patients yrs). In 7/28 MV patients, cine images were acquired within 10 min after administration of 0.2 mmol/kg of Gd-DTPA. CMR expert drawn myocardial contours served as the reference. The LVEF computation program written in MATLAB automatically runs in the background as an extension of the acquisition protocol on the scanner console  and does not affect the subsequent data acquisition. The key algorithmic steps are pictorially represented in Fig. The total computation time for LV stack was < 2.5 s. The algorithm successfully delineated the endocardial boundary with clinically acceptable accuracy in 1047 (93%) of the 1131 SA slices. The algorithm-derived contours for clinically unacceptable slices, which had the LV outflow tract and an extremely small (< 2 cc) LV section, were retraced manually. The bias and standard deviation of the difference for the apical, mid-cavity, and basal regions (Table Compared to previously reported in-line LV segmentation algorithms , 3, the


There was also no significant difference between MI size3-slices and MI sizefull LV (P = 0.93) with an excellent correlation between the two (R2 0.92) but a small bias of 0.5% and a wide limit of agreement of ±7.7%. Although MSI was similar between the 2 approaches, MSI3-slices performed poorly when MSI was <0.50. Furthermore, using AAR3-slices and MI sizefull LV resulted in ‘negative’ MSI in 7/48 patients. Full LV coverage T1 and T2 mapping are more accurate than a 3-slice approach for delineating the AAR, especially in those with MSI < 0.50 and we would advocate full LV coverage in future studies.T2-weighted cardiovascular magnetic resonance (CMR) using a 3-slice approach has been shown to accurately quantify the edema-based area-at-risk (AAR) in ST-segment elevation myocardial infarction (STEMI). We aimed to compare the performance of a 3-slice approach to full left ventricular (LV) coverage for the AAR by T1 and T2 mapping and MI size. Forty-eight STEMI patients were prospectively recruited and underwent a CMR at 4 ± 2 days. There was no difference between the AAR To assess MSI, knowledge of both the MI size and the area-at-risk (AAR) are required and can be calculated using the formula MSI = 1 − (MI/AAR). Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for quantifying MI size4, and it can also provide information on the edema-based AAR7. T2-weighted short tau inversion recovery (STIR) imaging in the first week following primary percutaneous coronary intervention (PPCI) has been used to delineate the AAR in reperfused STEMI patients, although its robustness has recently been questioned8. T2-mapping10 has emerged as a more robust technique for the AAR and native T1 mapping has also been shown to perform well against T2 mapping in a canine model of MI11, and in clinical patients at 3.0 T5.Myocardial salvage index (MSI) is considered a more accurate measure to assess the cardioprotective efficacy of novel therapies aiming to reduce myocardial infarct (MI) size in reperfused ST-segment elevation myocardial infarction (STEMI) patients12. The main aim of this study was to assess whether the 3-slice approach will also perform as well as full LV coverage, using T1 and T2 mapping to delineate the AAR. Secondly, we aimed to assess the impact of a 3-slice approach for the AAR and MI size on MSI.The accurate quantification of the AAR conventionally requires full left ventricular (LV) coverage. Recently, a 3-slice approach has been proposed for T2-weighted STIR imaging, with the obvious benefit of shorter scan and analysis timeBaseline clinical characteristics of the 48 patients are listed in Table full LV was not significantly different between the 2 mapping techniques  with an excellent correlation and agreement on Bland-Altman analysis .In the 30 patients with full LV coverage for T1 and T2 maps, The AARfull LV and AAR3-slices by T1 mapping  and there was a good correlation between the two (R2 0.85). However, there was a small bias of 1.7% LV and the limits of agreement were quite wide at ±9.4% LV.There was no difference between the AARfull LV and AAR3-slices  and there was a good correlation between the two (R2 0.75)  Fig. . However75) Fig. .Figure 13-slices and MI sizefull LV (P = 0.93) with a very good correlation between the two (R2 0.92) as shown in Fig. There was no significant difference between MI sizeMSI was calculated using the formula MSI = 1 − (MI size/AAR), where MI size was quantified using full LV short axis coverage and AAR was quantified by using full LV coverage or 3 slices by T2 mapping and T1 mapping.full LV and 0.34 (0.14–0.54) for T2 AAR3-slices, P = 0.050 , Fig. 2 of the remaining 41 patients for MSI3-slices versus MSIfull LV was 0.90, with a bias of 0 but limits of agreement of ±0.15, which is still wide for clinical application.For T2 mapping n = 48), the MSI was 0.35 (0.18–0.55) for T2 AAR8, the MS2 was 0.94 for MSI > 0.50 and was 0.43 for MSI < 0.50 (3 out of 30 patients resulted in a negative MSI using the 3-slice strategy).The same pattern was observed for T1 mapping (n = 30). The Rfull LV and the MSI3-slices (P = 0.11) as shown in the box and whisker plots in Fig. 2 0.79) and Bland-Altman analysis showed a small bias of 0.03 but a wide limit of agreement of ±0.24. Of note, none of the MSI obtained were negative. Visually, there was a wider dispersion between the points and the correlation line for those with MSI < 0.50 than those with MSI > 0.50 in Fig. 2 was 0.28 for those with MSI < 0.50 and 0.65 for those with MSI > 0.50.When MSI was calculated using 3 slices for both MI size and T2 AAR, there was no significant difference between MSIet al.12, this approach underestimated the AAR in 7/48 patients for T2 mapping and 3/30 patients for T1 mapping and resulted in a negative MSI, which is not plausible in practice and would impact on mean MSI in a cardioprotection study. In the clinical setting, it is difficult to know whether a patient would have MSI more than or less than 0.50 prior to acquiring the images and the analysis the MI size and AAR data and therefore full LV acquisition of T1 or T2 maps is recommended when the edema-based AAR needs to be assessed.These results suggest that although a 3-slice approach had a good correlation with the full LV approach both for the edema-based AAR and MI size, the limits of agreements were quite wide for clinical application and the derived MSI was inadequate, especially when the MSI was <0.50. Furthermore, when MSI was calculated using whole LV coverage for MI size and the 3 slices for AAR as previously done by Hamshere 12. However, T2-weighted imaging has several limitations including the subjective interpretation of the images, variations in regional myocardial intensity due to changes in sensitivity of surface coils, blood-pooling artefacts at the subendocardial border, its relatively low contrast-to-noise ratio between normal and abnormal myocardium, and its susceptibility to breathing and motion artefacts14. T1 and T2 mapping has recently emerged as a more robust technique to delineate the edema-based AAR11 and both these techniques at 1.5 T correlated well with the AAR by single photon emission tomography15 and performed equally well against each other in the clinical setting5. However, unlike in the study by Hamshere et al.12, the 3-slice approach did not perform well against full LV approach using T1 and T2 mapping, especially in those patients with MSI < 0.50. Although they included a larger number of patients, the mean MI size and AAR was much smaller in their cohort  and MSI was larger (41% versus 35%) when compared to our cohort.Performing a comprehensive CMR study for research purposes to obtain information on MI size, edema-based AAR, MVO and extracellular volume fraction in a patient with a recent STEMI can take up to 1 hour and therefore shortening the CMR duration is highly desirable. Recently, a 3-slice approach for assessing the AAR by T2-weighted STIR imaging has been shown to perform as well as full LV coverage and offered the possibility to shorten the scan time12 and no formal power calculation was performed prospectively. However, we used the more robust edema-based AAR technique (both T1 and T2 mapping) and included patients with a range of MI size and AAR. A retrospective power calculation . NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass) for paired measurements