The 3D architecture of the ventricular mass is poorly known, although in vivo imaging techniques show the physiological inhomogeneity of ventricular walls mechanics. Polarized light imaging makes it possible to quantitatively analyse the myosin filament orientation.In this paper, we focus on the study the 3D architecture and regional isotropy of myocardial cells.Twenty normal human hearts, 10 from the perinatal period and 10 from the post-neonatal period were studied by polarized light microscopy. In each voxel of the ventricular mass (90 × 90 × 500 µm) the principal orientation segment was automatically and unambiguously extracted as well as a regional isotropy index .During the first months of postnatal age, the median regional isotropy values decreased in the ventricular mesh. This global decrease was not homogeneous across the ventricular walls. From the perinatal to the neonatal period, this decrease was more marked in the inner two-third of the lateral left ventricular wall and in the right part of the interventricular septum. There was a progressive post-neonatal appearance of a particularly inhomogeneous secondary arrangement of myocardial cells with alternation of thick low-RI and thin high-RI areas.This study has shown a postnatal change in ventricular myocardial architecture, which became more inhomogeneous. The cell rearrangements responsible for the inhomogeneity in ventricular myocardial architecture are revealed by a variation of the regional isotropy index. These major changes are probably an adaptive consequence of the major haemodynamic changes occurring after birth during the neonatal period that generates major parietal stress variations and parietal remodelling.The online version of this article (10.1007/s00276-017-1945-5) contains supplementary material, which is available to authorized users. Ventricular myocardium is a complex three-dimensional mesh of cardiomyocytes supported within a matrix of connective tissue, but the organization of this mesh at the ventricular level continues to be debated. Difficulties are numerous: the ventricular mesh has an inhomogeneous branching architecture, the heart is a multi-tissue organ made of myocardial, conjunctive and vascular cells, with multiple levels of organization. It became clear that there are no discrete structures in the ventricular mass but the inhomogeneity of cell arrangements is still unsettled , 22. TheAs for any complex structure, it must be studied by breaking it down into simpler components, while attempting not to lose the overall picture or at least not overstating the results obtained from a single component or subregion. In this study, we focus on the principal orientation of the myosin filaments measured by polarized light imaging (PLI), which provides a robust measurement of the orientation of cardiomyocytes .While studying the 3D arrangement of myocardial cells during foetal life and postnatal life with PLI, we observed major 3D rearrangements of cardiomyocytes that occur during postnatal cardiovascular adaptation , 11. In The aim of this study was to describe the modifications of the 3D cardiomyocyte orientation of the ventricular mass during perinatal and post-neonatal period.Grenoble University Hospital (GUH) owns a legally declared collection of embedded tissue sections collected after autopsy for perinatal and infant death performed for a diagnostic purpose. Written consent was obtained from the parents or guardians at the time of the request for autopsy authorization and for research authorization on normal and abnormal development. The research protocol has been approved by the institutional review board of GUH. Samples dedicated to research purposes were kept anonymous. The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments.Twenty hearts of eutrophic newborns and infants, without detectable cardiac anomalies, were studied. There were 10 perinatal hearts  and ten post-neonatal deaths at 8–43 weeks.R) along the heart short axis. Due to the thickness of the wire saw, 500 µm were lost and consequently, the section spacing was 1 mm. The use of MMA made it possible to cancel the form birefringence of collagen because MMA and collagen refraction indices matched well. We previously demonstrated that in this condition the birefringence of the myocardium is essentially due to the crystalline uniaxial positive birefringence of myosin. The orientation information can then be extracted with the classical PLI techniques on a three-axis rotation stage adapted to biology, particularly to the low value of birefringence and the size of the samples. This allows extracting the voxel principal orientation that is the mean orientation of all myosin filaments contained in a voxel (90 × 90 × 500 μm3). Such a voxel contains around 500 myocardial cells. The orientation information is expressed by two angles: the azimuth angle, that is the angle between the east–west axis of the optical bench stage and the projection of the voxel principal orientation on the stage plane (0°–180°); and the elevation angle, that is the angle corresponding to the obliquity of the voxel principal orientation with respect to the plane of the section, in other words it is the way the voxel principal orientation escapes from the section plane (− 90° to + 90°). Both these angles are defined in an absolute 3D Cartesian coordinate system. Registration of the successive sections was obtained by aligning the fiducial markers.The protocol is the same as reported in previous publications , 11, as λ1, λ2, λ3), which are the diameters of the scattering ellipsoid of the neighbourhood orientations  called tensor of orientations is built from the product of the previous matrix by its transpose. Diagonalization of the resulting inertia matrix provides its eigenvalues , every neighbourhood voxels have the same orientation as the centre voxel, and 1 for pure isotropy (λ1 = λ2 = λ3), all possible orientations are observed, meaning the variation of orientation is maximal between centre and neighbourhood.RI varies from 0 to 1, that is 0 for complete anisotropy  investigated by diffusion tensor MRI, where iffusion .Quantitative studies of the variation of RI during perinatal and post-neonatal development were conducted on each of the 20 hearts studied while analysing the distribution of RI in three consecutive sections of the mid-ventricular mass. The RI distributions were shown with box and whisker plots. The relationships between growth  and RI were investigated with classical linear regression analysis and tested with the Spearman test.The linear transmural plot profile of RI was also studied across the left ventricular free wall and the interventricular septum at the equatorial level. Thickness of the measurement line was 5 pixels for averaging purpose. The statistical differences between the minimum and the maximum transmural values of RI in the perinatal and the post-neonatal hearts were investigated by Student-test.x, y, z) and the more frequently used cylindrical or semi-spheroidal coordinate system that defines the principal orientation by the helical and imbrication angles. Cylindrical and semi-spheroidal coordinate system have clear advantages for visualization when studying structures with approximate rotational symmetry, the left ventricle for example. As we study the whole ventricular mass, a complex geometrical structure with 2 cavities and highly variable curvature of the walls and interventricular septum (IVS), we choose the 3D Cartesian coordinate system for visualization because it does not require to define a symmetry axis. It is also required for the RI index calculations. To provide readable and comprehensive information on myocardial cell orientations, we also used a streamline representation based on a classical Line Integral Convolution (LIC) algorithm [The orientation measurements were summarized with false colour maps encoding for the values of azimuth angles, elevation angles and RI values. These maps share a common Cartesian reference system such that the inferior side of the ventricular mass is set parallel to a horizontal axis . There is a strict mathematical correspondence between the Cartesian coordinate system  but which is actually preceded by a variable gestational duration that can only be approximated.r = − 0.748, p = 0.0008). This correlation is also statistically significant with age but lesser , as could be expected because of the lack of robustness of the estimated gestational duration.There is a progressive decrease in RI values during the 1st year of postnatal life Fig. . Linear Visually, the combined examination of the short-axis and horizontal long-axis sections Fig.  shows thThe low-RI index layers smaller than 0.3  were analysed within the ventricular mass and two stages are illustrated in Fig. There are strong relationships between the vector field of cardiomyocytes orientation, as represented by line integral convolution, and the force field resulting from cardiomyocytes contraction. Thus, the post-natal remodelling of myocardial cells network is correlated with postnatal modifications of ventricular wall motions.The RI index decreases from perinatal to post-neonatal period, from an isotropic towards a more anisotropic organization. But this global trend is not homogeneous across the ventricular walls, the mid RI peak in the LVW and the minimum RI in the right part of the IVS decrease significantly more than in the other areas. We have already demonstrated  that theThe terms “cleavage plane” have also be used in another meaning by Legrice  to descrThis post-neonatal appearance of an inhomogeneous pattern in 3D myocardial cells architecture is a new result that has to be added to all the postnatal changes already documented from a hemodynamic, anatomical and histological point of view , 15, 19.This new result offers new perspectives to comprehend heart developmental remodelling. The change from the geodesic foetal fibre architecture to the post-neonatal inhomogeneous pattern is developmentally significant. As a matter of fact, a geodesic pathway generally results from an optimization process when there is no permanent obstacle to the reorientation of the principal orientation of the myocardial cells in the osculatory plane. Thus, only a limitation of reorientation ability combined with the drastic postnatal haemodynamic changes could lead to the new post-neonatal distribution of low- and high-RI layers described blurring the geodesical pattern. Post-natal increase of the collagen scaffold could be this obstacle to reorientation of myocardial cells. Data about developmental changes in heart collagen content in big animals are scarce; in pig, the collagen content and the cross-links increase significantly from birth to yearling piglet . UnfortuThe postnatal inhomogeneous 3D architecture we describe supports the observations of regional inhomogeneity of postnatal mechanical shortening and lengthening sequences in the LV wall, which result in a highly efficient overall function of the normal heart adaptive to the post-neonatal haemodynamic conditions . The timThis study has shown a postnatal change in ventricular myocardial architecture, which became more inhomogeneous. The cell rearrangements responsible for the inhomogeneity in ventricular myocardial architecture are revealed by a variation of the regional isotropy index. These major changes are probably an adaptive consequence of the major haemodynamic changes occurring after birth during the neonatal period that generates major parietal stress variations and parietal remodelling.Below is the link to the electronic supplementary material.Supplementary material 1 (AVI 772 KB)Supplementary material 2 (AVI 694 KB)Supplementary material 3 (AVI 2151 KB)Supplementary material 4 (AVI 1895 KB)Supplementary material 5 (DOCX 4 KB)


