BackgroundMethamphetamine use is associated with cardiovascular disease and significant morbidity and mortality. There is only one previous study performed on echocardiographic parameters in patients with methamphetamine cardiomyopathy.MethodsWe performed a retrospective review of medical records in a county hospital in Southern California with a high population of methamphetamine users. We reviewed medical records and echocardiogram findings in patients seen in our institution from November 2019 to November 2020 who had cardiomyopathy with and without methamphetamine use. We excluded patients who either left the hospital or expired before appropriate assessment. We divided our patient population into a case group (methamphetamine users) and a control group (non-methamphetamine users) to study and compare their echocardiographic parameters.Results2 ± 40.66 vs. 108.62 grams/m2 ± 32.82, p=0.0000), left ventricle end diastolic volume index  and marginally significant right ventricle systolic pressure Case group included a total of 254 patients and control group included 268 patients. Majority of the patient population were males - 178 (70%) and 180 (67%) in the case and control group respectively. Age was found to be statistically significant with the younger population in the case group (p = 0.0000). Our analysis revealed statistically significant difference in methamphetamine users compared to non-users in regards to left ventricle ejection fraction , left ventricle mass index (122.49 grams/mConclusionOur results indicated that methamphetamine users had echocardiogram findings with decreased ejection fraction and increased left ventricular mass index, end-diastolic volume index, and right ventricular systolic pressure consistent with worse dilated cardiomyopathy comparison to non-users. The exa2 . The rig2 . The purWe intended to perform a case-control study in heart failure patients (HF) patients with active methamphetamine usage compared to patients with cardiomyopathy without methamphetamine use. We observed the echocardiographic characteristics in both patient populations. The primary aim of this study is to determine whether there is any significant difference in echocardiographic parameters in heart failure patients with a history of methamphetamine use that would potentially determine their prognosis compared to patients without methamphetamine use. We included Right Ventricular Systolic Pressure (RVSP), Left Ventricular Ejection Fraction (LVEF), Left Ventricular Mass Index (LVMI), End Diastolic Volume Index (EDVI), grade of Diastolic Dysfunction (DD) along with age and gender to determine if there is any statistical difference between the two groups. The ejection fraction was calculated using the Modified Simpson Method (biplane method of disks).After obtaining institutional review board (IRB) approval, we performed a retrospective chart review. We screened patient charts from November 1, 2019, to November 1, 2020, using heart failure related International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10 CM) codes that showed 1410 records. Our inclusion criteria included patients aged 18 years and above with clinical heart failure and active and recent methamphetamine use (in the last six months) based on history provided or urine toxicology, along with patients who underwent echocardiography during the index admission. We excluded patients who either left the hospital or expired before an echocardiogram was obtained. The final case group included 254 patients  and 180 (67%) in the case and control group respectively which was not statistically significant  . The mean value LVEF in the control group was higher than in the case group (p= 0.0000), suggesting better left ventricular systolic function in patients without methamphetamine use. LVMI, which signifies the mass of left ventricle as per body surface area, was significantly higher in the case group (p= 0.0000). So was the EDV Index (p=0.0000), signifying greater left ventricular dilatation in methamphetamine users. In patients where RVSP value was available , mild statistical significance  was observed in the difference in RVSP between case and control groups (cases having higher RVSP). Given that not all the patients had RVSP reported, results may have been impacted by a smaller sample size Table .While comparing diastolic dysfunction between cases  and controls  where dysfunction was defined as any grade ; the odds ratio was 1.07, not statistically significant (p = 0.807) which means that the incidence of diastolic dysfunction was similar in both groups. Diastolic dysfunction was also broken down as per the grade, which again showed no statistical significance (p = 0.77), demonstrating similar incidence between two groups regarding different dysfunction grades. However, the sample size was smaller in individual grade groups , end-diastolic volume (EDV), left ventricle mass index (LVMI), right ventricle systolic pressure (RVSP). In this study performed by Ito et al., in Hawaii in 2009, 28 methamphetamine users (case group) were compared to non-users revealing a statistically significant decrease in LVEF, increase in LV EDV; however, the results for LVMI and RVSP were not statistically significant. This possibly was due to their small sample size. Similar to cocaine, methamphetamine is hypothesized to activate the calcium/calmodulin-dependent protein kinase pathway that causes myocardial fibrosis and necrosis; methamphetamine likely cause the same effect physiologically. Though this study did not show a statistically significant increase in LVMI, they acknowledged their limitations due to the small sample size. Their results were still consistent with autopsy studies performed in San Francisco, California, that supported evidence of methamphetamine users to have enlarged hearts that weighed more than their age-matched controls. Our study showed statistically significant results for an increase in LVMI in methamphetamine users, which we hypothesize due to a chronic burden of hypertension and tachycardia leading to LV hypertrophy. The exact mechanism of myocardial injury remains unknown; however, a combination of LV hypertrophy due to significant vasoconstriction increased myocardial afterload and myocardial necrosis, fibrosis leading to eccentric dilatation and impaired relaxation causes this distinctive catastrophic heart failure .Cocaine abuse causes higher LVMI, and lower EF ,17. MethOur study is limited by several factors but mainly by the inclusion of only select echocardiographic parameters. We also did not include any demographic data other than age and gender. The small sample size also limits our study as we only looked into patients' data spanning one year (from 2019 to 2020) due to a change in our electronic medical record database before the year 2019. Our case group included patients with heart failure that had recent or active methamphetamine usage as correlating factor, not necessarily as the only causation of heart failure.In conclusion, patients with methamphetamine-related cardiomyopathy tend to be younger and had worse cardiomyopathy related echocardiogram parameters when compared to patients with cardiomyopathy without methamphetamine use. Methamphetamine users had increased LV mass index, worse systolic dysfunction and increased chances of developing right heart failure from increased overall RVSP. Further large scale, randomized controlled trials are needed to confirm these findings of methamphetamine-related cardiomyopathy.


An increasing number of Nuclear Medicine sites in Europe are using cardiac-centered gamma cameras for myocardial perfusion scintigraphy (MPS). Three cardiac-centered gamma cameras are currently the most frequently used in Europe: the D-SPECT (Spectrum Dynamics), the Alcyone , and the IQ-SPECT . The increased myocardial count sensitivity of these three cardiac-centered systems has allowed for a decrease in the activities of radiopharmaceuticals injected to patients for myocardial perfusion imaging and, consequently, radiation exposure of patients. When setting up protocols for MPS, the overall objective should be to maintain high diagnostic accuracy of MPS, while injecting the lowest activities reasonably achievable to reduce the level of radiation exposure of patient and staff. These guidelines aim at providing recommendations for acquisition protocols and image interpretation using cardiac-centered cameras. As each imaging system has specific design and features for image acquisition and analysis, these guidelines have been separated into three sections for each gamma camera system. These recommendations have been written by the members of the Cardiovascular Committee of EANM and were based on their own experience with each of these systems and on the existing literature. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985.These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines.The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.These guidelines summarize the views of the Cardiovascular Committee of the EANM and reflect recommendations for which the EANM cannot be held responsible. The recommendations should be taken into context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions. The guidelines were brought to the attention of all other EANM Committees and to the National Societies of Nuclear Medicine. The comments and suggestions from the French and Israelian national societies are highly appreciated and have been considered for these guidelines.−6) of injected activities being detected within the myocardial area , the Alcyone , and the IQ-SPECT . The heart-centric method of collimation of these systems explains the enhanced count sensitivity, when compared with conventional Anger cameras. In addition, iterative reconstruction methods taking into account the collimation geometry have improved image contrast and decreased the level of noise  perfusion tracers should be preferred in most clinical situations over 201Thallium (201Tl), as the level of radiation exposure for patients is significantly lower. Two 99mTc-labeled perfusion tracers are commercially available: 99mTc-2-methoxyisobutylisonitrile (MIBI) and 99mTc-1,2-bis [bis (2-ethoxyethyl) phosphino]-ethane (Tetrofosmin). When setting up protocols for MPS, the overall objective should be to maintain high diagnostic accuracy of MPS, while injecting the lowest activities reasonably achievable to reduce the level of radiation exposure of patient and staff (ALARA principle). Nevertheless, the amount of activity of radiopharmaceutical to be injected into patients will depend on the organization of the Nuclear Medicine site for performing stress tests, the performance of the camera (sensitivity of the system), the perfusion tracer (99mTc-labeled perfusion tracers vs.201Tl), the acquisition protocol (one-day vs. two-day), and the image quality required to maintain high diagnostic performance of MPS.The enhanced myocardial count sensitivity of these three cardiac-centered systems has allowed for a decrease in the activities of radiopharmaceuticals injected into patients for MPS translating into lower radiation exposure . When selecting the activity of perfusion radiotracer injected to patients, the reduction in activities should be prioritized following the as low as reasonably possible (ALARA) principle Table . Neverth99mTc generator delivers an eluate with high activity. As 99mTc-labeled perfusion tracers are “sticky,” a significant and variable amount of tracer may adhere to the inner part of the syringe and may thus not be injected into the patient. While this activity is negligible for protocols with conventional gamma cameras, the “true” activity injected into patients might be significantly reduced in syringes containing very small volumes according to ultra-low dose protocols resulting into long acquisition times and poor image quality. The residual activity in syringes should thus be monitored carefully with ultra-low dose