P = .025). In older individuals, CEP T2* values did not associate with disc degeneration (P = .39‐.62). Precision errors in T2* ranged from 1.7 to 2.6 ms, and reliability was good‐to‐excellent (ICC = 0.89‐0.94). These findings suggest that deficits in CEP composition, as indicated by low T2* values, associate with severer disc degeneration during the mild‐to‐moderate stages. Measuring CEP T2* values with UTE MRI may clarify the role of CEP composition in patients with mild‐to‐moderate disc degeneration.Cartilage endplate (CEP) biochemical composition may influence disc degeneration and regeneration. However, evaluating CEP composition in patients remains a challenge. We used T2* mapping from ultrashort echo‐time (UTE) magnetic resonance imaging (MRI), which is sensitive to CEP hydration, to investigate spatial variations in CEP T2* values and to determine how CEP T2* values correlate with adjacent disc degeneration. Thirteen human cadavers (56.4 ± 12.7 years) and seven volunteers (36.9 ± 10.9 years) underwent 3T MRI, including UTE and T1ρ mapping sequences. Spatial mappings of T2* values in L4‐S1 CEPs were generated from UTE images and compared between subregions. In the abutting discs, mean T1ρ values in the nucleus pulposus were compared between CEPs with high vs low T2* values. To assess in vivo repeatability, precision errors in mean T2* values, and intraclass correlation coefficients (ICC) were measured from repeat scans. Results showed that CEP T2* values were highest centrally and lowest posteriorly. In the youngest individuals (<50 years), who had mild‐to‐moderately degenerated Pfirrmann grade II‐III discs, low CEP T2* values associated with severer disc degeneration: T1ρ values were 26.7% lower in subjects with low CEP T2* values ( For example, nutrients entering the avascular disc and exiting metabolites must pass through the CEP,The biochemical composition of the CEP consists mainly of type II collagen, glycosaminoglycans (GAGs), and water.Recent advances in MRI enable visualization of the CEP2This study was approved by our Institutional Review Board. Informed consent was obtained from each subject.2.1Thirteen whole, fresh unfixed cadavers within 5 days postmortem  and seven healthy human subjects without prior history of back pain or spinal pathology  were studied. Major exclusion criteria for the subjects and cadavers included pregnancy, spondylolisthesis, scoliosis, prior lumbar surgery, disc herniation, and compression fracture. Additional exclusion criteria that were applied to the subjects included diabetes, positive smoking status, cancer, and active use of osteoporosis medication(s).2.2am, with the duration between repeat scans ranging from 15 to 30 minutes. Clinical fast spin‐echo images with T2 weighting  were also acquired in the sagittal orientation and used for Pfirrmann grading.Clinical MRI was performed on a Discovery MR 750 3T scanner using an 8‐channel Cervical Thoracic Lumbar Coil . Cadaver MRI was performed on a Discovery MR 750W 3T scanner using a Geometry Embracing Method coil contained within the table. Imaging consisted of 3D multi‐echo UTE Cones2.33. Custom software was written in IDL  to generate CEP T2* maps. The algorithm included the following steps:A total of 23 structurally intact CEPs  caudal to the L4‐L5 (n = 5) or L5‐S1 (n = 18) discs were analyzed. The L4‐L5 and L5‐S1 levels were selected based on orientation criteria for imaging the CEP and measuring T2* values with UTE MRI. Specifically, the orientation of the selected CEPs with respect to the magnetic field (range: 48°‐60°) was close to 54.7°, the magic angle, thereby ensuring the resultant T2* values mainly reflect unbound water.SIN and SIC are the SI values for N and C. Location‐specific T1 and T2 refer to the SI difference between CEP and bony endplate and CEP and NP, respectively, and account for the varying image intensity and contrast across the endplate.(a) CEP segmentation: we analyzed all sagittal slices that contained CEP voxels, which ranged from 51 to 88 slices depending on the CEP. On each sagittal MRI slice, the anterior and posterior ends of the CEP were located, and a contour line (thickness = 1 voxel) was created by tracing the voxels with high signal intensity (SI) between the two identified points. The resultant contour was masked over the original image, and the masked area was subsequently dilated using a voxel‐based region‐dependent inclusion criteria. For example, for a voxel C on the contour line, suppose voxel N is one of its cranially or caudally adjacent neighbors. N was included in the masked area if the following condition was met:(b) T2* mapping: T2* relaxation times of the segmented CEP voxels from all sagittal slices were calculated on a voxel‐by‐voxel basis by fitting the measured SI to an exponential decay function.(c) Establish coordinate system: The principal axes of the segmented CEP were identified, and the CEP was rotated so that the principal axes aligned with the x‐, y‐ and z‐axes, which coincided with the anterior‐posterior, inferior‐superior, and medial‐lateral axes, respectively.(d) Define reference template: to map the CEP voxels into standard reference template and exclude non‐CEP voxels, Cartesian coordinates for each voxel were converted to polar coordinates. Voxels with polar coordinates outside of the area bounded by Mizrahi's equation(e) Define subregions: the shape of a central subregion was concentric with the outer margin of the CEP at 50% of the outer margin distance. The remaining area was divided into four subregions  between CEP subregions. Independent associations between mean NP T1ρ, mean CEP T2* and age were quantified by the Pearson correlation coefficient. To investigate the nonmonotonic relationship between disc degeneration and CEP composition, the discs were grouped to achieve some degree of age distinction while ensuring a similar number of discs in each group. To determine “low” and “high” CEP T2* values in each age group, the CEPs within a particular age group were rank‐ordered from lowest to highest according to their mean T2* value. Then the CEPs were split into two equal‐sized groups using the median T2* value for that particular age group as the cutoff between “low” and “high” T2* values. Two‐way analysis of variance with interaction was used to test the effects of age and mean CEP T2* values on mean NP T1ρ values. Within each age group, independent two‐sample ttests were used to compare mean NP T1ρ values and mean CEP T2* values between discs with the “low” vs “high” mean CEP T2* values. Short‐term repeatability was estimated by the precision error, defined as the root‐mean‐square average of the precision errors in mean T2* values for the seven subjects.Paired 33.1P < .001), left  and right subregions . The between‐CEP variability in CEP T2* values overall was 0.31 (coefficient of variation) for cadavers and 0.16 for human subjects.Mean T2* values, indicative of CEP hydration and inversely related to the collagen‐to‐GAG ratio,3.2r = −.72, P < .001, Figure r = −.45, P = .032, Figure r = .34, P = .11, Figure P = .045), suggesting that the effect of CEP T2* values on NP T1ρ values depends on age. Specifically, in the youngest group (<50 years), the discs that were adjacent to CEPs with shorter T2* values  had 26.7% lower NP T1ρ values . Also, NP T1ρ values were significantly correlated with CEP T2* values , but only in the youngest age group . The discs in the youngest age group had Pfirrmann grades II to III; in the two older age groups, grades III to IV with one grade II , and accordingly, the mean NP T1ρ values in the cadavers were lower . Mean T2* values were similar for the cadavers and subjects .The cadavers were significantly older than the human subjects  was smaller than the reported mean CEP thickness, and the segmented CEP masks were between 1 and 3 voxels thick (1.8 voxels on average), there may be some partial volume averaging of the boney endplate or NP that affects the interquartile range in some locations. Nevertheless, we believe any partial volume effects are likely to have a small impact on mean T2* values, since a prior study comparing histologic measures of CEP thickness to UTE measurements of CEP thickness with the same in‐plane resolution reported that the overestimation was not significantly different than zero .Mean T2* values were the highest centrally and lowest posteriorly, suggesting that water and sGAG contents are likewise highest centrally and lowest posteriorly. This finding is consistent with results from previous biochemical analyses of CEP sections from three human subjects.A clinically relevant finding of this study is that low CEP T2* values coincided with greater extent of disc degeneration during the mild‐to‐moderate stages. Previous ex vivo studies found that the relationship between disc degeneration and CEP composition and permeability is nonmonotonic. Specifically, disc degeneration associated with deficits in CEP composition and permeability, but only in the earlier stages of disc degeneration,2‐weighted sequences with long echo times. Our finding that mean T2* measurements from UTE MRI had good‐to‐excellent short‐term repeatability in vivo and that differences among individuals greatly exceeded differences between repeat tests indicates that T2* measurement can provide reliable, indirect assessments of CEP composition. This suggests that T2* measurement could be used to clarify the role of deficits in CEP composition in patients with Pfirrmann grade II to III discs, and by extension, T2* measurement could be used to test if CEP composition influences the response to biologic therapies meant to regenerate mild‐to‐moderately degenerated discs.A second clinical implication relates to the repeatability of T2* assessment. Although deficits in CEP biochemical composition are believed to influence disc degeneration and regeneration, the composition and integrity of the CEP are not routinely evaluated in a clinical setting because CEP signal is not captured by conventional TWe limited our analysis to L4‐L5 and L5‐S1 CEPs because those CEPs were oriented with respect to the magnetic field at angles nearest to the magic angle. At that angle, the contributions of matrix‐bound water to T2* are minimized, and thus the measured variations in T2* values mainly reflect variations in the amount of mobile water and the collagen‐to‐GAG ratio.An important limitation of this study was the relatively small number of discs, and results should be interpreted carefully and not overgeneralized. Based on the age group with the largest observed variance in mean T1ρ (SD = 13.5 ms) and a power of 0.8, the minimum detectable difference in mean T1ρ was 20.3 ms. The amount of variation in T1ρ—whether due to natural biologic heterogeneity or to noise in the MRI measurement—may necessitate larger sample sizes if more subtle differences between groups are to be detected. Related, correlation between NP T1ρ and CEP T2* values in Pfirrmann grade II to III discs suggests CEP composition as a relevant factor, and this should be validated in larger studies. A second limitation was that histologic or biochemical validation of the MRI findings was not possible. However, prior studies reported significant correlations between T1ρ values and NP GAG contentIn summary, we used T2* mapping from UTE MRI to noninvasively study the biochemical composition of the CEP ex vivo and in vivo. Our findings suggest that deficits in CEP composition, as indicated by low T2* values, associate with more severe disc degeneration during the mild‐to‐moderate stages (Pfirrmann grades II‐III) in younger individuals. Future longitudinal studies will use CEP T2* assessment to clarify the role of CEP composition in disc degeneration and in patient's response to treatment.(a) Substantial contributions to research design, or the acquisition, analysis, or interpretation of data; (b) drafting of the paper or revising it critically; (c) approval of the submitted and final version.Linshanshan Wang: a, b, c; Misung Han: a, c; Jason Wong: a, c; Patricia Zheng: a, c; Ann Lazar: a, c; Roland Krug: a, c; Aaron Fields: a, b, c.Supplementary informationClick here for additional data file.Supplementary informationClick here for additional data file.