We also investigated the influence of the body temperature and postmortem interval on T1 and T2 values.We performed hepatic PMMR imaging of 22 deceased adults  whose deaths were for reasons other than liver injury or disease at a mean of 27.7 hours after death. Before imaging, the bodies were kept in cold storage at 4°C . We measured T1 values of PMMR imaging were 524 ± 112 ms and 472 ± 104 ms (mean ± standard deviation), respectively; while T2 values were 42 ± 6 ms and 43 ± 8 ms, respectively. T1 and T2 values did not differ significantly between the two sites (P ≧ 0.05). Regarding temperature, the T2 values of hepatic PMMR imaging were linearly correlated with the body temperature, but the T1 values were not. The T1 and T2 values of the two sites in the liver did not correlate with the postmortem interval.In the anterior segment of the right lobe and the lateral segment of the left lobe, T1 and T2 value changes in the liver on PMMR imaging.Reduction in body temperature after death is considered to induce T A newly published first-impression postmortem study using a 3.0T scanner reported that different magnetic field strengths, such as 1.5T, would result in different quantitative values for T1 and T2 for the same tissue and temperature.16 We report the T1 and T2 values of 1.5T PMMR imaging of an adult human liver in vivo.Postmortem magnetic resonance (PMMR) imaging can provide more detailed information with better contrast resolution than postmortem computed tomography (PMCT), and depict some pathological conditions that are difficult to identify with PMCT.We examined PMMR imaging data of 22 adults  who died suddenly and unexpectedly and did not have abnormal results nor indications of fatty liver on hepatopathological examination. Both ascites around the liver and putrefaction gas formation were ruled out using whole-body PMCT immediately before PMMR imaging. Their bodies were kept in cold storage at 4°C and subjected to PMMR imaging 7 to 96 hours after the confirmation of death (mean: 27.7 hours). Their rectal temperatures, measured immediately after PMMR imaging with an industrial thermometer , were 5–31°C (mean: 17.6°C).Autopsy was performed on each subject after PMMR imaging. Causes of death were 5 cases of trauma not involving the abdomen , 5 cases of ischemic heart disease , 5 cases of acute heart failure due to fatal arrhythmia, 3 cases of drowning in the bathtub, 2 cases of cerebral hemorrhage, and 1 case each of subarachnoid hemorrhage and acute drug intoxication.1 and T2 values with a relaxation time map creation tool .231 mapping. T2 mapping was based on a multi-echo spin echo sequence. However, the first echo was ignored in the pixel-wise calculation of the T2 map, since it consistently yielded a lower signal than the second echo. Inhomogeneity correction was performed for static magnetic field (B0); however, it was not performed for radiofrequency magnetic field (B1).With the permission of our institutional ethics committee, we performed PMMR imaging using a 1.5T MR imaging clinical scanner  with a dedicated 6-channel body matrix coil and spine matrix coil. We measured TA radiological technologist (T.K.) with 16 years of experience defined 2-cm-diameter circular regions of interest (ROIs) in the liver in both the anterior segment of the right lobe and the lateral segment of the left lobe excluding the vessels and bile ducts on axial images at the level of the main trunk of the portal vein .P < 0.05 for group differences.Statistical analyses were performed using statistical software  with Statcel 2  an add-in software. Parametric statistics  and Student’s t-test were used with a significance value of 1 values, T2 values, and rectal temperatures were analyzed with Pearson’s correlation coefficient using the least squares methods. Also, the relationships among T1 values, T2 values, and postmortem intervals were analyzed using the same methods.The relationships among T1 values of the anterior segment of the right lobe and the lateral segment of the left lobe were 524 ± 112 ms and 472 ± 104 ms (means ± SD), respectively ). The T2 values of the anterior segment of the right lobe and the lateral segment of the left lobe were 42 ± 6 ms and 43 ± 8 ms, respectively ).A diagnostic radiologist (S.S.) with 24 years of experience observed no specific abnormality, except for signal intensity and contrast, between PMMR imaging  and clinectively , showingectively , showing1 values of the anterior segment of the right lobe did not correlate significantly with the temperature .1 values were shorter than the reported clinical MR imaging22 in the lateral segment of the left lobe, but not much difference was found in the anterior segment of the right lobe. This T1-shortening effect is due to the effect of fat and water at low temperatures. However, T1 values on hepatic PMMR imaging did not correlate significantly with the rectal temperature. Matsumoto et al.38 reported that the T1 value of a pig liver in vitro decreased linearly with a temperature reduction range of 10–50°C, although the T1 value increased between the range of 0–10°C. Moser et al.28 reported that in a temperature below 37°C, at 4 hours after biopsy excision, T1 values were higher in a rat liver in vitro at 22, 15, 30, 7, and 37°C, in this order. Namely, T1 value reduction was not proportional to the temperature reduction. In our study, the T1 value of the postmortem liver varied at low temperature over a similar range, which is considered to be the reason for not showing linearity regarding the relationship between the T1 value and rectal temperature.In the liver of our PMMR imaging, T2 values, compared with clinical MR imaging of the liver, hepatic PMMR imaging did not show any significant change. For the liver, T2 prolongation due to a reduced pH, T2 shortening due to fat, water, and paramagnetic substances at low temperature negated each other. However, T2 values on hepatic PMMR imaging were correlated significantly with the rectal temperature. Also, according to Moser et al., at 4 hours after biopsy excision in a temperature below 37°C, high T2 values of a rat liver in vitro were observed at 37, 30, 22, 15, and 7°C in this decreasing order, showing the proportional reduction of T2 values relative to the temperature. In our study, the relationship between T2 value and rectal temperature of the liver showed linearity.Regarding T1 values did not correlate significantly with the rectal temperature, but T2 values significantly correlated. On the other hand, with cerebral PMMR imaging, it has been known that T1 values correlates significantly with rectal temperature, though T2 values did not.13 This discrepancy between hepatic and cerebral PMMR imaging suggests organ-specific MR relaxation times after death.With hepatic PMMR imaging, T1 and T2 values depend on the type of MR imaging unit and scan conditions; thus may differ on different imaging units or with different parameters.23 In our study, we had to compare hepatic PMMR imaging data we generated with published data from clinical MR imaging of the liver in the literature. The second limitation is that the standard deviation of T1 value of our subjects were large compared to that of living subjects as reported by de Bazelaire et al.22 Decomposition of the liver progresses in cases in which a long period of time elapsed after death. In our study, PMMR imaging was performed 7–96 hours after the confirmation of death. Our subjects had been kept in cold storage, which reduces decomposition of the body. Nevertheless, the wide deviation in the time after death may have caused differences of the degree of decomposition in each body, thereby resulting in increased standard deviation values. Also, a possible uneven rate of decomposition within the liver of a deceased subject may cause a difference in T1 shortening effects between the right anterior and left lateral segments of the liver. The third limitation is that B1 inhomogeneity correction was not performed with our relaxation time map creation tool, which is considered to have resulted in regional signal variation. A greater variation can be induced in the T1 map which is based on gradient echo sequences than the T2 map which is based on spin echo sequences. The fourth limitation is that we did not directly measure the pH, fat, water, and paramagnetic substances. Such measurement with an MR imaging system48 would enable estimation of the level of effect of relaxation time changes of each factor on the total liver relaxation time.Our study has four limitations. One is that we could not examine 1.5T MR imaging data of healthy volunteers, because an approximately 2-minute breath hold is necessary to obtain comparative imaging data. T1 values did not significantly correlate with the rectal temperature, but T2 values did correlate. Postmortem interval had no effect on T1 and T2 values on hepatic PMMR imaging. Reduction in body temperature after death is considered to induce T1 and T2 value changes on hepatic PMMR imaging.In conclusion, with hepatic PMMR imaging, T


Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure–volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus.Rat models of T1DM  and T2DM  and corresponding control animals  were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis.In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis.Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling.The online version of this article (10.1186/s12933-017-0645-0) contains supplementary material, which is available to authorized users. Diabetes mellitus (DM) can be divided into four major types including type-1 (T1DM) and type-2 DM (T2DM). T1DM accounts for 5% of all diabetes cases, while T2DM is more common , 4. ManyPressure–volume (PV) analysis is the gold standard method for the detailed hemodynamic characterization of the heart . PV analTransthoracic echocardiography may be an alternative approach and due to its non-invasive nature it may be used in follow-up studies as well. However, conventional parameters derived from two-dimensional and M-mode echocardiographic images suffer from several shortcomings, including modest sensitivity and technical limitations , 11. ThuBased upon that, in the current study we aimed at comparing STE with PV analysis for the detection of characteristic differences between T1DM- and T2DM-associated cardiac dysfunction in relevant rodent models.Animals were housed individually in a room with constant temperature and 12/12 h light/dark cycles.® Sensor, Roche, Mannheim, Germany). Animals with a random blood glucose level > 15 mmol/l were considered diabetic and included in the study. The following study groups were established: non-diabetic control animals  and animals with type-1 DM . Experiments were performed after 8 weeks of diabetes duration.For T1DM 8-week-old male Sprague–Dawley rats  were used. Animals received standard laboratory rat diet and water ad libitum. T1DM was induced with a single i.p. injection of streptozotocin (60 mg/kg) . Streptozotocin was dissolved in citrate buffer . Control animals received only the buffer. 72 h after the injection blood glucose concentration was determined by using a digital blood glucose meter (Accu-ChekFor T2DM 7-week-old Zucker Diabetic Fatty (ZDF) rats (Charles River) were used . Animals® Sensor, Roche, Mannheim, Germany) from a drop of blood collected from the saphenous vein at the end of the study period.Non-fasting blood glucose was measured by a digital blood glucose meter . Images were analyzed with an image analysis software . Long-axis and mid-papillary level short-axis B-mode images were used to measure left ventricular (LV) anterior (AW), posterior wall (PW) thicknesses and LV internal diameter (ID) in end-diastole (d) and in end-systole (s). End-systole was defined at minimal, while end-diastole was defined at maximal LVID. Heart rate was determined from M-mode images taken at the mid-papillary level in the short-axis view of the LV. Values of three consecutive cycles were averaged and used for statistical analysis. LV mass was calculated by the following equation: LVmass = 1.04 × [(LVAWd + LVIDd + LVPWd)3 − LVIDd3]. LVmass was normalized to the tibia length and body weight . Fractional shortening (FS) was calculated as FS = (LVIDd − LVIDs)/LVIDd * 100.Echocardiography was performed at the end of the experimental period as described elsewhere . In brieLoops of short-axis views of the mid-papillary level dedicated for speckle-tracking analysis were acquired at least three times using a constant frame rate 218 Hz). Analysis was performed in a blinded fashion by an experienced operator (EchoPAC v113). Segmental and global circumferential strain (GCS), circumferential systolic (SrS), isovolumic (SrIVR) and early diastolic (SrE) strain rate values were calculated , maximal slope of diastolic pressure decrement (dP/dtmin), time constant of LV pressure decay , maximal power were calculated. The slope of the LV end-systolic PV relationship , preload recruitable stroke work (PRSW), maximal elastance (Emax) and dP/dtmax—end-diastolic volume relationship were used as load- and heart rate-independent indices of LV contractility. The slope of the LV end-diastolic PV relationship  was determined as an index of LV diastolic stiffness. A special PV analysis software  was used for data analysis. Heart weight (g) was measured after euthanization.Invasive hemodynamic investigation was performed as described previously . A pressFive µm thin myocardial sections were stained with Masson’s trichrome and hematoxylin–eosin staining. Interstitial fibrosis (excluding vascular spaces) was evaluated on Masson’s trichrome stained sections. Briefly, fibrotic to total tissue area of the myocardium was determined by ImageJ software  using thresholding on red–green–blue stack images of Masson’s trichrome sections by two independent observers. Cardiomyocyte hypertrophy was evaluated by the measurement of cardiomyocyte diameter on hematoxylin–eosin stained sections as described previously .t test or Mann–Whitney U test was used to compare experimental groups to the corresponding control groups. Pearson or Spearman test was used for correlation analysis appropriately. Individual data of the diabetic animals were normalized to the mean of their corresponding control group. Diabetes associated percent changes were derived and compared with unpaired two-sided Student’s t test to compare changes between the two models. To test intra- and interobserver variability of STE measurements, 3 animals from each group were randomly selected and analyzed again using the aforementioned protocol by the first and also by a second operator blinded to previous results. Lin’s concordance correlation coefficient values were calculated. A p < 0.05 was considered significant.Data are presented as mean ± SEM. Shapiro–Wilk test was used to confirm normal distribution. Based on that, unpaired two-sided Student’s In T1DM diabetic animals showed significant decrease in body weight, while in T2DM it remained unchanged . GCS showed almost no difference between intra- and interobserver variability (0.950 and 0.947). SrE (0.971 and 0.929) and SrIVR (0.969 and 0.922) had similar intra-, while lower interobserver reproducibility. Intraclass correlation coefficient values of GRS were lower (0.876 and 0.811).In the present study we showed that: (a) STE-derived measurements are sensitive in the detection of diabetes associated impairment of cardiac contractility as well as diastolic function, (b) STE-derived parameters correlate with cardiac contractility, active relaxation and stiffness measured by PV analysis and (c) indices of STE correlate with the markers of histological remodeling (hypertrophy and fibrosis) in T2DM related diabetic cardiomyopathy.The rat model of streptozotocin-induced T1DM and the ZDF rat as a model of T2DM are widely used in studies focusing on the characterization of diabetic cardiomyopathy. Depending on the type of DM it is associated with characteristic changes in body weight and blood glucose levels. T1DM is associated with insulinopenia and weight loss, while T2DM is often associated with obesity and hyperinsulinemia . In lineG [Characterization of cardiac performance is challenging in DM due to the changes in MAP and heart rate . These pG . In our G , while mG . Based oG . MoreoveG , 29.G, dP/dtmin; SrIVR) in our T1DM model by PV analysis and by STE. On the contrary, our T2DM animal model has been shown to develop insulin resistance together with hyperinsulinemia and insulinopenia at a later stage of the disease [Depending on its type, DM is associated with characteristic changes of cardiac function. Diastolic dysfunction is an early sign in DM associated cardiomyopathy before the onset of detectable systolic dysfunction . However disease . Accordi disease . Our pre disease , 16. Add disease  includin disease . Consist disease  and hype disease  as well  disease  and hype disease . HoweverOur study has some assumptions and limitations. Firstly, the number of investigated animals may serve as a limitation, however, the current case numbers are reasonable in experimental studies and are based on previous statistical calculations . This should also affect some of the calculated correlation coefficients, where beyond the peak values, the dispersion of data is higher in the mid-range. While we should be cautious with the interpretation of the exact r values, the presence of a correlation is assured. Second, the echocardiographic hardware and software environment is not dedicated to small animal models. Nevertheless, the correlations with PV analysis, and also the reported intra- and interobserver values suggest that both the sensitivity and the reproducibility of our setup is comparable to dedicated, higher frequency systems , 39. LonAccording to our knowledge, this is the first study to compare STE-derived systolic and also diastolic functional measurements with PV analysis in detecting the characteristic differences between T1DM- and T2DM-associated cardiac dysfunction in experimental animal models. Based on our results, strain and strain rate parameters might be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM by serial assessment. Moreover, these parameters may be reliable tools for experimental studies focusing on the pathophysiology and on the monitoring of therapeutic interventions in both type-1 and type-2 DM.


Cardiac rehabilitation is a key program which significantly reduces the mortality in at-risk patients with ischemic heart disease; however, there is a lack of accessibility to these programs in health centers. To resolve this issue, home-based programs for cardiac rehabilitation have arisen as a potential solution. In this work, we present an approach based on a new generation of wrist-worn devices which have improved the quality of heart rate sensors and applications. Real-time monitoring of rehabilitation sessions based on high-quality clinical guidelines is embedded in a wearable application. For this, a fuzzy temporal linguistic approach models the clinical protocol. An evaluation based on cases is developed by a cardiac rehabilitation team. Home-based e-health programs are being increasingly used due to the proliferation of wearable devices and portable medical sensors which are seamlessly integrated into the daily lives of users to monitor vital signs and physical activity . In thisMoreover, wearable devices have been demonstrated to favor strategies for changes to healthy habits and the promotion of healthy physical activity . To achiMotivated by these recent advances, in this work a cardiac rehabilitation program is embedded in a wrist-worn device with a heart rate sensor, which provides real-time monitoring of physical activity during sessions in a safe and effective way. For this, a linguistic approach based on fuzzy logic  is propoThe remainder of the paper is structured as follows: in Cardiac rehabilitation (CR) is defined as the sum of the activities required to favorably influence the underlying cause of heart disease, as well as ensuring the best physical, social and mental conditions, thus enabling patients to occupy by their own means a normal place in society [Cardiovascular diseases represent a major health problem in developed countries according to the World Health Organization (WHO) . Around  society . For the society ,19,20. H society ,20,21. M society .In the literature, we highlighted recent works and reviews where the effectiveness of smart health monitoring systems is described and summarized ,22,23. Iindividual coaching by telephone weekly after uploading training data. In [future healthcare environments. In [In , a home-data. In , a home-data. In , a combients. In , the carents. In , a mobilents. In , Fitbit ents. In , the heabe a boon to mHealth technologies in physical activity sensing thanks to the recent tools and operating systems which enable application development [In this way, previous works have foregrounded the relevance and efficacy of integrating cardiac rehabilitation programs (CRPs) into home-based solutions, but with the limitations of non-programmable heart rate sensors or burdensome devices in the early stages of implantation. However recently, a new generation of smart-watches and wrist-worn devices has improved the quality of measures in heart rate (HR), achieving a median error below 5% in laboratory-based activities . Moreoveelopment .Wear and play devices. Wrist-worn devices are noninvasive because of the heart rate sensor is embedded. In addition, they do not require placement of electrodes on the body prior to physical activity. Moreover, they are worn as a watch in an everyday manner.Modeling a theoretical high-quality CRP. A standardized