protocols to have an accurate estimation of the true activity injected into patients. A dilution of the radiopharmaceutical after radiolabelling and before injection allows for an increase in the volumes of tracer injected into patients and may help to reduce the proportion of activity remaining in the syringe.The reduction in activities injected to patients imaged with cardiac-centered gamma cameras results in syringes with small volumes, in particular, if the 99mTc-labeled perfusion tracer for stress and rest studies.The average activity injected into patients should be in the range between 3 MBq/kg and 5 MBq/kg of 99mTc-labeled perfusion tracer  and, for the second acquisition (stress or rest), in the range between 7.5–10.5 MBq/kg of 191 99mTc-labeled perfusion tracer . Stress-first protocols should be preferred for one-day protocols because, in case of normal stress MPS, the second injection can be avoided resulting into a significant reduction of the radiation exposure of patients.For the first acquisition (stress or rest) , the injected activity should be in the range between 2.5–3.5 MBq/kg of 99mTc-labeled perfusion tracer at rest after administration of nitrates.The activity injected into patients should be in the range between 3 MBq/kg and 5 MBq/kg of Ultra-low dose protocols with injection of fixed activities between 100 and 120 MBq provide also good image quality in non-obese patients  arranged in a curved configuration that encloses the left side of the patient’s chest. The camera is equipped with tungsten parallel-hole collimators that are shorter and have larger square holes compared to standard lead parallel-hole LEHR collimators. Behind each collimator column, there is an array of 2.46 × 2.46 mm, 5-mm-thick CZT crystals  , even with 99mTc-labeled perfusion tracers and 0.6 and 0.8 million counts for MPS acquisitions with 201Tl. The selection of the total number of myocardial counts for SPECT acquisition on the D-SPECT camera results from a compromise between injected activities, mean duration of SPECT acquisitions, and image quality.The duration of SPECT acquisitions can either be of fixed length or adjusted to the counts measured in the myocardium that are estimated by placing a circular region of interest placed in the cardiac area on the scout view. The activity-based approach should be preferred as it allows for the adjustment of the duration of the SPECT acquisition to injected activity, myocardial extraction of the radiotracer, and tissue attenuation. Nevertheless, attention should be given to ensure that the ROI is placed exclusively on the heart and does not include extra-cardiac activities  that might otherwise reduce inappropriately the duration of SPECT acquisitions and result in poor image quality. This count-based approach permits also to acquire stress and rest acquisitions with 1-day protocol images in similar conditions, even though the activities injected at stress and at rest differ by a factor of 3. The usual targeted activities selected for total myocardial counts are in the range between 0.7 and 1.3 million counts for MPS acquisitions with The tomographic acquisition on the D-SPECT camera is composed of two parts of equal duration. During the first part of the acquisition, the detectors rotate inside the arm of the camera and cover the cardiac region. At half of the acquisition time, the detectors are moved automatically in the horizontal direction for a short distance which provides additional angles of projections for the detectors. Consequently, if the acquisition is stopped prematurely on this camera, no image can be reconstructed and the whole acquisition needs to be repeated. For patients who are not able to stay immobile during the SPECT acquisition, it is therefore recommended to shorten the total length of SPECT acquisitions in order to get interpretable images.Quality control of the camera should be performed on a daily basis with a cobalt rod source positioned in a dedicated arm that is attached to the machine to confirm that all detectors are functioning correctly and provide a homogeneous signal before starting any acquisition. At the end of each acquisition, the quality of SPECT data should be checked systematically using the dedicated tool available on the workstation Fig. . A sinogIn a window, the histograms of R-R intervals during the acquisition are visualized. As acquisitions are saved in a list mode, the software provides the possibility to select with two bars the interval of R-R values for the reconstruction of gated images. This tool is particularly useful to select only regular cycles in patients with supra-ventricular or ventricular extrasystoles. Of note, the exclusion of a significant proportion of R-R cycles may result in a degradation of the quality of gated images, in particular, if more than 30% of the cycles are excluded. If arrhythmia is identified before starting SPECT acquisitions, 30% or 50% time can be added to the duration estimated on the scout image in order to maintain image quality of gated images after exclusion of the arrhythmic cycles at the end of the acquisition.A view of the thorax is reconstructed and allows to visualize the heart and the structures surrounding the heart. This image is particularly useful to evaluate the intensity of extra-cardiac digestive or liver signal and the presence of increased lung uptake and to identify structures  that might cause attenuation artifacts on MPS. Even though this view looks similar to the aspect of SPECT projections from conventional gamma cameras, it is already a 3D-reconstruction from the projection of the detectors and cannot be used to identify patient movements or to correct images for motion.MPS images are reconstructed on the workstation of the D-SPECT camera using a dedicated algorithm that takes into consideration the geometry of the detecting system, the distance from the detectors, and the shape of the heart. Reconstruction is performed in 2 steps. In the first step with 3 iterations, the left ventricular (LV) region and orientation are determined and LV counts are calculated. Four further iterations are subsequently performed . In very obese patients, the most frequent limitation to perform the SPECT acquisition is the size of the inner circumference of the camera arm containing the detectors. It is therefore recommended to confirm before the injection of any radiotracer that the arm of the detector can be moved close enough to the thorax of the patient to allow for SPECT acquisitions. If the heart of the patients is placed too far from the detectors, image quality is degraded. Repeating acquisition after optimizing the positioning of the patient and the detector arm can help to improve image quality significantly. On the D-SPECT camera, attenuation artifacts caused by the diaphragm usually predominate in the apical segments of the inferior and infero lateral walls because of the semi-supine position of the patient during acquisitions . Verger et al. (r = 0.86) and infarction area (r = 0.80) measured on the D-SPECT in comparison to Anger cameras, with slightly lower correlation for the extent of myocardial ischemia (r = 0.72). In the MultIcenter nucLear Low-dose Imaging at a milliSIEVERT (MILLISIEVERT) study  and using a conventional Anger camera with a standard low-dose protocol (average activity of 278 MBq of 99mTc-labeled perfusion tracer). Overall image quality was superior with the D-SPECT in comparison to the conventional gamma camera with twice as many studies graded excellent quality; correlations between MPS acquired with each gamma camera was high for summed rest score , total perfusion deficit , and LV ejection fraction . High image quality could also be reached in 118 obese patients (60 of them were morbidly obese) with the D-SPECT. None of the patients had a non-diagnostic study. In obese patients, the upright position was associated with a lower rate of equivocal studies than the supine position and should be preferred , Perrin et al. . Similar results were documented when assessing myocardial counts normalized to injected activities in humans for the Alcyone technology and standard SPECT . The central spatial resolution of the Discovery NM 530c was measured 6.7 mm compared to 15.3 mm with standard SPECT, also in accordance with the analysis of the sharpness of myocardial contours on human images . These data document a dramatic enhancement in image quality mainly because of a lower proportion of Compton photons within the acquisition energy window. Moreover, CZT image quality was further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum-likelihood expectation maximization (MLEM), which corrected for the loss in spatial resolution due to line response function of the collimator .201Tl, acquisitions can be performed 5–10 min after the injection at stress and at rest. For 99mTc-sestamibi or 99mTc-tetrofosmin, acquisitions at rest or after pharmacological test are usually performed between 15 to 45 min after injection in order to allow for clearance of the radiopharmaceutical from the liver and to reduce background signal in the digestive tract. In patients stressed with physical exercise, acquisitions can be started 15 min after injection because the myocardial extraction of 99mTc-labeled radiopharmaceutical is increased by exercise and the background signal in the digestive tract is usually reduced. In presence of extra-cardiac activity that degrades the quality of myocardial perfusion images, the acquisition should be repeated 45 min after ingestion of a lipid-rich meal and cold sparkling water that help decrease the intensity of the liver and digestive background signal.For The quality of SPECT acquisitions should be checked systematically on the dedicated tool of the workstation  or phase-mode acquisition . Time and phase modes are equivalent as long as the heart rate is stable throughout the scan. As phase mode tends to blur systolic and early diastolic phenomena at low and moderate heart rates, time mode should be preferred. At high heart rates or if just the visualization of wall motion is required, phase mode may be preferred. Patients with severe arrhythmia do not usually provide interpretable gated scans.99mTc. List mode files are acquired and stored. Images should be reconstructed on a standard workstation  using a dedicated iterative algorithm. All studies should be reconstructed using a standard iterative algorithm with ordered-subset expectation maximization with 50 iterations, without resolution recovery, or attenuation correction. A Butterworth post-processing filter  is applied to the reconstructed slices. The tomographic studies are re-projected into 60 planar projections to emulate a standard SPECT layout.All images are acquired with a 32 × 32 matrix and a 20% energy window centered at the 140 keV photopeak of Gated stress and rest images are reconstructed in 16 frames and analyzed using the commercially available software. In patients with inadequate border detection, manual editing should be performed.x,y,z coordinates of myocardium center of mass are derived for each time bin and automatically corrected if necessary. A dedicated tool may be available for attenuation correction: attenuation correction QC. A customization parameter allows images to contain either the unmasked left ventricle or the left ventricle masked according to left ventricle-based contours. In 2010, Herzog ; data are reconstructed into 5 dynamic images from 5 central pinholes. An ellipsoid mask on dynamic images is created and finally, The first demonstration of the origin of artifacts deriving from Alcyone technology has been published in 2014 by Liu et al. . An anth99mTc-tetrofosmin rest/stress imaging protocol and were imaged both the GE camera with Alcyone technology and a conventional dual-detector SPECT gamma camera. Rest and stress acquisition times in patients with the same injected activities were 4 and 2 min for the GE camera with Alcyone technology and 14 and 