Traditional echocardiographic imaging mainly identifies cardiac diseases when symptoms are clear. This makes the innovation of new methods for the prediction and early diagnosis of cardiac diseases inevitable, especially when diastolic function evaluation is needed. Generally, non-invasive assessment of heart function is currently attracting great attention away from sophisticated techniques. With the development of color M-mode echocardiography (CMME), the derived intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) created a breakthrough in the non-invasive assessment of diastolic function in animal models as well as in some companion animals and human studies. They are beneficial for continuous data acquisition without invasive interference, and their results showed good relatedness with the measurements acquired from the catheterization technique.The assessment of diastolic function has received great interest in order to comprehend its crucial role in the pathophysiology of heart failure and for the early identification of cardiac events. Silent changes in the intraventricular flow (IVF) dynamics occur before the deterioration of the cardiac wall, although they cannot be detected using conventional echocardiography. Collective information on left ventricular (LV) pressures throughout the cardiac cycle has great value when dealing with patients with altered hemodynamics. Accurate pressure measurement inside the ventricle can be obtained by invasive methods to determine the LV diastolic pressures, which reflect the myocardial relaxation and compliance. However, catheterization is only feasible in the laboratory setting and is not suitable for clinical use due to its disadvantages. In contrast, echocardiography is simple, safe, and accessible. Color M-mode echocardiography (CMME) is an advanced cardiac evaluation technique that can measure the intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) based on the Doppler shift of the IVF. Recently, the assessment of IVPD and IVPG has gained growing interest in the cardiovascular literature in both animal and human studies as a non-invasive method for the early diagnosis of cardiac dysfunctions, especially diastolic ones. The usability of IVPD and IVPG has been reported in various surgically induced heart failure or pharmacologically altered cardiac functions in rats, dogs, cats, and goats. This report aims to give an overview of the current studies of CMME-derived IVPD and IVPG in animal studies and its feasibility for clinical application in veterinary practice and to provide the prospects of the technique’s ability to improve our understanding. Heart failure is one of the most common causes of death globally; these cases include both diastolic and systolic dysfunctions. In humans and companion animals, heart failure is the second leading cause of death after cancer ,2. The dCurrently, it is believed that measuring diastolic function is crucial for a thorough understanding and early identification of heart diseases since diastolic dysfunction (DD) precedes systolic dysfunction in many cardiac disorders ,7. DiffeDespite numerous methods that have been established to determine diastolic performance, the evaluation of diastolic parameters by catheterization remains the gold standard method which can efficiently measure compliance, relaxation of the myocardium, and filling pressure. However, its invasiveness and the requirement of preoperative measures limit its clinical applicability ,12. LikeRecently, with the development of color M-mode echocardiography (CMME), the derived intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) have created a breakthrough in the non-invasive assessment of diastolic function in animal models as well as in some companion animals and human studies. A literature search was conducted in English through PubMed databases and the publications included in this review are up to January 2023. Selected articles were chosen based on the presence of animal studies having either experimental, preclinical, or clinical trials using the following keywords: color M-mode echocardiography, intraventricular pressure gradients, IVPG, intraventricular pressure difference, IVPD, diastolic function.Generally, it is widely believed that silent changes in the IVF dynamics occur earlier than deteriorations of the cardiac wall; however, IVF changes cannot be detected by conventional echocardiography. The development of Doppler echocardiography has allowed non-invasive measurement of the intracardiac flow. In the normal heart, there is an IVF dynamic including pressure differences. The IVPD is generally defined as the pressure difference that is generated in early diastole between distinct segments within the LV when the apical pressure in the LV drops below the basal pressure . PressurAssessment of IVPD was first uncovered in 1979 when Ling et al.  reportedThe CMME-derived IVPD measurements have started to be used as a non-invasive metric for cardiac function evaluation because of the rapid advancement of echocardiographic technology and the introduction of CMME. Since the IVPD has been approximated from CMME by solving Euler equations, it became possible to determine the sucking force of the ventricle without using any intrusive methods, as stated by Greenberg et al. . Since tTakahashi and colleagues  modified3), v denotes velocity, s denotes position along the color M-mode streamline, and t denotes time. MATLAB is used to obtain v, s, and t and then measure the relative pressures in the region of interest [MATLAB  is used to calculate the IVPD following CMME image acquisition . The folinterest ,21,27. Tinterest .IVPG is calculated by dividing the IVPD by the LV length to exclude the effect of the left ventricular size using the following equation [equation :(2)IVPG A.Rat models of cardiovascular disordersUpdated studies that used CMME-calculated IVPD and IVPG measurements in heart failure are illustrated in murine studies .(a)Changes in IVPD and IVPG in loading conditionsThe current conventional echocardiographic evaluation methods for the assessment of diastolic function have certain recognized limitations, especially under various loading states. The accuracy of conventional echocardiographic methods for diagnosis of DD, such as mitral inflow E-wave velocity (E) using pulsed-wave Doppler echocardiography and mitral annular early diastolic velocity (Em) using tissue Doppler imaging (TDI), is controversial, since they can be influenced by loading conditions with limited efficiency in expressing regional myocardial dysfunction .The effect of loading changes on IVPD and IVPG variables measured through CMME was studied in rats after hydroxyethyl starch and milrinone infusion. The result revealed that mid-to-apical IVPG, mid-IVPG, and apical IVPD were elevated significantly with milrinone infusion; meanwhile, total IVPD and basal IVPD were significantly increased following the infusion of hydroxyethyl starch . The abo(b)Hypertrophic cardiomyopathy (HCM)Advanced heart failure secondary to HCM frequently occurs in humans and cats. Nonetheless, there is still a limited clinical ability of current diagnostic approaches to detect HCM in patients at risk of heart failure ,31. DD iDuring the development of LV hypertrophy in the rat model, total and basal IVPG was increased approximately one month after aortic coarctation , Table 1In veterinary practice, feline HCM is the most frequently detected heart disease in cats; it occurs due to breed predisposition  or due to several genetic mutations. However, for most cats with HCM, the cause is unknown ,34. Enla(c)Diabetic cardiomyopathyThe number of human patients with diabetes mellitus (DM) is rapidly growing in the industrialized world. In DM patients, subclinical LV cardiomyopathy and LA dysfunction usually occur . The patCharacterization of cardiac dysfunction in DM patients usually appears in the advanced stages of the disease. A recent trial found a reduction in longitudinal deformation in all layers and epicardial and mid-myocardial circumferential deformation at the basal level in type-1 DM patients using speckle-tracking echocardiography (STE) . AnotherIn an experimental trial, Kitpipatkun et al. studied the pathophysiologic changes in the IVF in diabetic cardiomyopathic rats, which was experimentally induced via streptozotocin. In this study, diastolic failure and delayed cardiac relaxation were observed in diabetic rats, as indicated by reduced mitral E velocity, E/A ratio, TDI measurements, and mid-to-apical IVPD .(d)Myocardial infarction modelMyocardial infarction (MI) is primarily a type of ischemic heart disease that is caused by an extended shortage of oxygen to the cardiac tissues, which occurs due to constriction or blockage of one or more branches of the coronary circulation ,46. The Two studies have been conducted to evaluate the usefulness of IVPG derived from CMME in MI models in rats , Table 1The second study was conducted to evaluate the efficiency of IVPG to detect subclinical heart failure in rats which were maintained for one month after the induction of MI, as well as to evaluate the efficiency of the new cardioprotective medication, trehalose, on cardiac function . In the (e)Uremic cardiomyopathyIn individuals with renal failure, uremic cardiomyopathy (UC) is traditionally characterized by diastolic dysfunction in conjunction with left ventricular hypertrophy and myocardial fibrosis. ,52. LV hB.IVPD and IVPG in experimental studies in dogs(a)Changes in IVPD and IVPG in loading conditionsMatsuura et al. experimentally sought the IVPD changes under different loading conditions in dogs using transthoracic CMME echocardiography and pressure–volume conductance catheter , Table 2(b)Chemotherapy-induced heart failureBecause DD can occur before the systolic failure, it may be possible to identify diastolic ventricular dysfunction preclinically. In adult cardiac disorders, IVPG is considered an important index of myocardial diastolic function ,9,57. CaThe utility of IVPG was examined for the early identification of subclinical LV dysfunction caused by doxorubicin in Beagle dogs , Table 2C.IVPD and IVPG measurements in the clinical setting in companion animal medicineIVPD and IVPG indices were evaluated in a serial study in dogs with pharmacologically modulated cardiac function as well as normal healthy dogs. Updated studies that used CMME-calculated IVPD and IVPG measurements in companion animals are illustrated in In addition, CMME-measured variables were evaluated in a clinical study of dogs with PDA . PDA is D.IVPD and IVPG in pigsCardiomyopathies, or conditions that affect the cardiac ability to pump blood, can be inherited or acquired; they can manifest as arrhythmogenic, dilated, hypertrophic, ischemic, or restricted conditions. Complex diagnostic standards must be used for these various types of heart failure, and both the pathophysiology and the approach to treatment vary greatly . DilatedThe right ventricular (RV) IVPD measured by CMME in a pig model with changed preload, afterload, and lusitropic states as well as in human patients with DCM has been studied . In pigsE.CMME-derived IVPD and IVPG in sheep and goatsSmall ruminants, especially goats and sheep, serve as good experimental models for cardiovascular research purposes because of the average body size, easy management, and relative heart size to those of humans and companion animals ,75. In aCMME has been studied in sheep and goats. In the sheep model of the LV aneurysm , simultaRecently, the feasibility of CMME-derived IVPD and IVPG measurements in wakeful and sedated goats as well as after pharmacological modulation of the heart was evaluated. Assessment of IVPD and IVPG from CMME was possible in goats and can be used for further cardiovascular experimentations . In goatThe clinical relevance of IVPD and IVPG measured by CMME as promising methods for the early diagnosis of cardiac dysfunction is still under research consideration in laboratory animals, pets, and humans for future validation in clinical cardiology. Characterization of the intracardiac flow dynamics via IVPD and IVPG assessment in feline and canine pediatric cardiology may be important to deepen our understanding of the pathophysiology, prognosis, and follow-up treatment courses, especially when the continuous assessment of the diastolic function is needed.The physiologic variation of IVPD and IVPG in client-owned healthy cats has been established . Future Concerning congenital heart disease (CHD), the evaluation of myocardial function has been widely researched. The systolic function has received the most attention in CHD to date due to its significance and measurement simplicity. However, the diastolic function as an important component of LV function is often overlooked. The conventional parameters which are used to assess diastolic function often measure the blood flow and are affected by the loading conditions of the heart. The problem in diastolic function assessment occurs when attempts are made to evaluate the myocardial relaxation independently of the preload and/or afterload. The interpretation of the diastolic function in the context of CHD requires some understanding of the effects of the lesions themselves on the established diastolic function parameters . CarefulAnother imaging technique, STE, can accurately and quantitatively evaluate diastolic and systolic myocardial performance . A detaiChemotherapeutic agents are known to adversely affect heart function either in an early or latent manner. Few studies demonstrated the efficiency of IVPD and IVPG in chemotherapy-related heart failure in humans and dogs ,62. SincThe current trend in cardiovascular disease diagnostic techniques is aimed at the prediction and early diagnosis of heart failure before the onset of clinical symptoms. For the efficient use of various animals as a candidate for cardiology research, novel echocardiographic techniques are also pertinent for validation in the used model for the accurate interpretation of pathological or pharmacological conditions ,83,84. CThus, the CMME-derived IVPD and IVPG have important theoretical significance and a wide range of application prospects in cardiac disorders as new imaging indices, particularly in the evaluation of diastolic function. In moving away from catheterization, IVPD and IVPG from CMME could be new echocardiographic indices that reflect the diastolic function changes and, in the future, may replace catheterization procedures to diagnose changes in diastolic function. In veterinary medicine, many research trials should be concerned with upcoming studies.