Patients suffering from heart failure often require circulatory support using ventricular assist devices (VADs). However, most existing VADs provide nonpulsatile flow, involve direct contact between the blood flow and the device's lumen and moving components, and require a driveline to connect to an external power source. These design features often lead to complications such as gastrointestinal bleeding, device thrombosis, and driveline infections. Here, a concept of magnetically active cardiac patches (MACPs) that can potentially function as non‐blood contacting, untethered pulsatile VADs inside a magnetic actuationsystem is reported. The MACPs, which are composed of permanent magnets and 3D‐printed patches, are attached to the epicardial surfaces, thus avoiding direct contact with the blood flow. They provide powerful actuation assisting native heart pumping inside a magnetic actuation system. In ex vivo experiments on a healthy pig's heart, it is shown that the ventricular ejection fractions are as high as 37% in the left ventricle and 63% in the right ventricle. Non‐blood contacting, untethered VADs can eliminate the risk of serious complications associated with existing devices, and provide an alternative solution for myocardial training and therapy for patients with heart failure. Cardiac patches become multifunctional platforms on epicardial surfaces for advanced therapy. By integrating permanent magnets on the cardiac patches, magnetically active cardiac patches can provide powerful actuations that assist heart pumping inside a magnetic actuation system. These new cardiac patches have potential to function as non‐blood contacting, untethered ventricular assist devices for patients with heart failure. The patches, which contain biomaterials and living cells, could deliver stem cells to the damaged area of the heart muscles. These stem cells will eventually differentiate into cardiomyocytes and replace the scar tissue to recover the heart function. Compared to conventional injections of stem cells into the blood stream, cardiac patches show a significant improvement in delivery efficiency and functionalities. Recently, researchers integrated new functions into the cardiac patches, including a microneedle array that can penetrate deep into the scar tissue, flexible electronics for disease monitoring, and a reservoir that can continuously deliver drugs from outside the body. These studies show the potential to turn cardiac patches into multifunctional platforms on the epicardial surfaces for advanced therapy and disease management.Cardiac patches are engineered materials and structures which are attached to epicardial surfaces to repair heart muscle damage caused by myocardial infarction.2, 3 Patients suffering from heart failure often require mechanical circulatory support provided by ventricular assist devices (VADs) to assist cardiac circulation. Most of the current VADs are used to bypass the diseased ventricle of the heart by rerouting blood through an artificial lumen in a mechanical pump. Clinically used VADs are durable pumps with portable battery systems, which allow weeks of support for patients with end‐stage HF, including in ambulatory settings.However, as the blood flow comes in contact with the foreign surfaces of the pump, users are required to routinely administer anticoagulate medications. In addition, current pumps provide a nonpulsatile flow, which leads to a loss in high‐molecular‐weight multimer of von Willebrand factor, and gastrointestinal bleeding in up to 30% of patients. A new type of VAD is currently under development, which directly compresses the heart using soft actuators or pressurized cups that either cover the entire epicardial surface or target just one of the diseased ventricles.To date, most cardiac patches do not provide significant mechanical actuation to the heart, making them unsuitable for treating end‐stage heart failure (HF). HF occurs when the heart is unable to pump sufficient blood to meet the body's needs. It affects 26 million people worldwide and is the leading cause of death in our society.12 Pat The shearing and torsion of the driveline against the tissue can disrupt the adherent interface, allowing organisms to enter and grow along the driveline. VAD‐related infections occur in 18–59% of patients after implantation. This affects the outcome of the mechanical circulatory support to a significant degree, including both early and long‐term mortality. A VAD that uses wireless energy transmission has been developed recently. However, the wireless energy transfer efficiency is limited to the coupling between the electromagnetic coils, which is sensitive to the relative coil positions.Both types of VADs require a cable connected to an external power source to allow the VADs to work continuously. This cable, known as a driveline, also requires an entry point into the human body and is the most common site of VAD‐related infections.26 The1)They are completely untethered and prevent driveline‐related infections. The MACP will only function inside the magnetic actuation system (MAS).2)They can augment native pulsatile contractions of the ventricles thus providing physiologic circulatory support and avoiding complications associated with gastrointestinal bleeding.3)They are non‐blood contacting. By avoiding direct contact between foreign surfaces and the blood flow, such a device design eliminates potential thrombosis formation and other complications. Patients would not require anticoagulation medications.4) By tuning the magnetization direction and size of the patches, we can achieve complex actuation patterns for the left and right ventricles, to match the natural motions of individual patient's heart muscles.Their design and actuation can be customized for individual patients.31 By Here, we present magnetically active cardiac patches (MACPs) that are surgically implanted on the surface of the heart and can be remotely actuated through externally generated magnetic fields. The patient is positioned inside the magnetic field throughout operation of the device. This device provides a unique solution enabling the use of cardiac patches with VAD functions. The MACPs have the following features:Figure  We performed proof‐of‐concept ex vivo experiments using a fresh pig's heart obtained on the day of the experiment.The system consists of two parts: an external MAS and MACPs implanted on the epicardial surfaces, as shown in Figure 33 We m = vM = 5.44 A m2, where v is the volume of the NdFeB magnet and M is the magnetization of the material. The magnetic torque τ generated on the MACP in an external magnetic field B can be expressed as τ = m × B. For example, the maximum possible torque generated in the 80 mT magnetic field is 0.435 N m. The 3D‐printed patch has a curved surface, corresponding to the epicardial surface. The fins on the 3D‐printed patch allow us to suture the patch onto the heart using standard surgical sutures for attachment. We designed separate magnet housings to easily swap the magnetization direction relative to the heart during the experiments. The NdFeB magnet used in this study weights 67 g. The 3D‐printed magnet housing and flexible patches are 6.5 and 9.5 g, respectively. The total weight of each MACP is 83 g.The structures of the MACPs are shown in Figure We prepared the heart using the following procedure: first, the heart was cleaned with warm water to remove all the thrombi, as any thrombi remaining in the ventricles would take up the volume of the ventricle, making the measurement inaccurate. The left and right atria were removed, and both tricuspid and mitral valves were sealed with special caps, as shown in Figure S1B (Supporting Information). The removal of the atria prevented the blood from flowing back to the atrium during the ventricular contraction, which gave us a better estimation of the performance. Two polycarbonate tubes (inner diameter: 1.2 cm) were inserted past the pulmonary and aortic valves, and were sealed with zip ties and cyanate glue. By doing this, both left and right ventricles were sealed, and the tubes were connected externally. We then filled both ventricles with colored water to make sure that there was no leakage. After sealing the heart, we sutured four MACPs onto the epicardial surface (two on the left ventricle and two on the right ventricle) using standard surgical sutures to ensure sufficient bonding between the cardiac patches and the epicardial surfaces. Sutures were placed in the areas of the epicardium away from the major coronary arteries. The two pairs of patches were positioned strategically opposing each other, in order to achieve large volume displacement from the respective ventricle Figure , right. Figure x–z plane in Figure S2 (Supporting Information), and y–z plane in Figure S3 (Supporting Information), respectively. This rotation is clearly undesirable; therefore, the zero net dipoles are the preferred arrangements  and the stiffening of the heart muscle under mechanical stretching. We calculated the ejection fraction by dividing the volumetric change by the relaxed volume in the ventricles. In the zero net dipole arrangements, maximum ejection fractions of 36.67% and 63.2% were reached for the left and right ventricles, respectively. As a comparison, the ejection fraction of a healthy human heart is about 55–70%. An ejection fraction lower than 25% is one of the