12 min for the conventional SPECT gamma camera. Agreement for presence or absence of myocardial perfusion defects on a per-patient analysis between the Alcyone and conventional gamma cameras was 91.9% and 92.5%, respectively. Correlation coefficients of rest and stress left ventricular ejection fractions were 0.87 (p < 0.01) and 0.90 (p < 0.01). Buechel et al.  and on per-vessel territory basis (96%), also allowing for more than a fivefold reduction in scan time while providing clinical results equivalent to conventional camera. In addition, ventricular volumes and LVEF calculated on gated MPS acquired with the CZT camera correlated well with the values measured on cardiac MRI despite a small underestimation of the LV volumes with SPECT  using GE camera with Alcyone technology in 124 patients. Using 10-min gated acquisitions in the supine position image quality, image quality was preserved even in obese patients and radiation exposure of patients was significantly reduced (4–5 mSv).In the study of Esteves et al. , 168 patl et al.  found si201Tl for stress, 99mTc-labeled perfusion tracer for rest) in 54 patients referred for coronary angiography, sensitivity, specificity, and diagnostic accuracy were measured at 93%, 69%, and 81% for the detection of coronary stenosis > 50% with FFR < 0.8 , the annual rate of cardiovascular event was measured at 0.5% after a 3-year follow-up for MPS classified as normal  in association with an exercise test was predictive of a low risk of cardiovascular events  after a mean follow-up of 39 months.The prognostic value of MPS with the Alcyone camera was shown to be similar for the prediction of cardiovascular events as for values observed with MPS using conventional gamma cameras  using a CT scan (CTAC) with 2 to 16 detector rows depending on the exact model of Symbia camera is an additional and essential feature for IQ-SPECT.z-axis tube current modulation. Both gated and non-gated acquisitions of 99mTc and 201Tl are supported. The entire patient set-up adds just one additional step to identify the position of the heart on the touch screen patient positioning monitor. The patient is placed on the bed in either a supine or prone position and moved under the gamma-detectors until the heart is approximately centered in the axial direction  to − 45° left posterior oblique (LPO), what covers the usual 180° in standard SPECT plus the two-fold fan angles of the collimator. For current SPECT imaging system, the imaging resolution is between 13 and 16 mm. The standard matrix size is 128 × 128 pixel, with a zoom factor of 1.00. The most commonly used acquisition mode of IQ-SPECT systems is the “step-and-shoot” method. In this approach, the camera acquires a projection but interrupts data recording during rotation to the next angle. For d Hawman . There i99mTc SPECT study does not exceed the traditionally necessary time for a non-gated SPECT study. Time per projection must be adjusted to obtain an adequate myocardial count rate per interval. In general, a total acquisition time between 4 and 10 min (depending on heart rhythm and injected activity) results in adequate image quality of gated acquisitions. This range is mainly based on the preferred balance of injected dose and acquisition time: the lower the dose, the longer the scanning time; the higher the dose, the shorter the acquisition time.The cardiac cycle is divided into frames representing different phases of the cardiac cycle. Using ECG-gated IQ-SPECT, the heartbeat is usually divided into 8 or 16 temporal frames or gates. The R-wave of the QRS complex serves as the signal and starting point (triggering point) of the cardiac cycle. Ideally, the length of acquisition (expressed in seconds per projection) for a gated For hybrid imaging systems, the CT configuration can be a low-resolution CT (non-diagnostic CT) or a multidetector-row CT with slices ranging from 2 up to 16. Any of these systems can be used for attenuation correction of MPS. For CACS, at least a 4-slice CT is required (≥ 6 slice recommended). For CCTA, at least a 16-slice scanner is required (≥ 64-slice multidetector-row CT recommended), with imaging capability for slice width of 0.4–0.6 mm and temporal resolution of 500 ms or less (≤ 350 ms is preferred).At the end of the acquisition, the quality of ECG gating, centering, and motion should be checked Fig. . Since tSymbia.net First User” workstation for reconstruction . Prone imaging does not eliminate attenuation artifacts, but simply changes its location. By comparing supine and prone images, artefactual defects will change their location, whereas true perfusion defects will remain fixed  myocardial counts in the inferior and inferolateral walls. Tissue attenuation counts are usually more pronounced in the inferior wall in males than in females. Prone imaging compensates for these attenuated inferior myocardial counts to some extent. Although AC compensated for inferior low myocardial counts, low counts at the apex were observed  showed myocardial ischemia. The discrepancy rate between MPS with IQ-SPECT and LEHR SPECT-CT was low (1.7%) for all coronary territories with a slightly lower discrepancy rate for IQ-SPECT acquired in prone than in supine position.Pirich et al.  compareda et al.  compared201Tl , the presence or absence of coronary artery disease, and previous myocardial infarction and the acquisition protocols . 99mTc agents should be preferred over 201Tl because of their shorter half-life, significantly lower effective dose, and superior image quality. For 1-day protocols, it is recommended to start with the stress acquisition. If the stress MPS results are normal, the rest scan can be omitted, with significant savings in cost, time, and radiotracer exposure to the patient (34). For MPS using the D-SPECT, the activities injected to patients can be reduced by about 30–50% in comparison to the usual recommended activities with Anger gamma cameras resulting into a reduction of the same level in patient radiation exposure. The average total radiation exposure of a stress/rest perfusion study with recommended injected activities for cardiac-centered cameras is approximatively 6–9 mSv with 99mTc-radiolabeled perfusion tracers and 10–15 mSv with 201Tl. In addition, ultra-low dose protocols with 99mTc-labeled perfusion tracers allow for an additional decrease in patient radiation exposure down to 1–2 mSv for stress-only acquisitions and 4–6 mSv for stress/rest acquisitions , the choice of radiopharmaceutical (


Patients with both double orifice mitral valve (DOMV) and bicuspid aortic valve (BAV) malformation are rare. Although DOMV or BAV can be detected in some genetic syndromes, it has not been reported to simultaneously appear in Turner syndrome (TS). TrueVue, TouchVue, and TrueVue Glass are the latest technologies in advanced three-dimensional echocardiography (3DE), which is an important information supplement to two-dimensional echocardiography (2DE) for the diagnosis of congenital cardiac malformations. Herein we report the novel use of the above-mentioned technologies in the diagnosis and evaluation of a rare, combined valve malformation. Meanwhile, we also reviewed the literature for cases involving both DOMV and BAV and their association with various genetic syndromes.We present the case of a 5-year-old girl diagnosed with TS because of a developmental delay. DOMV and BAV were found through echocardiographic examination. Three-dimensional transthoracic echocardiography as well as a series of novel advanced techniques were applied to clearly display the spatial structure of all tiers of the mitral valve apparatus, aortic valve, and arch to facilitate an accurate diagnosis.This is the first case in which both DOMV and BAV were associated with TS. Innovative TrueVue and TrueVue Glass offer unprecedented photographic stereoscopic images, while TouchVue technology greatly improved the ultrasonic diagnostic workflow and the diagnostic performance of rare valve malformations by adding virtual light sources to display realistic light-shadow effects.The online version contains supplementary material available at 10.1186/s12872-021-02184-2. The double orifice mitral valve (DOMV) is considered a rare congenital heart malformation due to the abnormal embryonic development of the endocardial cushion and myocardium, characterized by a two-channel atrioventricular valve in the left ventricle and accounting for about 0.05% of all congenital heart diseases , 2. The Turner syndrome (TS), known as congenital chromosomal disorder, is caused by the partial or complete deficiency of the X chromosome and is reported to have a higher incidence of congenital heart diseases, of which AV malformation is one of the most common changes , 8. RepoThe two-dimensional echocardiography (2DE) is the most common and important method for detecting congenital heart valvular disease . MeanwhiHere, we report a case with TS and congenital cardiac valvular malformations with DOMV and BAV, wherein we applied these advanced 3DE imaging technologies, which played an important role by providing images and diagnostic information that were previously unavailable.A 5-year-old girl presented to our hospital with a complaint of short stature and mild backache. She was found to have vitamin D deficiency, spina bifida, and small pituitary volume. Her peripheral blood chromosome result indicated “45, X,” consistent with TS.2. At the level of the papillary muscle, four papillary muscles were revealed by 2D-TTE, traditional 3D-TTE, and TrueVue images, but were transparent and only the borders were revealed in the TrueVue Glass image  was performed using Philips EPIQ CVx cardiovascular specific ultrasonic diagnostic equipment . The 2DE scan application was conducted via a S9-2 (2–9 MHz) probe. The X5-1 (1–5 MHz) probe was used for the 3DE examination. As diagnoses of both DOMV and BAV were suspected, the MV apparatus and AV-related structures were examined by 3D-TTE for further morphological and functional evaluation. On the basis of traditional 3D imaging, we launched the new TrueVue imaging mode. In TouchVue, in addition to being able to directly zoom and rotate the image with two fingers on the touch screen, more importantly, a single finger click on the target structure can display and move the position and depth of a virtual light source. Based on the TrueVue image, we further applied the Glass mode to obtain a transparent rendering effect. The short-axis view at the level of the MV via above-mentioned four techniques demonstrated that there were asymmetric double left atrioventricular orifices divided by a complete fibrous bridge, of which the anterolateral orifice was larger (Fig. age Fig. . The reaWe further reviewed 24 patients with both DOMV and BAV in 16 references from 1988 to 2020 (Table An invasive TEE is not usually necessary for diagnosis due to the excellent acoustic window. Clear display of children’s valves via traditional 2DE and 3DE has certain difficulties due to their thinness, easily leading to misdiagnosis by inexperienced sonographers . TrueVueLesions of the MV apparatus sometimes occur simultaneously and do not involve just the leaflets . In thisThe patient is not currently undergoing surgery because there is no significant valve regurgitation or stenosis. However, with aging, valve elasticity decreases, which will aggravate valve dysfunction ; therefoIn conclusion, this case extended the possible complex lesions in TS and endorses 3D transillumination rendering techniques in detecting valvular malformations.Additional file 1: Video 1. TrueVue Glass color Doppler shows the two streams of blood entering the left ventricle from the left atrium through the double orifice mitral valve, viewed from the side of the left ventricle.Additional file 2: Video 2. The short-axis view of the left ventricle shows the two orifices of the mitral valve and the corresponding four papillary muscles simultaneously through the 3D “dual volume” imaging mode.