CRP, which was developed by the CRU of Hospital Complex of Jaen (Spain) was introduced in the home-base approach for each patient’s care in a personalized way. A linguistic approach based on fuzzy logic [zy logic  is incluReal-time smart monitoring is embedded in the wrist-worn device in order to: (1) show patients the adherence to CRP during physical activity; and (2) prevent unsuitable and inadequate HR ranges.Practical methods are described for applying the theoretical model to wearable computing.Based on this context, in this work, we describe real-time monitoring and evaluation of cardiac rehabilitation sessions (CRSs) at home using wearable wrist-worn devices with heart rate sensors. The highlights of this approach are:In In this section, we describe a standardized CRP for patients with ischemic heart disease, a disease where patients suffer from a kind of restriction in the blood supply to the tissues. In the literature, several models for handling CRPs have been proposed and analyzed in many countries . In thisThe maximal or peak heart rate  min to an interval of (30–40) min for trained patients .bpmThe optimal heart rate training zones (OHRTZs). These are defined by the clinical protocol in each session, as percentage ranges Marvonen  allows ttarget heart rateThe middle point between Duration of the progressive stage μadeqhigh, which is described by a fuzzy set characterized by the trapezoidal membership function that is defined by Equation μhighlow, which is described by a fuzzy set characterized by the trapezoidal membership function that is defined by Equation μlowr−Vr∩TSecondly, the degrees of membership over the fuzzy temporal window are aggregated using the t-conorm operator in order to obtain a single degree of both fuzzy sets Equation .(7)Vr∪TWe note several fuzzy operators can be applied to implement the aggregation. However in this paper, we propose a fuzzy weighted average  as is reThe definition and adequacy of several temporal windows, which model the evolution of linguistic terms in the heart rate stream, are discussed in Previous sections describe real-time monitoring of heart rate stream within a wearable device based on fuzzy logic. Once the rehabilitation session has been finished by the patient, evaluating the further session at the end to provide a feedback is fairly intuitive.Based on the degree of a fuzzy term Equation .(9)low the raw data from the HR of the session in a timeline ; (2) the real-time monitoring provided for the patient using gradual colors: A cloud web application for the cardiac rehabilitation team. Requiring previous authentication through login credentials, this includes the next use cases:-Synchronization of the parameters of the next sessions from the CRP, which are defined by the cardiac rehabilitation team and are collected in the web server, in the mobile device using a web service under wireless network technology (3G/4G or WiFi).-Synchronization of the session data from the wrist-worn wearable device into the mobile device using an ad-hoc Bluetooth connection.-Uploading of the session data from the mobile device into the web server using a web service under wireless network technology (3G/4G or WiFi).-blue, green, red; and (3) a summarized indicator of the session using a 4-star scale.Showing and evaluating the CRSs. In the same way as the cardiac rehabilitation team, patients can observe the following information in their mobile devices for each session: (1) the raw data from the HR of sessions in a timeline; (2) the real-time monitoring provided using gradually changing colors A mobile application for patients in order to show the sessions and communicate the data between the web server and the wearable devices. It has been developed for Android and included the next use cases:-Updating the the parameters of sessions from the mobile device into the wrist-worn wearable device using an ad-hoc Bluetooth connection.-blue, green, red based on the degree of the terms Monitoring the session in the wearable device with regard to the CRP providing a real-time monitoring by means of showing (1) the current HR of the patient; (2) the target HR; (3) a graphical evaluation using gradually changing colors -To synchronize the data of sessions, which contains the monitoring and raw HR, from the wrist-worn wearable device into the mobile device using an ad hoc Bluetooth connection.A wearable application for patient in order to develop the sessions with regard to the CRP. This has been developed for Android to include the next use cases:Hence, the approach includes three applications: a wearable application, a mobile application, and a web application, whose use cases are:Images from wearable, mobile, and web applications are shown in https://www.polar.com/us-en/products/sport/M600-GPS-smartwatch) was chosen as an Android Wear device due to the high-quality optical heart rate monitor. The strength specifications of Polar M600 include : (1) optical heart rate measurement with six LEDs; (2) its waterproof nature (IPX8 10 m); (3) low weight (63 g); (4) reduced dimensions (45 × 36 × 13 mm); and (5) long-life battery (500 mAh Li-pol for a 2-day average uptime per charge or 8 h of training).Polar M600  at home using wearable wrist-worn devices with heart rate sensors. As we discussed previously in adequate, low, and high. However, the values of HR between these optimal zones need to change gradually. This progression between optimal zones has been modeled and evaluated using several modifiers.In this section, we describe an evaluation of the linguistic modifiers for the terms defined in low, adequate, and high with regards to In this work, we have evaluated three models using different modifiers to adjust the progression in the trapezoidal membership functions of the terms low term is strong and the adequate term is weak; (B) a neutral model, where neutral modifiers are applied to both terms; and (C) a yielding model, where the adequate term is stronger than the low term, which is weaker. The strong, neutral, and weak properties have been defined by the parameters First, we have evaluated low–adequate values of the heart rate by means of three models: (A) a severe model, where the {value -2, value -1, value 0, value +1, value +2}, for which results are detailed in To evaluate the impact of fuzzy modifiers, we have included a survey of 10 cases with key fragments of low values from the heart rate of a sessions, which were colored with blue and green, based on the degree of the terms low and adequate, respectively. In Second, in a similar way, high–adequate values of heart rate have been evaluated by means of three models: (A) a severe model; (B) a neutral model; and (C) a yielding model. A second survey, which contains 10 cases with key fragments of high values from the heart rate of sessions, was evaluated by the cardiac rehabilitation team using the 5-point Likert scale. Results are detailed in In this section, we describe an evaluation on the fuzzy temporal windows over linguistic terms which describe the heart rate stream during rehabilitation sessions. As we detailed previously, the theoretical thresholds of the heart range zones from CRP are defined theoretically missing the temporal permanence in OHRTZs. In some critical situations when patients develop the CRP, the evolution of heart rate between OHRTZs is prompt and inconstant. In those cases, the adherence and adequacy could not be just defined by the current value of HR.In order to analyze the impact of the temporal windows, a survey with 15 key fragments of prompt and inconstant heart rate streams from the CRSs was designed to evaluate three temporal windows. The cardiac rehabilitation team from the Hospital Complex of Jaen (Spain) analyzed the impact of temporal windows for each term The temporal windows to evaluate are  suits in the adequate zone requiring a minimal permanence within, and also suits in the low zone without critical differences with regard to other models.On the other hand, based on expert evaluation presented in In this way, we can note the adequacy of the clinical protocol for real-time monitoring the CRSs in wrist-worn devices. In addition, the use of a fuzzy model including modifiers and temporal windows has provided a methodology to obtain more accurate terms. This methodology can be extended to model other health contexts based on data stream processing.Although previous works have been mainly focused on ECG sensors ,26, the On translating the approach to other devices and health contexts, we advise that the quality and precision of heart rate is critical to ensure patient safety. High-risk patients and those with other pathologies could require more accurate devices such as ECGs. In this way, the proposed wrist-worn device just provides a measurement of HR. ECG devices could provide further signal processing of HR where heart rate variability or QRS could be described by means of the here-proposed linguistic terms and fuzzy temporal windows, due to the expanding importance of short-term beat windows in patient analysis .Finally, we note the light processing to compute our methodology, which is based on fuzzy logic, enabling low-cost wrist-worn devices to incorporate it without a computational burden. Other approaches based on similar devices, such as the Fitbit  or GarmiThe main motivation of this work is enabling the high-quality real-time monitoring of CRPs at the homes of patients, designed and supervised remotely by the cardiac rehabilitation team. For this, we have proposed: (1) integrating a high-quality protocol based on clinical guidelines for monitoring the HR of the patient in a personalized way; (2) providing a real-time monitoring during sessions using a wearable wrist-worn device with heart rate sensor; and (3) using a wearable-mobile-cloud platform for collecting and synchronizing data between patients and the cardiac rehabilitation team.low, adequate, and high. Fuzzy modifiers and fuzzy temporal windows are included in the methodology. The fuzzy approach provides a flexible evaluation of the HR stream: (1) enabling a intuitive real-time monitoring in wrist-worn wearable devices during sessions; and (2) providing visual and gradual advice, for which intensity is related to the degree of the terms.The methodology of this work has been focused on modeling the theoretical approaches for developing an wearable application for real-time monitoring using wrist-worn devices. In order to address this challenge, first, a fuzzy model is proposed to describe under a linguistic approach the heart rate stream by means of three representative terms: On the other hand, an evaluation of fuzzy modifiers and fuzzy temporal windows is included to generate more accurate and flexible terms. In In future works, the approach will be extended to generate linguistic recommendations and summaries of the further sessions for the patients and the cardiac rehabilitation team. In this work, we have introduced the aggregation as a straight indicator in a 4-star scale, but a further analysis of the heart rate stream will provide intelligent and automatic feedback for cardiologists to detect weak points in the sessions of patients.