from a sample size of 48 achieved 100% power to detect non-inferiority using a one-sided t-test when the margin of non-inferiority was set at 0.00% and the true difference between the mean (1.70%) and the standard deviation (6.45%) were derived from the Bland-Altman analysis  of 0.15). We did not have T2-weighted STIR images acquired for these patients for comparison.Our sample size for comparing 3-slice versus full LV coverage was 48 compared to 85 in the previous studyDespite the clear benefits of a shorter scan and analysis time, we caution against using a 3-slice approach for the edema-based AAR by T1 and T2 mapping, especially in those with MSI < 0.50. Full LV coverage should remain the quantification approach of choice for the AAR in clinical cardioprotection studies.20. In brief, the London-Harrow Research Ethics Committee approved this study. These patients were prospectively recruited between August 2013 and July 2014 following informed consent. All research-related procedures were performed in accordance with the local guidelines and regulations. The management of STEMI was as per current guidelines21. Study exclusion criteria were known previous MI and standard recognized contraindications to CMR.48 acute STEMI patients reperfused by PPCI from a recently reported cohort were included in this studyAll CMR scans were performed on a 1.5 Tesla scanner  using a 32-channel phased-array cardiac coil. Full LV coverage native T1 mapping was available in 30 patients. Full LV coverage for T2 mapping and late gadolinium enhancement (LGE) were available in all 48 patients.22. Motion correction and a non-linear least-square curve fitting of the set of images acquired at different inversion times were performed inline by the scanner to generate a pixel-wise colored T1 map23.Native T1 maps were acquired with a steady state free precession (SSFP)-based modified Look-Locker inversion recovery (MOLLI) sequence  using a 5s(3s)3s modified sampling protocol9 after acquiring 3 single-shot images  at different T2 preparation times .Colored T2 maps consisting of pixel-wise T2 values  were generated following motion correction and fitting to estimate T2 relaxation times25 at 10–15 minutes after the injection of 0.1 mmol/kg of Gadoterate meglumine .LGE imaging was acquired with a standard segmented ‘fast low-angle shot’ two-dimensional inversion-recovery gradient echo sequence or a respiratory motion-corrected, free-breathing single shot SSFP averaged phase sensitive inversion recovery sequence18. In brief, the endocardial and epicardial borders were manually drawn on the LGE, T1 and T2 maps. Areas of hypo-intense core of microvascular obstruction were included as part of the MI zone and AAR.All imaging analysis was performed using CVI42 software . The imaging analysis methods have been previously described4 and expressed as a percentage of the whole LV (% LV). All the short axis LGE images covering the whole LV were used to quantify MI size. The full LV edema-based AAR (AARfull LV) from the T1 and T2 maps were quantified using a threshold of 2-SD above the remote myocardium and expressed as % LV.For the full LV coverage approach, MI size was quantified using a signal intensity threshold of 5 standard deviations (SD) above the normal remote myocardiumet al.12 and as illustrated in Fig. 3-slices and MI size3-slices quantification.For the 3-slice approach, only basal, mid and apical LV slices for MI size and AAR were analyzed using the same approach by Hamshere SPSS version 22  was used for all statistical analysis. Shapiro-Wilk Test was used to assess for normality. Continuous data was expressed as mean ± standard deviation (SD) or median (interquartile range) and categorical data was reported as frequencies and percentages. Groups were compared using paired Student t-test/Wilcoxon signed rank test or unpaired Student t-test/Mann Whitney U test where appropriate. Correlation was assessed using either Pearson’s correlation coefficient for normally distributed data or Spearman’s rho for non-normally distributed data. Bland-Altman analysis was performed for inter-method agreement and expressed as bias and limits of agreement (±2 SD). All statistical tests were two-tailed, and P < 0.05 was considered statistically significant.


Statins are associated with improved heart structure andfunction, according to research presented recently atEuroCMR 2017. The benefits were above and beyond thecholesterol-lowering effect of statins.‘Statins are primarily used to lower cholesterol’, said leadauthor Dr Nay Aung, a cardiologist and Wellcome Trustresearch fellow, William Harvey Research Institute, QueenMary University of London, UK. ‘They are highly effectivein preventing cardiovascular events in patients who have hada heart attack or are at risk of heart disease.’He continued: ‘Statins have other beneficial, non-cholesterollowering,effects. They can improve the function of the bloodvessels, reduce inflammation, and stabilise fatty plaques in theblood vessels. Studies in mice and small studies in humanshave shown that statins also reduce the thickness of heartmuscle but this needed to be confirmed in a larger study.’This study investigated the association between statinsand heart structure and function. The study included 4 622people without cardiovascular disease from the UK Biobank,a large community-based cohort study. Cardiac magneticresonance imaging was used to measure left and rightventricular volumes and left ventricular mass. Informationon statin use was obtained from medical records and a selfreporting questionnaire.The relationship between statin use and heart structure and function was assessed using a statistical technique called multiple regression, which adjusts for potential confounders that can have an effect on the heart, such as ethnicity, gender, age, and body mass index (BMI).Nearly 17% of participants were taking statins. Those taking statins were older, had higher BMI and blood pressure, and were more likely to have diabetes and hypertension. ‘This was not surprising because we prescribe statins to patients at high risk of heart disease and these are all known risk factors’, said Dr Aung.Patients taking statins had a 2.4% lower left ventricular mass and lower left and right ventricular volumes. Dr Aung said: ‘People using statins were less likely to have a thickened heart muscle (left ventricular hypertrophy) and less likely to have a large heart chamber. Having a thick, large heart is a strong predictor of future heart attack, heart failure or stroke and taking statins appears to reverse the negative changes in the heart which, in turn, could lower the risk of adverse outcomes.’‘It is important to note that in our study, the people taking statins were at higher risk of having heart problems than those not using statins yet they still had positive heart remodelling compared to the healthier control group’, added Dr Aung.In terms of how statins might reduce the thickness and volume of the heart, Dr Aung said several studies have demonstrated that statins reduce oxidative stress and dampen the production of growth factors that stimulate cell growth. Statins also increase the production of nitric oxide by the cells lining the blood vessels, leading to vasodilatation, improved blood flow, lower blood pressure, and lower stress on the heart, which is less likely to become hypertrophied.The findings raise the issue of extending statin prescriptions to anyone above the age of 40 years, but Dr Aung said that was probably not the way to go.‘There are clear guidelines on who should receive statins’, he said. ‘There is debate about whether we should lower the bar and the question is when do you stop. What we found is that for patients already taking statins, there are beneficial effects beyond cholesterol lowering and that’s a good thing. But instead of a blanket prescription, we need to identify people most likely to benefit, that is, personalised medicine.’Dr Aung said: ‘A dual approach should be considered to identify people who will benefit most from statins. That means looking at not only clinical risk factors, such as smoking and high blood pressure, but also genetic (hereditary) factors, which can predict individuals’ response to statins. This is an area of growing interest and one that we are also investigating in our lab with our collaborators.’