Multimodality imaging is a comprehensive strategy to investigate left ventricular hypertrophy (LVH), providing morphologic, functional, and often clinical information to clinicians. Hypertrophic cardiomyopathy (HCM) is defined by an increased LV wall thickness not only explainable by abnormal loading conditions. In the context of HCM, multimodality imaging, by different imaging techniques, such as echocardiography, cardiac magnetic resonance, cardiac computer tomography, and cardiac nuclear imaging, provides essential information for diagnosis, sudden cardiac death stratification, and management. Furthermore, it is essential to uncover the specific cause of HCM, such as Fabry disease and cardiac amyloidosis, which can benefit of specific treatments. This review aims to elucidate the current role of multimodality imaging in adult patients with HCM. Left ventricular hypertrophy (LVH) is characterized by the increase of LV mass in response to different stimuli  caused by various conditions and diseases . TherefoHypertrophic cardiomyopathy (HCM) is defined by an increased LV wall thickness not only explainable by abnormal loading conditions ,5. It isIn more than half of patients, mutations in genes encoding for sarcomeric proteins are accountable for the development of the disease ,9. HowevMultimodality imaging is an important screening tool for identifying LVH and often provides the first clinical suspicion for specific aetiologies, especially when the medical and familiar history is mute. By a stepwise selection of appropriate diagnostic techniques, especially in the field of multimodality imaging, to collect those clinical and instrumental findings (red flags) that may suggest a specific cause, the identification of an underlying systemic disease with a potential tailored treatment becomes more and more achievable in clinical practice.In HCM, multimodality imaging, by different imaging techniques, such as echocardiography, cardiac magnetic resonance (CMR), cardiac computer tomography (CCT), and cardiac nuclear imaging (CNI), provides essential information for diagnosis, sudden cardiac death (SCD) stratification, and management .This review aims to elucidate the current role of multimodality imaging in adult patients with HCM.Echocardiography, being non-invasive and easily repeatable, has a fundamental role in detecting the different LVH/HCM phenotypes, suggesting disease causes, cardiac morphology and hemodynamic, and disease severity, all steps necessary in clinical practice for the management and treatment strategies. Echocardiography is a key tool for HCM diagnosis when an unexplained maximum wall thickness (MWT) > 15 mm in any myocardial segment of the LV is evidenced . Near 30Myocardial deformation parameters, such as GLS, are often reduced in pathological hypertrophy despite a normal LVEF, even in carriers who had not developed LVH . GLS is typically reduced at the site of LVH. The site of maximal hypertrophy is also and often the site of replacement fibrosis, evaluated by CMR as late gadolinium enhancement (LGE) ,20. MoreMyocardial work (MW), a novel technique for LV systolic assessment derived by speckle-tracking echocardiography, was recently applied in nonobstructive HCM ,22,23. PHCM caused by mutations in sarcomeric genes must be differentiated by other conditions which may mimic HCM phenotype but show a different aetiology and treatment ,25,26,27Cardiac amyloidosis (CA) is caused by extracellular deposition of insoluble fibrils determining multifactorial myocardial damage, LV wall thickening (pseudo-hypertrophy), and consequently, early systolic and diastolic dysfunction leading to heart failure . Both foSeveral echocardiographic red flags may raise the suspicion of CA. A prospective multicenter Italian study is currently investigating the prevalence of echocardiographic red flags of CA in consecutive patients ≥55 years who performed routine transthoracic echocardiography .Ventricular involvement in CA is characterized by early basal involvement that starts from the subendocardial layers, acquiring a transmural fashion subsequently with mid-ventricular involvement and LV apical sparing, responsible for generating the same pattern using longitudinal strain analysis ,31. ThisMany diagnostic scores were recently proposed to improve CA early diagnosis in patients with unexplained LVH. A multicenter study has recently developed two different multiparametric echocardiographic scores to suggest the diagnosis of CA. The first was formulated to detect myocardial involvement in systemic AL amyloidosis, and the second was to facilitate CA diagnosis in patients with increased LV wall thickness (IWT). The score is based on four variables , E/e’ ratio, GLS, tricuspid annular plane systolic excursion (TAPSE)) for AL-CA patients and five variables for IWT  . Monda eHowever, these results were based on a small cohort; indeed, further investigation is needed.FD is an X-linked multisystemic lysosomal storage disorder caused by the deficiency of the α-galactosidase enzyme, thus resulting in an accumulation of glycosphingolipids within several tissues , mainly Patients with FD cardiomyopathy show severe concentric LVH. The development of replacement fibrosis, commonly identified in the basal segment of the posterolateral wall, and the afterload changes related to FD vasculopathy, are responsible for an increase in LV volumes, which lead to a more spherical shape ,44,45. TThe glycosphingolipids accumulation in FD predominantly involves the subendocardial ventricular layers. Using layer-specific strain imaging, it was evidenced that the GLS reduction was mainly the result of the involvement of subepicardial strain, which is responsible for the increase in longitudinal strain myocardial gradient ,51.Cardiac magnetic resonance (CMR) plays an essential role in diagnosing and managing patients with HCM ,5 or othAccording to the current guidelines, CMR should be considered at the baseline assessment of each patient with suspected or confirmed HCM, if available ,5. It coCMR can also evaluate the presence of myocardial fibrosis. Indeed, LGE can be found in about two-thirds of patients . Two maj-to identify the presence of apical aneurysms, defined as a discrete thin-walled dyskinetic or akinetic segment of the distal portion of the LV chamber, which represents a significant risk factor for SCD ;-to measure the MWT of the LV, in particular in patients with poor echocardiographic acoustic windows, keeping in mind that this parameter is linearly associated with increased SCD and a value of ≥30 mm is a significant risk factor for SCD ,68;-to detect patients with systolic dysfunction (LV ejection fraction < 50%), the “end-stage” phase of HCM, associated with poor outcomes and increased risk for SCD ;-to describe the presence and the extent of LGE, with a threshold of ≥15% defined as associated with an increase in SCD risk ,66.Thus, CMR is crucial to properly perform the SCD risk stratification of patients with HCM ,5. In thHowever, while the first three parameters are recognized as strong risk factors for SCD and in their presence an ICD implantation should be considered, less clear is the management of patients with extensive LGE and no other risk factors. Therefore, the incorporation of LGE into the risk assessment for SCD in patients falling into the “grey zone”, such as those with an intermediate HCM risk score between 4% and 6%) or without major AHA/ACC risk factors, it is reasonable % and 6% . In the context of multimodality imaging, the role of machine learning and artificial intelligence is gaining attention. Among others, possible applications in HCM are the evaluation of LV myocardial fibrosis  and MWT CMR should be considered when planning a surgical myectomy, especially if the transesophageal acoustic windows are suboptimal and in patients with multi-level or biventricular outflow obstruction .Recently, the value of T1 and T2 mapping in HCM was investigated. It was found that native T1 and T2 values were significantly elevated in hypertrophic and even non-hypertrophic segments, suggesting that tissue remodeling may precede the morpho-functional changes of the LV . MoreoveFinally, the role of CMR is gaining attention for its potential use in evaluating myocardial stiffness, which plays a crucial role in the diastolic function of the LV. In HCM, myocardial stiffness and, of consequence, diastolic dysfunction is mainly caused by fibrosis and myocyte disarray. The non-invasive evaluation of myocardial stiffness is complex in clinical practice, and it is generally indirectly evaluated by assessing biomarkers  and echocardiographic parameters . CMR offers the possibility to investigate the two major determinants of myocardial stiffness in HCM, such as the myocardial fibrosis and the collagen volume fraction, using LGE and ECV, respectively ,76. FurtSeveral diagnostic clues suggestive for specific causes of HCM  should be identified using CMR, and their presence can guide the subsequent investigation ,76,79. TCardiac amyloidosis produces a unique pattern of subendocardial LGE, or, in rare cases, the distribution of LGE may be patchy, diffuse, or transmural . In cardAlthough HCM patients with chest pain have shown a lower incidence of epicardial coronary artery stenosis compared with the risk-adjusted general population , severe Non-invasive multimodality imaging may be useful to exclude obstructive CAD, particularly in specific clinical settings, as among patients with chest pain, unexplained left ventricular systolic dysfunction, or in case of disproportion between the magnitude of dyspnoea and heart failure symptoms. However, non-invasive studies are limited by the high prevalence of microvascular disease in HCM, accounting for low predictive positive value (PPV), according to pre-test probability and clinical presentation .Echocardiography with high-dose dipyridamole (0.84 mg/kg iv in 6 min) is used to assess regional wall kinesis and coronary flow reserve (CFR) response during stress. The combination of a new stress-induced wall-motion abnormality and reduced CFR velocity on the LAD reaches high diagnostic accuracy to identify CAD .SPECT with Tc99 or Tl-201 may be performed in patients with a low pre-test probability of CAD ,96. Howep < 0.001) and significantly lower false-positive rates compared with SPECT or PET [Unlike SPECT, PET with N13-labelled ammonia or O15-labelled water allows a quantitative measurement of the absolute myocardial blood flow; however, false-positive results are common in the presence of significant myocardial fibrosis or in cases of severe hypertrophy ,98. CoroT or PET . Given tT or PET . HoweverT or PET .In conclusion, CCTA may be the preferred imaging technique in patients with a low pre-test probability of CAD, whereas coronary angiography remains the cornerstone in patients with high pre-test probability or when non-invasive studies show unequivocal findings.The suspicion of cardiac amyloidosis may be triggered by some relevant clinical scenarios, such as low-flow low-gradient aortic stenosis, HFpEF, or when increased LV wall thickness (>12 mm) is associated with extracardiac red flags ,29,101. False-positive results for bone scintigraphy may be associated to AL amyloidosis, hydroxychloroquine toxicity, or apolipoprotein amyloidosis. On the other hand, particular conditions, such as rib fractures, technical errors, and recent myocardial infarction, may mask an underlying positive bone scintigraphy. Histological confirmation by means of endomyocardial biopsy may be required in case of non-concordant findings and when the clinical presentation is highly suspicious for an underlying ATTR-CA . There is compelling evidence to demonstrate the usefulness of molecular imaging based on amyloid-binding PET tracers  to diagnose cardiac amyloidosis, to quantify the extent of amyloid infiltration, and to detect molecular changes in their composition, thus being potential markers of therapeutic response ,110,111.Many observational studies have investigated the use of I123-metaiodobenzylguanidine (MIBG) scintigraphy to assess the extent of autonomic dysfunction in Anderson–Fabry disease (FD). Decreased MIBG uptake seemed to correlate with the extent of fibrosis diagnosed by means of late gadolinium enhancement (LGE), although autonomic dysfunction seemed to precede myocardial fibrosis . On the Multimodality imaging is crucial to first confirm the diagnosis of HCM and then to accurately evaluate features associated with high-risk of SCD. In addition, proper identification of patients with specific causes of HCM is crucial to start appropriate treatment. While echocardiography remains the first-line technique for the assessment of patients with HCM, the role of CMR, CCT, and CNI is expected to increase in the future, given their importance in providing some details nonevaluable by echocardiography alone.