indications for VAD implantation. We also observed a better pumping performance in the right ventricle in most cases. This can be explained by the anatomical differences between the left and right ventricles; the left ventricle has thicker muscle walls than the right ventricle, making compressions more difficult when using external actuators. Further improvements could be achieved by changing the magnet size for the MACPs to match the pumping volume to suit the individual patient's needs.In the static experiments, the pumping volume did not increase linearly with the magnetic field strength. This is due to the nonlinearity of the magnetic torque  as a temporary support for in‐hospital patients who are immobilized, e.g., in an intensive care unit, and 2) as a “training” support aimed at myocardial regeneration in patients who have HF with reduced ejection fraction and who are unresponsive to medical therapy, but with the option to reverse remodeling of the myocardium. Currently, mechanical circulatory support is not part of the standard care for the second group of patients, who usually receive cardiac resynchronization therapy (CRT). However, 30% of CRT recipients do not show any beneficial responses.35 MusSince the MAS used in this study was not designed for this specific application, higher magnetic fields and faster responses could be achieved by designing an MAS dedicated to this purpose. A higher magnetic field would provide stronger actuations. Importantly, this would also reduce the magnet size inside the MACPs. Improved dynamic responses in an MAS could cover the range of natural beating frequencies of the human heart, providing better synchronization with the systolic contraction phase. which would lead to less invasive and faster attachments in the near future.The second limitation is the attachment procedures of MACPs onto the epicardial surface. In this study, we directly sutured the MACPs onto the heart muscle; however, strong hydrogel tissue adhesives are currently being developed,39 whi Phase differences could be explored to optimize the volumetric output of the heart. With improved field strength, the weight and volume of the MACP could be reduced, and the development of advanced tissue adhesives would eliminate the need for manual sutures during the experiments.Future works should focus on the development of a portable MAS for VAD applications. Using this specific system, more experiments, including in vivo experiments on the porcine model, would be possible. We can use the real‐time heart beat signals from the surface electrogram to synchronize with the native ventricular actuation patterns.40 PhaThe patch and the sealing cap were printed by Form 2 (FormLabs). The durable resin  was chosen because the material is semirigid with an excellent mechanical resilience to large deformations. All printed parts were cured inside the FormCure (FormLabs) for 1 h at 60 °C. The Young's modulus was about 31.8 MPa after curing, in accordance with the manual. The housing of the magnet was printed by a fused deposition modeling (FDM) 3D‐printer using polylactic acid (PLA) filaments. The thickness of the housing surrounding the magnet was 1 mm. The hexagon prism NdFeB magnet was purchased from HKCM with N35 grade, with a hexagon length of 8.7 mm and a height of 30 mm. The NdFeB magnet used in this study weighed 67 g. The 3D‐printed magnet housing and flexible patches were 6.5 and 9.5 g, respectively. The total weight of each MACP was 83 g. The flux density inside the magnet was 1.17 Tesla.A fresh pig's heart was purchased from the abattoir on the morning of the experiment. The pericardium was removed first, and then the aorta and the pulmonary artery were cut a few centimeters away from their ventricular base. The heart was then rinsed with warm running water in order to remove the remaining blood and thrombi that could reduce the actual volume of the ventricles. The atria were sealed using stereolithography (SLA) 3D‐printed “caps,” which were inserted at the top of the atrioventricular valves and sutured onto the muscle tissue of the heart once the atrial tissue had been removed. Polyvinyl chloride (PVC) tubes  were inserted into the aorta and pulmonary artery up to the aortic and pulmonary valves to allow the water to be discharged from the ventricles during the recreated systole. Finally, the patches were sutured onto the ventricular walls following the natural orientation of the ventricles and avoiding the major coronary arteries. During this process (about 3 h), the hearts were regularly massaged and moistened to maintain tissue elasticity.z‐axis were used, so the eMNS was over dimensioned in terms of functionality and not representative of a dedicated MAS for MACPs. The heart containing the MACPs was placed on the system, as depicted in Figure S2 (Supporting Information). The two tubes were fixed with a clamp, allowing the heart to have some freedom of movement. After fixing the heart, both tubes were filled with water colored by rhodamine B, and the bubbles inside the heart were removed by tilting and squeezing the heart muscles. A flat glass Petri dish was placed under the heart to collect any drops from the heart due to small leakages. The heart motion and the water levels in both tubes were recorded simultaneously in all the experiments.The magnetic fields used to actuate the patches were generated by the MAS CardioMag  which is an eight‐coil electromagnetic navigation system (eMNS) capable of generating magnetic fields in a workspace of 20 cm × 20 cm × 20 cm. This eMNS can control the magnetic field direction and the magnetic field gradient to navigate magnetic catheters and magnetic microrobots. In the scope of this paper, only magnetic fields aligned with the V = πr2 (th – h0), where V is the volumetric change, r is the inner radius of the tube, th is the water level at time t, and h0 is the initial water level. The tracked data can be found in Figures S6–S10 (Supporting Information).To analyze the pumping performance, a digital camera (Canon EOS 5D Mark IV) was used to record the heart motion and the water levels during the experiments. After the experiments, the changing water levels were tracked with respect to time using an opensource software Tracker . The pumping volume was calculated by The authors declare no conflict of interest.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.


Diabetes Mellitus (DM) causes damage in multiple organs and the vessels due to the metabolic state of hyperglycemia and insulin resistance. Increased arterial stiffness may be an important pathway linking DM to the increased cardiovascular (CV) risk by mechanisms of increased cardiac afterload, augmentation of pulse pressure, a subsequent transmission of high pulsatile flow to the end organs and furthermore as a representative of arteriosclerosis. Magnetic Resonance (MR) assessment of aortic pulse wave velocity (PWV) offers a good reproducible non-invasive tool for the detection of arterial stiffness. Furthermore MRI is an accurate tool for the detection of cardiac dysfunction and vascular cerebral lesions, like white matter hyperintensities (WMHs). To our knowledge, MRI has not previously been used to simultaneously determine end organ damage in the aorta, heart and the brain in patients with DM. We hypothesize that there is an important role for DM induced aortic stiffness in the underlying mechanism of cardiac failure and cerebral white matter hyperintensities in DM patients.Accordingly, the purpose of this study is to examine the possible association between aortic PWV, cardiac left ventricular (LV) function and cerebral white matter hyperintensities in DM patients using MRI.MRI of the aorta, the heart and the brain was performed in 81 consecutively included subjects with proven DM . PWV (defined as the propagation speed of the systolic wave front) was assessed using velocity-encoded MRI at two predefined levels in the aorta: in the aortic arch and the descending aorta. Short-axis MRI using a steady-state free precession sequence was performed to assess LV ejection fraction and LV mass. Transmitral flow measurements were performed by means of velocity-encoded MRI for the evaluation of LV diastolic function. WMHs on spin-echo T2-weighted and FLAIR sequences were separately evaluated according to their two anatomical subtypes – periventricular (pv) and subcortical (sc) – and respectively quantified using the Fazekas classification. Spearman correlation, independent student t-test, multivariate linear and logistic regression models were applied for statistical analysis.PWV in the aortic arch was significantly associated with LV diastolic function , LV ejection fraction  and periventricular WMHs (p = 0.006). PWV in the descending aorta was significantly associated with LV diastolic function  and subcortical WMHs (p = 0.002). Furthermore, in multivariate regression analysis with confounding age, gender, smoking and duration of DM, PWV in the aortic arch was an independent predictor of LV diastolic function , LV ejection fraction , LV mass indexed for body surface area  and pv WMHs .Stiffening of the aorta is associated with cardiac LV dysfunction and lesions of the cerebral white matter in DM. Moreover, PWV of the aortic arch is an independent predictor of cardiac LV diastolic and systolic function, LV mass and cerebral periventricular white matter hyperintensities in DM patients.