Contemporary advances in low-field magnetic resonance imaging systems can potentially widen access to cardiovascular magnetic resonance (CMR) imaging. We present our initial experience in building a comprehensive CMR protocol on a commercial 0.55 T system with a gradient performance of 26 mT/m amplitude and 45 T/m/s slew rate. To achieve sufficient image quality, we adapted standard imaging techniques when possible, and implemented compressed-sensing (CS) based techniques when needed in an effort to compensate for the inherently low signal-to-noise ratio at lower field strength.A prototype CMR exam was built on an 80 cm, ultra-wide bore commercial 0.55 T MR system. Implementation of all components aimed to overcome the inherently lower signal of low-field and the relatively longer echo and repetition times owing to the slower gradients. CS-based breath-held and real-time cine imaging was built utilizing high acceleration rates to meet nominal spatial and temporal resolution recommendations. Similarly, CS 2D phase-contrast cine was implemented for flow. Dark-blood turbo spin echo sequences with deep learning based denoising were implemented for morphology assessment. Magnetization-prepared single-shot myocardial mapping techniques incorporated additional source images. CS-based dynamic contrast-enhanced imaging was implemented for myocardial perfusion and 3D MR angiography. Non-contrast 3D MR angiography was built with electrocardiogram-triggered, navigator-gated magnetization-prepared methods. Late gadolinium enhanced (LGE) tissue characterization methods included breath-held segmented and free-breathing single-shot imaging with motion correction and averaging using an increased number of source images. Proof-of-concept was demonstrated through porcine infarct model, healthy volunteer, and patient scans.Reasonable image quality was demonstrated for cardiovascular structure, function, flow, and LGE assessment. Low-field afforded utilization of higher flip angles for cine and MR angiography. CS-based techniques were able to overcome gradient speed limitations and meet spatial and temporal resolution recommendations with imaging times comparable to higher performance scanners. Tissue mapping and perfusion imaging require further development.We implemented cardiac applications demonstrating the potential for comprehensive CMR on a novel commercial 0.55 T system. Further development and validation studies are needed before this technology can be applied clinically. Cardiovascular magnetic resonance (CMR) imaging is gaining traction as a preferred imaging modality for comprehensive non-invasive cardiac assessment due to its unparalleled soft tissue contrast in the absence of iodinated contrast and ionizing radiation . HoweverThe feasibility of contemporary CMR techniques has been explored  and demoUnder these conditions of low-field strength and gradient performance, we sought to implement the cardiac techniques needed for a comprehensive cardiac MRI exam on this commercially available system. To overcome the challenges of low SNR and limited gradient performance, we leveraged the use of compressed sensing (CS)  based imAll animal and human subject studies were performed on a commercial 0.55 T MR system . The system has a bore size of 80 cm diameter with a table weight limit of 550 lbs. The system gradients have a maximum amplitude of 26 mT/m and slew rate of 45 T/m/s. All animal studies were approved by the Institutional Animal Care and Use Committee. The animals were anesthetized with isoflurane and mechanically ventilated on 100% oxygen during the study. Breath-hold for cardiac sequences was achieved by holding the ventilator at expiration. All human subject studies were approved by The Ohio State University Biomedical Sciences Institutional Review Board and participants provided written informed consent. As the system is not equipped with an electrocardiographic (ECG) monitoring and triggering unit, two different MRI compatible patient monitoring devices  were used to provide external trigger inputs to the system. All participants and animals were positioned head-first into the scanner bore. Following ECG electrode placement, a large flexible six-element phased array receiver coil (two rows of three elements each) was placed over the chest and used in combination with the nine spine coil elements (three rows of three elements each) embedded within the magnet bore and under the patient table. All cardiac imaging sequences investigated in this study are not commercially available and are prototype research pulse sequences that were either provided by the manufacturer under our research collaboration, or developed in-house at our institution.We applied both balanced steady-state free precession (bSSFP) and gradient echo (GRE) cine, and also implemented breath-held segmented and free-breathing real-time (RT) cine on the 0.55 T system . AcquisiFor breath-held segmented bSSFP cine, a CS-accelerated sequence with a variable density sampling k-space pattern and Cartesian readout was utilized. For free-breathing real-time cine, a CS-accelerated bSSFP sequence was implemented with an acceleration rate 13, similar to what is used at higher field with an acquisition time of 2.5 seconds per slice , 3. The While the reduced SNR at low field can make spoiled gradient echo (GRE) based sequences challenging, GRE is often used in patients with implanted devices to limit metal artifacts; therefore, we implemented a segmented CS GRE cine sequence using TR/TE 7.02/2.99 ms, flip angles around 15–25 degrees and receiver bandwidth (RBW) of 250 Hz/pixel. Images acquired in a healthy volunteer are shown in As the exemplary images in Phase contrast (PC) imaging is the standard MRI method used to measure blood flow . While lWe found that GRAPPA PC MRI at 0.55 T required 20 HB, while the scan time of CS PC MRI at 13 HB was comparable to 3 T GRAPPA PC MRI at 12 HB. As shown in Although quantitative parametric mapping techniques are replacing qualitative T1 and T2 weighted dark-blood turbo spin echo (TSE) sequences for myocardial tissue characterization, TSE sequences remain useful to distinguish morphological features and to characterize masses and tumors. We therefore sought to implement dark-blood Half-Fourier Acquisition Single-shot Turbo Spin Echo (HASTE), as well as T1 and T2 weighted, and T2 weighted short-tau inversion recovery (T2-STIR) TSE sequences , 16. ImaMyocardial longitudinal (T1) and transverse (T2) relaxation times are elevated with fibrosis, edema, and inflammation. Quantitative myocardial parameter mapping methods are being used clinically at higher field to evaluate myocardial tissue characteristics , 18. We As the native myocardial T1 time is shorter at 0.55 T [~700 ms  were observed in some T2 maps, as shown in the porcine images. In some instances, these artifacts extended across the septum, resulting in lower T2 measured in the septum compared to the lateral wall. In addition, the motion correction algorithm used routinely with success at higher field has been challenging at 0.55 T, most likely due to the low SNR of the individual source images. In instances where the motion correction did not perform well, deformation of the individual motion-corrected images resulted in blurring of the myocardial boundaries in the resulting maps. Further research into optimal image registration and motion correction strategies are ongoing.2, TE/TR 1.81/4.25 ms, image matrix 160 × 125, flip angle 90°, acceleration rate 5 using pseudo-random variable density sampling, called Golden Ratio Offset Sampling (GRO) . The acquired data were reconstructed inline using a Gadgetron  was administered to the animals and volunteers at 4 ml/second. The data were collected during free-breathing using a fat-suppressed, saturation-recovery T1-weighted GRE sequence. The scan parameters were: FOV ~380 × 296 mmadgetron , 19, 20.Late gadolinium enhancement (LGE) reveals myocardial scar and fibrosis and is a key component of the basic CMR exam. The standard technique is based on inversion recovery (IR) prepared GRE or bSSFP  and tendFor free-breathing LGE, twelve averages requiring 24 HB per slice were used to boost SNR, compared to the standard 8 averages employed in our 1.5 T and 3 T protocols. We observed failures of the motion correction algorithm, similar to what we observed in cardiac mapping, most likely due to the low SNR of the single-shot source images. This limited the benefits of increased averaging. The preliminary example images from animals and patients with positive LGE confirmed on 1.5 T and 3 T systems are promising. Additional assessments are warranted to correlate the extent of LGE to that depicted by 1.5 T and 3 T systems.MR angiography, with and without gadolinium-based contrast agents, is an important component of the comprehensive cardiovascular imaging exam. Thoracic MRA is widely used in the evaluation of aortic disease, congenital heart disease, and to map out the anatomy of the pulmonary veins. We implemented magnetization-prepared non-contrast MRA and contrast-enhanced MRA on the Free.Max system. Acquisition parameters for all protocols are listed in Non-contrast MRA of the thoracic aorta was implemented using a magnetization-prepared, ECG-triggered, navigator-gated, 3D bSSFP sequence . The tec3, averages 2, GRAPPA acceleration rate 2 with 24 integrated reference lines, turbo factor 25 and echo train duration 110 ms, and RBW of 630 Hz/pixel.A variable flip-angle, fat-suppressed, dark-blood 3D SPACE MRA  sequenceECG-gating in CE-MRA can significantly reduce image blurring, improve image quality and vessel sharpness in thoracic vessels compared to non-gated acquisitions , 27. Con3, flip angle 30°, rate 2 GRAPPA with integrated 24 reference lines and RBW of 350 Hz/pixel. An example image acquired in a patient with dilated thoracic aorta is shown in A slab-selective, 3D CE-MRA without ECG gating was also implemented as an alternative for patients who are incapable of breath-holding . AcquisiAs shown in the reformatted images in 2, respectively, had previously attempted to undergo a CMR exam on our standard 70 cm bore 1.5 T and 3 T systems. Physical discomfort and anxiety prevented Patient A from entering the scanner bore. Patient B was able to enter the bore but could not remain for the complete study. Breath-held segmented cine, CS 2D PC MR flow and LGE images were acquired at 0.55 T for the two exams. Both patients demonstrated normal biventricular systolic function with non-ischemic fibrosis evident from the LGE images. Having conducted these initial experiments to build the individual techniques required for a complete CMR exam, we performed pilot exams on two patients who were clinically indicated for a CMR evaluation. These patients (A and B), having a BMI of 48 and 57 kg/mEach of the two exams described here did not include all of the CMR components described in previous sections. However, they incorporated a variety of pulse sequences and serve as anecdotal examples of the potential for this novel 0.55 T, ultra-wide bore system to extend CMR service to patients currently constrained by standard MR system dimensions. Both patients reported feeling less anxious and more comfortable in the 80 cm bore, therefore increasing their compliance and ability to complete the exam.We built and implemented the imaging techniques required for a comprehensive CMR imaging protocol on a novel, commercial 0.55 T whole body MRI system with limited gradient performance. This initial experience demonstrates that a comprehensive CMR imaging protocol is feasible on this system, thus paving the way for more extensive evaluation and comparison with higher field results in patients.Prototype GRAPPA and CS-based techniques were implemented, and increased averages and slice thicknesses were utilized when possible to boost SNR, while meeting spatial and temporal resolution requirements for clinical imaging within a reasonable scan time. All techniques, especially those that employ image registration and motion correction, require additional investigation and optimization. Visual assessment from pilot exams in healthy volunteers, porcine models, and patients diagnosed with cardiac pathologies demonstrated an image quality in cine, flow, segmented LGE, and both non-contrast and contrast MRA protocols, that provides the confidence to move forward with systematic validation studies to establish diagnostic accuracy and sensitivity with respect to clinically standard high field systems.We anticipate this future evaluation will lead to a robust and comprehensive clinical CMR protocol that can ultimately be utilized with clinical confidence in patient cohorts currently unable to undergo an exam on narrower bore, higher field systems due to severe obesity or claustrophobia.