Progressive cardiac fibrosis is the central aspect of the myocardial involvement in systemic sclerosis (SSc). We hypothesized that circulating biomarkers of the cardiac fibrosis may be useful in the early diagnosis of the cardiac manifestation in this disease. Thus, we investigated the potential correlations between the levels of galectin-3, soluble suppression of tumorigenicity-2 (sST2) and the echocardiographic markers of the myocardial mechanics in SSc patients.Forty patients  were investigated. In addition to the conventional echocardiography, tissue Doppler and speckle tracking-derived strain techniques were used to assess the function of both ventricles and atria. To estimate the correlations between galectin-3 and sST2 levels and the echocardiographic variables, partial correlation method was used with age as correcting factor.p = 0.005); grade of left ventricular diastolic dysfunction ; septal e’ ; septal E/e’  and with the grade of mitral regurgitation . No significant correlation was found between sST2 levels and the echocardiographic variables.In age adjusted analysis galectin-3 level showed significant correlation with left ventricular global longitudinal strain (r = 0.460, Galectin-3 levels, but not sST2 levels show significant correlation with the parameters of the left ventricular systolic and diastolic function. Galectin-3 may be a useful biomarker for the screening and early diagnosis of SSc patients with cardiac involvement. Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular abnormalities and diffuse fibrosis of the skin and various internal organs . AlthougCardiac involvement implies poor prognosis in SSc , 17, thuGalectin-3 is a beta-galactoside-binding protein member of the lectin family that activates a variety of profibrotic factors, supports fibroblast proliferation and transformation, and mediates collagen production . It playSoluble suppression of tumorigenicity-2 (sST2) is member of the interleukin-1 receptor family. It enhances myocardial hypertrophy and fibrosis by blocking the favourable influence of IL-33 . Its proBoth galectin-3 and sST2 concentrations showed significant correlation with the echocardiographic markers of LV or LA size and function in heart failure patients –31. BesiThus, in this study we aimed to investigate the potential associations between the levels of galectin-3 and sST2 and the echocardiographic markers of the myocardial mechanics in SSc patients.Our prospective study included 40 consecutive SSc patients diagnosed in the tertiary centre of the Department of Rheumatology and Immunology, University of Pécs. All enrolled cases fulfilled the updated ACR/EULAR classification criteria . PatientThe study complied with the Declaration of Helsinki. The institutional ethics committee approved the study. Written informed consent was obtained from all patients.All patients underwent echocardiographic examination performed by a single investigator using Philips EPIQ 7 ultrasound system . M-mode and 2D data were collected: LV ejection fraction measured by biplane Simpson’s method; basal, mid-cavity, and longitudinal dimensions of the RV corrected for body surface area; tricuspid annular plane systolic excursion (TAPSE); RV fractional area change (RVFAC); maximal and minimal diameters of the inferior vena cava (IVC); collapsibility index of IVC (the percent decrease in the diameter during inspiration). LV mass was calculated according to the Devereux formula and corrected for body surface area (LV mass index). RV wall thickness was measured at end-diastole , 37. MitFor strain analysis, three consecutive heart cycles were recorded digitally. Care was taken to obtain true apical images using standard anatomic landmarks in each view. Foreshortening was avoided. Recordings were processed off-line, using a dedicated software . Analysis was performed by a single investigator, blinded to the clinical and conventional echocardiographic data.To estimate LV GLS, apical four-, three- and two-chamber movies were obtained using 2D echocardiography. The frame rate was set between 50 and 55 frames per second. Regional peak systolic longitudinal strain was determined in all 17 segments. LV GLS was automatically provided by the software as the average of the regional peak systolic longitudinal strain values.For atrial speckle tracking analysis, atrium-focused apical four- and two-chamber view movies  were obtained. The frame rate was set between 80 and 90 frames per second. The onset of R-wave on the electrocardiogram was used as zero-reference point of the strain analysis. Reservoir strain was defined as the peak systolic strain, just before mitral valve opening. This was followed by a plateau and a second late peak at the onset of the P-wave indicating the contractile strain. Conduit strain was calculated as the difference between reservoir and contractile strain. Results obtained in apical four- and two-chamber views were averaged for LA strain analysis .Atrial volume curves were generated by the same software using the endocardial borders created for speckle tracking analysis. The following atrial volumes were obtained: maximal volume (Vmax) at the end of T wave on electrocardiogram, just before the opening of the mitral valve; minimal volume (Vmin) at QRS complex, just at the closure of the mitral valve; and preceding atrial contraction, at the beginning of P wave (Vp). LA volumes obtained in apical four- and two-chamber views were averaged. All volume values were corrected for body surface area .Blood samples were obtained immediately prior to the echocardiographic studies. Samples were stored at − 80 ∘C until testing.Analysis of galectin-3 levels was performed using Human Galectin-3 Platinum ELISA kit developed by eBioscience .Analysis of sST2 levels was performed using Presage ST2 assay kit developed by Critical Diagnostics .Plasma concentrations of NT-proBNP were analysed by electrochemiluminescence immunoassay .p value of < 0.05 was considered significant. Data were analysed using IBM SPSS 25 statistical software.Categorical data were expressed as frequencies and percentages; continuous data were expressed as mean ± SD. Mann–Whitney U-test was used for comparisons of variables between two subgroups. Since concentrations of galectin-3, sST2 and NT-proBNP did not show normal distribution, logarithmic transformation was performed. Pearson bivariate method was used to investigate the correlations between ln galectin-3, ln sST2 and the other single variables. As age-related changes in the echocardiographic parameters are well known, in a second step, partial correlation method was applied using age as correcting factor. Partial regression plots were used to visualize these correlations. As creatinine or estimated glomerular filtration rate did not show correlation with galecin-3 or sST2 levels in our study, partial correlations were not adjusted for renal function. A A total of 40 SSc patients were enrolled into the study. Detailed clinical data of the patients are reported in Tables Standard echocardiographic and tissue Doppler measurements were successfully performed in all patients. GLS, LA atrial strain and RA strain data were successfully obtained in 38, 39 and 37 patients, respectively. Rest of the measurements have failed due to inadequate acoustic window or foreshortening.Correlations between clinical variables and biomarker levels are reported in Table LV ejection fraction was preserved (≥ 55%) in 39 (97.5%), whereas mildly reduced (45–54%) in 1 (2.5%) patients. LV diastolic function was impaired (Grade I diastolic dysfunction) in 17 (42.5%) patients whereas echocardiographic data suggested elevated LV filling pressure in 12 (30%) patients . No patients with restrictive pattern (Grade III) were found.RVFAC < 35%, TAPSE < 16 mm and tricuspid S < 10 cm/s were found in 1 (2.5%), 1 (2.5%) and 4 (10%) patients, respectively. Tricuspid E/e’ suggested elevated RV filling pressure in 13 (32.5%) patients. Elevated pulmonary artery systolic pressure (tricuspid Vmax> 2.8 m/s) was obtained in 11 patients with a maximum of 41 mmHg. Detailed echocardiographic data of the study population as well as correlations between galectin-3 and sST2 levels and the echocardiographic variables are reported in Tables Galectin-3 levels showed significant correlation with GLS Fig. A, with tProgressive cardiac fibrosis has been reported as a central aspect of the myocardial involvement in SSc . Thus - ST2 is part of the interleukin (IL)-1 receptor family which may be found on cardiac myocytes and fibroblasts. ST2 exists in two forms. The transmembrane isoform (ST2L) is responsible for the cardioprotective effect of IL-33: IL-33 has antihypertrophic and antifibrotic effects transduced by ST2L. The soluble isoform (sST2), in contrast, eliminates the cardioprotective pathway of the IL-33/ST2L interaction, by binding circulating IL-33 molecules. All clinical conditions that increase wall stress, inflammation and macrophage activation increase sST2 level and may therefore lead to an increase of cardiac fibrosis . sST2 haThe behaviour of the IL-33/ST2 pathway has already been widely investigated is SSc. Serum IL-33 levels were elevated in SSc patients compared with healthy individuals, especially in patients with diffuse cutaneous form. IL-33 levels correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis . CorrelaRecent studies suggest that galectin-3 plays key role in the fibrogenesis in different organ systems, such as liver, kidney and lung . In addiAlthough the pathogenic role of galectin-3 is not proved in SSc, the potential associations between serum galectin-3 levels and the clinical features of the patients have already been investigated. Taniguchi et al. found that serum galectin-3 levels were significantly lower in the early diffuse cutaneous form of the disease compared with control subjects and showed significant correlation with total skin score. On the other hand, galectin-3 levels showed increase with the course of the disease and were higher in SSc patients with elevated right ventricular systolic pressure than in those without pulmonary hypertension . RecentlLV diastolic dysfunction is frequent in SSc –6, as itReduced LV ejection fraction is not common in SSc , but myoSpeckle tracking technique and, to a lesser extent, tissue Doppler imaging are useful in recognizing early myocardial involvement not only in the LV, but in the other cardiac chambers. Subclinical RV dysfunction was proved in SSc patients using tissue Doppler or speckle tracking measurements –12. ImpaSome limitations of our study need to be acknowledged. First, in the lack of healthy control group, we could not define the cut-of value between normal and elevated serum galectin-3 or sST2 levels. Recent data suggest, however, that in the general population normal plasma concentration of galectin-3 is < 11.0 ng/ml , whereasCirculating levels of the tested fibrosis markers may not reflect the histologically proven cardiac fibrosis. Thus, circulating biomarker levels require careful interpretation in relation to myocardial involvement .RV strain may better reflect the subclinical impairment of the RV systolic function than our traditional and tissue Doppler parameters. Nevertheless, in the lack of appropriate analytical software, RV strain analysis was not performed in our study.In SSc patients, galectin-3 levels show significant correlation with the parameters of LV diastolic function and with GLS, a parameter reflecting the subclinical impairment of LV systolic function. Our results suggest that galectin-3 may be a useful and simple biomarker for the screening and early identification of SSc patients with cardiac involvement. Our data does not support the use of sST2 for the same purpose.