This study aimed to appraise the application of right ventricular longitudinal strain for assessing right ventricular dysfunction and severe hemodynamic changes in pulmonary hypertension. The study included 53 patients clinically diagnosed with PH. Tissue Doppler–derived tricuspid lateral annular systolic velocity (s’), early diastolic peak velocity (e’), late diastolic peak velocity (a’), tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), and right ventricular fractional area change (FAC) were determined. The STI parameter was RV free wall longitudinal peak systolic strain (RV LPSS). The patients were assigned into two groups based on a RV LPSS value of − 19%.P < 0.05). RV LPSS was negatively correlated with TAPSE  and FAC  and positively correlated with RIMP . The optimal cut-off value of RV LPSS to reveal an mPAP ≥ 45 mmHg defined based on the receiver operating characteristic curve analysis was − 19.26% with a sensitivity of 83.9% and a specificity of 73.4%.RV LPSS, s’, TAPSE, RIMP, FAC, a’ and e’/a’ showed significant differences. PH patients with an RV LPSS≥ −19% exhibited a lower RV function (Distinguishing the degree of RV dysfunction by 2D-STI may help physicians to determine the state of cardiac function and degree of PH in patients and offer a basis for subsequent clinical diagnosis and therapy. Our study demonstrates the superiority of RV LPSS for uncovering severe PH over the traditional echocardiographic parameters. RHC showed a low morbidity (1.1%) and mortality (0.055%) when conducted at professional centers. Transthoracic echocardiography is used to image the pulmonary artery pressure in the heart and to estimate the PAP from the impact of continuous wave Doppler measurements. With regard to PH, echocardiography is not sufficient for determining the appropriate treatment decision, and cardiac catheterization is required. However, RHC is invasive and impractical for serial assessment. Therefore, a noninvasive method to detect pulmonary hemodynamics is needed.Right ventricular (RV) function is a valuable predictor of prognosis for patients with pulmonary hypertension (PH), because it is well correlated to clinical consequences, severity of illness, and the quality of patient's daily life. Although pulmonary load is a significant determinant of RV systolic function, there remains great variability in RV adaptation to PH. Therefore, correct assessment of RV function is relevant in the clinical managing of these patients. PH is a pathophysiological disorder that is present in multiple clinical manifestations and complicates a variety of cardiovascular and respiratory diseases. RV fractional area change (RVFAC), and RV myocardial performance index (RIMP).,5 However, in those studies, the free lateral wall of the RV was appraised with M-Mode and tissue Doppler imaging only in 1 plane and was employed as a surrogate for RV function. Hence, the present parameters that are measured by echocardiographic techniques only under a simple algorithm are not suitable for calculating RV function.Two-dimensional (2D) echocardiography is the widely utilized means for appraisal of the RV function in clinical practice. Several studies showed the application of a number of echocardiographic parameters in the evaluation of RV function, including tricuspid annular plane systolic excursion (TAPSE), the tricuspid annular plane systolic velocity (s′),,8 Longitudinal strain (LS) is independent of global cardiac movement, thus allowing a quantitative analysis of regional myocardial deformation in different RV segments. A previous study demonstrated that RV longitudinal strain as assessed with speckle tracking strain imaging was severely impaired in patients with PH, and that it was inversely correlated with systolic pulmonary arterial pressure (SPAP) and RV dimensions.Myocardial deformation evaluated by strain is more valuable than wall motion analysis (velocity and displacement) in detecting regional myocardial abnormalities. Recently, several studies demonstrated that two-dimensional speckle tracking strain imaging (2D-STI) is a functional modality in the appraisal of RV function.In this study, we measured the RV myocardial longitudinal strain (RV LPSS) of PH patients using 2D-STI and analyzed the correlation between RV LPSS and the change in RV function. We also detected severe PH (mPAP ≥45 mm Hg) by RV LPSS and investigated the ability of RV LPSS to predict severe PH in patients using 2D-STI.22.1 The exclusion criteria included: RHC was not performed; poor echocardiography image quality; coronary artery disease, moderate to severe aortic and/or mitral valval heart disease, left-sided heart failure, and atrial fibrillation/flutter. All patients were extensively screened to confirm the diagnosis of PH. Invasive measurement of pulmonary pressures was performed with right heart catheterization when SPAP was 36 mm Hg. After the application of the exclusion criteria, 53 cases with PH were included in our study. The study cohort included 25 patients with chronic thromboembolic PH, 18 with idiopathic PH, 6 with PH associated with connective tissue disease, 2 with PH associated with congenital heart disease, and 2 with heritable PH. This study was in compliance with the guidelines of the Declaration of Helsinki. The Ethics Committee of our Hospital approved this study. All participants provided informed consent for participation in this study.A total of 76 consecutive patients with PH who visited our Hospital from August 2013 to December 2014 were enrolled in our study. Diagnosis of PH was defined as a mean PAP ≥25 mm Hg assessed with RHC, or SPAP ≥36 mm Hg estimated with echocardiography.2.2All echocardiography was performed with an Artida ultrasound system . Images were obtained with the patient in the left lateral decubitus position. M-mode was employed to assess the TAPSE. The M-mode cursor was positioned through the lateral side of the tricuspid annulus in such a way that the position of annulus changed along with the cursor. The systolic displacement of annular was assessed from end-diastole to end-systole. The tricuspid annular systolic velocity (s′) was measured in the apical 4-chamber view though tissue Doppler imaging. The isovolumic acceleration of the RV was computed as the peak isovolumic myocardial velocity divided by the time to peak velocity, as assessed by tissue Doppler imaging at the lateral tricuspid annulus. The RVFAC was computed as reported (ref): (RV diastolic area–RV systolic area)/RV diastolic area × 100%. The RV diastolic and systolic areas were acquired from the apical 4-chamber view. RVFAC = the right ventricular index of myocardial performance (RIMP) was the isovolumic time divided by the ejecting time, which was evaluated in the same pulsed. The isovolumic time was computed by subtracting the ejecting time from the tricuspid closure time. The ratio of the RV transverse diameter to the left ventricular transverse diameter was calculated at the basal segment at the end of diastole in the apical 4-chamber view.2.3Three cardiac cycles were used to continuously image the right ventricle as the center of the 4 chambers, with a frame rate >60 frames/s. With 2D-STI performed online with dedicated software, the longitudinal strain of RV free wall was evaluated from an RV-focused apical 4-chamber view. Generally, we traced a region of interest by point-and-click approach on the endocardium at end-diastole in RV from the RV-focused view. A second larger region of interest was further produced and manually fine-tuned near the epicardium. The region of interest was carefully adjusted using