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of The Ohio State University. The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by Institutional Animal Care and Use Committee of The Ohio State University.JV, NJ, and OPS performed the MRI studies including protocol optimization. NJ, DG, CC, YL, and YP contributed toward pulse sequence development and implementation on the scanner. MS and MK designed the animal experiments. JV, NJ, CC, NN, YH, and OPS drafted sections of the manuscript. JV drafted the figures. JV, NJ, MT, RA, YH, and OPS were involved in overall study design and image quality evaluation. All authors contributed to the article and approved the submitted version.


In our healthy patient cohort, a systematic underestimation of the end-systolic volume resulted in a significant overestimation of the SV . The functional calculations from the 3D whole-heart method proved to be highly accurate and correlated well with function measurements from the phase-contrast sequences. Our study is the first to demonstrate the superiority of 3D whole-heart volumetry over 2D-cine volumetry and sheds light on the systematic error inherent in 2D-cine measurements.This study investigates the crucial factors influencing the end-systolic and end-diastolic volumes in MRI volumetry and their direct effects on the derived functional parameters. Through the simultaneous acquisition of 2D-cine and 3D whole-heart slices in end-diastole and end-systole, we present a novel direct comparison of the volumetric measurements from both methods. A prospective study was conducted with 18 healthy participants. Both 2D-cine and 3D whole-heart sequences were obtained. Despite the differences in the creation of 3D volumes and trigger points, the impact on the LV volume was minimal (134.9 mL ± 16.9 mL vs. 136.6 mL ± 16.6 mL,  The accurate determination of cardiac function is central to cardiac diagnostics. One of the most important aspects is the representation of the pumping performance, i.e., stroke volume (SV). This is strongly dependent on the geometry of the heart in end-diastole and end-systole. Therefore, most imaging techniques for cardiac function measurement are based on volumetric methods that attempt to represent the cardiac geometry over time as accurately as possible. From this, important directly measurable parameters, such as the end-diastolic volume (EDV) and end-systolic volume (ESV), can be determined, from which parameters, such as the ejection fraction (EF) and SV, can be derived.In the early days of cardiac imaging, it was not possible to present the heart three-dimensionally in its morphology and its geometric changes over time. Hence, estimates were made by measuring the conformational change in a small area of the heart wall and extrapolating to the deformation of the entire ventricle. These measurements usually assumed a cylindrical shape of the left ventricle (LV) . The simTherefore, the ability to fully capture the heart in 2D slice images opened the option for more reproducible volumetry and thus more accurate cardiac function diagnostics. MRI 2D-cine technology has become the gold standard of volumetric analysis . In thisIn addition to the volumetric approach, it was possible at a very early stage to directly determine the SV by measuring the blood flow velocities, assuming the diameter of the aorta is known. The phase-contrast (PC) measurement carried out for this in MRI is considered extremely valid and not time-consuming, and is therefore the gold standard in determining SV ,12. HoweA crucial point that has not been considered in the previous discussion is the fact that only the incomplete acquisition of the volume is possible through the 2D-cine technique ,19. DespIn contrast, there is also the possibility of fully capturing the geometry of the heart in three dimensions during a single measurement. Unlike the 2D-cine method, where different individual measurements have to be coordinated using the temporal position in the cardiac cycle, a complete acquisition of the 3D volume is carried out at a certain point in time, which allows a more complete and much more true-to-nature segmentation of the heart ,22. The In isolated studies, it has already been shown that this image acquisition methodology is theoretically also suitable for performing LV volumetry, by creating two images; one in end-systole and one in end-diastole . DespiteThe aim of the present work is to uncover causes for the discrepancy in LV volumetry of the new 3D-wh technique compared to the established 2D-Cine MRI procedure, and to evaluate the benefit of 3D-wh MRI for volumetry.A prospective study was conducted involving 18 healthy students aged 23–25. The intent of the study was solely to refine the measurement of MRI volumetry. The study was conducted in accordance with Good Clinical Practice guidelines. Written consent was obtained from all participants prior to the acquisition of MRI scans. All MRI sequences were performed on each student in a single session. No contrast agent was administered. The study was approved by the hospital’s ethics committee.Measurements were performed on a 3T MRI scanner  using a 30-channel phased-array coil.Images were acquired using a balanced steady-state free precession (bSSFP) technique with retrospective ECG gating. Respiratory synchronization was achieved through breath commands given during the end-expiration phase, aligning with our approach for the 3D whole-heart MRI. Depending on heart size, a series of 20–25 short-axis slices perpendicular to the aortic root were acquired. Each 2D short-axis slice represented one cardiac cycle and consisted of 20–25 frames, depending on heart rate. The following settings were used: acquisition matrix 256/146, TR/TE 48.3 ms/1.5 ms, flip angle 38°, turbo field echo factor 9–13, number of cardiac phases 20, temporal resolution 30–40 ms, duration of breath-holding approximately 8 to 12 s, number of signal averages 1, in-plane spatial resolution 1 × 1 mm, 20–25 slices, section thickness 6–8 mm.A 3D radial fat-saturated SSFP prototype sequence using self-navigation was performed. This self-navigation technique captures the respiratory motion directly from the ventricular blood pool signal throughout the respiratory cycle, eliminating the need for navigator placement . AccordiFlow velocity was measured at the ascending aorta using 20 2D-cine PC images acquired during one cardiac cycle. The following settings were used: acquisition matrix 115/192, TR/TE 46 ms/2.5 ms, flip angle 20°, turbo field echo factor 3–4, number of signal averages 2, slice resolution 1 mm.For accurate alignment of the acquisition over the aorta, two orthogonal balanced steady-state free precession (SSFP) scout images were acquired, perpendicular to each other . The velocity encoding settings were initially set to 150 cm/s, and in the presence of aliasing artifacts, they were increased to 200 cm/s. Analysis was performed using a commercially available workstation .2) by the SD of the extra thoracic background noise (ROI = 2.2 ± 0.1 cm2) measured from the air surrounding the patient. For the CNR, the mean signal intensity of the LV muscle (ROI = 1.2 ± 0.1 mm2) was subtracted from the mean signal intensity of the aorta and afterwards divided by the SD of the background noise.The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were determined via regions of interest (ROIs) using the software syngo.via, version VB60A, accessed on May 2021. The SNR was calculated by dividing the mean signal intensity of the aorta in cross-section . Manual delineation of the endocardium, including the papillary muscles, was performed for each phase . The end3D-wh Volumehttp://www.slicer.org, accessed on May 2022) was utilized. The 3D-wh DICOM dataset, acquired in an axial orientation, was imported into the software. Before performing the manual segmentation, the 3D data were converted into short-axis slices using the software’s reformatting tools of 3D-slicer. This orientation facilitates a more straightforward analysis of the LV volumes and mimics the traditional approach used in 2D imaging. Segmentation of the LV volume was then manually executed by setting an optimal threshold, distinguishing the blood pool from the myocardium and vessels, while excluding the papillary muscles. This segmentation extended up to the mitral and aortic valves.For the assessment of LV volumes using the whole-heart sequences, the open-source software 3D-Slicer  by integrating the flow velocity in the ascending aorta and the corresponding vessel area. For volumetric measurements, the ESV was subtracted from the EDV. This also provided the EF by dividing the SV by the corresponding EDV.The two commonly used standard methods, the Dice coefficient and Hausdorff distance, were employed to assess the degree of three-dimensional overlap between the different LV volumes. The Dice coefficient was calculated by summing the overlapping surfaces divided by the average sum of the two surface contours, according to the general equation:A high Dice’s coefficient value close to 1 indicates a high similarity and strong overlap between the surfaces, while a low value near 0 suggests low similarity or minimal overlap. Multiplying the Dice coefficient by 100 allows expressing it as a percentage of overlap.The Hausdorff distance measures the average distance between surfaces in three-dimensional space and is reported in millimeters.http://www.slicer.org, accessed on May 2022). Both metrics were used to compare the volume of 2D-cine with 3D-wh. To enable a fair comparison, only the cylindrical portion of both volumes was considered. Instead of using the 3D-wh volume, the 3D-wh-cylinder was utilized for the analysis. This approach ensured that only the relevant cylindrical section of the LV was compared between the two volumetric measurements.These calculations were performed automatically using the SegmentComparison module of the software 3D-slicer .t-tests were used for comparisons of means. A p-value of less than 0.05 was considered statistically significant. The mean differences between the different LV volumes and SV were depicted using Bland–Altman analysis. The mean bias with standard deviation and the 95% confidence interval (mean ± 1.96 SD) were shown. To assess the relationship between the differences in SV and the variations in LV volume measurement, a Pearson’s correlation analysis was performed. A statistical significance level of p < 0.05 was considered.The volumes of the LV and individual volume compartments, as well as the SVs, were