The most common cause of heart failure in the United States is ischemic left heart disease; accordingly, a vast amount of work has been done to elucidate the molecular mechanisms underlying pathologies of the left ventricle (LV) as a general model of heart failure. Until recently, little attention has been paid to the right ventricle (RV) and it has commonly been thought that the mechanical and biochemical properties of the RV are similar to those of the LV. However, therapies used to treat LV failure often fail to improve ventricular function in RV failure underscoring, the need to better understand the unique physiologic and pathophysiologic properties of the RV. Importantly, hemodynamic stresses (such as pressure overload) often underlie right heart failure further differentiating RV failure as unique from LV failure. There are significant structural, mechanical, and biochemical properties distinctive to the RV that influences its function and it is likely that adaptations of the RV occur uniquely across the lifespan. We have previously reviewed the adult RV compared to the LV but there is little known about differences in the pediatric or aged RV. Accordingly, in this mini-review, we will examine the subtle distinctions between the RV and LV that are maintained physiologically across the lifespan and will highlight significant knowledge gaps in our understanding of pediatric and aging RV. Consideration of how RV function is altered in different disease states in an age-specific manner may enable us to define RV function in health and importantly, in response to pathology. While the majority of studies in cardiac dysfunction focus on the left ventricle (LV), it is clear that function and regulation of the right ventricle (RV) are distinct from the LV. Understanding normal physiological differences between the LV and RV is essential to elucidating unique aspects of pathophysiology in each ventricle. Even more importantly, age-specific regulation of cardiac structure and function is emerging as key distinctions in cardiac physiology. This review considers the physiology of the RV across the lifespan with the goal of emphasizing the need to improve our understanding of mechanisms unique to each ventricle at each life stage in order to tailor therapies and improve patient outcomes.It is important to remember that the RV derives from unique progenitor cells during development; the LV cardiomyocytes arise from the heart tube, whereas RV cardiomyocytes derive from precursor cells in the anterior heart field . This dein-vivo cardiac function and echocardiographic analysis of LV function is robust and reliable. Analysis of RV function, though, is less reliable, due to its sub-sternal position and its complex geometry. However, tricuspid annular plane systolic excursion (TAPSE), a measure of RV longitudinal shortening, has been shown to be an accurate measure of RV contraction and is the most commonly used parameter for quantifying RV function  and two-dimensional speckle tracking echocardiography are emerging as important tools in the early identification of RV dysfunction in patients of all ages  and cardex-vivo cardiac muscle function and we have recently reviewed these methods in detail (Ex-vivo cardiac muscle function can be assessed from the whole heart level using Langendorff preparations to the level of sarcomere or even of isolated protein-protein interactions. One of the most commonly used preparations for assessing cardiac muscle function is the trabeculae (or papillary muscle) preparation. This multicellular preparation allows for analysis of several mechanical properties  and provides information about the impact of the extracellular matrix on these mechanical measurements. Isolated cardiomyocyte preparations allow analysis of similar parameters in the absence of the influence of the extracellular matrix. Experiments using the cardiac muscle preparation or the isolated myocyte preparation can be conducted on intact or skinned preparations, the latter proving direct analysis of calcium sensitivity of the preparation. Each analysis technique has both strengths and weaknesses and often need to be used in conjunction with one another to create a comprehensive view of overall cardiac function.Several methods exist for quantifying n detail . Ex-vivoin vivo function , providing a more substantial O2 reserve. The RV can quickly adapt to increases in O2 demand by increasing coronary blood flow and increasing O2 extraction. Clinically, this has recently been elegantly demonstrated in healthy adults using RV conductance catheters to collect real-time pressure-volumes loops  from the RV and LV. It has been shown that in tissues isolated from the RV, force production  and sarcAs described above, chamber-specific energy utilization is different with the RV demonstrating lower energy expenditure. Interestingly, transcriptome analysis of metabolic pathways demonstrated significant differences in gene expression between the RV and LV . While dStudies aimed at elucidating differences in ventricular-specific responses to volume and pressure overload have further highlighted cellular differences between the ventricles. For example, the RV upregulates significantly more growth factors and has a more robust fibrotic response than the LV in response to volume overload , several1-and β2-adrenergic receptors were significantly less abundant in the RV of control animals and that there was a significant upregulation of the β2-adrenergic receptor in the RV of injured animals in contrast to unchanged receptor expression in the LV. Similarly, in the isolated perfused heart preparation, chronic infusion of norepinephrine increased RV systolic pressure by more than 100%, whereas it increased LV systolic pressure by less than 20%  are often used to improve LV function in heart failure but have failed to demonstrate improvement in RV function . ConversThere is an interesting contrast in therapies such as phosphodiesterase inhibitors (PDEi) that have been found to be effective and safe in pediatric patients with heart failure but not as safe in adults (reviewed; Overall, more studies are needed to determine how therapies impact the function of RV across the lifespan. Importantly, these differences indicate that physiologic mechanisms distinct to the RV play an important role in response to therapies.Even less is known about differences in RV molecular and biochemical properties in pediatric RV. In fact, it has been assumed that pediatric hearts are simply smaller versions of adult hearts. However, it is becoming increasingly clear that there are key differences in regulation and molecular function of the RV in pediatric hearts.Since pediatric development encompasses the time from birth to 18 years of age, this represents a continuum of physical changes; therefore, it is important to consider the various functions that the RV is called upon to complete at different life stages. It is likely that the changing demands occurring over the lifespan underlie the unique function of the RV. In the developing fetus, the RV works together with the LV to provide systemic circulation and ejects blood at relatively high pressures, largely bypassing the nonventilated lung through the patent foramen ovale and ductus arteriosus. While the systemic pressures during this time are low, the RV wall is thick and the force the RV produces is equivalent to LV force . It is cAt birth, the RV and LV wall thickness is approximately the same . HoweverLittle is known about whether RV molecular function differs between pediatric and adult hearts. Once again, there is some assumption of underlying age differences as the RV undergoes radical changes at birth. In this sense, it is reasonable to presume that different molecular function parallels the structural differences between pediatric and adult cardiomyocytes and that RV cardiomyocytes may retain unique features through childhood. One important finding suggests that the RV from juvenile Yorkshire piglets exposed to acute or chronic pulmonary banding inadequately adjusts substrate oxidation resulting in an energy imbalance , 2019. FIn addition to indications that RV metabolism is unique in an age dependent manner, a study defining RV failure in a neonatal calf model of pulmonary hypertension suggests that although sarcomeric proteins undergo post-translational modifications consistently reported in the failing LV, the mechanical response is distinctly different in the RV . This meSimilar to what has been reported in adult LV failure, RV dysfunction has been reported in severe cases of LV failure in children . ImportaAs with pediatric hearts, the function of the aging RV has often been assumed to be the same as adult function. However, there are changes associated with physiologic aging that impact RV function and warrant consideration.Similar to observations in the LV, studies have demonstrated decreased RV systolic function, decreased early RV filling during diastole, and lower diastolic velocities in the RV associated with aging . AdditioWhile a number of studies have observed functional changes in the aging RV, fewer studies have described molecular and biochemical changes the aging RV. One study in rats suggests that resting tension is higher and duration of contraction is shorter in right papillary muscles compared to papillary muscles isolated from the LV. However, in aged rats, the dynamics of papillary muscles from the RV were resistant to changes that occurred in the LV papillary muscles  and RV pInterestingly, several studies have investigated the impact of aging on β-adrenergic receptor density and activity between the RV and the LV. Studies in aging rats demonstrated no differences in RV β-adrenergic receptor density ; while aExtracellular collagen is increased in the RV of aging rats . InteresIn aging LV, studies have demonstrated that myocytes undergo cell death. However, it is unclear if similar myocyte loss occurs in the RV. Metabolic changes have also been reported in aging RV, with 24-month-old rat RVs demonstrating a differential activity of phosphofructokinase compared to LV . SimilarIt is becoming abundantly clear that the RV is functionally and molecularly unique from the LV. However, historically, little attention has been devoted to quantifying genetic, proteomic, and functional characteristics of the RV and accordingly, there is a paucity of information regarding the unique features of the RV. Complicating our understanding of chamber-specific differences is age-specific changes in hemodynamic stresses that the RV is subject to fetal development through adulthood and aging. Given the unique regulation and differences in response to therapies observed in the adult RV, it is imperative to also consider that age will also play a role in differential response to therapy.Both authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Ventricular tachycardia (VT) is characterized as a ventricular rhythm with a QRS >120 milliseconds (ms) and >100 beats-per-minute (BPM) in the absence of an aberrant conduction. It is classified as sustained when lasting >30 seconds. Risk factors associated with the development of VT include increasing age and coronary artery disease with concurrent left ventricular dysfunction, other forms of structural heart disease and acquired or congenital abnormalities in the cardiac sodium, potassium or calcium channels. Diagnosing VT is challenging based on history and physical exam alone. Combination of electrocardiogram (EKG), electrolytes and cardiac enzymes, echocardiogram, cardiac catheterization, and electrophysiology testing are required to appropriately diagnose and characterize the etiology. The case below describes an 84-year-old female with a known history of symptomatic bradycardia status post pacemaker who presented to the emergency department (ED) after a routine device check which revealed VT with associated dyspnea. The patient did not do well with medical therapy and required ablative therapy to resolve VT. An electrical storm refers to a life-threatening syndrome that entails a state of cardiac electrical instability with three or more episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) in a short period of time, typically within 24 hours . StudiesThis is an 84-year-old female with a past medical history significant for hypertension, type 2 diabetes mellitus (DM), peripheral neuropathy secondary to DM, hyperlipidemia, and hypothyroidism. Pertinent cardiac history includes bradycardia with syncope, status post dual chamber pacemaker placement eight months prior to presentation. During a routine cardiology follow up, she had a device check which confirmed VT with a rate of 180 beats per minute. Subsequently, paramedics were called and she was taken to the emergency department (ED). Her only complaints were shortness of breath and dizziness. She denied chest pain, palpitations and syncope. Initial electrocardiogram (EKG) showed wide complex monomorphic tachycardia Figure . She wasShe was subsequently treated with IV amiodarone bolus twice, followed by an amiodarone drip. She went back into VT, and was given IV lidocaine and cardioverted at 300 joules. An esmolol drip was started and she was transferred to the intensive care unit. Her initial labs showed a complete blood count with normal white blood count, no evidence of anemia, basic metabolic profile showed no electrolyte abnormalities, and normal thyroid stimulating hormone (TSH) levels were seen.Transthoracic echocardiogram was done to evaluate possible myocardial scar, left ventricular hypertrophy, infiltrative or dilated cardiomyopathies. The echocardiogram showed normal ventricular systolic function with an ejection fraction of 60%-65%. She did appear to have a diastolic filling pattern showing impaired relaxation, mild tricuspid and mitral regurgitation, and moderate pulmonary hypertension (right ventricular systolic pressure of 50.06 mmHg). There was no ventricular or septal thickening, no speckled appearance of the myocardium, or focal areas of edema suggesting an infiltrative disease process Figure .Myocardial perfusion imaging was performed which revealed homogenous radiotracer uptake on stress imaging, as well as no evidence of scar or ischemia and demonstrated normal ejection fraction. A left heart catheterization was performed to rule out ischemic cause, which revealed non-obstructive coronary artery disease. When the esmolol drip was stopped, breakthrough VT occurred. An electrophysiologist was consulted for possible ablation. Prior to the procedure, she was found to have a wide complex non-sustained ventricular tachycardia Figure . During Three-dimensional mapping was done that showed the site of earliest activation to be around the parahisian area Figure . Aggressive ablation had to be performed which resulted in successful ablation of the VT but she became pacemaker dependent Figure .However, the patient remained stable and was discharged home the following day. During her post-hospitalization follow up at the cardiology outpatient clinic, she remained asymptomatic with no evidence of VT recurrence.Electrical storm can present as either polymorphic tachycardia, monomorphic tachycardia, or ventricular fibrillation. This phenomenon is encountered more frequently in patients with structural heart disease and infiltrative diseases . Reversible causes include myocardial ischemia, electrolyte imbalances, thyrotoxicity, QT prolongation, and drug toxicity. It is also seen in reperfusion after acute ischemic episodes and myocardial scars that become potential arrhythmogenic foci. Polymorphic VT is usually seen with acute ischemia following reperfusion, hypertrophic cardiomyopathy and electrolyte imbalances . MonomorThere is a subset of patients, like the patient is this case report, that can have a milder presentation despite having this potentially fatal arrhythmia. It is essential to investigate potential causes and treating them for arrhythmic cessation. However, if an arrhythmia is refractory to medical management, radiofrequency catheter ablation is the next step. Close outpatient follow up is recommended also due to the mortality risk that is greatest within the first three months after the procedure . VT ablaHere we have presented the case of a patient who had a very mild presentation in the setting of a life-threatening electrical storm. We have highlighted the different types of arrhythmias comprising electrical storm, and the factors most commonly leading to it. A step-wise approach is necessary in the management of an electrical storm; this includes establishing hemodynamic stability and recognizing the initial rhythm and reversible causes. It is important to differentiate wide complex ventricular tachycardia from supraventricular tachycardia with aberrancy. Most patients benefit from antiarrhythmic medication and catheter ablation.