We describe a patient with GCA and cardiac involvement, presented as myocardial inflammation with reduced biventricular ejection fraction and diagnosed using cardiovascular magnetic resonance (CMR). She was treated successfully with sacubitril/valsartan in parallel with anti-rheumatic medication and the post-treatment CMR showed improvement of biventricular function and disappearance of myocardial inflammation. This fact obliged us to restart steroids, and the patient is waiting for re-evaluation in due course.A 68-year-old woman was admitted to the hospital of Volos, internal medicine department, with fever (up to 39.5°C) despite pervious treatment with clarithromycin and, subsequently, amoxycillin/clavulanic acid. During hospitalisation, cardiac echocardiogram revealed reduced ejection fraction, and cardiac troponin was elevated. Thorough search for infectious causes of the fever was inconclusive, and the fever did not respond to several antibiotic regimens. At this time a temporal artery biopsy was performed that was positive for giant cell arteritis, and the patient was referred for rheumatological evaluation. Treatment with 32 mg methylprednisolone was instituted in June 2019. In parallel cardiac medication including b-blockers and ACE inhibitors was also started. After this treatment, the fever subsided, and laboratory markers of inflammation normalised. An echocardiogram performed in September 2019 showed LVEF=45–50%. Additionally, the first CMR in October 2019 showed reduced biventricular function, but myocardial inflammation was not identified, due to lack of collaboration with the patient. An echocardiogram in April 2020 showed LVEF=40.5%. After detailed instructions to the patient regarding how she should collaborate, a second CMR was performed in September 2020 and showed evidence of myocardial inflammation with reduced biventricular ejection fraction. Six months after the initial treatment, methotrexate was introduced to allow for faster tapering of corticosteroids. Tapering was successful, with no relapse in inflammatory markers, until September 2020, when the patient was receiving 3 mg methylprednisolone. Intriguingly, at this time inflammatory markers remained normal, but the third CMR evaluation showed myocardial inflammation and biventricular ejection fraction reduction. Methylprednisolone was re-escalated at 24 mg and tocilizumab was initiated (162 mg per week). In parallel treatment with Entresto (saccubitril+sartan) bid was started. A fourth CMR evaluation performed in January 2021 showed normalisation of biventricular ejection fraction and lack of myocardial inflammation. Finally, when we started the reduction of steroids, a 51 Detailed CMR data and inflammatory indices are presented in Table 1.The evaluation of blood inflammatory indices (ESR and CRP) in parallel with the CMR study did not reveal evidence of inflammation. This is in agreement with our previous studies supporting that the blood inflammatory indices do not always mirror the presence of myocardial inflammation.7 However, PET uses radiation, is extremely expensive and not widely available. Recently, CMR has been successfully used to diagnose myocarditis using both the classic Lake Louise criteria and the parametric imaging.8 To our knowledge, our paper is the second in the literature describing myocarditis during the course of GCA, diagnosed using CMR with evaluation before and after treatment. In the first paper, myocarditis was identified in 4/139 pts with Takayasu arteritis and GCA patients using CMR and aggressive immunosuppressive therapy led to remission of myocardial inflammation and improvement of LV function.9GCA is a systemic vasculitis of large vessels, manifested mainly as temporal arteritis or large vessel vasculitis of the aorta and its branches. Myocarditis is a rare complication in GCA and all cases in the literature were diagnosed using positron emission tomography (PET).10 It has been recently published in NEJM that tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with GCA.11 A significant reduction of cumulative glucocorticoid dose, prolonged relapse-free remission and reduced number of adverse events in the treatment groups have been demonstrated, supporting that tocilizumab can serve as effective glucocorticoid sparing agent.11 Furthermore, tocilizumab treatment may have contributed to the restoration of myocardial function, according to reports indicating improvement of myocardial function in RA patients following IL-6 inhibition.12Glucocorticoid therapy is essential and should be continued over a period of 1.5–2 years, with the cost of increasing adverse effects. Adjunctive methotrexate may reduce the cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in GCA.13It is already known that long-term morbidity/mortality is improved in heart failure with reduced ejection fraction (HFrEF) using treatments targeting the renin-angiotensinaldosterone system (RAAS). Additionally, PARADIGM-HF, a large, phase III, randomized, controlled clinical trial proved that the enhancement of the activity of natriuretic peptides (NPs) can benefit patients with HFrEF. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that simultaneously suppresses RAAS activation through blockade of angiotensin II type 1 receptors and enhances vasoactive peptides including NPs through inhibition of neprilysin, the enzyme responsible for their degradation. In PARADIGM-HF, patients with HFrEF treated with sacubitril/valsartan had 20% less risk for cardiovascular death or hospitalization for heart failure, 20% less risk for cardiovascular death, 21% less risk for first hospitalization for heart failure, and 16% less risk for death from any cause, compared with enalapril .The crucial role of CMR in the detection of myocardial inflammation, although the patient was asymptomatic and the inflammatory indices normal. In this context, CMR was the only non-invasive examination supporting the presence of myocardial inflammation although the clinical and laboratory evaluation was normal.In comparison to echocardiography, CMR can provide reliable information about biventricular function in parallel with tissue characterisation for assessment of oedema, replacement, and diffuse fibrosis. This direct information of myocardial status can be used to individualise treatment protocols according to disease stage in each patient.The significant improvement of ventricular function after treatment with sacubitril/valsartan in a patient where ACE inhibitors and b-blockers failed.The important findings of our case were:To our knowledge, our patient is the first in the literature that was diagnosed with GCA and treated successfully with sacubitril/valsartan in parallel with anti-rheumatic treatment. The significant improvement of biventricular function in our patient should encourage the use of sacubitril/valsartan in HFrEF patients, due to autoimmune rheumatic diseases (ARDs), in parallel with anti-rheumatic treatment.To conclude, CMR can reliably diagnose myocarditis in GCA using both the classic and the parametric criteria, even if the underlying disease is under control. The combination treatment with corticosteroids, tocilizumab and sacubitril/valsartan can dramatically improve the intractable HFrEF in GCA.


Pongo pygmaeus pygmaeus). Transthoracic echocardiography is usually performed under anesthesia in great apes, which may be stressful and increase risks of peri-anesthetic complications in case of cardiac alteration. The aim of the present pilot study was hence to develop a quick and non-stressful echocardiographic method  in awake Borneo orangutans (CardiOvascular examination in awake Orangutans: Low-stress Echocardiography including Speckle Tracking imaging) and assess the variability of corresponding variables.Cardiovascular diseases have been identified as a major cause of mortality and morbidity in Borneo orangutans , M-mode and anatomic M-mode (n = 6), Doppler (n = 7), and speckle tracking imaging (n = 3)), representing a total of 2,688 measurements. A general linear model was used to determine the within-day and between-day coefficients of variation.Mean±SD (minimum-maximum) images acquisition duration was 3.8±1.6 minutes (1.3–6.3). All within-day and between-day coefficients of variation but one  were <15%, and most  were <10% including those of speckle tracking systolic strain variables (2.7% to 5.4%).Heart morphology as well as global and regional myocardial function can be assessed in awake orangutans with good to excellent repeatability and reproducibility.This non-stressful method may be used for longitudinal cardiac follow-up in awake orangutans. Pongo pygmaeus pygmaeus) under managed care [Cardiovascular diseases have been identified as a major cause of mortality and morbidity in great apes including Borneo orangutans  mode, M-mode, and conventional Doppler modes. More recent advances in ultrasound technology with the introduction of specific imaging modalities, such as 2D speckle tracking imaging (STI), have provided several complementary parameters to assess global and regional myocardial performance [Transthoracic echocardiography (TTE) has become a major non-invasive imaging tool for the formance . Regardiformance . Accordiformance . Howeverformance . MoreoveThe aims of the present pilot prospective study were therefore 1) to develop and assess the feasibility of a quick and non-stressful TTE method  in awake captive BO (CardiOvascular examination in awake Orangutans: Low-stress Echocardiography including Speckle Tracking imaging), and then 2) to determine the intra-observer within-day (repeatability) and between-day (reproducibility) variability of the corresponding measurements.Four apparently healthy adult BO were involved in the study, i.e., 3 females  and 1 male . This study was approved by the Ethics Committee of the National Museum of Natural History. No anaesthesia nor invasive procedure were performed for the purpose of the study protocol, and all BO remained in their normal environment during the whole study period. The BO facilities at La Ménagerie, le zoo du Jardin des Plantes at the Museum National d’Histoire Naturelle , included five indoor enclosures with controlled access to an outdoor area. Furnitures in the indoor and outdoor enclosures added physical complexity to their environment . A staff of six keepers worked with the BO, with at least two being present on site each day. Additionally, three full time veterinarians were involved in the health care and welfare of these animals that were fed five times a day  with Mazuri  primate maintenance biscuits, vegetables, fruits, and browse. All BO also received enrichments  on a daily basis. Lastly, they were involved in a daily medical and husbandry training by operant conditioning techniques. When they were successful at exhibiting the requested behaviour, the keeper produced a clicker sound as a secondary reinforcer and gave a reward  and verbal praise.Transthoracic echocardiographic examinations were performed in the orangutans’ indoor enclosure in the Ménagerie, le Zoo du Jardin des Plantes  using a portable cardiovascular ultrasound system  equipped with a 3S phased-array transducer (1.5–3.5 MHz).Animal training for the TTE procedure was based on operant conditioning with exclusively positive reinforcement. Orangutans were first trained to sit