presented as mean ± standard deviation. Paired The study included 18 subjects with an average age of 23.6 ± 0.6 years, of which 60% were female. The required MRI sequences were successfully performed on all subjects and were free from artifacts. In terms of the total duration for acquisition and post-processing, 3D-wh imaging required significantly more time compared to 2D-cine . This dip = 0.05). This similarity allows for a direct comparison of the trigger points. Significant differences were observed between the 2D-cine and 3D-wh methods for both the end-diastolic and end-systolic trigger points. In end-systole, the trigger occurred later on average in the 2D-cine imaging compared to the 3D-wh capture , while in end-diastole, the trigger point in the 2D-cine sequence was earlier on average than in the 3D-wh sequence .All subjects exhibited a sinus rhythm without significant frequency variability during the examination, with similar heart rates during the acquisition of both the 2D-cine and 3D-wh images  and end-systole , there was a slight but significant increase in the volume.To investigate the influence of different trigger points on the actual volume of the LV, the ESV and EDV were recalculated from the 2D-cine slices using adjusted trigger points that matched those of the 3D-wh measurement. Subsequently, these 2D-cine-trigger volumes  for 3D-wh . On averNext, the extent to which differences in the detection of the edge structures (2D-cine-lost) and papillary muscles (papillary-3D-wh) influence volumetry was examined. To address this, the 2D-cine volume was corrected by incorporating the missing edge structures and excluding the papillary muscle components from the LV volume. The comparison with the appropriately adjusted volume 2D-cine-adjust demonstrates a notable alignment between the 2D-cine volumes and the 3D-wh volumes in both end-diastole and end-systole .ES: 17.5 mL ± 3.5 mL; ED: 12.4 mL ± 3.7 mL; p < 0.01). In contrast, the variations in the papillary muscle volumes between systole and diastole are relatively small, with the volume in systole of the whole-heart sequence being approximately 1 mL smaller compared to diastole . To investigate the influence of these factors on volume differences, a corrected cine volume (2D-cine-adjust) was constructed, taking into account the adjusted papillary and edge structures for ES and ED. As shown in In comparison to the 3D-wh volume, the 2D-cine-generated volumes consistently exhibit a lack of small LV segments from the upper basal and lower apical cardiac structures, which we will refer to as edge structures throughout this analysis c,d. To gA minimal difference in the volume is observed for the papillary muscles between ED and ES. However, a significant disparity in the volume is evident for the edge structures, 2D-cine-lost, with a larger volume in end-systole compared to end-diastole.The aim of this part of the study was to assess the accuracy of the cardiac function measurements derived from 3D-wh and 2D-cine MRI by comparing them to the gold standard method of PC.PC: 78.8 mL ± 12.0 mL; p < 0.01, mean difference 5.6 ± 2.5 mL). However, there was no significant difference between the SVs determined by the 3D-wh measurements and the results obtained from the PC measurements . When incorporating the edge structures and papillary muscles, the volumetry correction for 2D-cine volumes resulted in a closer approximation to the SV obtained from the PC measurements . To assess the influence of the edge structures and papillary muscles on the difference in SV between the 2D-cine SV and PC SV, a correlation analysis was conducted. The results revealed a strong correlation between the differences in the SV and the difference in the residual volumes between end-diastole and end-systole . A higheAdvancements in medical imaging technology consistently provide novel opportunities for cardiac volumetry. Currently, 2D-cine imaging holds the clinical gold standard for the determination of cardiac functional parameters. More recent studies have increasingly deployed the 3D-wh technique for cardiac volume measurement ,24, due Consistent with Goo’s study , a discrThe results in Both the 2D-cine and 3D-wh recordings were performed sequentially for each patient, with no significant deviations in the heart rate observed between the two recordings. This allowed for a direct comparison of the recording times based on the registered trigger times. Consistent with the findings of Goo et al. , our meaAs shown in In summary, it can be concluded that minor deviations in the trigger time around the end-systole and end-diastole phases have only a marginal influence on volumetric measurements.The method of reconstructing the EDV and ESV fundamentally differs between the 2D-cine and the 3D-wh procedures . In the In contrast, the 3D-wh method does not rely on interpolation; the data capture of the entire heart occurs in one measurement, each at a precisely defined trigger time, in ED or ES . Here, tIn various studies, the influence of the papillary muscles on volumetry has been investigated. Similar to our findings, most studies show significant differences in the EDV and ESV depending on whether the papillary muscles are included or excluded from the blood volume during 2D-cine reconstruction. The inclusion of the papillary muscles in the LV blood volume and their exclusion from the blood volume are common procedures, leading to the inconsistent handling of measurements ,33,34,35Despite the demonstrated influence on the calculated blood volume in end-systole and end-diastole, most studies show only a minor impact on functional parameters such as the EF and SV ,37. EvenConsistent with our results in healthy subjects, the consideration of papillary muscle volumes has a negligible impact on the SV. In our measurements, the papillary muscle volumes in ES and ED were comparable , with a One particular challenge in volumetry using 2D-cine is the inaccurate capture of the basal and apical edge structures. Early on, it was recognized that incomplete acquisition, especially of the basal structures, occurs during short-axis 2D-cine imaging . This isGiven this knowledge, the significant deviations in the ESV from those of the 3D-wh measurements are understandable. Since in many slices, the first possible slice is still located just above the AV plane within the atrium, we are forced to use the next slice as the first slice for LV cylinder reconstruction, which results in a portion of the LV volume at the heart base not being considered . This leConstructing corrected 2D-cine cylinders (2D-cine-adj) in ES and ED including the edge structures resulted in a volume alignment when directly compared to the 2D-cine volumes in both ED and ES , Table 3Although the issue has long been recognized, to our knowledge, this is the first study to demonstrate this systemic error in a study involving healthy subjects.To achieve a better approximation of the LV volume to reality, there have been attempts to correct the created cine cylinders for a long time. One of the initial methods addressing the inaccuracy of systolic volumes involved including the slices predominantly created in the atrium and subsequently subtracting the atrial volumes . More reWhen comparing the calculated SVs of both volumetric measurement methods with the gold standard of cardiac functional measurement, PC MRI, a consistent overestimation of the SV parameter is observed in 2D-cine derived measurements . In contAccurate anatomical reconstruction of the true ventricular inner lumens at the respective time points is crucial for calculating the SV from the ESV and EDV. Various factors, such as reconstruction errors in the 3D volume in 2D-cine methods, the inclusion or exclusion of the papillary muscles in the blood volume fraction, and incomplete volumes due to missing edge structures directly affect the EDV and ESV and subsequently influence the calculated functional parameters. Despite the awareness of these factors, there is a lack of studies systematically analyzing their impact on 2D-cine volumetry.To address these issues, we performed corrections on the volumes derived from 2D-cine slices by accounting for missing regions resulting from heart motion and inclusion of the papillary muscles using the whole-heart slices. The resulting functional parameters after this correction aligned well with the measurements from PC MRI .Similar to our findings, many other research groups have also reported a significant overestimation of functional parameters, such as the EF and SV, from 2D-cine slices compared to PC measurements. These results contradict the intuitive expectation of underestimation due to the smaller cylindrical shape. However, no study has provided a conclusive explanation for this discrepancy based on measurements. Speculations have been made regarding volume loss through myocardial infarction or the influence of included papillary muscles.In this study, we demonstrate for the first time that the crucial effect leading to the observed discrepancies lies in the incomplete ventricle capture during the 2D-cine method, with differences in the manifestation between systole and diastole. Our results show a systematic underestimation of the ESV, resulting in an increase in the derived functional parameters (SV and EF). This finding is further supported by a strong linear correlation between the differences in volume changes and the differences in the SV compared to the gold standard. Interestingly, no such correlation is observed for the papillary muscles .In this study, we systematically compared 2D-cine and 3D-wh MRI volumetry, advancing our understanding of the differences between these two methods. We found that discrepancies between the methods were not significantly influenced by the creation of 3D volumes or trigger time points, but were impacted by the inclusion of the papillary musculature and the incomplete acquisition of the edge structures in 2D-cine due to heart motion. In direct comparison with the PK measurements, deviations in the papillary muscle volume minimally affected the SV; however, the systematic underestimation of the ESV due to the incomplete acquisition of edge structures in 2D-cine led to a significant overestimation of the SV. This systematic error may be more pronounced in pathologies affecting heart morphology or longitudinal movement. Automated correction strategies for 2D-cine volumes, including landmark recognition or deep learning, have potential to improve the accuracy of 2D-cine volumetry but are rarely used in clinical practice. The accuracy of these methods remains insufficiently verified.In conclusion, based on our study’s findings, we believe that the application of 3D whole-heart volumetry is superior to the current clinical usage of 2D-cine volumetry.Regarding limitations, our study’s patient cohort is relatively small, potentially affecting the statistical power and generalizability of our findings. Additionally, the cohort comprises only healthy individuals, raising uncertainty about the transferability of the results to patients with cardiac pathologies, particularly those with regional wall motion abnormalities. Another point to consider is the inaccuracy of PC measurement when taken at the ascending aorta. Various studies have demonstrated that measurements taken directly at the valvular level, especially in heart pathologies, can lead to an underestimation of volume ,45. Such


Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI. The contemporary definition of successful reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI) is shifting towards optimal reperfusion at the microvascular level as well as epicardial flow. Despite advances in primary percutaneous coronary intervention (PPCI), suboptimal microvascular reperfusion remains a significant challenge in patients presenting with STEMI and a source of mortality and morbidity occurring in up to half of PPCIs with seemingly few therapeutic options in routine practice ,2.Early experimental studies highlighted the concept of impaired tissue perfusion despite adequate epicardial flow  with subThe pathophysiology underpinning MVO is a complex interplay between the distal embolisation of thrombus and plaque debris, microvascular vasospasm, endothelial dysfunction, and direct myocardial injury and oedema caused by ischaemia and reperfusion injury . This ulp = 0.03) [Some of these elements, such as distal embolization and large thrombus burden, have been directly linked with worse clinical outcomes. In a patient-level meta-analysis, Jolly et al. demonstrated that a high thrombus burden (TIMI thrombus grade ≥ 3) confers an increased risk of cardiovascular death  .Direct myocardial injury, quantified using mapping techniques, has been linked to large infarct size and extent of MVO ,12. MVO A better understanding of the impact of dysfunctional endothelial cells on microcirculatory function may help to guide novel therapeutic targets to limit MVO. Defective endothelial cells lower the threshold for coronary vasospasm, facilitate thrombogenesis and ultimately undergo apoptosis and fibrotic replacement as a consequence of impaired mitochondrial functions. Endothelial dysfunction is also associated with microvascular degeneration and negative cardiac remodelling in acute myocardial infarction . FurtherFinally, the inconsistency in detecting MVO using various invasive and non-invasive tools, alongside its complex pathophysiology, adds more challenges to the management of MVO. There was discordance between MVO (detected on CMR) and high-index microcirculatory resistance  in more than one-third of patients presenting with STEMI . MVO cou2, respectively, p = 0.001) [Imaging studies have shown that MVO is associated with adverse left ventricular remodelling and increased left ventricular end systolic volumes (LVESV) compared to patients without MVO  . MVO app= 0.001) . Intramy= 0.001) . The myoClinical outcomes studies have corroborated imaging data with MVO associated with worse clinical outcomes. For every 1% absolute increase in the extent of MVO, there was a 14% relative increase in 1-year all-cause mortality and an 8% increase in 1-year heart failure hospitalization [Any strategy to explore the reduction of MVO requires an accurate means of identifying and predicting patients who may subsequently develop MVO at the time of PPCI. The ability to accurately identify such patients would provide an opportunity to test novel strategies at the earliest stage of STEMI management. Certain clinical and angiographic parameters, such as age, high thrombus burden, delayed presentation , and pre-stenting IMR, have been identified as potential predictors of MVO ,30. CombA better understanding of the pathophysiology of MVO enables us to assess treatment options to manage patients at risk of MVO. Numerous treatments for MVO have been studied and are presented in p = 0.004) [p < 0.01) [Suboptimal platelet inhibition around the time of PPCI, assessed by platelet aggregation testing, is relatively common and was observed in almost one-third of patients treated with contemporary dual antiplatelet therapy . Patient= 0.004) . They we < 0.01) .2Y12 inhibitor may also impact the extent of MVO. In a study of 128 patients with non-ST segment elevation myocardial infarction (NSTEMI), Xu et al. reported lower pre- and post-PCI IMR in patients treated with ticagrelor compared to clopidogrel  [The choice of P = 0.02) . The RED = 0.02) . Therefo2Y12 inhibitor, in addition to standard aspirin and ticagrelor therapy in patients undergoing PPCI, on LV remodelling, infarct size, and MVO as assessed by CMR.Novel agents such as the sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to increase platelet inhibition . The PREp = 0.03). The data on the optimal route to deliver GP IIb/IIIa are even more conflicting. Thiele et al. reported smaller MVO and infarct size comparing IC versus IV abciximab [Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors are potent platelet aggregation inhibitors intracoronary (IC) or intravenously (IV) administered. However, there is conflicting evidence of benefits of STEMI. The INFUSE-AMI  trial, abciximab . Howeverbciximab .p = 0.009 for the trend [The role of thrombolytic therapy in primary PCI was first described by Sezer et al. who compared low-dose IC streptokinase versus standard therapy immediately after PPCI in 41 patients . The authe trend .Despite these discordant results, it is important to highlight important differences in their designs relating to the thrombolytic agent used and timing of administration, i.e., pre or post stenting. Therefore, further studies are needed to establish the utility (or futility) of using thrombolytic agents as adjunctive treatment in PPCI. The RESTORE-MI (NCT03998319) trial aims to identify patients with MVO based on post-PPCI IMR > 32 and then to randomise to low-dose IC tenecteplase or placebo. The primary endpoints will be a composite clinical outcome and CMR endpoints that include MVO and intramyocardial haemorrhage. Similarly, the RECOVER II (NCT04571580) trial will assess low-dose reteplase as adjunctive therapy in patients with anterior STEMI, after reperfusion but prior to stent implantation, with CMR infarct size as the primary endpoint.In clinical practice, adenosine, epinephrine, sodium nitroprusside (SNP), and verapamil have been used as vasodilator agents to help reduce MVO and no-reflow. The evidence to support their use is limited given the small sample sizes, the heterogeneity of administered doses, and the lack of CMR endpoints. The REFLO-STEMI trial compared the use of SNP or adenosine to standard treatment and showed no reduction in MVO or infarct size on CMR with either treatment . There wOn the other hand, intra-coronary epinephrine showed better efficacy and improvement in TIMI flow, MBG, and resolution of ST-segment elevation with a signal for reduction in adverse clinical outcomes at 30 days ,43,44. AHigh-dose statins immediately administered prior to PPCI were associated with improved TIMI flow, MBG, and ST-segment resolution compared to those who received them post-PPCI . The undResults in reference to the use of thrombectomy aspiration catheters in STEMI are variable. Early randomised clinical trials reported angiographic benefits when using manual thrombus aspiration compared to routine PCI, which translated into improved clinical outcomes at 30 days . HoweverTM  rheolytic thrombectomy system was not associated with a reduction in infarct size or mortality at 30 days [Nevertheless, mechanical thrombus aspiration using the AngioJet 30 days . The CHE 30 days . In this 30 days . Recentl 30 days . Future Selective intracoronary hypothermia hypothesizes that rapidly and selectively cooling the infarct territory to approximately 6 °C below body temperature prior to reperfusion will mitigate reperfusion and/or ischaemic injury whilst avoiding the delays, inadequacy, and deleterious effects of systemic hypothermia . ReperfuThe EURO-ICE trial (NCT03447834) is a prospective, multicentre, randomised proof-of-concept trial designed to ascertain the impact of SIH against the standard of care in anterior STEMI patients. It will assess CMR-derived infarct size at 3 months and composite clinical endpoints at 3 months and 1 year. The safety of this treatment has been reported using the first 50 patients recruited compared with the first 50 patients randomised to the control arm of the trial . In-hosp®  is a pressure-controlled balloon catheter placed in the coronary sinus during PPCI. It intermittently increases mean coronary sinus pressure and coronary sinus pulse pressure to maintain microcirculatory patency, redistributing blood flow to areas of ischemic myocardium [® compared to standard therapy [® patients as assessed by CMR imaging  [PiCSOocardium . Non-ran therapy ,58. Howe= 0.006) ,58.® in patients presenting with anterior STEMI and TIMI 0 or 1 compared to standard therapy.The PiCSO-AMI-1 (NCT03625869) trial will be the first randomised trial exploring the safety and efficacy of PiCSO® , a transvalvular axial flow-pump, which is currently used in high-risk PCI and cardiogenic shock, has renewed interests in LV unloading in the setting of STEMI without cardiogenic shock [® followed by immediate reperfusion or LV unloading for 30 min prior to reperfusion, there was no safety signal in delaying reperfusion by 30 min [® for 30 min followed by reperfusion or conventional PPCI. The primary endpoint is infarct size on CMR. Whether unloading the left ventricle will ameliorate reperfusion injury and improve MVO is yet to be determined.Animal studies have demonstrated that left ventricular unloading prior to reperfusion reduces infarct size by 40–50% . The proic shock . In a piy 30 min . Importay 30 min . Additioy 30 min . Any futy 30 min . NonetheSonothrombolysis is a novel strategy in managing STEMI patients achieved by inducing microbubble cavitation using high-mechanical index ultrasonic impulses from conventional transducers after the infusion of intravenous ultrasound-enhancing agents . A small2) between 760 and 1000 mmHg to the left coronary artery through a coronary catheter after PPCI [2 in patients presenting with STEMI. Experimental studies suggested that SSO2 decreased tissue oedema, reduced the formation of lipid peroxide radicals, and inhibited inflammatory cell adherence, leading to improved coronary microcirculation [Supersaturated oxygen therapy provides oxygenated blood with a partial arterial pressure (PaOter PPCI . Differeculation ,65.2, which may be related to the position of the delivery catheter within the stented segment [2 to the left main artery, remote from the stented segment [Previous randomsied clinical trials reported smaller infarct sizes in patients presenting with anterior STEMI and subjected to supersaturated oxygen ,66. Howe segment ,66. A re segment .The potential advantage of deferred stenting in STEMI is to avoid slow-flow or no-reflow with subsequent deleterious effects on microvasculature, thereby improving myocardial salvage and reducing infarct size . PreviouIt is important to note that prolonged GP IIb/IIIa infusion is a corner-stone of this strategy, reflecting the near 100% usage in most of these studies. However, conflicting data on the efficacy of this routine use combined with the optimal duration of the deferral strategy remain unclear ,72. The The presence of MVO after STEMI is associated with increased infarct size, adverse LV remodelling, and poor patient outcomes, and its management remains challenging. A better understanding of the mechanistic processes contributing to MVO would enable us to design tailored treatments for its underlying complex and multifactorial pathophysiology. A reliable and accurate diagnostic and/or imaging modality would allow the characterization and identification of patients most likely to benefit from intervention. A variety of innovative pharmacological and device-based therapies have been and are currently being tested and the best approach may be an integrated approach of some of these promising interventions.The delayed impact of MVO on morbidity and mortality is a burden on patients, their carers, and healthcare providers underscores the need for further research in the prevention, diagnosis, and treatment of this condition.