The biggest challenge faced in minimally invasive pediatric cardiac surgeryis cannulation for cardiopulmonary bypass. Our technique and experience ofcervical cannulation in infants and small children for repair of congenitalcardiac defects is reported in this study.nd intercostalspace.From January 2013 to June 2015, 37 children  with mean age of17.97±8.63 months and weight of 8.06±1.59 kg were operated onfor congenital cardiac defects through right lateral thoracotomy. The mostcommon diagnosis was ventricular septal defect (18 patients). In allpatients, right common carotid artery, right internal jugular vein andinferior vena cava were cannulated for institution of cardiopulmonary bypassand aorta was cross clamped through right 2There were no deaths or any major complications related to cervicalcannulation. Common carotid artery cannulation provided adequate arterialinflow while internal jugular vein with inferior vena cava provided adequatevenous return in all patients. No patient required conversion to sternotomyor developed vascular, neurological or wound related complications. Threepatients had residual lesions  and onepatient had mild left ventricular dysfunction. At discharge, both commoncarotid artery and internal jugular vein were patent on color Dopplerultrasonography in all patients. In a mean follow-up period of11.4±2.85 months, all patients were doing well. No patient had anywound related, neurological or vascular complication. No patient hadresidual leak across ventricular septal defect patch.Cervical cannulation of common carotid artery and internal jugular vein is asafe, reliable, efficient and quick method for institution ofcardiopulmonary bypass in minimally invasive pediatric cardiac surgery. In pediatric patients, restricted exposure and complicationsassociated with peripheral vascular cannulation has limited the use of minimallyinvasive techniques predominantly in larger children and for simple congenitalcardiac defects. Whenever performed in infants and smaller children, total centralcannulation is the preferred technique,3. However, thismakes the operative field cluttered and reduces the space for instrumentmaneuverability.In the last three decades, there has been significant advancement in minimallyinvasive cardiac surgery in adults-6. Similarly, directcannulation of CCA and internal jugular vein (IJV) has been safely used forinstitution of extracorporeal membrane oxygenator (ECMO) in neonates and infantswith minimal risk of long-term vascular complications and stroke. Studies havefailed to find any definitive association between CCA ligation and risk ofstroke,8.Over the years, innominate artery and common carotid artery (CCA) cannulation forarterial inflow has been proved as safe technique for commencement ofcardiopulmonary bypass (CPB) in pediatric and adult patients, respectively forcomplex aortic surgeries without complicationsCCA cannulation was performed at our institute in 5 pediatric patients operated forre-do cardiac surgery (unpublished data). CCA cannulation was performed eitherbecause patients sustained cardiac injury (three patients) or heart was adherent tosternum on preoperative computed tomography of chest (two patients). In all fivepatients, femoral and iliac vessels were found unsuitable for cannulation eitherbecause of adhesions from previous cannulation or small size of vessels. All fivepatients had an uneventful recovery without neurological or vascular complicationand both CCA and IJV were patent on postoperative Doppler ultrasonography. Using thesimilar technique of cervical cannulation, infants and small children were operatedon with congenital cardiac lesions through a limited right lateral thoracotomy. CPBwas instituted by cannulation of CCA, IJV and inferior vena cava (IVC). The aim ofthis study was to evaluate our technique's clinical usefulness and efficiency interms of postoperative complications especially neurologic outcomes.From January 2013 to June 2015, 37 pediatric patients  with mean age of17.9±8.63 months and mean weight of 8.06±1.59 kg were operated on forcongenital cardiac lesions by lateral thoracotomy using cervical cannulation forCPB. Demographic profile of the patients is shown in In all the patients, preoperative cardiac diagnosis was determined by trans-thoracicechocardiography (TTE). Other investigation, like contrast enhanced computedtomography (CECT) and angiography of heart and cardiac catheterization, wereperformed, if indicated.2) wasmeasured using near-infrared spectroscopy (NIRS)  and right sided rSO2 was maintained at >90%.Central venous catheterization was performed intraoperatively through rightfemoral vein and arterial access was obtained through right radial arterycatheterization. Trans-esophageal echocardiography (TEE) was performed toconfirm the diagnosis, de-airing and adequacy for surgical procedure. Afterinduction, bilateral regional cerebral oxygen saturation (rSOAll the patients were transferred to intensive care unit (ICU), intubated andwere managed as per ICU protocol. Repeat TTE was performed in all the patientsbefore extubation to rule out ventricular dysfunction and pericardial collectionand at the time of discharge to assess the ventricular function and rule out anyresidual lesion. Color Doppler ultrasonography of neck vessels was performed inall the patients in order to assess the patency of CCA and IJV.All the patients were followed up with physical examination in the first week,first month and then in the third month or as required after surgery to assessthem clinically for symptoms, wound healing and any restriction of shouldermotility. TTE was performed in all the patients to assess the status of anyresidual defect and ventricular function.Patient lay supine with ring under the head and head turned to the left. Rightside of the body was elevated by 30° with a bolster under the right shoulder andright arm was flexed at shoulder and elbow joint to expose the secondintercostal space. The patient was draped to expose the base of neck, axilla andchest up to left nipple. A 3-5 cm vertical incision was placed in mid-axillaryline in third or fourth intercostal space and after dividing the muscles,pleural space entered. Intercostal space was chosen depending upon the midpointof the right atrium (RA) on preoperative chest x-ray .2, 12Fr DLP femoral arterial cannulae and 12FrBiomedicus One Piece Femoral Venous Arterial Cannulae  were used for CCA and IJV cannulation respectively; whilein patients with BSA 0.5-0.69 m2, similar cannula of 14Fr size wereused. For IVC cannulation, DLP single stage venous cannulae with right anglemetal tip  used was one size larger thanIJV cannula.A transverse cervical incision 1.5-2 cm in length was made one finger's breadthabove the clavicle over the lower part of sternocleidomastoid muscle where twoheads of the muscle divide. Subcutaneous tissue and platysma divided andsternocleidomastoid muscle exposed. Mastoid retractor applied and dissectionperformed between two heads of the muscle. Both, CCA and IJV were isolated incarotid sheath, looped and mobilized along length. Care was taken whilemobilizing IJV to avoid induction of spasm, which would make subsequentintroduction of venous cannula difficult. Whenever found, a small branch on themedial aspect of IJV was ligated and divided. Rest of the mobilization of boththe vessels was safe as they don't have any other branch in the neck. Both thevessels were looped and the patient was heparinized with 400 U/kg. Three minuteslater, 5 mm polytetrafluoroethylene (PTFE) graft was anastomosed to CCA arteryafter clamping  and syntAfter achieving the adequate activated clotting time (ACT), CPB was initiated andattention was turned to thoracotomy. Mechanical ventilation was disconnected andpericardiotomy was performed parallel and 2-3 cm anterior to phrenic nerve toexpose the ascending aorta cranially and IVC caudally and pericardial stays wereinserted. Carbon dioxide was continuously insufflated into the operative fieldthroughout the procedure to displace intra-cardiac air. IVC was dissected,looped and cannulated with angled venous cannula that was advanced into thepericardial cavity through a stab incision in subxiphoid area. IVC was snuggedand snugger was left in the pleural cavity to keep it out of the operativefield. Mild hypothermia (30-32°C) was established. Assisted venous drainage wasused, if required, with a median vacuum pressure of 30 mmHg .RA appendage was retracted towards IVC and dissection was performed withscissors between aorta and right pulmonary artery to mobilize the aorta. DeBakey atraumatic coarctation clamp was passed through a stab incision in rightsecond intercostal space in mid-axillary line and aorta was cross clamped at thelevel of right pulmonary artery. Del Nido cardioplegia was delivered into theaortic root using 16G needle puncture. When cardioplegia delivery was finished,cardioplegia puncture site was enlarged with sharp scissors and a 5-0 plegtedpolypropylene (prolene) suture was placed around the puncture site and leftloose. IJV cannula was pulled back into superior vena cava (SVC). SVC wassnugged and snugger was left into the pleural cavity as for IVC snugger. RA wasopened and a vent was inserted into the left atrium through patent foramen ovaleor atrial septal defect (ASD). When defect was absent, it was created and ventwas inserted.Repair was performed depending upon the cardiac lesion similar to midlinesternotomy approach except in patients with ventricular septal defect (VSD). Forrepair of VSD, anterior leaflet of the tricuspid valve was detached from annulusto expose the borders of VSD.In our series, three patients with ostium secundum atrial septal defect (OS-ASD)had associated left superior vena cava (LSVC). In one patient, we were able toloop and snug the LSVC by retracting the aorta and pulmonary artery; it wassnugged to prevent the flooding of operative field. In other two patients,straight venous cannula was inserted in the LSVC through coronary sinus andconnected to cardiotomy sucker for drainage.When intra-cardiac repair was finished, RA was repaired and SVC and IVC snuggerswere removed. After RA closure, carbon dioxide insufflation was stopped.Ventricular pacing wire was placed. De-airing was performed by gentlycompressing the heart against the spine with rear end of De Bakey forceps andthe lungs were ventilated manually. Aortic root was vented by allowing bleedingfrom the cardioplegia puncture site into the pericardial cavity. Under lowflows, aortic cross clamp was removed and IJV cannula was advanced into RA. Timewas allowed for the heart to recover the sinus rhythm with good contractility ofthe ventricles. After re-warming of the patient, IVC cannula was removed and IVCrepaired. After confirming the adequate de-airing on TEE, cardioplegia puncturesite was repaired. Finally, CPB was terminated in usual fashion.When the procedure was finished, IJV cannula was removed and IJV was repairedwith interrupted 6-0 prolene sutures. Heparin was reversed with protaminesulfate using dose of 1.0 mg/100 U of heparin. The PTFE graft was severed nearthe anastomosis with CCA and was oversewn to prevent any residual stump. CCApulsation was confirmed. After hemostasis, both heads of sternocleidomastoidmuscle were approximated. Platysma and subcutaneous tissues were sutured. Apericardial drain inserted through subxiphoid incision and another right pleuraldrain through axillary incision. Pericardium was loosely approximated. Ribs wereloosely approximated with absorbable suture. Subcutaneous tissue and skin wererepaired with absorbable sutures.Results are expressed as mean ± standard deviation (SD). All data analysiswas performed using SPSS for windows, version 20.0 .Thoracotomy was performed in the third intercostal space in 31 patients and in thefourth intercostal space in 6 patients. The lenght of axillary skin incision variedbetween 3 and 6 cm and of cervical incision between 1.5 and 2 cm. Two patientsrequired enlargement of thoracotomy incision to improve the exposure of VSD.Intraoperative and postoperative data is shown in Mean postoperative drain output was 13.37±16.01 ml and no patient requiredre-exploration for bleeding. Postoperatively, all patients regained consciousnesswithout neurological complication. Mean duration of mechanical ventilation was7.45±1.7 hours. All patients remained in sinus rhythm and postoperative TTErevealed satisfactory repair without residual defect or ventricular dysfunction. Twopatients had 1 mm and 2 mm residual defect across VSD patch, respectively. Onepatient with ostium primum ASD had grade II left atrioventricular valveregurgitation. Another patient with VSD had mild left ventricular dysfunction. Twopatients developed stridor after extubation and were managed conservatively. Nopatient developed any temporary or permanent, focal or generalized neurologicaldeficit during the hospital stay. Color Doppler ultrasonography of neck vesselsconfirmed patency of both CCA and IJV in all the patients . There wThree patients who had associated LSVC, difficulty was experienced in accessingthe LSVC to cannulate and snug.Follow-up was 100% complete and mean duration of follow-up period was11.4±2.85 months. During follow-up, all patients were asymptomaticwithout any evidence of vascular complication or neurologic impairment. Allpatients had healing of both cervical and thoracotomy wound without keloidformation or shoulder movement deficit. Follow-up TTE confirmed normal leftventricular function in all the patients. In one patient with grade II leftatrioventricular valve regurgitation, regurgitation reduced to grade I. None ofthe patients had tricuspid regurgitation. No residual leak was observed in anyof the two patients with leak across VSD patch at the time of discharge.