Chemotherapeutic agents have many side effects; among them is cardiotoxicity. Ejection fraction fails to detect the subtle alterations of left ventricular (LV) function; that is why there is a need for a more sensitive tool. The aim is to detect subclinical LV systolic dysfunction after chemotherapeutic treatment, using NT-BNP plasma level as well as speckle tracking echo-global longitudinal strain (STE-GLS). Seventy-four asymptomatic, non-metastasizing breast cancer female patients without risk factors were included. They were assessed before and 6 weeks after taking their first chemotherapeutic session. Assessment included clinical characteristics, conventional two-dimensional (2D) and three-dimensional (3D) echocardiography, and 2D STE-GLS. Blood samples for NT-BNP plasma level were collected on both visits and were later analyzed using a Sandwich ELISA technique.The median NT-proBNP almost doubled after 6 weeks of chemotherapy . Only two patients showed significant reduction of LVEF >10% to less <55%. One patient died before her scheduled follow-up visit, and the cause of death is unknown. Fifty patients showed elevated follow-up levels of the NT-BNP. As compared to the baseline visit, 12 patients had a high relative reduction of the LV-GLS (>15%) and all of them had a relatively higher NT-proBNP. A 2.2 relative elevation of the NT-proBNP was able to define a relative reduction of LV-GLS >15% by a 100% sensitivity and 81.8% specificity.The relative reduction of LV-GLS and the relative elevation of NT-proBNP were successful in defining subclinical, subtle chemotherapy-induced cardiotoxicity after 6 weeks of the first chemotherapeutic agent administration. Breast cancer is a major public health and economical issue; that is why research on new therapies, and monitoring their safety use, should be a priority. Globally, breast cancer is the most commonly diagnosed cancer in women, and it is the fifth leading cause of cancer death , 2.In Egypt, the incidence of breast cancer among females/100,000 population of individual cancer in Lower, Middle, and Upper Egypt were 33.22%, 26.84%, and 38.72% respectively [Numerous studies had shown the cardiotoxicity of specific classes of chemotherapeutic agents. Congestive heart failure and left ventricular dysfunction are associated with the use of anthracyclines, a cumulative-dose reaction, which is more frequently seen in women with previous cardiac diseases and after mediastinal irradiation .Recommendations for the diagnosis of chemotherapy-induced cardiotoxicity included functional and structural changes derived from conventional echocardiography, such as left ventricular diameters and volumes, fractional shortening (FS), and left ventricular EF (LVEF) , 7. HoweThere are several cardiac biomarkers of myocardial injury, such as troponin T (TnT), troponin I (TnI), B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-ProBNP), and myeloperoxidase (MPO). These biomarkers could detect early cardiotoxic effect of chemotherapeutic drugs after and preferably during their administration , 10. RecThe aim of this study is the early detection of subtle chemotherapy-induced cardiotoxicity, using echocardiography LV-GLS and NT-proBNP plasma level.2)) as well as patients with abnormal baseline LVEF (less than 50%) were also excluded.This is a non-randomized, observational cohort study that included 74 asymptomatic female patients who were planned to receive chemotherapy for breast cancer in the period between November 2017 and July 2018. Exclusion criteria included a history of coronary artery disease, a hemodynamically significant valvular heart disease, and a previous chemotherapy or chest radiotherapy. Patients with known cardiovascular risk factors , and the Faculty of Medicine, Cairo University ethics committee has approved the research protocol. A written informed consent has been obtained from the patients.2)}, and heart rate and blood pressure (BP) measurements (BP was measured using the mercury sphygmomanometer).All patients were assessed clinically and this included oncological history, type and site of cancer, a family history of breast cancer, body weight and height measurements, body mass index (BMI) {BMI was calculated according to the following formula; BMI = body weight (kg)/height , the chemotherapeutic agents used , and the doses to be given. The cardiotoxic effects have been reported with doxorubicin doses >400 mg/m40 mg/kg .A twelve-lead ECG was done via the department machine SCHILLER, AT-101, looking out for changes in voltage, PR interval, QRS duration, QTc interval using Bazett’s formula   and kidney function tests (serum creatinine and blood urea nitrogen).g at 2~8 °C. The supernatant was collected for the assay and stored at – 20 °C or – 80 °C till analysis [It was measured using the enzyme-linked immunosorbent assay (ELISA) technique  . Three manalysis .Resting conventional 2D-TTE was done by a single experienced operator using a commercially available machine (Philips IE-33), equipped with a 2.5 MHz transducer, where a 2D, M-mode and Doppler images were digitally recorded for subsequent analysis. Measurements included LV dimensions and volumes, LVEF , left atrial volume index, mitral inflow Doppler parameters, and mitral lateral annulus tissue Doppler (TDI) values. The Tei index was calculated by the following formula: (IVCT+IVRT/ET), where IVCT is the isovolumetric contraction time , IVRT is the isovolumetric relaxation time , and the ET is the ejection time .Loops of the different apical views (two (A2), four (A4), and three (A3) chamber views) were stored for offline analysis of STE and GLS using a (Q-LAB 10.0) program. A good quality ECG was ensured during recording as a prerequisite for a proper speckle tracking analysis. LV longitudinal strain parameters were measured from the apical views, and the myocardium was divided into 6 segments per view . A2-GLS, A3-GLS, and A4-GLS were reported. The overall GLS was automatically calculated as the average of the 18 segments measured in the 3 apical views.All patients underwent 3D echocardiography by an experienced operator using Philips IE-33 machine equipped with an xMATRIX transducer. Within a single breath-hold, 4 wedge-shaped sub-volumes were acquired from an apical view to create full-volume data sets. Care was taken to include the entire LV within the 3D scan volume by decreasing the depth and sector width as much as possible to improve the temporal and spatial resolution of the images.Quantitative analysis was done by using (Q-LAB 10.0) software. A semi-automated border detection biplane LV analysis was performed. For the quantification of LV volumes and function, the longitudinal axes were aligned in the first frame of the loop which corresponds to LV end-diastole in both the apical four-chamber and two-chamber views. Care was taken for the proper definition of both apical views and orthogonal views to avoid foreshortening. Then, tracing was performed by marking five points: septal, lateral, anterior, and inferior points of the mitral annulus and a fifth point on the LV apex. A semi-automated blood–endocardial interface detection algorithm then automatically identified the endocardial border and calculated the LV end-diastolic volume (LVEDV). Unsatisfactory delineation of the endocardial border was manually adjusted. The end-systole was selected by visually identifying the frame with the smallest LV cavity size just before mitral valve opening where tracing was repeated in the same manner as for the end-diastole to obtain the LV end-systolic volume (LVESV). The software automatically detects the endocardial borders in the three dimensions, throughout the cardiac cycle and calculates LV volumes and EF –17.Patients were asked to follow up after 6 weeks of the 1st chemotherapy session. Patients went through routine clinical assessment, searching for symptoms and signs of heart failure.Electrocardiography was done and analyzed for any changes (compared to the baseline ECG). Echocardiographic assessment  was repeated, and the same study parameters were reported). Blood samples were collected for NT-pro BNP plasma level using the same ELISA technique.The primary end point for this study was the early detection of left ventricular systolic dysfunction, based on elevated NT-pro BNP plasma levels as well as reduction of the LV-GLS in breast cancer patients receiving chemotherapy.Cardiotoxicity is defined as a decrease of LVEF from baseline values by >5% to an EF <55% (in the presence of heart failure (HF) symptoms and signs) or an asymptomatic decrease in LVEF by > 10% to an EF < 55% , 19. Abnt test  or a Mann–Whitney test  was used to compare data at the baselines and follow-up visits. Spearman correlation test was used to define the degree and direction of the relationship between the delta change of LV GLS and that of NT-proBNP plasma levels. The delta values of the NT-proBNP, 2D-LVEF, 3D LVEF, and 2D LV-GLS were calculated as the follow-up value minus the baseline value. The relative change of the GLS and the NT-proBNP were calculated as follows . A multivariate linear regression analysis was used and age, laboratory data, and echocardiographic data were introduced into the regression model to identify the independent predictors of the delta change of NT-proBNP level as well as the delta change of the GLS. A receiver