and present their chest to the trainers against the enclosure mesh with their arms up. They were then desensitized to the ultrasound coupling gel  that was generously applied on the thorax through the enclosure mesh, and thereafter to the probe placement on their thorax. After three months of training, the four BO were easily conditioned to stay in the optimal position during several minutes for acquisition of images and video loops.All transthoracic echocardiograms and corresponding measurements were performed by one single observer (VC), diplomate of the European College of Veterinary Internal Medicine (Cardiology), who was trained to the procedure during five sessions of trial before the beginning of the study. Echocardiographic variables  volumes, tricuspid annular plane systolic excursion (TAPSE)) were indexed based on the last recorded weight of the animals (one to four months before the study start).Fig 1). Each examination was timed and systematically included four 2D views [The final TTE method was the following: trainers were always responsible for bringing BO to an appropriate place, the closest as possible to both the enclosure mesh and the observer. While they were distracting BO by gently and quietly talking to them and giving them some food, optimal acoustic windows were identified and obtained as promptly as possible by the observer, with the transducer placed through the enclosure mesh on BO thorax previously covered by coupling gel  [Fig 2B). As no arrhythmia was detected, heart rate was simply assessed by calculating the time interval between two consecutive peak velocities of early diastolic transmitral flow.M-mode echocardiograms showing at least five consecutive cardiac cycles were obtained for offline mitral annular motion measurement  . Pulsed-Fig 2C), perpendicular to myocardial walls, and just proximal to mitral leaflet tips at their maximal diastolic opening. End-diastole was defined as the frame showing the largest LV cavity after mitral valve closure, and end-systole as the last frame before mitral valve opening. The corresponding fractional shortening was then calculated. Additionally, the end-diastolic and end-systolic LV volumes were automatically assessed using the Simpson’s method of discs by manually tracing the LV endocardial border at blood-tissue interface, from the septal mitral annulus, up to the apex, and then to the lateral mitral annulus, with exclusion of papillary muscles from the traced border [Fig 2D) [The apical 4-chamber view was also recorded as video loops including at least five consecutive cardiac cycles, that were digitally stored for offline analysis and assessment of left heart dimensions and function. The end-diastolic and end-systolic LV internal diameters were measured from inner edge to inner edge of the LV cavity  . Left atFurthermore, maximal thickness of the anterior and posterior mitral valve leaflets was measured from the same 2D loops at their maximal diastolic opening.Fig 3) [4chv) was then calculated.Finally, the apical 4-chamber loops were also used to assess the STI longitudinal LV systolic strain (StS), as previously described  . BrieflyFig 4A). Additionally, the apical 5-chamber view was recorded as video loops including at least five consecutive cardiac cycles, that were digitally stored for offline analysis. Anatomic M-mode (AMM) images were generated from these digital 2D video loops. The electronic AMM cursor was carefully placed across the LA and the aortic root, perpendicular to the aortic and LA walls . The LA end-systolic AMM diameter and the aortic end-diastolic AMM diameter were measured from inner edge to inner edge, and the corresponding LA:Aorta AMM ratio was then calculated.The apical 5-chamber view was obtained from the apical 4-chamber view as described in the GAHP report, by tilting and sliding the transducer beam cranially . Continu5chv), as described above for StS4chv . The global LV StS  was assessed by calculating the mean of StS5chv and StS4chv.The same video loops were used to assess the STI longitudinal LV StS , slightly modified for optimal visualization of the tricuspid annulus and offline TAPSE measurement. In addition, TAPSE values were indexed to body weight. Heart rate was assessed by calculating the time interval between two consecutive maximal tricuspid annular systolic excursions on M-mode echocardiograms.M-mode echocardiograms showing at least five consecutive cardiac cycles were obtained using either apical 4- or 5-chamber view  views, with offline assessment of 28 variables. A general linear model was used to determine the within-day and between-day coefficients of variation (CV).ijk is the kth value measured for BO j on day i, μ is the general mean, dayi is the differential effect of day i, BOj is the differential effect of BO j, (day × BO)ij is the interaction term between day and BO, and εijk is the model error. The SD of repeatability was estimated as the residual SD of the model and the SD of reproducibility as the SD of the differential effect of day. The corresponding CV values were determined by dividing each SD by the mean. The level of significance was set at P<0.05.Data are expressed as mean ± standard deviation (SD). Statistical analyses were performed using a computer software (R Core Team (2018). R version 3.5.2: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria). Briefly, and as already described in our previous ultrasound imaging validation studies performed on wild or exotic animals , 14, theAll 96 TTE examinations could be performed, with a mean image acquisition duration of 3.8 ± 1.6 minutes (1.3–6.3).All of the 28 tested variables , M-mode and anatomic M-mode (n = 6), Doppler (n = 7), and STI (n = 3)) could be assessed offline, representing a total of 2,688 measurements.The mean heart rate ± SD during TTE examinations was 93 ± 9 beats per minute (76–118).Tables 1 and 2 give the values for the 2,688 repeated TTE measurements, i.e., 2D, M-mode and AMM variables in Table 1, and Doppler and STI variables in Table 2. The corresponding within-day and between-day SD and CV values are shown in Tables 4, respectively.Nearly all within-day and between-day CV values  were <15%, except for the between-day CV value of the end-diastolic left atrial length (16.8%).Most within-day and between-day CV values  were <10%, including those of STI StS variables (2.7% to 5.4%), the lowest being observed for the end-diastolic LV internal diameter .A significant BO effect was observed for all TTE variables (P<0.05), except for the LV fractional shortening (P = 0.33). No significant day effect was observed for all of the 28 tested variables, except for the less reproductible one, i.e., the end-diastolic left atrial length (P = 0.04), and for the peak aortic flow velocity (P = 0.03).antemortem diagnosis and longitudinal follow-up of BO heart diseases.Knowledge of cardiology in BO is scarce. To the best of the authors’ knowledge, no study has yet provided quantitative data on heart morphology and function in awake BO, and LV myocardial function has never been quantitatively evaluated using STI in great apes. As optimal diagnostic techniques require precision , accuracy, specificity, and sensitivity, the present study has investigated the feasibility and variability of TTE including STI in awake BO. This non-invasive and non-stressful imaging approach represents an essential initial step in the development of valuable diagnostic tools for the non-invasive Pongo spp.), chimpanzees (Pan troglotydes), gorillas (Gorilla spp.), and bonobos (Pan paniscus), respectively [Borneo orangutans are classified as critically endangered according to the International Union for the Conservation of Nature . Main caectively . TransthDue to the various disadvantages of general anesthesia which limit the use of TTE as a routine diagnostic tool  , the pre4chv). Similarly, one single video loop of the apical 5-chamber view allowed the post-processing assessment of three anatomic M-mode variables  as well as one STI longitudinal LV StS variable (StS5chv), with then calculation of the global LV StS (as the mean of StS5chv and StS4chv). To summarize, a total of 18 variables could be assessed using only two video loops of apical views. The other 10 of the 28 tested imaging variables were technically more challenging because they needed the pre-processing placement of either the M-mode cursor  or the sample volume and Doppler cursor for spectral Doppler variables . Unlike for systolic arterial flows, pulsed-wave Doppler mode was used for transmitral flow assessment, as this is the spectral Doppler mode recommended to evaluate LV diastolic function, which may be altered in the case of myocardial fibrosis [The innovative veterinary program called the GAHP has provided guidelines for TTE in great apes, with suggestions for standardization of nomenclature, cardiac imaging views, and measurements . Severalfibrosis   and body weight (47 to 74 kg) of the four involved BO. As already described in the GAPH report , becauseThis preliminary work on TTE in BO presents several limitations. Neither cardiac auscultation nor diagnostic tests were performed on BO at inclusion in the study to confirm healthy condition of the animals . Color-flow Doppler mode was not used to rule out the presence of valve regurgitation or other potential abnormal flows (as this was not on the scope of the present study whose aim was to develop and assess the feasibility and variability of a non-stressful TTE method using quantitative variables). Quantitative measurements were limited to the left heart and aorta, as these were the easiest to detect and analyze. The right heart size was not evaluated, and TAPSE (indexed or not to body weight) was the only right ventricular function tested parameter. Additionally our previous studies in dogs and cats showed that TTE is a highly observer-dependent examination , 21. TheIn conclusion, our results demonstrate that TTE can be performed in awake BO after three months of animal training, providing the assessment of more than 20 2D, M-mode, spectral Doppler, and STI variables with good to excellent repeatability and reproducibility as well as minimal animal restraint. The non-stressful nature of the present method relies on several factors including the use of positive reinforcement for BO training to the technique, and rapidity of image acquisition (mean duration of 4 minutes), as only four 2D views are required, with subsequent offline post-processing analysis. This TTE method may be useful for longitudinal follow-up of heart morphology and function in awake BO, which is of particular interest as cardiovascular diseases  have been identified as a major cause of mortality and morbidity in this endangered species. One can also speculate that this TTE method could be tested and applied to other great apes, which could be of practical interest as all taxa are known to be highly predisposed to heart diseases .S1 VideoThe animal is sitting and presenting its chest to the trainer against the enclosure mesh with its arms raised, for recording transthoracic echocardiographic images and video loops. The transducer is placed by the observer through the enclosure mesh, after generously applying coupling gel to the acoustic window, while the trainer is talking and feeding the orangutan.(MP4)Click here for additional data file.