-6. In neonates, selective unilateralCCA cannulation is performed by advancing the arterial cannula from ascending aortaor innominate artery to CCA and used for ascending aorta and arch repair during deephypothermia for antegrade cerebral perfusion. Studies have found the technique to be safe withoutincreased risk of neurological complications. As per literatute, direct cannulationof CCA, however, has not been used in pediatric cardiac surgery.Direct CCA cannulation has gained popularity for total body circulation as well asantegrade cerebral perfusion during deep hypothermia in adult patients operated onfor complex aortic and re-do cardiac surgeries. This technique has proved itsefficacy and neurological safety. In our previous experience of 5 patients, CCA was found to be ofsufficient size even in small children to supply the total cardiac output. The flowin CCA is distributed to whole body without causing ipsilateral brainhyperperfusion. This is confirmed by the results of our study. We observed adequateradial artery pressures during CPB and absence of any neurological, myocardial orabdominal organ dysfunction in postoperative period in all patients. The possibleexplanation may lie in an experimental study by Zéicourt et al.. Authors using a realistichypoplastic neonatal aorta template as the base geometry for effect of cannulationtechnique on flow distribution, found that flow distribution to the differentvascular beds in neonates was dictated by the downstream vascular resistances ratherthan the cannulation strategy. The similar mechanism may be responsible for flowdistribution in infants, children and adults as other studies in adults have alsofailed to find any sign of hyperperfusion with this technique,6.CCA is easily accessible at the base of neck and like innominate artery or aorta, itis sturdy and not easily damaged.Similarly, IJV is sufficiently large and easily accessible for venous return duringCPB. Due to same reasons, cervical cannulation of CCA and IJV are preferred routefor establishment of pediatric ECMO. However, in contrast to ECMO, our techniquedoes not require ligation of either CCA or IJV; thus prevents the risk of stroke andcerebral and facial edema. Absence ofpostoperative neurological complications in any patient confirms our assumption.An important concern during CCA cannulation is the risk of neurological injury.Therefore, NIRS was used to detect any decrease in cerebral oxygen saturation fromthe time of anastomosing the graft to CCA and during CPB. In our study, no patienthad >15% fall in NIRS from baseline during CPB. This was probably because thecerebral flow was maintained through both the carotid arteries even during aorticcross clamping as blood supply to whole brain including posterior circulation ismaintained by rich network of anastomoses interconnecting the cervical, vertebral,occipital, and carotid arteries designated as 'suboccipital carrefour orknot'. As aorta is away fromthoracotomy incision, there is poor control of depth of arterial cannula insertion.This increases the risk of vascular accidents as well as neurological complications.Second, cervical cannulation along with aortic cross clamp insertion through aseparate stab incision moves the entire hardware away from the operative field. Thisimproves the working space and freedom of instrument maneuverability. Other authorshave also emphasized the importance of peripheral cannulation to prevent clutteringin the operative field. However, femoral cannulation is better suited for olderchildren, while cervical cannulation can be performed even in neonates andinfants-14.Cervical cannulation for institution of CPB has several advantages over centralcannulation. First, it completely avoids the need to gain control of the aorta forarterial cannulation, an important limitation of lateral thoracotomyThird, straight multi-hole cannula inserted into IJV is easily advanced into RA andleads to almost complete emptying of the heart. Therefore, mechanical ventilationcan be discontinued as soon as CPB is commenced. This improves the exposure ofpericardium and heart and ease the insertion and removal of IVC cannula. The IVCcannula can be removed early after removal of aortic cross clamp withoutcompromising the venous drainage. Fourth, this technique of CPB avoids additionalgroin incisions and potential peripheral vascular complications. Fifth, cannulationof graft rather than direct cannulation of CCA almost nullifies the risk of intimalinjury and narrowing of CCA. De-airing can be adequately performed by enlarging thecardioplegia puncture site and TEE guidance. All of our patients readily regainedconsciousness without neurological complications. This further confirms the adequacyof de-airing of the heart.. However, we did not perform the TCD in our study due tonon-availability. Our strategy to prevent hyperperfusion was to reduce the arterialpressure during CPB while monitoring the NIRS because cerebral blood flow ispredominantly determined by arterial pressure rather than the CPB flow. In ourstudy, no patient developed symptoms of cerebral hyperperfusion, although, we didnot specifically investigated this. However, even if brain hyperperfusion isdetected on TCD, it can easily be corrected by looping the CCA cranial to graftanastomoses and applying the clip to partially snug the artery to adjust the TCDvelocity.An important concern with CCA cannulation is the potential risk of cerebralhyperperfusion during CPB. Transcranial Doppler (TCD) rather than NIRS is bettermodality to detect the hyperperfusion. However,there are certain shortcoming of this approach e.g. difficulty incannulation of aorta, IVC and limited exposure of the right ventricle free wall andleft sided structures of the heart as the heart falls farther away to the left as itgets empty. Cervical cannulation and single dose del-Nido cardioplegia overcome the difficultiesassociated with cannulation. We, however, believe this incision is suitable only forrepair of simple congenital cardiac defects that can be accomplished through RA. Inour experience, apical, mid-muscular, doubly committed and outlet VSDs are thecontraindications for this approach. We also consider the presence of LSVC as arelative contraindication as it makes the operative procedure cumbersome and theoperative field cluttered. We have not operated any patients of tetralogy of Fallotthrough this approach, however, we consider it a challenge.We choose lateral thoracotomy as it is cosmetically and functionallysuperiorCervical cannulation for CPB can be used with any minimally invasive approach andeven in pediatric patients operated for re-do or aortic arch surgeries as in ourinitial experience. In our experience, this technique adds 15-20 minutes tooperative time, however, lots of struggle associated with central cannulation andexposure can be avoided. Further studies with technique may pave the path for thisapproach as an alternative safe technique for establishment of CPB in pediatricpatients.Limitations of our study include its retrospective nature and small sample size.However, it does contribute to establish cervical cannulation as an alternativetechnique for CPB in minimally invasive and complex aortic pediatric cardiacsurgeries.Cervical cannulation using side-graft on CCA for arterial inflow and IJV cannulationfor venous return is a reliable and safe method for installation of CPB in minimallyinvasive pediatric cardiac surgery. This technique is safe, efficient, and quick inits execution and compared to minimally invasive technique, this technique avoidsthe handling of the aorta and the SVC. Complications directly associated withcervical cannulation are uncommon.


Cardiac involvement in patients with sarcoidosis is an independent predictor of mortality and associated with very poor prognosis. Inflammatory processes within the myocardium as well as subsequent fibrotic myocardial alterations may lead to diastolic dysfunction and at worst sudden death resulting from ventricular tachy-arrhythmias or conduction block. Diastolic dysfunction as a sign of left ventricular (LV) impairment can be assessed accurately by the measurement of early diastolic strain rate (EDSR). In this follow up study we performed cardiovascular magnetic resonance (CMR) feature tracking (FT) in patients with and without cardiac involvement of sarcoidosis in order to investigate its impact on systolic and especially diastolic function over time.Patients with systemic sarcoidosis were consecultively enrolled into the study. They underwent clinically routine CMR exams on a 1.5 Tesla Philips INGENIA scanner. CMR exams were classified as "cardiac involvement" if at least one of the following pathologies occured: pathological relative enhancement, late enhancement findings consistent with (post-) inflammatory changes, myocardial edema, pericardial effusion. Patients with cardiac involvement underwent a follow up CMR exam within a time frame of 36 ± 3,5 months. According to CMR results patients were divided into 4 different groups (Gr.): group 1 (n = 14): patients with positive findings in both exams, group 2 (n = 9): patients with positive findings only in the initial exam; group 3 (n = 37): patients with sarcoidosis but inconspicuous initial CMR exam and group 4 (n = 20): a control group of healthy age matched volunteers with no medical history of sarcoidosis or cardiac disease. In addition in each CMR exam FT derived systolic and diastolic circumferential strain parameters were calculated from SSFP-cine images in midventricular short axis, which were acquired prior to contrast agent injection. Peak systolic strain rate (PSSR), peak diastolic strain rate (PDSR), Peak systolic circumferential strain (PSECC) as well as early diastolic strain rate (EDSR) were calculated and compared between groups. Patient characteristics are demonstrated in table EDSR in group1 patients was significantly lower 53,24 ± 15,26) compared to all other groups (Gr.2: 75,1 ± 22,62, Gr.3: 77,25 ± 5,06, Gr.4: 79,74 ± 25,59 respecitvely; p < 0,05; table 4 ± 15,26This study reveals 2 major findings. First patients with consistent cardiac involvement of sarcoidosis have a significantly reduced EDSR. Second diastolic function in patients with sarcoidosis and significantly impaired EDSR is not likely to recover over time.