visual assessment to assure that every segment was tracked perfectly. The right ventricle was partitioned into 6 standard segments at 3 levels , correspondingly generating 6 time-strain curves Fig. . RV LPSS2.4Hemodynamic measurements were obtained in all patients via right-heart cardiac catheterization. The measured indices were mPAP, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). Cardiac output was determined by the Fick method. An investigator blinded to the echocardiographic measurements evaluated the pressure.2.5P value less than 0.05 was considered statistically significant. All statistical analysis and graphic presentation were performed with the statistical software SPSS .Continuous variables are presented as mean ± standard deviation. Normality was evaluated using the 1-sample Kolmogorov–Smirnov test. Linear regression analysis was used to evaluate the relationships between the 2 variables. The abilities of RV LPSS, FAC, RIMP, s′, and TAPSE to detect severe PH were appraised with receiver operating characteristic (ROC) curves to yield optimal values for an area under the curve (AUC). ROC curves were established to confirm the optimal cut-off value of RV LPSS that indicated elevated mPAP. The optimal cut-off value was determined as the point nearest to 1 in the top left corner. Reliability was assessed as the absolute difference in strain measurements between the 2 observers divided by the mean of both measurements and expressed as a percentage. Interobserver and intraobserver intraclass correlation coefficients (ICCs) for quantitative measurement of RV LPSS were calculated in a 2-way mixed model with 95% confidence intervals (CIs). The agreement between interobserver and intraobserver reliability analyses was tested by the Bland–Altman method. A 33.12  (n = 14) and Group II: patients with RV LPSS ≥−19%  (n = 39).3.2MPA), inner diameter of left arterial branch (DLPA), and inner diameter of right pulmonary arterial branch (DRPA). Only right ventricular transverse diameter (RVTD) and RVTD/ LVTD showed significant differences between Group I and II (P <0.05). For right ventricular function, RV LPSS, TAPSE, s′, RIMP, FAC, a′, and e′/a′ had significantly statistic differences between Group I and II (P <0.05). Patients with RV LPSS ≥−19% exhibited lower RV function , inner diameter of main pulmonary artery , FAC ), RIMP ), and s′   between the 2 groups were observed. For RV structure, only RVTD showed a difference. This illustrated that patients in these 2 groups were similar with regard to the hemodynamic and structural changes, which included enlargement of the right heart, broadening of the main pulmonary artery and left and right pulmonary artery branch, regurgitation of the tricuspid valve, and elevation of systolic pulmonary artery pressure. It is difficult to discern the severity of the disease only from 2D images. The 2010 ASE Guidelines for the Echocardiographic Assessment of the Right Heart in Adults proposed that a number of conventional echocardiographic parameters including TAPSE, s′, FAC, and MPI that can be readily assessed with high reliability and reproducibility should be considered in the diagnosis of PH. conducted a study on precapillary PH patients by using 2D-STI and found that a chronical increase in RV pressure directly impacts RV longitudinal systolic deformation. Increased RV pressure further affects interventricular septal and LV geometry, thus impairing LV torsion, segmental longitudinal strain, and circumferential strain. Sachdev et al found that pulmonary arterial hypertension patients exhibited a reduced RV systolic strain. Moreover, an RV free wall strain less than 12.5% was linked to a higher degree of disease progression within 6 months, and it was also predictive for 1-, 2-, 3-, and 4-year mortality. After adjustment for age, sex, PH cause, and functional classification, patients exhibited a 2.9-fold higher mortality rate per 5% absolute decline in RV free wall strain at 1 year. In a long-term follow-up study on patients with PH, Motoji et al found that patients with an RV-free >19.4% suffered from fewer cardiovascular events than those with an RV-free ≤19.4%. What is more, an RV-free ≤19.4% combined with a TAPSE <16 mm was correlated with the highest incidence of cardiovascular events.Puwanant et al indicated that RV global longitudinal strain was more often altered in patients with severe PAH compared with mild PAH, and that global longitudinal strain and global longitudinal strain rate were associated with CMR-derived RVEF. Sunbul et al appraised RV function in CTEPH patients and discussed the association with activity tolerance by measuring RV longitudinal deformation using 2D-STI. They illustrated that patients with a shorter six-minute walk test (6MWT) distance exhibited a significantly larger RV but had a greatly lower RV fractional area change and higher myocardial performance index. Also, these patients had significantly lower RV basal-lateral strain and strain rate assessments compared with those with longer 6MWT distances. In addition, these patients exhibited lower RV basal-septal, mid-lateral, and global strain measures. In a previous study, RV LPSS was used to detect RV dysfunction in patients with severe PH, as well as early RV dysfunction in patients with mild PH. Consistent with the above finding, our study demonstrated the superiority of RV LPSS for uncovering severe PH (≥45 mm Hg) over the conventional parameters such as RIMP, TAPSE, s′, and RV FAC.Our study indicated that RV LPSS was well correlated with TAPSE, FAC, RIMP, and s′ and thus, RV LPSS could reflect the degree of reduction in right heart function of PH patients. Li et al suggested that the biomechanical and microstructural changes of the RV free wall myocardium should be used in future computational models, which may eventually be used to predict the response to altered hemodynamic states. Ventricular interdependence is defined as the size, shape, and compliance of 1 ventricle affecting the function of the other ventricle. The existence of an interventricular septum, involving 2 ventricles, limits expansion through the restricted pericardium, and RV increases load conditions, which adapts to the characteristics of the related cardiovascular system. Ricardo et al showed that impaired LV contractility in patients with PAH as assessed by speckle tracking strain was independent of ventricular septal involvement.Pressure overload in PH leads to changes in the RV free wall that eventually result in RV failure. Hill et al5Several limitations present in our study need to be pointed out. First, echocardiographic studies and RHC were not performed simultaneously. Second, we did not include control subjects with an mPAP <25 mm Hg. Third, because RHC is an invasive examination, its clinical application has indications, and not all patients could undergo the examination. Fourth, PVR is an important index of pulmonary hemodynamics as reflected in the pulmonary circulation pressure flow relationship. Therefore, the elevation of PVR is also considered a generalized pulmonary arterial hypertension. However, our study included several types of PH and demonstrated the issue of heterogeneity to some degree. Thus, elevated PVR was not considered in our study. In our future study, we will increase the sample size to make a more comprehensive analysis between the subgroups.6Distinguishing the degree of RV dysfunction by 2D-STI may help physicians to determine the state of cardiac function and the degree of PH in patients, which will offer a basis for the clinical diagnosis and treatment of PH.