Twenty-two patients  with an acute phase of myocarditis and epicardial GCS −13.0% or less had oedema confirmed by CMR. Conclusions: 2D STE can help to set the diagnosis of AM in patients with acute chest pain with a normal coronary angiogram. The epicardial GCS can serve as a diagnostic factor for oedema in patients with early stage of AM. In patients presenting with signs of AM (oedema in CMR), the epicardial GCS is modified in comparison with a subgroup without oedema; therefore, this parameter could be used to improve the performance of ultrasound.Background: The aim of present study was to assess left ventricular myocardial deformation detected by 2D STE in patients with suspected acute myocarditis (AM) early on admission in whom later cardiac magnetic resonance (CMR) evaluation was performed. Methods: A total of 47 patients with suspected AM based on clinical practice were prospectively enrolled. Coronary angiography was performed on all patients to rule out significant coronary artery disease. CMR confirmed myocardial inflammation, oedema, and regional necrosis meeting the Lake Louise criteria in 25 patients  subgroup). In the remaining patients, only LGE was confirmed in the sub-epicardial or intramuscular localization  subgroup). Early on admission, echocardiography with measurements of global and segmental longitudinal strains (GLS), circumferential strains (GCS) at the endocardial  and epicardial  layers, transmural GCS, and radial strains (RS) were performed. Results: Mild reduction of GLS, GRS, and transmural GCS values were found in patients with oedema (+) subgroup. The epicardial GCS turned out to be the diagnostic factor for oedema with a cut-off point of 13,0% (AUC 0.747,  Acute myocarditis (AM) is an inflammatory disease of the myocardium usually caused by viral infection. The clinical presentation of AM is heterogenous and includes an asymptomatic course, mimicking acute coronary syndrome, severe acute heart failure, ventricular arrhythmia, or sudden death presentation. Therefore, the prognosis varies in the above-mentioned clinical scenarios. AM was reported in up to 12% of cases of sudden cardiac deaths, with arrhythmia as the most common underlying mechanism .The gold standard for the diagnosis of myocarditis was endomyocardial biopsy (EMB) in the past and more recently, cardiac magnetic resonance (CMR). However, endomyocardial biopsy has a low yield due to often patchy involvement of the myocardium ,5,6 and A total of 47 consecutive patients with suspicion of AM admitted to the Interventional Cardiology Clinic were prospectively enrolled in our study . The iniCoronary angiography was performed on all patients to rule out significant coronary artery disease on the first day of hospitalization. Conventional electrocardiography, echocardiography, chest X-ray, and lab tests excluded arrhythmias, congenital valve and myocardial pathologies, and other causes of chest pain. CMR confirmed myocardial inflammation, oedema, and regional necrosis—LGE in 25 patients (53%) meeting the Lake Louise criteria I for the diagnosis of AM [Echocardiography was performed using a Vivid E9 ultrasound system with a 3.5-Mhz transducer  on the first day of hospitalization. Images were optimized for gain, compression, depth, and sector width, and acquired at frame rates of 70–90 frames/s. Apical 4- and 2-chamber views, parasternal long-axis views, and parasternal short-axis views at the basal, papillary, and apical ventricular levels were acquired. In each plane, images from three consecutive cardiac cycles were acquired during a breath-hold at end-expiration. The LV end-diastolic and end-systolic volumes were measured from the apical 2- and 4-chamber views, and the ejection fraction (EF) was calculated using the modified Simpson rule.All participants underwent a comprehensive echocardiographic examination with detailed two-dimensional speckle-tracking echocardiography on the first day of hospitalization. Analysis was performed offline with the aid of a commercially available software package . Speckle-tracking strain analysis is a novel method based on gray-scale two-dimensional (2D) images, which permits the assessment of myocardial deformation in two dimensions. Using apical and parasternal short-axis views, three different patterns of myocardial deformation can be assessed: radial strain (RS) represents the myocardial thickening in a short-axis plane; circumferential strain (CS) represents myocardial shortening in a short-axis plane; and longitudinal strain (LS) represents the myocardial shortening in the long-axis plane. Moreover, circumferential strain was calculated transmurally  and for myocardial layers—epicardium  and endocardium , in the assumption that changes in myocarditis are layer-specific with the distribution of oedema in the mid-wall and LGE in the epi- and mid-wall. The ROI (region of interest) was manually adjusted using a point-and-click approach. Images were automatically divided into six standard segments, respectively, and time-strain curves generated from each segment. From the curves, regional and global  peak and time-to-peak values were obtained .The prevalence of subclinical cardiac systolic dysfunction in our study was defined in relation to previously reported strain values obtained from the Nagata et al. study, defined as GLS < 18.0% to 22%, GCS 18.5% to 23.1%, epicardial GCS 13.3% to 17.3%, endocardial GCS 25.5% to 31.5% in the healthy subjects , and GRSCMR was performed within 48 h of admission on a 1.5 T scanner (Siemens Magnetom Avanto). CMR images were acquired during breath hold and with ECG-gating. Image analysis was performed by an experienced radiologist specialized in the assessment of cardiac images. A combination of 2018 expert recommendation for updated CMR criteria in acute myocardial inflammation  was evaluated in each case—myocardial oedema (elevated T2-weighted) and non-ischemic injury (elevated T1 and/or ECV and/or LGE) . Regionap value < 0.05 was considered statistically significant.Categorical variables were summarized as frequencies with percentages. The Shapiro–Wilk test was used to assess normally distributed of variables. Due to a lack of normal distribution in the majority of variables, non-parametric tests were used. Continuous variables were expressed as medians with an interquartile range. Correlations were assessed using the Spearman’s rank correlation coefficient. Differences between two continuous variables were compared by using the Mann–Whitney U test. Whereas the chi-squared test with Yates’s correction for continuity was applied to assess differences between categorical variables. Receiver operating characteristics analysis was performed to compare diagnostic performance. All statistical analyses were performed using STATISTICA 13.1 . A The study protocol was approved by the local ethics committee  and followed guidelines of the Declaration of Helsinki (RNN/03/20/KE).The mean age was thirty-two (IQR 22–43), the prevalence of female gender was 19% (nine patients). All of the patients presented with chest pain. A total of fourteen patients (30%) had a fever on admission, four (9%) had muscle pain typical for a viral infection , and twenty-two patients (47%) had symptoms of upper respiratory tract infection . C-reactive protein was elevated in 41 patients (87%) and leucocytes (WBC) were elevated in 21 (45%) out of the 47 patients. Furthermore, 33 patients (70%) had a history of infection 7 to 14 days before hospitalization. ST-segment elevation was observed in 36 patients (77%). Cardiac necrosis biomarkers  were elevated in all patients.The baseline characteristics of the patients are summarized in p < 0.028). Additionally, more affected LGE segments were in patients with oedema in comparison with the rest of the patients with statistical significance (p < 0.016). CMR parameters are shown in CMR was performed in all the patients. EF was slightly but significantly lower in patients with oedema , similar to the magnetic resonance methods . According to the ESC standards, the systolic function of the left ventricle is preserved in those two subgroups (EF above 50%) and clinically, it would be difficult to exploit such a result to differentiate these two groups on the basis of the left ventricular ejection fraction only.In 2D STE analysis, we observed the decreased values of global longitudinal strain (mild only in oedema (+) group), global radial strain (mild only in oedema (+) group), and a more pronounced transmural circumferential strain . Noteworthy is small but significant difference in LV EF between subgroups with present or absent oedema in the myocardium measured by classical echocardiography  and in the circumferential strain  from those without oedema in CMR  (As shown in  0.0005) . Twenty- 0.0005) .The area between the dashed lines: normal range for GLS LAX, 18 to 22%; for GCS, 18.5 to 23.1%; for epicardial GCS, 13.3 to 17.3%; for endocardial GCS, 25.5 to 31.5%.2D STE indicates two-dimensional speckle-tracking echocardiography; GLS LAX indicates global longitudinal strain in long axis; GCS indicates global circumferential strain.2D STE indicates two-dimensional speckle-tracking echocardiography; GCS indicates global circumferential strain; CMR indicates cardiac magnetic resonance.CMR indicates cardiac magnetic resonance; LGE indicates late gadolinium enhancement; 2D STE indicates two-dimensional speckle-tracking echocardiography; GCS Epi indicates global circumferential strain epicardial layer.The diagnosis of AM can be challenging because of its clinical presentation mimicking other cardiologic diseases and an inaccessibility of the main non-invasive diagnostic imaging modality—CMR—in the early phase of the disease in several institutions. Some patients have contraindications to CMR, e.g., implanted metal elements in the body or a history of allergy to contrast agents. EMB, still the gold-standard method for the diagnosis of AM, is reserved for patients with hemodynamic instability, presenting as acute HF or cardiogenic shock, and rapidly deteriorating .So far, little is known about the transition time from acute to subacute and chronic disease in myocarditis. Patients report at different times from the onset of infectious symptoms, at different stages of the disease, and usually the infectious agent is unknown. The oedema in AM can be best visualized during the first days of the disease. In the study by Monney et al., myocardial oedema decreased from 84% to 39% after a >3-week follow-up . In the The diagnostic value of echocardiography still has been limited by the fact that many patients with less severe AM have a normal echocardiogram. Novel strain parameters (2D STE) allow it to compete with CMR due to setting the diagnosis on the early stages of the disease with better availability and the possibility of performing a bedside examination. Strain analysis by 2D STE appears to be very informative in AM. It facilitates diagnosis and may be a new tool to detect and monitor inflammatory myocardial injuries  during the course of AM . The lefConsidering regional changes in strain values, we can expect that the segmental changes may correspond to the location of the oedema. Often, these changes are patchy and go beyond the vascularization of a particular coronary artery, in contrast to the ischemic lesions with their predictable vascularization pattern.p = 0.0005). A total of 23 out of 25 (92%) patients with an acute phase of myocarditis and an epicardial GCS of 13.0% or less had oedema confirmed by CMR.Until now, most of the studies on myocarditis and STE assessment have analyzed the relationship between changes in the myocardium found in CMR  and only with GLS ,18,19,20In contrast, in the Logstrup et al. study , 2D STE p = 0.023) and CK-MB maximal values (p = 0.049). Conversely, there was no such relationship between C-reactive protein and the presence of oedema in CMR (p = 0.346). These relationships require further studies because they have not been analyzed in the available literature so far.Moreover, in our study, patients with the presence of myocardial oedema compared to patients without it had higher hsTnT levels  patients with epicardial GCS of 13.0% or less, with a sensitivity of 92% and a specificity of 50%, had oedema confirmed by CMR. In patients presenting with signs of acute myocarditis (oedema in CMR), the epicardial GCS is modified in comparison with a subgroup without oedema; therefore, this parameter could be used to improve the performance of ultrasound. Furthermore, multi-layer 2D STE analysis may be a promising method for monitoring the course and resolution of myocarditis instead of repeated CMR investigations.The present study has several limitations. Our study represents a single-center experience in a relatively small sample size. We did not confirm the diagnosis by performing EMB, which is the gold standard for the diagnosis of AM. The main findings of the present study are valid in the subgroup of patients who presented with the specific infarct-related symptoms. In addition, the CMRs were performed 2 days after the initial 2D STE measurements. We had no opportunity to calculate T1 and T2 relaxation times in patients with positive LGE but without oedema in CMR. Furthermore, the LGE lesions in patients without oedema in CMR could correspond to old lesions of myocardial injury (it could be a subacute or chronic phase of myocarditis or even a past myocarditis). This may be a confounding factor in the study.Since 2D STE strain values may differ between several vendors, it would be useful to confirm the findings of our study through a different software.