operator characteristic (ROC) analysis was used to detect the relative change of NT-proBNP that was capable of defining a 15% relative change of the GLS with a good sensitivity and specificity. Two-tailed p value <0.05 was considered significant.Data was analyzed using Statistical Package of Social Science (SPSS) version 20. Categorical data are described as numbers and percentages and continuous data are described as means and SD or median and range. A paired sample Student’s Seventy-four female patients were included in our sample, the minimum age of whom was 24 and the maximum was 65 years, and 9 patients (12%) were older than 60 years.Twenty patients (27.1%) were planned to receive chemotherapy before surgery , and thus, their follow-up was done before surgery.2 (3 cycles) while the mean cumulative dose of epirubicin was 405 mg/m2 (3 cycles), none of the mean cumulative doses exceeded the cardiotoxic range for doxorubicin or epirubicin.Almost all patients had received anthracycline-type chemotherapy, with the mean cumulative dose of doxorubicin, at the FU visit = 312 mg/mIn the follow-up (FU) visit, all patients, but one, had completed three sessions of their chemotherapy. None of the patients had heart failure symptoms or signs. Eleven patients (14.9%) developed marked hemoglobin drop but only 2 of them needed blood transfusion. Two other patients (2.7%) suffered from low leukocytic count that necessitated delaying of the next chemotherapeutic session. One patient died, before her follow-up visit. She was 50-year-old with IDC II in the left breast T3N1M0 and positive HER2 and PR receptors. She received two cycles of epirubicin (110 mg/cycle) and cyclophosphamide (1100 mg/cycle) with surgery being planned post chemotherapy. Her baseline NT-pro BNP was 48 pg/ml. She had a normal clinical, ECG and echocardiographic parameters before chemotherapy. The cause of her death is unknown.Table The median NT-proBNP remained within the normal range, yet almost doubled in the FU visit, as demonstrated in Table In the follow-up visit, the 3D-LVEF was significantly lower (with a mean difference of − 2.0%) while the LVESV (by 2D and 3D) as well as the Tei index were significantly higher as compared to the baseline levels, yet all remained within the normal range. None of the patients had left ventricular systolic dysfunction . The mean follow-up TAPSE and S-wave TDI TV velocity were high yet all were within the normal ranges (Table Only two patients showed relative reduction of the EF >10% to less than 55% (patients’ numbers 52 and 57) using a 2D biplane Simpson’s method and both of them had elevated follow-up NT-proBNP . Using 3D images, only one patient fulfilled the criteria of reduction of LVEF .In concordance with the 2D echocardiography results, 3D LVESV was significantly higher and the EF was significantly lower in the follow-up visit compared to baseline visit, yet remained within the normal range.Only 61 patients 82.4%) had eligible echocardiographic images for STE analysis (Table % had elin=26) in the FU visit compared to patients with normal GLS . On the other hand, the median NT-proBNP levels were significantly higher in patients with bigger (>15%) relative reduction of GLS compared to patients with less relative reduction of GLS . Figure r = 0.833, p < 0.001).The median NT-proBNP was higher in patients with abnormally low (less negative) GLS ( bigger >5% relatin = 50) and those who did not (n = 23) . Those 5 patients had IDC II, pre-chemotherapy surgery, and all were positive in HER 2 receptors Table . There wp <0.001)  by a sensitivity of 100% and a specificity of 81.8%  was able to predict the change in NT-proBNP level with an adjusted R square of 29.2%.A multivariate regression model with the delta NT-proBNP as the dependent variable showed that the Tei index , 3D-LVEDV , 3D-LVESV , and 3D-EF  were able to predict the change in the GLS with an adjusted R square of 21.1%.While a multivariate regression model with the delta GLS as the dependent variable showed that the Tei index  has been shown to be more sensitive than LVEF as a measure of systolic function, and it has been used to identify sub-clinical LV dysfunction in patients with cardiomyopathies . HoweverNatriuretic peptides are the most commonly used cardiac biomarkers in HF, and in cardiotoxicity . The ESCA combination of GLS with cardiac biomarkers has been proposed to increase the diagnostic accuracy in detecting early cardiotoxicity. Particularly, the integration of NT-proBNP and LV-GLS could be helpful to identify individual patients who have subtle LV systolic dysfunction. Early recognition and appropriate management of those patients can improve outcomes and decrease progression to overt heart failure , 27.The aim of this study was to assess the value of NT-proBNP in addition to the LV-GLS in detecting early sub clinical ventricular dysfunction (as early as 6 weeks of the first chemotherapy dose) in breast cancer female patients.n = 70, 94.6%). The baseline conventional 2D and 3D echocardiographic parameters were normal in all patients. Almost all patients showed normal baseline LV-GLS values (more negative than − 20) except for one patient who had a low baseline LV-GLS (− 16) and that was associated with a high baseline NT-proBNP (459 pg/ml).The study included 74 middle-aged females with non-metastasizing breast cancer who received 2 types of chemotherapeutic agents, one of them was, mostly, an anthracycline . All patients came to follow-up, except for one patient who died of unknown etiology just before her scheduled FU visit.Fifty patients (68.5%) had their NT-pro BNP elevated in the FU visit. They did not experience any heart failure symptoms or signs, yet there was a significant reduction in the 2D and 3D LVEF, as compared to their baseline levels, a finding that was not shown in patients who did not have elevated FU levels of NT-proBNP. In a multivariate analysis model that included all clinical and echocardiographic parameters of the study population, the Tei index was found to be the only predictor of the change in the NT-proBNP plasma level.2) and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography and NT-pro BNP were done at baseline and at the end of the fourth cycle of chemotherapy. No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from a mean of 70.7% at baseline to 67.0% at the follow-up. After chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF. They concluded that asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin and that NT-proBNP may serve as a convenient serum biomarker for early detection of cardiotoxicity induced by anthracycline [Kittiwarawut et al. collected data from 52 female breast cancer patients receiving doxorubicin  patients of those with elevated follow-up levels of NT-proBNP were found to have absolute reduction of the FU LV-GLS to values less than (less negative than) − 20 and 12 patients (24%) had a relative reduction of GLS >15%. This is similar to what Calle et al.  had founA relative reduction in the GLS >15% compared with baseline values was found to be of clinical significance in chemotherapy induced cardiotoxicity . In thisA marked elevation of the follow-up NT-pro BNP plasma levels (>200 pg/ml) was found in 5 patients (6.8%). All of them had a lower LV-GLS in the FU visit and 4 of them had a high relative reduction of the LV-GLS (>15%). Neither the 2D-LVEF nor the 3D-LVEF could identify any of these patients as being abnormal.This study demonstrated the inability of the absolute LVEF values (either 2D or 3D) to detect the early subtle chemotherapy-induced myocardial injury, which was shown by the elevated NT-proBNP values. Even the absolute GLS values were not as accurate as the relative GLS reduction in defining cardiac dysfunction. On the other hand, the association between the relative elevation of the NT-proBNP and the relative reduction of the LV-GLS showed promising results in defining patients with cardiac injury with an excellent sensitivity and a good specificity. Identification of those patients is pertinent as management plans including cardioprotective agents (renin angiotensin blockade and/or beta blockers) could reverse the myocardial injury or at least prevent the progression to cardiac dysfunction.This study focused only on the short-term outcomes. Future studies should extend the follow-up beyond 6 months for better evaluation of the long-term effects on patients with apparently normal LVEF. We could not include larger sample size because of the restricted financial resources.Integration of relative elevation of NT-proBNP plasma level and relative reduction of the 2D LV-GLS may be helpful in the early detection (as early as 6 weeks after the first chemotherapy dose) of chemotherapy-induced cardiotoxicity in asymptomatic breast cancer female patients. The conventional 2D and 3D measurement of LVEF failed to detect these early cardiac abnormalities. Patients who develop a higher relative elevation of NT-proBNP and a higher relative reduction of the LV-GLS (>15%) should be candidates for more meticulous and frequent follow-ups. Early detection of subclinical LV dysfunction will prompt early cardioprotective measures and thus helps to improve the clinical outcomes. Future studies focusing on the role of cardioprotective drugs in patients with subclinical LV dysfunction are recommended.