Here, we demonstrated that rapamycin ameliorates myocardial ischaemia reperfusion injury by rescuing the defective cytoprotective mechanisms in hypertrophic heart. Our results showed that chronic rapamycin treatment markedly reduced the phosphorylated mTOR and ribosomal protein S6 expression, but not Akt in both normal and aortic‐banded mice. Moreover, chronic rapamycin treatment significantly mitigated TAC‐induced autophagy dysfunction demonstrated by prompted Beclin‐1 activation, elevated LC3‐II/LC3‐I ratio and increased autophagosome abundance. Most importantly, we found that MI/R‐induced myocardial injury was markedly reduced by rapamycin treatment manifested by the inhibition of myocardial apoptosis, the reduction of myocardial infarct size and the improvement of cardiac function in hypertrophic heart. Mechanically, rapamycin reduced the MI/R‐induced iNOS/gp91phox protein expression and decreased the generation of NO and superoxide, as well as the cytotoxic peroxynitrite. Moreover, rapamycin significantly mitigated MI/R‐induced endoplasmic reticulum stress and mitochondrial impairment demonstrated by reduced Caspase‐12 activity, inhibited CHOP activation, decreased cytoplasmic Cyto‐C release and preserved intact mitochondria. In addition, inhibition of mTOR also enhanced the phosphorylated ERK and eNOS, and inactivated GSK3β, a pivotal downstream target of Akt and ERK signallings. Taken together, these results suggest that mTOR signalling protects against MI/R injury through autophagy induction and ERK‐mediated antioxidative and anti‐nitrative stress in mice with hypertrophic myocardium.Pathological cardiac hypertrophy aggravated myocardial infarction and is causally related to autophagy dysfunction and increased oxidative stress. Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin ( Emerging evidence has demonstrated that left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular events Cardiac hypertrophy is an important adaptive response to haemodynamic overload, such as pressure overload in vivoet al. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase and its role in regulating autophagy, oxidative stress and cardiovascular disease has received intense attention Therefore, this study was performed to investigate whether rapamycin may ameliorate myocardial ischaemia reperfusion injury in hypertrophic heart. Given that cardiac hypertrophy is causally related to autophagy dysfunction and increased oxidative stress Male C57BL/6J mice were supplied by the Shanghai Laboratory Animal Center. All the protocols used conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health , and they were approved by the Institutional Review Board of Zhongshan Hospital at Fudan University.Male C57BL/6J mice aged 8 weeks were given rapamycin daily  or vehicle  for consecutive 14 days. To determine the effects of chronic mTOR inhibition on myocardial ischaemia reperfusion in mice with or without LVH, LVH was produced in mice by TAC, and then, the mice were treated with rapamycin daily  or vehicle  for 14 days. Myocardial ischaemia–reperfusion was produced by occluding the left coronary artery for 40 min followed by reperfusion for 24 hrs in mice after 14 days of treatment.Mice were anaesthetized using 2% isoflurane and mechanical ventilation. The aorta between the origin of the right innominate and left common carotid arteries was constricted with a 6‐0 silk suture by tieing the aorta with a bent 27‐gauge needle, which was removed after ligation. Sham‐operated animals underwent the same procedure except that the artery was not ligated. After the surgery, the mice were housed in standard animal housing conditions for 2 weeks. Then, the diastolic left ventricular posterior wall thickness was assessed using echocardiography.After 2 weeks of rapamycin treatment, the surgical procedures were carried out as described previously 91phox , iNOS  and GAPDH  were determined by immunoblotting The expression of myocardial mTOR , p‐mTOR , S6 ribosomal protein , p‐S6 ribosomal protein , Akt , p‐Akt , LC3B , Beclin‐1 , p62 , ERK1/2 , p‐ERK1/2 , GSK3β , p‐GSK3β , eNOS , p‐eNOS , CHOP , Cyto‐C , VDAC , gpThe cardiac tissue was fixed with 2% glutaraldehyde for 2 hrs, then fixed in 1% OsO4 for 2 hrs and embedded in resin. The ultrathin sections were stained with uranyl acetate and lead citrate and observed under an electron microscope . Random horizons were acquired by an electron microscope technician.After 24 hrs of reperfusion, the mouse was anaesthetized with 1% isoflurane. M‐mode images of left ventricular were obtained at the level of the papillary muscle tips using a Vevo 770 imaging system . The ejection fraction (EF) fractional shortening (FS) was calculated using the Teichholz formula.The myocardial infarct size was assessed using 2,3,5‐triphenyltetrazolium chloride  staining after reperfusion for 24 hrs. Briefly, the coronary artery was religated, and 0.2 ml 2% Evans blue dye was injected into the right ventricular cavity to identify the unstained area as the area at risk. The hearts were harvested and frozen, sectioned into 2‐mm slices and stained in 1% TTC solution at 37°C for 10 min. The myocardial infarct size (IS) was analysed using ImageJ 1.37 software . The myocardial infarct size was expressed as a percentage of the area at risk. The area at risk was expressed as a percentage of the left ventricular.in situ cell death detection kit  as we described elsewhere Myocardial apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick‐end labelling (TUNEL) staining using a fluorescein Myocardial Caspase‐3, Caspase‐8, Caspase‐9 and Caspase‐12 activity was assessed using Caspase Fluorometric Assay Kits  according to respective instruction of the manufacturer. The activities of Caspase‐3 Caspase‐8, Caspase‐9 and Caspase‐12 were expressed as fold over the corresponding control.in situ ROS levels Dihydroethidium (DHE) staining was used to assess The hearts were harvested after 3 hrs of reperfusion and were cut into sections of 5 μm thick after 4% paraformaldehyde fixation. The slices were by embedded by paraffin and stained with