Higher NT-proBNP levels identify HFpEF patients with worse LV stiffness because of more severe myocardial extracellular matrix remodeling, representing an advanced stage of HFpEF.In heart failure with preserved ejection fraction (HFpEF), natriuretic peptide (NP) levels are frequently lower. In several trials, the outcome differed between patients with low and high NP levels. This suggests that NP could be used to identify distinct stages of left ventricular (LV) remodeling and myocardial tissue composition. This study investigated cardiac remodeling/dysfunction and myocardial tissue characteristics assessed by echocardiography and cardiac magnetic resonance (CMR) in HFpEF patients in relation to NP levels. Clinical and echocardiographic data of 152 HFpEF patients were derived from outpatient visits. A total of 71 HFpEF patients underwent CMR-derived T1-mapping. Multivariable regression analyses were performed to examine the association of NT-proBNP categories (</> median) and NT-proBNP as continuous variable with echocardiography and CMR-derived T1-mapping. Mean age was 71 ± 9, 93% of patients were women and median NT-proBNP was 195 pg/mL, with 35% of patients below the diagnostic cut-off value (<125 pg/mL). Patients with high NT-proBNP had comparable LV systolic function and LV relaxation but significantly worse LV stiffness and left atrial function compared with patients with low NT-proBNP. Higher NT-proBNP was significantly associated with higher LV stiffness and extracellular volume fraction (ECV) (β = 1.82, 95% CI: 0.19;3.44,  Heart failure (HF) with preserved ejection fraction  is characterized by a rising prevalence and similarly dismal outcome as HF with reduced EF (HFrEF) ,2. HFpEFn = 12) or paroxysmal (n = 22), together 22.4%. Median plasma NT-proBNP value was 194.9 pg/mL (interquartile range 84.7–436.4) , type 2diabetes mellitus  and obesity (53.9%) and frequent use of cardiovascular drugs. Thirty-four HFpEF patients had atrial fibrillation  . The mea2), depressed LA reservoir function  = 44.6 ± 9.0%) as well as LA conduit (LA passive ef = 25.2 ± 7.7%) and pump (LA active ef = 26.5 ± 9.4%) functions (All HFpEF patients had evidence of LV diastolic dysfunction consisting of a prolonged DT (206.5 ± 41.5 ms), reduced E′ velocity (mean E′ = 6.5 ± 1.4 cm/s), elevated E/E′ (mean E/E′ = 13.9 ± 4.7), reduced mean A’ velocity (8.7 ± 2.1 cm/s), dilated left atrial (LA) volumes (max LA volum index (LAVI) = 43.6 ± 11.8, pre-A LAVI = 32.4 ± 9.8 and min LAVI = 25.0 ± 9.4 mL/munctions .The distribution of HFpEF patients in accordance with plasma NT-proBNP is shown in To detect differences in clinical and cardiac characteristics in relation to plasma NT-proBNP levels, HFpEF patients were categorized into low or high NT-proBNP groups based on their NT-proBNP being lower or higher than the median value of 194.9 pg/mL . HFpEF pIn terms of cardiac phenotype, HFpEF patients with high NT-proBNP had a similar LV geometry, LV systolic function and LV relaxation  compared with HFpEF patients with low NT-proBNP .However, patients with high NT-proBNP showed a significantly deteriorated LV diastolic stiffness, as evident from higher E/E′ ratios  at comparable LV end diastolic volume (LVEDV), additional LA enlargement  and additional worsening of LA function  . These dConversely, with increasing values of log-transformed NT-proBNP, all indices of LV diastolic stiffness deteriorated . Additionally, increasing NT-proBNP levels were significantly associated with larger right atrial volume (RAV) . SensitiThe association between NT-proBNP as a continuous variable and CMR indices of myocardial fibrosis was investigated in 71 HFpEF patients. The clinical and echocardiographic characteristics of this subgroup reflected those of the whole study population . Log-traThe present study investigated the association between cardiac remodeling and dysfunction measures and NT-proBNP plasma levels in a chronic, stable HFpEF population that consisted predominantly of postmenopausal women with a high prevalence of metabolic comorbidities and hypertension. Compared with patients with lower NT-proBNP levels, those with higher NT-proBNP levels had comparable evidence of LV concentric remodeling, systolic function and slow LV relaxation, but substantially higher LV stiffness . The anaIn a subgroup of HFpEF patients undergoing CMR, increased levels of NT-proBNP were associated with more advanced myocardial ECM remodeling, evident from higher ECV. Previously, in HFpEF patients, NP levels were shown to correlate with higher LV filling pressure , collageIn the present study, median NT-proBNP was relatively low (194.9 pg/mL) and 34.9% of the population fell below the diagnostic cut-off value proposed by current guidelines ≤125.0 pg/mL), whereas 70.4% of the patients had a NT-proBNP level below 360 pg/mL, the cut-off level suggested for risk enrichment in HFpEF trials . Conditi.0 pg/mL,Despite relatively low to even normal plasma NT-proBNP levels in a subset of our HFpEF patient population, HFpEF patients with NT-proBNP levels in the lower range showed concentric LV remodeling, diastolic LV dysfunction and LA dilatation and dysfunction . Our resClinicalTrials.gov identifier NCT04475042) [Markedly elevated NT-proBNP levels are used as an inclusion criterion in phase III HFpEF trials . A relatIn the present study, we demonstrate that NP levels can be used to identify distinct stages of cardiac structural and functional remodeling in patients with HFpEF. Low NP levels identify an earlier stage of myocardial disease progression, with diastolic LV dysfunction characterized by impaired relaxation, LA remodeling and dysfunction and minor ECM remodeling. In contrast, high NP levels identify a more advanced stage of myocardial disease progression, with similar concentric remodeling and impaired relaxation, but elevated LV stiffness and more advanced LA and ECM remodeling. Therefore, NP levels in HFpEF could aid in improving phenotypic and pathophysiologic stratification and may potentially also be of interest for improving patient selection for individualized therapeutic inroads.Data of chronic HFpEF patients (n = 152) were derived from their routine outpatient clinic visits at OLVG hospital, Amsterdam, from January 2016 onwards. All patients presented with symptoms of dyspnoea (New York Heart Association (NYHA) Class II to III), LVEF ≥ 50% and echocardiographic evidence of LV diastolic dysfunction, according to the American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) criteria and European Society of Cardiology—Heart Failure Association (ESC-HFA) consensus recommendation for HFpEF diagnosis ,43. To eEchocardiographic examinations were performed on a GE Vivid9 ultrasound machine  using a specific protocol involving 2-dimensional (2D), M-mode, Doppler, tissue Doppler and 2D speckle tracking (STE) imaging in accordance with current recommendations . LA voluCMR examination of 71 HFpEF patients was performed within 6 months from echocardiography on a Philips 1.5-T scanner . All scans were performed following a protocol consisting of functional analysis, T1-weighted images and late gadolinium enhancement. T1-mapping images were obtained using a modified look-locker inversion recovery (MOLLI) sequence before and fifteen minutes after intravenous gadolinium administration. Images were obtained in short-axis on basal, midventricular and apical section. Post-processing evaluation of T1-mapping values and ECV was performed using dedicated software . T1-mapping analysis was performed on short-axis images on basal, mid, and apical slices. Images were manually contoured in native and post-contrast images by an investigator and verified by a magnetic resonance imaging level 3 cardio-radiologist. Papillary muscles were excluded from myocardial tissue. The equation used for ECV measurement was the following :ECV=(1−h2) (model 1). The fully adjusted model additionally included systolic blood pressure (mmHg), use of beta blockers (yes/no) and use of loop and thiazide diuretics (yes/no).Data are shown as mean and standard deviation (continuous data) or as count and percentage . Because NT-proBNP, lateral E/E′ and T1-mapping indices distributions were skewed, they are reported as medians and interquartile ranges. We categorized patients into two groups according to the median value of NT-proBNP, and we used multivariate linear regression analysis to compare the groups in terms of clinical characteristics and echocardiographic measures. For this analysis, we used predefined models to adjust for potential confounders. A minimally adjusted model included age (years), sex, plasma creatinine (mg/dL) and body mass index  . All anaSome limitations of this study should be considered. First, sexes were not equally distributed in our study population, which mostly consisted of women. Although it is well known that women outnumber men in HFpEF, the proportion of women in our study is higher than other reports, and this might induce difficulties with the comparison of results across studies. A possible explanation for this distribution may be the applied stratification of patients, with the exclusion of patients with obstructive CAD and cardiomyopathies. Second, the size of the overall study population and of the subgroup undergoing CMR is relatively small; however, these patients were well-phenotyped with NP, a comprehensive echocardiographic analysis and myocardial tissue characteristics. Furthermore, the subgroup of patients undergoing CMR showed clinical and echocardiographic characteristics comparable to the overall study population. Third, CMR was not performed on the same day as echocardiography and biomarker assessment, which may create differences in loading conditions. However, the NT-proBNP measurement was repeated the day of the CMR examination, and this value was used for comparison with T1-mapping indices. Furthermore, our study included multiple echocardiographic markers, such as LA volumes, that reflect long-term exposure to LV filling pressure as well as measures of myocardial remodeling and tissue composition that are not affected by changes in volume status and do not vary in the short-term.Compared to HFpEF patients with lower NT-proBNP plasma levels, those with higher NT-proBNP levels had comparable LV structure and LV relaxation but higher LV stiffness and ECV on CMR imaging in a study population with a comorbidity-driven HFpEF phenotype. The latter suggests that patients with high NT-proBNP have a more advanced stage of LV and LA remodeling with more severe myocardial ECM remodeling.As NT-proBNP reflects the severity of cardiac dysfunction and remodeling in HFpEF, it may potentially serve a contributory role in improving pathophysiologic and therapeutic stratification in patients with HFpEF.