MYH7 mutations may have a worse prognosis than MYBPC3 mutation carriers. Myocardial deformation analysis is superior to standard echocardiography in detecting subtle myocardial dysfunction and scar formation, but studies evaluating the association with HCM genotype are scarce. We therefore aimed to compare myocardial strain parameters between MYBPC3 and MYH7 mutation carriers with proven HCM. Participants of the prospective Graz HCM Registry carrying at least one causative mutation in MYBPC3 (n = 39) or MYH7 (n = 18) were enrolled. MYBPC3 mutation carriers were older, predominantly male and more often treated with an implantable cardioverter-defibrillator . Using analyses of covariance, there were no significant differences between MYBPC3 and MYH7 mutation carriers with regard to left ventricular global longitudinal strain  and right ventricular 6-segments endocardial strain . Our study suggests, that myocardial deformation analysis may not be helpful in concluding on the underlying HCM genotype, and vice versa.Accumulating evidence suggests that individuals with sarcomeric hypertrophic cardiomyopathy (HCM) carrying  MYBPC3  and MYH7 (encoding β cardiac myosin heavy chain) account for the majority of cases [Sarcomeric hypertrophic cardiomyopathy (HCM) is a heritable cardiac disease affecting 1 in 200 to 500 people. While left ventricular hypertrophy is considered the hallmark of sarcomeric HCM, also the right ventricle can be affected. The clinical spectrum ranges from normal to severely impaired myocardial function leading to restrictive cardiomyopathy [of cases .MYH7 mutations are associated with an earlier onset of symptoms [MYBPC3 [MYH7 and MYBPC3 mutations affect the thick filament of the sarcomere [MYH7, more than 95% of known disease causing variants are missense mutations leading to integration of altered myosin into the sarcomere [MYBPC3 mutations lead to diminished levels of cMyBPC in the sarcomere resulting in haploinsufficiency [MYBPC3 and MYH7 mutation carriers.Accumulating evidence suggests that symptoms ,6,7, mor [MYBPC3 ,9. Both,arcomere , but viaarcomere . Most MYficiency . Mutatioficiency . PreviouMYH7 mutations compared to MYBPC3, although differences were often marginal and non-significant [Some imaging studies were suggestive of a more severe phenotype in individuals carrying a pathogenic genetic variant in nificant ,12. Othenificant ,14. Mostnificant . MoreoveMYH7- and MYBPC3-associated HCM.Therefore, the aim of the present study was to compare echocardiographic characteristics applying myocardial deformation analysis of both the left and the right ventricle, on top of standard echocardiographic parameters in This is a cross-sectional analysis of the Graz HCM Registry (EC-No 30-286 ex 17/18). The Graz HCM Registry is a prospective cohort study launched in February 2019 and includes all patients aged over 18 years who are admitted to the HCM outpatient clinic of the Department of Cardiology of the Medical University of Graz, and provide written informed consent for participation. Registry procedures include a systematic transthoracic echocardiographic examination (TTE), a 12-lead electrocardiogram (ECG) and a structured patient interview. For the present study we included participants with genetically proven sarcomeric HCM . PatientMYBPC3 or MYH7 classified as pathogenic or likely pathogenic and enddiastolic left ventricular wall thickness of ≥13 mm evidenced by TTE [Clinical and medication history were systematically assessed during the patient interview at registry inclusion and complemented using medical records. NYHA class > II was defined as breathlessness, fatigue or palpitations at less than ordinary activities, e.g., at walking distance less than 1000 m or walking uphill . Sarcomed by TTE ,17. Patid by TTE . Septal MYBPC3 and MYH7 were included in the study . An ECG was recorded during each study to define end-diastole (ED) and end-systole (ES). Images and cine-loops with frame rates from 40 to 80 Hz were stored and digitally archived in IntelliSpace Cardiovascular  ,22,23. M2D speckle-tracking echocardiography (2D STE) was performed by experienced investigators  who were blinded to patients’ clinical characteristics, using the vendor-independent post-processing software TomTec-Arena including 2D Cardiac Performance Analysis . Cine-loops with the best image quality were selected for 2D STE. In patients with atrial fibrillation, special care was taken to choose cardiac cycles of similar duration. If tracking did not match the visual impression of wall motion, contours were readjusted until optimal tracking was achieved .For the present study, we focused on endocardial strain analysis. LV global longitudinal strain (LV GLS) was calculated using the entire endocardial line length while computing LV deformation from the apical four-, three- and two-chamber views; conducted in two separate cardiac cycles whenever possible and reported as mean values. The endocardium was tracked as the region of interest using two different methods, once automatically generated  and once user-defined  . AdditioRight ventricular (RV) longitudinal strain was calculated by averaging peak longitudinal systolic strain values of equal segment lengths of the free wall and septum  as well as the free wall only ; obtained in the apical four-chamber view. ED was defined by tricuspid valve closure and ES as the moment at which the RV was at its smallest ,26. If ft-test or Chi-Square test, as appropriate.Categorical variables were expressed as counts (percentages), continuous variables were shown as mean ± standard deviation (SD) in case of normal distribution or as medians with interquartile range if non-normally distributed. Distribution of variables was evaluated by test of Kolmogorov-Smirnov, kurtosis, skewness, concordance between the mean and median, and visual inspection. For univariate group comparisons, we used Mann-Whitney U test, Student’s MYBPC3 and MYH7 mutation carriers, analyses of covariance (ANCOVA) were used and adjusted for potentially confounding parameters including age, sex and history of septal reduction therapy. Means are reported as estimated marginal means and standard error derived from multivariate ANCOVA.In order to compare echocardiography derived parameters between p > 0.05). The residuals were normally distributed, as determined by the Kolmogorov-Smirnov test (p > 0.05). The assumptions of homogeneity of variances were found to be satisfied, as assessed by Levene’s test (p > 0.05).Homogeneity of regression slopes was not violated with regard to the dependent variable, as the interaction terms were not statistically significant  with MYH7 mutation. There was one patient with two disease causing mutations in MYBPC3 and one patient with a disease-causing mutation in MYBPC3 and MYH6. In 10 patients with MYBPC3 mutation and in six patients with MYH7 mutation, there was at least one additional variant of unknown significance .The cohort comprised 57 patients, including 39 (68%) with MYBPC3 mutation were significantly older than those with MYH7 mutation  and were less often female . Patients carrying a MYBPC3 mutation had a lower estimated glomerular filtration rate  and were more often treated with a loop diuretic . Fifteen MYBPC3 mutation carriers had a previous implantation of an implantable cardioverter-defibrillator (ICD) compared with 0 patients carrying a MYH7 mutation . Nine patients received an ICD for primary prevention, and six patients for secondary prevention after survived sudden cardiac death (SCD). One SCD survivor with MYH7 mutation had refused ICD implantation for personal reasons. Atrial fibrillation was more common in MYBPC3 mutation carriers . Clinical characteristics are listed in more detail in Mean age was 49.1 ± 15.2 and 28 patients (49.1%) were females. Patients with MYBPC3 and MYH7 mutation carriers with regard to LV GLS , as illustrated in MYBPC3 mutation carriers when compared to MYH7 mutation carriers without reaching statistical significance . Parameters of LV structure were similar between the groups.Using analyses of covariates (ANCOVA), there were no significant differences between MYBPC3 group , but in relation to the transmitral early diastolic velocity (E/e′) no significant difference could be observed (p = 0.630). The mean left atrial volume index (LAVi) was similar between both groups , as shown in The mitral annular early diastolic velocity (e′ average) was significantly higher in the MYBPC3 and MYH7 mutation carriers . Fractional area change of the right ventricle (RVFAC) showed significantly lower values in the MYBPC3 cohort . Tricuspid annular plane systolic excursion (TAPSE) showed similar values in both groups  regulates myocardial contractility, with reduced cMyBPC levels leading to hypercontractility and impaired relaxation. MYBPC3 mutations are supposed to cause HCM by haploinsufficiency. Myosin is a mechanoenzyme that drives ventricular contraction and produces force when binding actin and hydrolyzing ATP [MYH7 mutations cluster between residues 181 and 937, forming the myosin head domain and approximately 20% are located in the coiled coil region forming the thick filament [MYH7 variants in our cohort were predominantly missense mutations (see The reason for the suggestively earlier onset of symptoms, worse prognosis and more pronounced hypertrophy in utations ,6,7,8,9 zing ATP . Most HCfilament . Mutant filament ,28,29,30filament , causal ions see .MYBPC3 are predominantly truncating [MYBPC3 variants in our cohort were primarily frameshift and splice site mutations (see MYBPC3-associated HCM shows a later disease onset with a variability in the rate of progression even within a family, influenced by lifestyle, environment and other genetic factors [Pathogenic variants in uncating ,32,33, wions see . Only a ions see . MYBPC3- factors ,34. The  factors .MYBPC3 patients. This is in line with a recent meta-analysis including 51 studies with 7675 HCM patients, where mutations in MYH7 were associated with earlier age of onset and higher risk of sudden cardiac death when compared to MYBPC3 [MYBPC3 and MYH7 mutation carriers [Our results showed a higher age of disease onset in o MYBPC3 . In contcarriers . MYBPC3 mutations carriers had significantly more often a history of ICD implantation. This is not in line with other and larger studies attributing a higher risk of SCD to MYH7 [MYH7 is associated with a high incidence of end-stage heart failure and premature death [MYBPC3 group had history of atrial fibrillation which is not in line with previous studies [Interestingly,  to MYH7 ,9. Patie to MYH7 . For insre death . Similar studies ,40. Both studies .MYH7 mutation were similar to MYBPC3 carriers in the majority of measured echocardiographic parameters. Only systolic anterior motion of the mitral valve and mitral valve calcification were significantly more common in MYH7 mutation carriers [MYBPC3 and MYH7 mutation carriers. In this study the authors concluded that LV morphology rather than genotype predicts myocardial deformation markers in HCM [Only a few studies compared echocardiographic parameters between HCM genotypes although none explicitly reported results of RV myocardial deformation analyses. One recent multicenter study including 63 adult individuals evaluated the association between mutations in both genes and phenotypes in patients with sarcomeric HCM. They found that patients carrying a carriers . It is wcarriers , predictcarriers  and cardcarriers . Evidencs in HCM . HoweverParticular strengths of our study include its novelty, since myocardial deformation, particularly of the RV, has not been sufficiently investigated in patients with sarcomeric HCM. A further strength of our study is the high quality of strain measurements which were performed by blinded investigators analyzing several cine loops per patient. Limitations of our study include the relatively low sample size and the single-center design. Moreover, characteristics of our cohort may be confounded by referral bias which may be inherent to our tertiary care setting, although we performed multivariate analysis to minimize this bias. Nevertheless, results may not be generalizable to other HCM populations.MYBPC3 and MYH7 mutation carrying individuals with sarcomeric HCM. Myocardial deformation analysis may not be helpful in concluding on the underlying HCM genotype, and vice versa.Echocardiographic myocardial deformation parameters of both RV and LV were similar between