Flow-Independent Dark-blood DeLayed Enhancement technique (FIDDLE) that increases the conspicuity of subendocardial hyperenhancement, by making the blood-pool black. In this study we investigated the prevalence of myocardial scarring as determined by DE-MRI and FIDDLE in CHD patients with LV pressure or volume overload.Congenital heart disease (CHD) can result in left ventricular pressure and/or volume overloaded states, which may result in myocardial scarring. Prior studies have suggested that the presence of myocardial scar may be associated with adverse outcome in patients with CHD. The current gold standard for scar imaging is delayed-enhancement MRI (DE-MRI). However, it may be difficult to distinguish hyperenhanced subendocardial scars from the bright blood-pool with DE-MRI. We have developed a new, Patients with CHD and LV pressure (n = 10) or volume overload (n = 11) were prospectively enrolled. Pressure overload required the presence of LV wall hypertrophy along with evidence of significant downstream obstruction . Volume overload required the presence of moderate or severe LV ventricular dilation along with evidence of significant aortic or mitral regurgitation. Patients with asymptomatic bicuspid AV with normal LV size and wall thickness without significant valvular stenosis or regurgitation were enrolled as controls (n = 4). Standard DE-MRI and FIDDLE were acquired in each patient 10-20 minutes after gadolinium administration (0.15 mmol/kg), using matched parameters . DE-MRI and FIDDLE images were analyzed independently using a 17-segment model and a 5-point scale for scar transmurality.Figure 1b. Note, the scar is nearly globally subendocardial throughout the LV (arrows). Even in patients with scar identified by DE-MRI, scar size was larger by FIDDLE compared with DE-MRI (p=0.0076).Characteristics of the 3 cohorts are shown in the Table Myocardial scarring is common in congenital heart disease patients with LV volume overload and ubiquitous in patients with LV pressure overload. FIDDLE is significantly more sensitive than DE-MRI at detecting subendocardial scarring.


P = 0.924). NYHA class, SAS and 6MWT also improved similarly in both groups at 12 months. Mortality in both groups was not significantly different . However, there was a significant difference in the time required for optimization by QuickOpt compared with echocardiography .In this trial, long-term therapeutic effects and clinical improvements in Chinese chronic heart failure patients optimized by QuickOpt or echocardiography were compared for atrioventricular (AV) and interventricular (VV) delay optimizations after cardiac resynchronization therapy (CRT) with pacing (CRT-P) or with pacing and defibrillator (CRT-D) therapy. One hundred and ninety-six subjects (50%) had dilated cardiomyopathy, 108 (27.6%) had ischemic heart disease and 112 (28.6%) were hypertensive and were randomized into QuickOpt (198) or echocardiographic optimization (control) (194) groups at ≤2-weeks post-implantation. Programmed AV/VV delay was optimized at baseline and at 3 and 6 months. Left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) class, specific activity scale (SAS), and the six-minute walk tests (6MWT) were evaluated by blinded researchers at 12 months. Of the QuickOpt group, LVESV decreased significantly by 24.7% ± 33.9% compared with baseline, while LVESV of Controls decreased by 25.1% ± 36.1% ( Even today, the prognosis of CHF is poor with studies from the United States (US) and Europe showing that 6-month and 5-year mortality rates remain high at 14% and 45%, respectively6. Due to its high incidence and mortality, CHF has been deemed to be a worldwide epidemic disease.Congestive heart failure (CHF) has been estimated to affect more than 26 million people worldwide11, including defibrillation capability (CRT-D) or with pacing only (CRT-P), is recommended for patients with heart failure who have left ventricular dysfunction with a left ventricular ejection fraction of ≤35%, on recommended medications as per consensus guidelines for the diagnosis and treatment of CHF.Currently, the use of cardiac resynchronization therapy (CRT)13, with the aim of interval optimization to reduce left ventricular dyssynchrony and mitral regurgitation. Optimization of both atrioventricular (AV) and ventricular-ventricular (VV) intervals improves the therapeutic effects of CRT15.In China, nearly 3 million CHF patients require CRT-P or CRT-D devices, and proper resynchronization optimization after implantation has become increasingly challenging. Common approaches to define the best AV interval rely on repeated echocardiographic assessments with program adjustments (iterative) and other methods16. The purpose of AV interval optimization is to maximize ventricular preload as well as to allow the mitral valve to close at the proper time. The purpose of VV interval optimization is to make the peak of the left and right ventricular activation meet in the vicinity of the ventricular septum, thereby reducing ventricular dyssynchrony. The effects of this optimization can be assessed by the left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV), New York Heart Association class (NYHA), 6-minute walk test (6MWT) and specific activity scale (SAS) according to the US guidelines for CHF diagnosis and therapy17.The key to obtaining the optimal AV interval is to synchronize ventricular systolic and diastolic phases. The optimized AV and VV intervals are calculated based on specific medical personnel perceptions and the intracardiac electrogram16.The QuickOpt algorithm  uses the timing cycle of the cardiac electrogram to perform rapid interval optimization, with a program for use at routine follow-up. It is a rapid (1–4 min) simple, automatic determination of optimal AV/VV delays. Compared with echocardiographic optimization, previous studies have demonstrated that the Aorta Velocity Time Index (AVTI) by QuickOpt optimization and the maximum AVTI by echocardiographic optimization are significantly correlated, with a correlation coefficient of 0.96–0.98Small sample sizes and short evaluation periods in existing studies have mainly prevented unequivocal acceptance of the results of CRT with QuickOpt optimization in China. To compare QuickOpt and echocardiographic optimization in the short and long-term, including the clinical outcomes of the two methods across China, we designed a multicenter, prospective, randomized, double blinded, parallel controlled trial.The main aims of our trial were to compare the therapeutic effects of optimization by QuickOpt or echocardiographic optimization on LVESV and other clinical parameters  in a 31-hospital collaborative cohort of Chinese patients, including adverse events (AE) over one year after CRT-P/D implantation.All patients were enrolled according to the following criteria for CRT-P/D indications: 1) left ventricular ejection fraction (LVEF) ≤35%; 2) New York Heart Association (NYHA) class III-IV heart failure; 3) QRS complex duration ≥120 ms.Based on the inclusion criteria, 400 patients with CHF in 31 different hospitals from May 2010 to February 2015 were implanted with CRT-P (260 patients) or CRT-D (140 patients) and then they were automatically assigned into the QuickOpt and Echo groups for optimization in a 1:1 ratio by software which linked in all the sites. One hundred and ninety-eight patients were randomized to the QuickOpt group, 194 patients to the echocardiography group after two weeks implantation, and 8 declined randomization because they could not follow up to the end of the research period. We performed CRT-P/D interval optimization during the first two weeks, at 3 months (±2 weeks) and 6 months (±2 weeks) after implantation, and programmed the optimal AV/VV interval in the CRT-P/D  or CRT-D  and lead systems  and received optimal medical therapy.patients <18-years;life expectancy <1 year;received intravenous-positive inotropic drug treatment;participating in other device or drug trials;being prepared for cardiac transplantation;hypertrophic cardiomyopathy;severe aortic or mitral stenosis or regurgitation without valve replacement; -pregnant or lactating women;coronary artery bypass surgery, percutaneous coronary intervention or cardiomyoplasty in previous 6 weeks;acute coronary syndrome;stroke;pre-excitation.Patients were excluded if they were suffering from severe sinus bradycardia (sinus rate ≤40 bpm) or had persistent chronic atrial tachyarrhythmia, including atrial fibrillation, atrial flutter and atrial tachycardia, or second- or third-degree AV block, or a QRS complex duration less than 120 ms. Other exclusion criteria were:11.The apical four-chamber view was used to measure the mitral inflow velocity profile at the mitral valve to optimize AV delay. The AV delay was initially set between 60 ms and 200 ms, and was varied in 20 ms steps. The EA duration was measured at each AV interval, and the optimal AV delay was defined as the maximal EA duration without truncating the A wave11.To optimize VV delay, an apical five-chamber view was used to determine the velocity-time integral (VTI) of the left ventricular outflow tract. The VV delay was set between −40 ms and +40 ms, with programmed adjustments in 20 ms increments; optimal VV delay resulted in a maximal VTIAV/VV delay optimization was performed at the intervals stated above with devices being programmed according to data obtained during QuickOpt optimization, namely optimized sensed AV, paced AV and VV intervals.Within 2 weeks after CRT-P/D implantation, we used Merlin 3650 PCS  to implement the QuickOpt algorithm, and separately kept 12-lead ECG data of dual chamber pacing for subsequent analysis  in this trial. The trial register number was NCT01172067 .This trial complied with the Declaration of Helsinki. Our protocol was approved by the Research Ethics Committee of all 31 hospitals participating  since the patients signed consent until the end of the study, regardless of the cause. Severe AEs that occurred during the course of the clinical study, such as the need for hospitalization, prolonged hospitalization, disability affecting patient’s work, life threatening events or death.worsening heart failure;pacing system infection;elevated pacing threshold;lead dislocation;lead fracture;lead insulation damage;death.AE related to CRT-P/D included, but were not limited to:Each center had a physician specifically responsible for collecting data and then filling in the Electronic Data Capture (EDC). The data were reliable and every record of death and hospitalization was documented.The report of death incidence consisted of two procedures. Once informed of a death, physicians evaluated the cause and reported it to the ethics department in the hospital within 24 hours. Then the ethics department reported to the China Food and Drug Administration (CFDA). In the meanwhile, physicians filled the death table in the electronic CRF within 3 days, and kept the original medical record as the initial document.t-test.We hypothesized that 12 months after implantation, the improvement in LVESV in the QuickOpt group would equal that of the echocardiography group. As the presumed lower limit value was −10%, the assumed significant difference was 0.05 (1-sided), the detection efficacy was 80%, the overall standard deviation was 0.35, and the difference between the two group averages was 0.1, we needed 306 cases in total and 153 cases for each group. Taking into account 20% loss of cases due to death, heart transplantation, loss to follow-up and other causes, we finally enrolled 200 cases in each group, with a total cohort size of 400 cases. For primary efficacy, the difference between the two types of optimization was evaluated by Student’s t-test. If the result was an obvious non-normal distribution and heterogeneity of variance according to the distribution of final data, we adopted one of the following non-parametric statistics: Wilcoxon rank sum test or the Kolmogorov-Smirbov test. The FAS was an ideal group of participants as close to the Intention To Treat (ITT) principle as possible, which included nearly all subjects after randomization. The data were analyzed according to the intention-to-treat principle. The per protocol set (PPS) was a subset of the full analysis set, and each subject in this data set showed good compliance without violating the program. In our study, there were 392 cases consistent with the FAS set and 226 consistent with the PPS set.For secondary efficacy, the improvements in the NYHA class and SAS evaluation between the two types of optimization were compared with a full analysis set (FAS) and a Cochran-Mantel-Haenszel test. If the results of a chi-square test yielded a homogeneous distribution, the Fisher exact test was used. The improvement in the 6MWT between the two optimization methods was also compared with FAS and any significant differences evaluated by means of a The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.The research cohort in this trial was comprised of 392 patients with CHF, in which 289 patients were male and 103 female. The mean age of the QuickOpt group was 61.38 ± 11.77 years and the echocardiography group 59.21 ± 11.36 years. 