Adverse ventricular remodeling is an inflexion point of disease progression in aortic stenosis (AS) and a major determinant of prognosis. Intervention before irreversible myocardial damage is of paramount importance to sustain favorable post-operative outcomes. Current guidelines recommend a left ventricular ejection fraction (LVEF)-based strategy to determine the threshold for intervention in AS. However, LVEF has several pitfalls: it denotes the left ventricular cavity volumetric changes and it is not suited to detecting subtle signs of myocardial damage. Strain has emerged as a contemporary imaging biomarker that describes intramyocardial contractile force, providing information on subclinical myocardial dysfunction due to fibrosis. A large body of evidence advocates its use to determine the switch from adaptive to maladaptive myocardial changes in AS, and to refine thresholds for intervention. Although mainly studied in echocardiography, studies exploring the role of strain in multi-detector row computed tomography and cardiac magnetic resonance are emerging. This review, therefore, summarizes contemporary evidence on the role of LVEF and strain imaging in AS prognosis, aiming to move from an LVEF-based to a strain-based approach for risk stratification and therapeutic decision-making in AS. Aortic stenosis (AS) poses pressure overload to the myocardium, causing ventricular damage that depends, among other things, on the afterload excess, and the period of exposure. In order to restore wall stress and maintain cardiac output under those circumstances, the myocardium will initially respond with compensatory hypertrophy of the left ventricle (LV), defined as excess mass, increase in relative wall thickness, and concentric hypertrophy . LV hypeIt is therefore imperative that intervention on the valve is implemented at an appropriate stage of the disease, in order to avoid irreversible myocardial damage and its consequences. While the guidelines recommend left ventricular ejection fraction (LVEF) as the gold standard to describe myocardial damage and proceed to therapeutic maneuvers ,6, a larSymptoms serve as a sign of established disease and dismal prognosis, and should prompt intervention, irrespective of LV function, in high-gradient severe AS, as long as the patient is not critically ill or overly fragile, for them to benefit from intervention . HoweverIn a retrospective analysis of 2017 symptomatic and asymptomatic AS patients undergoing surgical aortic valve replacement (AVR), Dahl et al. demonstrated a stepwise increase in all-cause mortality with lower preoperative LVEF values . Similar2 had the worst survival rates . Gl. Gl20]. Longitudinal subendocardial fibers are the most susceptible to increased wall stress and reduced perfusion, and will be the first to be impaired by the afterload excess. GLS is capable of highlighting such subtle myocardial changes at the subendocardial level before a drop in LVEF occurs ,25. YingGLS is an invaluable marker of LV dysfunction in paradoxical low flow, low gradient (LFLG) AS with prominent concentric remodeling and small cavity size, where LVEF will be supranormal and not representative of LV function. This was indicated by Kamperidis et al. in a group of 134 paradoxical LFLGAS patients, who had worse all-cause mortality with GLS > −15% , and wasAfter the intervention, if the valve-related pressure overload has been retracted from the ventricle on time, regression of diffuse fibrosis and myocardial cellular hypertrophy may occur. In this instance, GLS is a sensitive marker of myocardial systolic recovery, while LVEF might fail to detect such subtle functional improvement ,36. It h(i)LV global work index, representing the total work within the LV pressure-strain loops;(ii)LV global constructive work, defined as the work performed during myocardial shortening in systole and the work during myocardial lengthening in isovolumic relaxation;(iii)LV global wasted work, representing the work contributing to the lengthening of the cardiac myocytes during systole and the shortening during isovolumic relaxation; and(iv)LV global work efficiency, defined as the percentage of effectively spent work by the LV myocytes, and obtained by the following formula:Despite being a sensitive surrogate of occult longitudinal systolic dysfunction, GLS still does not account for the global afterload which differs with AS severity and peripheral vascular resistance. Global afterload is the cause of increased metabolic demand and oxygen consumption of cardiomyocytes in order to maintain cardiac output. Russel et al. described a novel non-invasive method that reflects those metabolic demands by assessing different parameters of the energy efficiency of the LV ,50. Thisp = 0.042, per 100 mmHg/% increase) and global work index , in a cohort of symptomatic severe AS patients, were the only echocardiography indices independently associated with heart failure symptoms, after adjustment for right ventricular free wall strain [Whereas normally non-invasive brachial blood pressure is entered in the module as the equivalent of the LV afterload, this is not the case for severe AS. In severe AS, global afterload is the composite of the peripheral vascular component  and the valvular component  posed to the ventricle. Taking this into account, Fortuni et al. developed a method to evaluate LV myocardial work in patients with severe AS, by adding the echocardiography-derived transvalvular mean gradient to the systolic blood pressure . Their fl strain . Accordil strain . The myoComputed tomography plays a prominent role in AS assessment, mainly by obtaining information regarding the extent of aortic calcification, aortic valve–aortic root anatomic relationship, and aortic valve area. It is the guideline-recommended modality for establishing severity in paradoxical LFLG AS, and in classical LFLG when there is no flow reserve by dobutamine stress echocardiography . Additio2 for male and >63.8 gr/m2 for female (Stage 1), left atrial or mitral damage; left atrial volume index > 56 mL/m2, atrial fibrillation or severe mitral annular calcification (Stage 2), right atrial damage; right atrial volume index > 70 mL/m2 (Stage 3) and right ventricular damage; right ventricular EF < 35% (Stage 4) [MDCT is the cardiac imaging modality that provides three-dimensional data of the heart with the best spatial resolution, and allows the volumetric quantification of each cardiac chamber and computation of the LVEF and right ventricular EF. Thus, a MDCT-derived staging system of extra-aortic cardiac damage has recently been validated in a population of 405 patients undergoing TAVR . The popStage 4) . This syStage 4) , and theStage 4) .p < 0.001) in a cohort of 214 TAVR recipients [Apart from the volumetric assessment of cardiac function with LVEF and right ventricular EF evaluation, a novel dynamic feature-tracking software has arisen, permitting GLS analysis from MDCT data. Hence, the emerging technology allows shifting from LVEF to LV GLS in MDCT, in parallel with the echocardiography shift from LVEF to LV GLS. MDCT-derived GLS showed excellent correlation with speckle-tracking-echocardiography-derived GLS  can extend beyond volumetric quantification and has the unique strength of myocardial tissue characterization. The extent of myocardial damage can be effectively quantified in the form of local fibrosis by late gadolinium enhancement and in the form of diffuse fibrosis by T1 mapping.The distribution of gadolinium corresponds to areas of focal replacement fibrosis, which, histologically, represents irreversible myocardial damage and cardiomyocyte death . Dweck eMyocardial T1 mapping expresses the degree of extracellular volume expansion and diffuse myocardial fibrosis, which presents earlier than focal replacement fibrosis and is reversible if a well-timed AVR is pursued . Higher Nonetheless, further software development has arisen which enables LV deformation assessment by feature-tracking CMR strain analysis in AS, which can be derived from steady-state free precession cine images . FeatureLVEF assessed by echocardiography is the main parameter for LV function evaluation in severe AS, endorsed by the current guidelines. However, LVEF is limited to a mere description of the LV volumetric changes during a cardiac cycle. GLS by speckle-tracking echocardiography has emerged as a more sensitive index of LV function, detecting even subtle LV intramyocardial changes that the volumetric LVEF may miss. Considering that LV dysfunction is used as a criterion for AVR, the evaluation of GLS may define the precise time-point for intervention, which is of paramount importance for prognosis, post-AVR. Evidence that GLS may be evaluated with feature-tracking MDCT and CMR has emerged, but the available data are still scarce and further research is warranted to determine its value in clinical practice.