anti‐nitrotyrosine antibody . The immunostaining was conducted by utilizing the Vectastain ABC kit , and the images were acquired under light microscopy. The cardiac nitrotyrosine content was quantified by utilizing the Nitrotyrosine ELISA Kit . The nitrotyrosine content was expressed as microgram/milligram of protein.Myocardial NO content was assessed by determining nitrite using the Griess methods. The samples from ischaemic area were harvested after 3 hrs of reperfusion. The NO content was detected by utilizing the Total Nitric Oxide Assay Kit  following the manufacturer's instruction.post hoc test was used for multigroup comparison. A P < 0.05 was considered statistically significant. All statistical analyses were performed using GraphPad Prism version 4.0 .The data are presented as the mean ± S.D. One‐way ANOVA following Newman–Keuls versus 0.75 ± 0.06 in TAC+ RAPA group, P < 0.05, Table versus 0.63 ± 0.05 in RAPA group, P > 0.05, Table To investigate the cardiac effects of rapamycin (RAPA) treatment in aortic‐banded mice, we treated mice with rapamycin or vehicle daily for 14 days after aortic‐banded surgery. The mortality did not significantly differ between the groups . To assess LV performance, echocardiography was performed to measure cardiac function after 14 days of aortic banding. As shown in Table versus 129.6 ± 3.5 and 7.4 ± 0.21 in TAC+ RAPA group, P < 0.05, Table versus 109.4 ± 2.8 and 6.4 ± 0.16 in RAPA group, P > 0.05, Table Then, mice were killed by overdose of pentobarbital sodium  after echocardiography. The body weight, heart weight and tibial length were recorded. We observed that chronic pressure overload remarkably induced left ventricular hypertrophy manifested by increased heart weight and heart weight/tibial length ratio. Rapamycin treatment hindered cardiac hypertrophic response by aortic banding demonstrated by diminished heart weight and heart weight/tibial length ratio (149.2 ± 4.2 and 8.5 ± 0.32 in TAC+ Vehicle group 473) is main target of mTORC2 Myocardial mTOR and S6 ribosomal protein is the downstream target of mTORC1, while the phosphorylated Akt  and Caspase‐9 activation (a participator for mitochondria‐mediated apoptosis) but did not alter Caspase‐8 activity  Fig. A. Moreovphox overexpression (Fig. phox overexpression (Fig. via down‐regulated gp91phox expression.Oxidative stress has been proved as an important upstream mediator of apoptosis ion Fig. A in normion Fig. B and C aion Fig. A. CollecIt is noteworthy that NO itself does not induce additional myocardial impairment under physiological conditions; however, NO interacts with superoxide and subsequently induces nitrative injury to mitochondria, protein and lipids under pathological conditions and scavenging peroxynitrite ameliorates ischaemia reperfusion injury We next sought to determine the mechanism in response to eNOS phosphorylation and iNOS expression by mTOR1 inhibition. Intriguingly, the NO signalling has been shown to relate to ERK pathway The salient findings from our study can be summarized as follows. First, hypertrophied myocardium is vulnerable to myocardial ischaemia reperfusion injury due to increased oxidative/nitrative stress. Second, we demonstrated for the first time that mTOR inhibition by rapamycin reduced myocardial infarct size, hindered cardiomyocyte apoptosis and preserved cardiac function in aortic‐banded mice following MI/R. Third, inhibition of myocardial mTOR signalling protects against MI/R injury through ERK‐mediated antioxidative and anti‐nitrative stress.Although intense research efforts have been devoted to dissect the role of autophagy in cardiac hypertrophy, it remains ambiguous regarding the precise role of autophagy in cardiac hypertrophy The effects of cardiac hypertrophy on MI/R have not yet been fully elucidated. Here, our study has shown markedly increased oxidative/nitrative stress in hypertrophic cardiac tissue. Furthermore, we observed increased myocardial infarct size, aggravated cardiac function and accentuated cardiomyocyte apoptosis in hypertrophic heart in comparison with that in normal ones following MI/R. Most importantly, we demonstrated for the first time that mTOR inhibition by rapamycin markedly decreased myocardial infarct size and apoptosis in aortic‐banded mice. Moreover, rapamycin treatment preserved cardiac function manifested by increased LVEF and LVFS in comparison with vehicle‐treated hypertrophic hearts. In parallel with our study, the myocardial infarct size was significantly augmented in spontaneously hypertensive rat in the setting of MI/R Apoptosis is the major contributor for programmed cell death after MI/R injury 91phox activation and superoxide generation in aortic‐banded mice followed by MI/R and thus ameliorated oxidative stress‐induced myocardial impairment. It is noteworthy that NO itself does not lead to additional myocardial impairment under physiological conditions; however, NO interacts with superoxide and subsequently induces oxidative/nitrative injury to mitochondria, protein and lipids under pathological conditions MI/R‐induced DNA damage and superoxide production is the primary contributor for cardiomyocyte death and is causally related to endoplasmic reticulum stress, mitochondrial injury and cardiomyocyte apoptosis et al. 91phox activation 91phox expression and superoxide generation through ERK1/2 signalling during MI/R.mTOR inhibition is not only confined to modulate oxidative stress, but also related to cardioprotective molecules via an ERK‐dependent mechanism.The inactivation of GSK3β has been proved to play a crucial role in preserving myocardial survival and function during MI/R In summary, our findings reveal that mTOR signalling protects against MI/R injury through autophagy induction and ERK‐mediated antioxidative and anti‐nitrative stress in mice with hypertrophic myocardium. These findings add to our understanding of MI/R in pathological cardiac hypertrophy and may help to develop novel therapeutic strategies to further reduce infarct size, preserve cardiac function and improve the outcome of AMI patients with LVH.None.