Very few reports have described the Doppler-derived echocardiographic parameters for mechanical pulmonary valve prosthesis (MPVP). This study aims to describe the normal Doppler hemodynamic profile of MPVP using Doppler echocardiography.The current prospective, single center observational study enrolled 108 patients who underwent pulmonary valve replacement (PVR) surgery for the first time and had a normally functioning prosthesis post-operation. The hemodynamic performance of MPVPs, considering flow dependent and flow independent parameters, was evaluated at two follow-up points, at week one and week four post-operation. All assessments were conducted by an experienced echocardiographer.2;and effective orifice area to body surface area ratio (EOA/ BSA): 1.81(±0.62) cm2/m2. Comparing these measurements with those obtained from the second follow-up (at week four post-op) failed to hold significant difference in all values except for PVAT, which had increased from its primary value (p = 0.038). Also, right ventricular (RV) function showed significant improvement throughout the follow up period.The mean age (±SD) of the participants was 26.4 (±8.98). Tetralogy of Fallot (ToF) was the most common underlying disease leading to PVR, with a prevalence of 88%. At first week post-operation, measurement of indices reported the following values (±SD): peak pressure gradient (PPG): 18.51(±7.64) mm Hg; mean pressure gradient (MPG): 10.88(±5.62) mm Hg; peak velocity (PV): 1.97(±0.43)m/s; doppler velocity index (DVI): 0.61(±18); pulmonary velocity acceleration time (PVAT): 87.35(±15.16) ms; effective orifice area (EOA): 2.98(±1.02) cmThe findings of this study help strengthen the previously scarce data pool and better establish the normal values for Doppler hemodynamics in mechanical pulmonary prosthesis. In recent years, mortality rates due to congenital cardiac anomalies have significantly declined, leading to the prolongation of lifespan in affected individuals. Amongst such anomalies, congenital defects of the right-side chambers are commonly managed with Pulmonary Valve Replacement (PVR). Individuals with Tetralogy of Fallot (ToF), the most common and perhaps the most widely known cause of cyanotic congenital cardiac diseases, now enjoy a longer life as a result of recent advances . HoweverTwo main type of valvular replacements are available: Biologic and Mechanical. Although mechanical valves are more durable, the use of these prosthesis is associated with an increased risk for thrombotic events requiring lifelong anticoagulation therapy. This renders them less favourable over the alternate option. However, it has been suggested that the implication of proper anticoagulation therapies can significantly reduce the risk of thrombotic events .The relatively less frequent application of mechanical valves has resulted in a lack of knowledge regarding the function of prosthetic valve replacements. Doppler echocardiography is the method of choice for evaluation, in both mechanical and biologic prosthesis, capable of assessing a wide range of haemodynamic parameters . SimilarNormal haemodynamic values have been previously determined for mitral and aortic valve prostheses . HoweverThis prospective cross-sectional study enrolled patients who underwent pulmonary valve replacement surgery at Shahid Rajaie Cardiovascular Medical and Research center, between August 2016 and September 2019. Data collection was performed at baseline (prior to surgery), at one week, time of discharge, and four weeks after surgery by trained staff with the use of a data collection checklist. This study was approved by the Ethics Committee of the Iran University of Medical Sciences.Patients who underwent PVR operation for the first time and those with normally functioning mechanical valve in pulmonary position were eligible for this study. The exclusion criteria were Suboptimal postoperative imaging view and previous history of the Rastelli procedure or other valve prostheses. All of the valves assessed in this study were mechanical and obtained from three different manufacturers: St. Jude , Carbomedics  and On-X , with a diameter size varying between 21 mm to 31 mm.Echocardiographic evaluation was performed in the left lateral decubitus position. In order to minimize anticipation bias, a single specialist was assigned with the assessment. In this study, we used a General Electric Vivid 7 phased array system  equipped with a multi-frequency 2.5–3.4 MHz transducer. Apical, parasternal, long and short axis views were assessed via electrocardiogram signals of desirable quality and a frame rate of 45–55 FPS.Left ventricular Ejection Fraction was assessed optically using the Simpson method. Right ventricular (RV) function was determined via visual assessment, tricuspid annulus tissue systolic velocity and tricuspid annular plain systolic excursion. The Likert scale was used to present variables such as RV function, tricuspid regurgitation. Left ventricular and RV size and function were graded according to the recommendations of the American society of echocardiography. MPVPs were considered functional when the normal bi-leaflet motion of the prosthetic valve was observed in parasternal short axis or parasternal RV outflow view see Fig. . DopplerP < 0.05. Statistical analyses were carried out using SPSS software package v.20 for Windows .Continuous variables were reported as means or median, standard deviation (SD) or in ranges. Categorical and nominal data were reported with absolute and relative frequencies, and comparisons were carried out using chi-square test and the Fisher’s exact test. Furthermore, continues variables were compared using the paired t-Test or, in instances which the data failed to fulfil the parametric features, the Wilcoxon rank-sum test. Also, one-way analysis of variance followed by Tukey Post hoc test was used to compare parameters between valve types. The Kruskal-Wallis H test was considered when the data failed to fulfil parametric traits. The association between continues variables was assessed using the Pearson Correlation test. The Spearman rank-correlation test was used to compare nonparametric data or ordinal measurements. To show the 95% confidence interval for non-parametric data Bootstrap method at 1000 repetitions was implemented. Two-tailed analysis was performed in all instances and significance was determined at n = 95;88%) was the most common underlying condition leading to PVR. Regarding the manufacturer of the prostheses, St Jude was implanted for 72 (66.7%) patients, which was the most frequent prosthesis used in this study. The baseline characteristics of the participants are summarized in Table During the recruitment period a total of 141 patients underwent PVR surgery. Of these cases 108 patients fulfill the eligibility criteria of this study and 33 patients were excluded. However, of all these 33 patients, non had history of previous PVR or any other cardiac surgery. Although all eligible cases were present for their first follow up, only 69 individuals visited the center for their second follow up. Lack of access to the remaining participants was the main cause of dropout . In addition, a marginal correlation was observed between <PPG and valve size . Moreover, the correlation between the right ventricular systolic pressure and the PPG showed a significant association of these two parameters . The doppler measurements of MPVPs based on the manufacturer and sized at this stage are summarized in Table The data on doppler measurement of all MPVPs for both stages was summarized in Table P = 0.006). Among the different measured hemodynamic parameters, non had significant change during the 3-week interval except PVAT which showed a significant increase(P = 0.038). At this time, RV showed significant reduction in size (P = 0.006) and improved function (P = 0.001) since the previous follow up. Moreover, no significant differences were observed regarding right ventricular systolic pressure and tricuspid regurgitation gradient. The former altered from 35.38 (±14.27) to 37.67 (±14.11), while the latter changed from 30.79 (±13.50) to 32.31 (±13.81), (both P > 0.05).In the second follow-up the hemodynamic profile was measured in 69 participants. Table In this study, we have described the normal hemodynamic profile for mechanical pulmonary valve prosthesis in the postoperative period. To achieve this goal, we performed early- and late-stage evaluation of the prosthesis, since it had been previously established in other prostheses that the results obtained from evaluation may deviate significantly from those of the early evaluation. Additionally, it was revealed that when abnormal function of prosthesis is suspected, previous evaluation may aid by providing a basis for comparison , 9. To dPVR is the most frequent cardiac operation and reoperation performed on patients with congenital heart disease and the Bioprosthetic valves are currently the choice for PVR in adults and children suffering from pulmonary insufficiency –15. BiopCharacterization and normal hemodynamic values of pulmonary valve prostheses is limited to pulmonary homograft valve conduits or xenograft pulmonary prosthesis . Data onP = 0.071). The reported coefficient in our study does not represent a strong relation. This may arise from differences in types of prosthesis models and discrepancies between the actual prosthesis size and that labeled by the manufacturer. A similar positive correlation between valve size with EOA/BSA ratio was observed in other heart prosthesis [Patient-prostheses mismatch and the selection of prosthesis valve size are of vital importance and in our study, we found a positive correlation between valve size with EOA/BSA ratio. However, in contrast to the study by Sadeghpour et al. , which sosthesis .The ideal time-points for postoperative transthoracic echocardiography assessment of implanted valves are at the time of discharge and 4–6 weeks after surgery . This peGradient is a flow-dependent parameter. Therefore, all factors affecting valvular flow are also capable of influencing the measured gradient. More importantly the flow is dependent to the cardiac load. The loading condition is one of such factors which may show variations in different subjects following surgery. In turn, loading condition itself is dependent on a number of other variables, such as preload and afterload and alterations in such parameters will also influence the measured gradient. The size of the prosthesis may also impact the measured gradient, although we have taken this parameter into consideration to better evaluate its impacts on the overall outcome. One major limitation regarded to doppler echocardiography is the alignment of doppler echocardiography with the prothesis. To address this, the utmost care was taken to maintain doppler echocardiography alignment with the prosthesis and reduce the θ° to the minimum amount. However, in plenty of ToF patients, the history of previous surgical events may have altered the anatomical and geometric features of the site of assessment, making it difficult, if not impossible to maintain the aforementioned alignment and hence obtaining the correct measure of gradients become considerably difficult. An important limitation of this study is was that only a select handful of valves, regarding both size and type, were available. This resulted in fewer instances of very large and very small sizes being used during the operations. Furthermore, a dramatic drop was observed in the number of cases participating for the second their second follow up, possibly impacting the results. Moreover, to establish a more sustainable profile of Doppler parameters, we recommend considering longer follow-up periods in further studies.This descriptive analysis of patients who underwent mechanical pulmonary valve replacement surgery presents previously unavailable data on the subject of hemodynamic indices of mechanical valves obtained in pulmonary position. Although the finds of this study report hemodynamic consistency throughout the study period, the high risk of coagulation after surgery mandates the recommendation of prophylactic anticoagulation therapy.