196 patients were diagnosed with dilated cardiomyopathy and 112 patients with hypertension, 47 patients with diabetes and <10 cases of hypertriglyceridemia, valvular heart disease, stroke or paroxysmal atrial fibrillation; however, there were 15 cases of stroke in both groups. In comparison of demographics, baseline data in the two groups showed no significant differences  interval in the QuickOpt group was significant longer than in the echocardiography group at baseline, 3 months and 6 months . The VV interval in the QuickOpt group was only significantly longer at baseline (32.53 ± 16.99 vs. 27.32 ± 15.72 ms), but there were no significant differences between the QuickOpt and the echocardiography groups in the AV  interval at any stage.P = 0.924. The LVEDV of the 2 groups over 12 months showed significant improvement but there was no significant difference between the two optimization groups. The LVEF was significantly increased 12 months after optimization in the QuickOpt and control groups, being 38.4 ± 44.3% and 38.4 ± 44.8%, respectively, which demonstrates that the primary efficacy of the QuickOpt optimization was not inferior to the efficacy of the echocardiography   Table .Table 7SP < 0.05).In the present study, we confirmed in a large-scale clinical trial using QuickOpt optimization against the standard echocardiographic method in Chinese congestive heart failure patients treated by cardiac resynchronization, that the hemodynamic efficacy of QuickOpt optimization was not inferior to the echocardiographic method. These results were achieved by using QuickOpt in a time as rapidly as 3 min compared with 56 min by echocardiography  and thus raising LVEF, mitral valve regurgitation was reduced. The two methods together with programmed control of AV/PV and VV have improved heart function (NYHA scores) and left ventricular end-systolic volume (LVESV)  Table . The 6MWet al.10 without adverse effects on the parameters of LV function.The PV delay time exhibited a significant difference between QuickOpt and echocardiography optimizations at baseline, 3 months and 6 months, due to the optimal AV delay defined as the maximal EA duration without truncating the A wave, combined with the optimal VV delay producing a maximal LV outflow velocity-time integral. This difference in PV was also seen in the small cohort study of Wang P < 0.05) is a valuable clinical benefit with this methodology, which is non-inferior to echocardiography and needing circa 50 min less time than echocardiographic analysis. In a busy medical environment, this time saving allows physicians and technologists to reallocate echocardiography services for other patients.The significant difference in the optimization time by QuickOpt compared with echocardiography  determined by QuickOpt and the maximum AVTI by echocardiography optimization are significantly correlated (correlation coefficient r = 0.96–0.98)10 reported similar findings in their smaller number of patients when assessed at 12 months after optimization. In our study, we clearly demonstrated that there were no significant differences in LVESV, LVEDV and LVEF between the two groups at 12 months (Table The other major aspect of our study is that we were able to demonstrate that the efficacy of QuickOpt optimization on parameters of cardiac function was comparable with that of the echocardiographic method. Further, LVEF was significantly increased at 12 months in both optimization groups, being 38.4 ± 44.3% and 38.4 ± 44.8%, respectively. Wang and colleaguesFinally, it is important to note that there were no significant differences in the incidence of device-related AEs and mortality rates between the QuickOpt and echocardiography groups Table .This multi-center and large cohort trial has shown that QuickOpt is a rapid and simple method to carry out optimization of AV and VV delays, which is non-inferior compared to the echocardiographic method in terms of resulting cardiac function and adverse events. For busy cardiology departments this will significantly free up precious clinical time.CONSORT 2010 checklistprotocolSupplementary Datasets


The right ventricle (RV) remains the cardiac chamber for which scientific data regarding structure, function, adaptation to load, or arrhythmogenic potential is still behind what we know for the left ventricle, despite more recent efforts in this field. RV function is critical in numerous pathologies, related to pressure overload , volume overload , and myocardial diseases  as well as right ventricular ischemia or infarction. Moreover, the adaptation of the RV to more extreme physiologic situations  opens windows for understanding its physiology.Despite data on the prognostic value of RV function, there is still debate on the best parameters that describe it and their clinical relevance. Important developments in right ventricular imaging have occurred during the last years, from myocardial deformation imaging to 3D-echocardiography and from cardiac MRI to right ventriculoarterial coupling studies, which have all contributed to a better understanding of right ventricular pathophysiology.The RV is the most anterior cardiac chamber and is situated immediately behind the sternum. With a triangular shape, it has three components: inlet (sinus) portion, apical trabecular section, and outlet (conus) section. The muscular wall of the RV is normally very thin 3–5 mm), adequately serving the ejection of blood in a low impedance pulmonary circulation . The RV –5 mm, adThe shape, architecture, and structure of the RV facilitate the understanding of its physiology. Owing to the curvature of the interventricular septum (IVS) in the normal heart, the RV is described as wrapping around the LV. This particular shape, as well as the connection of the two ventricles through the IVS, constitute the interventricular dependence. In consequence, in cross section, the RV has a crescent shape which is formed because of its lower pressures, thinner walls, and greater compliance compared to the LV .RV contraction has a longitudinal “peristaltic” pattern, with a 30–40 ms delay from the onset of contraction of the RV free wall from apex to the outflow tract , facilitSeveral studies have tried to understand the mechanisms of adaptation and maladaptation of the RV to volume and pressure overload, respectively. A few years ago, we demonstrated that at similar levels of pressure overload the RV is less dilated and performs better in patients with pulmonary stenosis as compared with those with pulmonary arterial hypertension (PAH) , which wMoreover, acute RV failure is increasingly seen in the intensive care unit and can cause or aggravate many common critical diseases. It can be due to either acute pressure or volume overload or other aggravating factors leading to a reduction of myocardial contractility owing to ischemia, cardiomyopathy, or arrhythmia . J. C. GIt has been demonstrated that, beyond etiology, a key element for establishing prognosis in patients with PAH is RV function . The RV While pulmonary vasodilators appear to have impacted on the natural history of PAH, there have been few investigations assessing the impact of these drugs on RV remodeling. In the study of N. Rai et al. from the present issue, both sildenafil and riociguat prevented the deterioration of RV function, as determined by a decrease in RV dilation and restoration of the RV ejection fraction, while riociguat also prevented RV fibrosis induced by pulmonary artery banding (a model of fixed RV pressure overload). These experimental data need further investigation in the clinical setting.It is well known that the most frequent cause of RV failure in clinical practice is related to pulmonary hypertension due to left heart disease  . The proVarious systemic or cardiac diseases can directly affect the RV. This has been described for genetic and nonhereditary cardiomyopathies. For example, diseases like hypertrophic cardiomyopathy, amyloidosis, Fabry's cardiomyopathy, and dilated cardiomyopathy can have biventricular involvement which occurs most often late during the disease evolution. T. cruzi protozoan infection, which can be at the root of more than 10% of heart failure cases in endemic regions (like Brazil). As it is often associated with systemic congestion, studies of RV involvement were started years ago, and the review of M. M. D. Romano et al. in this issue has discussed the role of imaging in the diagnosis of RV involvement in Chagas cardiomyopathy. While no specific cardiovascular imaging tools appear to assess myocardial involvement in this infectious disease, there is a place for speckle tracking imaging and cardiac MRI to identify early functional changes during the course of disease.Not only cardiomyopathies but also immune and inflammatory diseases with cardiac tropism can affect the RV as well. Chagas disease is a tropical disease caused bySystemic sclerosis (SSc) is a disease which can involve the RV in various ways. Being the leading cause of pulmonary arterial hypertension (PAH) among connective tissue diseases, it has been reported to result in increased pressure afterload of the RV in up to 12% of cases, which can subsequently result in right ventricular failure. Moreover, a direct effect of scleroderma on the myocardium consists of increased fibrosis and inflammatory lesions, and autopsy studies identified significant cardiac fibrotic changes in 70–80% of the examined patients . MoreoveMore studies investigating the normal right ventricle structure and function and especially its adaptation to physiological states  and disease are warranted. While its relation to prognosis in PAH was demonstrated, quantitative parameters of RV dysfunction are not yet considered a part of risk stratification for these patients, proving insufficient knowledge of the best parameter to follow.Ruxandra JurcutKristina HaugaaAndre La Gerche