Left ventricular assist device (LVAD) implantation is a viable therapy for patients with severe end-stage heart failure, providing effective haemodynamic support and improved quality of life. The Heart Assist 5  continuous-flow LVAD has been on the market in Europe since May 2009.We evaluated nine Heart Assist 5 LVAD patients with two- and three-dimensional transthoracic echocardiographic (TTE) and transoesophageal echocardiographic (TEE) parameters between December 2011 and December 2013. The pre-operative TTE LVAD evaluations included left ventricular (LV) function and structure, quantification of right ventricular (RV) function and tricuspid regurgitation (TR), assessment of aortic and mitral regurgitation, and presence of patent foramen ovale and intra-cardiac clots. Peri-operative TEE determined the inflow cannula and septum position, and assessed the de-airing process while weaning from cardiopulmonary bypass. Post-operative serial follow-up TTE showed the surgical results of LVAD implantation, determined the overall structure and function of the LV, RV and TR, and observed the inflow and outflow cannula position.Nine patients who had undergone Heart Assist 5 LVAD implantation and had been followed up for more than 30 days were included in this study. Eight patients had ischaemic cardiomyopathy and one had adriamycin-induced cardiomyopathy. Pre-implantation data: the mean age of the patients was 52 ± 13 (34–64) years, mean body surface area (BSA) was 1.8 ± 0.2 (1.6–2.0) m2, mean cardiac index (CI) was 2.04 ± 0.4 (1.5–2.6) l/min/m2, mean cardiac output (CO) was 3.7 ± 0.7 (2.6–4.2) l/min, mean ejection fraction (EF) was 23 ± 5 (18–28)%, and right ventricular fractional area contraction (RVFAC) was 43 ± 9 (35–55)%. One patient had aortic valve replacement (AVR) during the LVAD implantation, and excess current alarms and increased power were suspected to be caused by a possible thrombus. Close follow up with TTE studies were carried out to clear the LV of thrombus formation, and the inflow cannula position was checked to maintain the septum in the midline, so preventing the suction cascade. Four patients were followed up for more than two years, and two were followed up for more than a year. Three patients died due to multi-organ failure. Follow-up speed-change TTE studies of six patients showed that the mean speed was 9 800 ± 600 (9 500–10 400) rpm, and mean CO was 4.7 ± 0.3 (4.3– 5.0) l/min during the three-month post-implant period.We believe that TTE can play a major role in managing LVAD patients to achieve optimal settings for each patient. A large series is mandatory for assessment of echocardiographic studies on Heart Assist 5 LVAD. Left ventricular assist devices (LVADs) are the accepted treatment modality for advanced end-stage heart failure patients.123412It has been reported that there is a knowledge gap on these new-generation, continuous-flow pumps and their effect on cardiac and end-organ physiology. There is a growing need for practising heart failure cardiologists and transplant surgeons who take care of these patients to evaluate the pumps and their effects in patients.123456Echocardiography is the most important non-invasive imaging tool for LVAD assessment at pre-, peri- and post- implant, and during long-term follow up.1234567The Heart Assist 5 LVAD  is small and compact, weighing 92 g and can easily be implanted above the diaphragm Although extensive data have been reported in the literature concerning echocardiographic evaluation of other continuousflow pumps, there are no data on the Heart Assist 5 LVAD and its long-term outcomes. The aim of our study was to describe this small, new-generation pump and the first implantation experience from Istanbul, Turkey.From December 2011 to December 2013, Heart Assist 5 LVADs were implanted in nine patients at our hospital. Eight patients had ischaemic cardiomyopathy and one had adriamycin-induced cardiomyopathy. The mean age of the patients was 53 ± 13 (34–64) years All patients’ pre-operative data  and haemodynamic status had been assessed at the hospital’s medical review board meeting to evaluate their selection for LVAD implantation. All patients had signed informed consent and the study protocol was approved by the institutional review board.In December 2011, 55 serial two-dimensional transthoracic echocardiographic (TTE) examinations had been performed on these patients with the Vivid 3 , and 16 serial three-dimensional TTE examinations had been done with the Philips IE33 xMATRIX . Nine transoesophageal echocardiograms (TEE) were done in the operating room under general anaesthesia during the LVAD implantation to evaluate inflow cannula and septum position, and to monitor the de-airing process while weaning from cardiopulmonary bypass. The specific protocol used for these echocardiographic studies included standard TTE parasternal, apical, subcostal and suprasternal notch views.12345678910111213All TTEs and TEEs were performed by certified cardiologists in different clinical settings. In hospital during the pre-implant period, they evaluated the intracardiac structure , chamber dimensions, left ventricular (LV) and right ventricular (RV) function, valvular structure and function, pericardial disease, volume status and abnormalities of the aorta. In hospital during the post-implant LVAD period, the aim was to visualise the septum and inflow cannula position, the intracardiac volume, outflow conduit, decompression of the left ventricle with rpm speed change and its effects on the aortic valve opening time. Doppler interrogation of the inlet cannula and outflow conduit flows were performed as described in the literature.Echo-specific parameters and differences in image quality or artifact generation were not evaluated in our study. During all echocardiographic studies, the transplant surgeons were at the bedside or in the out-patient clinic, in communication with the heart failure cardiologist setting up the pump parameters, optimising the LVAD speed, and observing the aortic valve opening times and septum inflow cannula position to prevent the suction cascade.Images from 55 TTEs were retrospectively analysed by the heart failure cardiologist who had mainly performed all these echo studies. The inlet cannula/outflow conduit velocities were measured in m/s by spectral Doppler. The pulsality index of the pump, LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD), interventricular septum (IVS), posterior wall thickness, RVFAC, and tricuspid annular plane systolic excursion (TAPSE) were measured, and the functioning of the valves was routinely evaluated pre-implant and at the second week, and first, third, sixth, ninth and 12th months post-implant.All echocardiographic data were collected in parallel with the patients’ laboratory parameters  in an electronic database, and descriptive statistics were calculated using Microsoft Excel . Continuous variables were expressed as the mean value ± standard deviation.As our Heart Assist 5 LVAD patient data were limited, we did not compare the patients’ outcome parameters pre- versus postimplant, knowing that with this small group, all analyses would be statistically non-significant. We therefore analysed these patients’ data as descriptive statistics.The titanium impeller of Heart Assist 5 LVAD is small, lightweight and located pericardially. The titanium housing enables direct visualisation of the impeller. The outflow and inflow cannulas were visualised in all studies. The inflow cannula and septum  position, outflow graft anastomosis to the aorta, aortic valve cusp status, and aortic valve opening times with speed changes were evaluated and visualised in all 55 echocardiographic studies Pre-implant echocardiographic data of the six patients: mean EF was 23 ± 5 (18–28)%, mean LVEDD was 6.9 ± 0.6 (6.3–7.7) cm, mean LVESD was 5.8 ± 0.5 (5.1–6.4) cm, mean IVS was 0.9 ± 0.1 (0.9–1.1) cm, mean RVFAC was 43 ± 9 (35–55)%, and mean TAPSE was 17 ± 4 (13–23) mm.The 12-month post-implant echocardiographic data of the six patients were: mean EF was 19 ± 6 (10–25)%, mean LVEDD was 6.4 ± 0.4 (6.1–7.0) cm, mean LVESD was 5.6 ± 0.3 (5.2–6.0) cm, mean RVFAC was 35 ± 11(21–43), mean TAPSE was 13 ± 2 (11–16) mm, mean rpm was 9 800 ± 600 (9 500–10 400) rpm, mean pulsality index (PI) was 2.79 ± 1.7 (1.9–4.9) m/s, outflow cannula velocity was 0.9 ± 0.2 (0.8–1.2) m/s, and aortic valve opening was observed every one-to-one cycle or one-to-three cycle.Since eight patients had ischaemic cardiomyopathy and one had had coronary artery bypass grafting (CABG) 10 years earlier, remission of their end-stage heart failure was not expected. All our patients had had automated internal cardioverter defibrillator (AICD) and cardiac resynchronisation therapy (CRT-D) implantation prior to the LVAD implantation. One patient had a ventricular fibrillation (VF) event in the ward and had cardiopulmonary resuscitation. He had his AICDCRT- D implanted prior to the LVAD surgery. Two patients had experienced ventricular tachycardia (VT) at home due to dehydration during the summer, and their AICD had been interrupted during the attacks.There were a few hospitalisations because of minor complications. One patient complained of a coffee-grinding noise coming from his pump three months post-implant, and the remote monitoring system also documented frequent excess current alarms and increased power at different hours of the day. The patient was hospitalised for possible thrombus formation or device malfunction. The data were analysed at Micromed Cardiovascular Inc, Houston, Texas. The coagulation profile was in the normal range for a LVAD patient, his INR was 3.2, and his lactate dehydrogenase level was 606 U/l, which was gradually elevated up to 120 days after LVAD implantation.Serial echocardiographic studies were done weekly to rule out possible thrombus formation in the left ventricle, the orifice of the inflow cannula, outflow conduit and aortic valve cusps. The patient received heparin infusion with close monitoring of his coagulation profile. There was no absolute finding in the echo studies to confirm thrombus formation or determine the reason for the coffee-grinding noise, since we were not able to visualise the titanium impeller. We guessed that there may have been a blood clot there, which caused the increased power. The noise stopped after the fifth day of heparin infusion.A female patient had uncontrolled diabetes, she had gradually gained 7 kg by the sixth month post-operatively, and suffered from recurrent urinary tract infections. She was admitted with fever, tachycardia, post-diabetic ketoacidosis and documented urinary tract infection. Her echocardiographic study was done in a sub-optimal position due to her tachycardia. She received anti-arrhythmic and antibiotic regimens, and a few days later she was in sinus rhythm, her heart rate was 89–95 beats per minute, and her fever was gone. Her echo studies were repeated and LVAD optimisation was done. She was discharged from hospital with 9 500 rpm, her CO was 4.7 l/min and the pulsality index was 2.31 m/s.Four patients were followed up for more than two years, and two for more than a year. Three patients died due to multi-organ failure. One international patient had heart transplantation in the Republic of China. The longest supported patient was for more than three years, with a good quality of life.All data for each patient had been collected in each portable console, Heart Attendant , so with the universal serial bus (usb) connection, all the data could be downloaded and could be easily analysed. Online connection of the Heart Attendant to the internet assists in patient care and provides 24 hours a day, seven days a week monitoring of the LVAD patient. This technology decreases hospital admissions for each alarm detection, as the clinicians can track the patient with the remote monitoring system and help him/her by phone.This technology differentiates Heart Assist 5 LVAD from other continuous-flow pumps. The implantable flow probe also helps to assess even minor dehydration problems, which can be solved without admission to hospital. We experienced low-flow alarms during the summer months and suggested our patients take in extra fluid during summer.There are reports of large single-centre echocardiographicstudies of other continuous-flow and centrifugal pumps in the literature.89101112et al demonstrated the modified Micromed axial flow pump has an in vitro responsivity approaching that of the natural heart.et al reported that the thrombogenicity of Heart Assist 5 was 2.5-fold lower than the HeartMate II LVAD.17Long-term outcomes of these pumps have been published recently in the literature.123456789101112Although our experience with Heart Assist 5 LVAD was not from a large series, compared with other continuous-flow and centrifugal pumps that we have implanted in our clinic, we tried to standardise pre-operative LVAD evaluations and post-implant follow up of LVAD patients in collaboration with the heart failure cardiologists. We believe that as a heart failure/transplant team, a systematic approach for the evaluation of these patients suffering from advanced heart failure is important. Close follow up of these patients will affect the success of LVAD surgery and long-term prognosis of the patients, which will lessen the side effects and enable rapid and accurate identification of mechanical and systemic malfunctions.Our group was the first to implant this version of Heart Assist 5 LVAD in Turkey. An earlier version of this pump was implanted in Turkey in April 2001.Our study has limitations since there were so few patients with Heart Assist 5 LVAD support in our group. However, if other centres start implanting Heart Assist 5 LVAD in their end-stage heart failure patients, more data on these pumps and their longterm outcome will be available for clinicians in the future. This pump has had CE approval in Europe since May 2009, and the National Health Government solved the reimbursement issues of these continuous-flow pumps in 2012.Our study was not designed for the appropriate combination of flow, power, pulsatily index and left ventricular unloading. It is impossible to establish or document cause–effect relationships while optimising LVAD parameters with so few patients. This study was an observational analysis of a new-generation pump. We believe that a concept should be studied in larger prospective series with different pumps using serial echocardiographic studies and comparing long-term outcomes of each pump.


CHD  patients is a challenging procedure because of the possibility of multiple circuits. Electroanatomical mapping and pacing maneuvers are crucial to determine critical isthmus. Moreover, vascular abnormalities and residual cardiac defects need to be known before the ablation to decide the better strategy for ablation.Atrial flutter ablation in  Atrial flutter is common in patients with surgically corrected congenital heart diseases. In these patients, anatomical abnormalities caused not only by congenital cardiac defect but also by surgical correction make the diagnosis and ablation more challenging. Moreover, vascular abnormalities related to cardiac disease can make the procedure even more difficult.This is a 70‐year‐old female patient that was referred to our grown‐up congenital heart disease outpatient clinic because of dyspnea grade II and palpitations. She referred that she had underwent surgical correction of a sinus venous atrial septal defect (ASD) with partial anomalous pulmonary venous connection at the age of 47 in another institution. She did not have any additional information about this operation.Physical examination showed mild peripheral cyanosis on rest, without signs of congestive heart failure. Baseline ECG Fig. . showed ® Ensite  as an electroanatomic mapping system. A decapolar catheter  was advanced within the coronary sinus (CS) through the left subclavian vein. The right jugular vein was punctured for accessing the right atrium, the right femoral vein was punctured to access the left. An irrigated‐tip catheter  was used for mapping and ablation. A complete electroanatomical map from both atria (Fig. The procedure was performed using NavXria Fig.  was obtaria Fig. , with paria Fig. . Becauseria Fig. . We contAtrial flutter is a common and potentially severe complication in patients that have undergone surgical correction of any congenital heart disease IR: conceived and designed the study. IR, NR: drafted the manuscript. IR, JF, JP, NR: acquired the data. LD, AP: revised the manuscript for key content in field of congenital heart disease. AMM, DGD: made critical revision of the manuscript for key intellectual content.None declared.