In recent years, significant advances have been made in the diagnosis and therapeutic management of hypertrophic cardiomyopathy (HCM) patients, which has led to an important improvement in their longevity and quality of life. The use of multimodality imaging has an essential role in the diagnosis, assessing the regional distribution and severity of the disease, with important prognostic implications. At the same time, imaging contributes to the identification of optimal treatment for patients with hypertrophic cardiomyopathy, whether it is pharmaceutical, interventional or surgical treatment. Novel pharmacotherapies (like myosin inhibitors), minimally invasive procedures  and gene-directed approaches, may soon become alternatives for HCM patients. However, there are only few data on the early diagnosis of patients with HCM, in order to initiate treatment as soon as possible, to reduce the risk of sudden cardiac death (SCD). The aim of our review is to highlight the advantages of contemporary imaging in choosing the optimal management strategies for HCM patients, considering the novel therapies which are currently applied or studied for these patients. Hypertrophic cardiomyopathy (HCM) is the most frequent genetic heart disease, usually caused by mutations in genes that encode sarcomeric proteins . It is dTransthoracic echocardiography remains the cornerstone of imaging in hypertrophic cardiomyopathy. It offers essential information regarding the presence, severity and location of LVH, the abnormalities of the mitral valve and subvalvular apparatus, left atrial enlargement, the systolic and diastolic function of the left ventricle and also evaluates the presence of left ventricular outflow tract obstruction ,17.Left ventricular wall thickness should be measured at end diastole, perpendicular to the left ventricular cavity, in order to avoid the inclusion of left or right ventricular trabeculations ,19. The When the 2-dimensional echo images are suboptimal and the severity of ventricular hypertrophy or the septal morphology is unclear, we may use the contrast imaging ,25. ContMitral valve abnormalities are relatively common in patients with HCM, including an increased length of the mitral valve leaflets, sometimes even an important elongation of either posterior (≥17 mm in length) or anterior (≥30 mm in length) leaflet . The incSubvalvular apparatus abnormalities, such as a hypertrophied anterolateral papillary muscle that is inserted directly on the anterior mitral leaflet, without chordae tendinea, can also cause a mid-cavity muscular obstruction, independent of systolic anterior motion (SAM). The presence of accessory papillary muscles or left ventricular muscle bundles can also cause outflow obstruction, by misplacing the mitral valve coaptation plane anteriorly, towards the interventricular septum ,28. As aLeft ventricular outflow obstruction appears secondary to the action of several complex mechanisms, represented by the reduced area of the left ventricular outflow tract, elongation of the anterior and/or posterior mitral leaflet, with an extension of them across from the coaptation point toward the interventricular septum and also the basal anteroseptal hypertrophy which bulges into LVOT ,5,26. AlIt is known and already demonstrated by several studies, the association between the presence of LVOT obstruction, especially at rest, and the increased risk of sudden cardiac death ,36. In aMost patients with HCM have a left atrial enlargement and its dimensions provide important information regarding the prognostic ,40,41. TIt is recommended to assess the left ventricular ejection fraction (LVEF) using biplane method of discs, and in cases when we have a difficult imaging window or when it is difficult to visualize the endocardial border, we may use cardiac magnetic resonance (CMR) .Approximately 10% of patients with nonobstructive HCM progress slowly to end-stage heart failure, being candidates for heart transplantation . In addiPatients with a left ventricular ejection fraction less than 50% often have a rapid clinical deterioration due to the microvascular dysfunction, which leads to a diffuse myocardial ischemia and fibrosis. Thus, for patients with HCM and a decreased left ventricular ejection fraction (≤50%), American College of Cardiology/ American Heart Association (ACC/AHA) guidelines highlight that implantable cardioverter defibrillator (ICD) implantation may be performed, considering their increased risk of adverse cardiac events . InsteadThe diastolic dysfunction is highly prevalent in HCM patients. Almost one half of patients with HCM and preserved ejection fraction have symptoms of end-stage heart failure caused by diastolic dysfunction . HoweverLeft ventricular apical aneurysm is defined as thin-walled, scared akinetic or dyskinetic wall segments, associated with both, midventricular and apical hypertrophy . Apical Echocardiography is the cornerstone investigation used for screening. During puberty, it is recommended to be carried out every 12 to 18 months and thereafter, to at least midlife, at every 3 to 5 years ,5.p = 0.006) [In patients with left ventricular hypertrophy, the left ventricular ejection fraction is not a suitable parameter for the evaluation of systolic function, considering that in cases of HCM it may be increased as a result of increase in radial thickening. Additionally, in the presence of left ventricular hypertrophy, the left ventricular cavity will be small which will cause a reduction in the stroke volume. In this context, a new and extremely important method to assess myocardial deformation and subsequently the left ventricular systolic function in patients with hypertrophic cardiomyopathy, is the two-dimensional strain. It derives from speckle tracking echocardiography and is a noninvasive and sensitive method that has been proposed as an additional test to differentiate physiological from pathological left ventricular hypertrophy ,58. Ther= 0.006) .This association between abnormal global longitudinal strain and adverse cardiac outcomes and ventricular arrhythmia was also demonstrated in a recent systematic review that included more than 3000 patients with HCM from a total of 14 observational studies. They observed that mean GLS was reduced, from −10% to −16%, in HCM patients and the lower the GLS values (less negative), the higher the risk of adverse cardiovascular events .In another study, the authors evaluated the effects of myocardial hypertrophy and cardiac afterload on the myocardial deformation, at rest and during standardized exercise, for asymptomatic patients with moderate to severe aortic stenosis and patients with hypertrophic cardiomyopathy. They demonstrated that during submaximal exercise, longitudinal and circumferential LV deformations were lower in patients with aortic stenosis compared with those with HCM. These differences were not present at rest, and they can be explained by the greater afterload noticed in these patients, which reduces the contractile reserve. Thus, the authors highlighted that moderate exercise echocardiography shows impaired myocardial contractility, which is not obvious at rest, for patients with similar forms of left ventricular hypertrophy, respectively, patients with hypertrophic cardiomyopathy and aortic stenosis .There are only a few studies that evaluated left ventricular segmental strain in patients with HCM and they demonstrated that regional LVH and myocardial fibrosis are independently and significantly associated with worse strain values ,67. HoweExercise testing is an essential noninvasive method for evaluation and for guiding treatment strategy in patients with HCM. There are various exercise testing methods that were previously underutilized in patients with HCM, and which have now become increasingly important.p = 0.002). In addition, patients with New York Heart Association functional class III/IV symptoms and provocable obstruction with exercise, are candidates for myectomy or alcohol septal ablation and those without obstruction are heart transplant candidates [Exercise (stress) echocardiography is more commonly used to assess left ventricular kinetic disorders in patients with suspicion of atherosclerotic coronary artery disease. Recently, this method has emerged as an important test for patients with HCM ,69. It pndidates . Thus, sndidates .2) is used to identify high-risk patients, potential heart transplant candidates [In order to measure oxygen capacity and thus evaluate the functional capacity, the cardiopulmonary (metabolic) exercise testing is very useful. The peak myocardial oxygen consumption with maximal exercise  method can detect the presence and type of LGE: Cine sequences are used for the evaluation of systolic function (ejection fraction), ventricular volumes and wall morphology; T2* imaging detects the iron deposition; T1 mapping is used for diffuse myocardial fibrosis and T2 mapping for tissue edema .Of all the CMR sequences, LGE images have the most important role in tissue characterization in HCM patients. By using gadolinium-based contrast agents, late gadolinium enhancement method ensures a high spatial resolution . It can detect with great accuracy small areas of myocardial fibrosis, myocardial disarray and scarring. LGE is found in about two-thirds of HCM patients, frequently in areas of hypertrophy or right ventricular insertion points  Figure .In recent years, there has been increased recognition that the presence and extent of LGE on CMR is an important risk factor for predicting sudden cardiac death in HCM patients. Multiple studies and meta-analyses demonstrated a high risk of cardiovascular mortality, heart failure and all-cause death in the presence of LGE in HCM patients ,65,82,83In a meta-analysis performed by Green et al., they included almost 1100 HCM patients from four studies, over an average follow-up of 3.1 years. They attempted to evaluate the risk of adverse events associated with the presence of LGE. Their results highlighted that the presence of LGE was statistically significantly associated with cardiac death, heart failure death and all-cause mortality in HCM patients, but they had no data regarding the extent of LGE .p = 0.005). The presence of LGE was also associated with a high risk of all-cause mortality, cardiovascular mortality and a trend for heart failure death [Another important meta-analysis that evaluated the predictive value of LGE-CMR for adverse events and death in HCM patients was published by Weng and coworkers. The meta-analysis included almost 3000 patients over a median follow-up of 3.1 years and the authors demonstrated that the extent of LGE is significantly associated with a high risk of SCD, even after adjusting for baseline characteristics (Hazard Ratio (HR) adjusted: 1.36/10% LGE; 95% CI: 1.10 to 1.69; re death .In another recent study, Mentias et al. aimed to assess the prognostic utility of LGE in patients with HCM with low/intermediate sudden cardiac death risk and preserved left ventricular ejection fraction. They demonstrated that in patients with HCM  with preserved LVEF and low/intermediate risk, the extent of LGE was statistically significantly associated with a higher rate of composite endpoints, giving incremental prognostic utility .The role of LGE-CMR in improving risk stratification strategies in HCM patients was also studied by Freitas et al. During a median follow-up of 3.4 years, their results suggest that the amount of LGE has an important prognostic value and that using LGE for sudden cardiac death risk stratification would correctly reclassify a considerable number of patients .All these studies demonstrated that LGE is an independent predictor of sudden cardiac death in HCM patients and may be considered useful in identifying patients who will most benefit from implantation of a cardioverter-defibrillator (ICD) for the primary prevention of sudden cardiac death ,82,83,84T1 mapping is a novel CMR technique used to measure the extracellular volume fraction and for further identification of diffuse interstitial fibrosis. Even though there are limited data regarding the association between increased native T1 times and extracellular volume with adverse outcomes, more studies suggest its clinical utility for differentiating HCM from Fabry disease, cardiac amyloidosis or hypertensive heart disease ,86,87.T2* mapping is able to detect ischemic segments, and in HCM patients potentially triggered through relative ischemia, they have had reduced T2* values . In a reIn Multimodality imaging is necessary to assess the complete morphology of hypertrophic cardiomyopathy and has an important role in choosing the optimal treatment and in the long-term prognosis of patients with HCM. Considering that patients with HCM that are at low risk, according to the current risk stratification models, may have adverse events, it is necessary to identify additional markers that can be used for predicting adverse events and, thus, choosing the optimal treatment. We believe that all the recent developments in the multimodality imaging for patients with HCM, will significantly transform their treatment in the coming years, considering the recent developments in gene-based therapies and minimally invasive procedural techniques. The use of new multimodality imaging methods, such as cardiac magnetic resonance, myocardial strain, computed tomography angiography or positron emission tomography, allows an improvement of the therapeutic strategies of HCM patients, which will improve their prognosis and quality of life.