When athlete’s heart occurs with its most marked expression, it may overlap with a differential diagnosis with certain structural cardiac diseases, including cardiomyopathies, valvular diseases, aortopathies, myocarditis, and coronary artery anomalies. Identifying the underlying cardiac is essential to reduce the potential for sudden cardiac death. For this purpose, a spectrum of imaging modalities, including rest and exercise stress echocardiography, speckle tracking echocardiography, cardiac magnetic resonance, computed tomography, and nuclear scintigraphy, can be undertaken. The objective of this review article is to provide to the clinician a practical step-by-step approach, aiming at distinguishing between extreme physiology and structural cardiac disease during the athlete’s cardiovascular evaluation.  The term “athlete’s heart” refers to a spectrum of electrical, morphological, and functional heart adaptations of the heart to athletic training ,2. When athlete’s heart occurs in its most marked expression, it can overlap with mild phenotypes of cardiac diseases. Therefore, it is important for the clinician to be able to differentiate this extreme form of physiological adaptation from pathology  non-compaction cardiomyopathy). For this purpose, different modern imaging modalities, including traditional and novel echocardiographic techniques, cardiac magnetic resonance (CMR), and computed tomography (CT), can be used. Identifying the pathologic cardiovascular condition which may be hidden behind athlete’s heart is crucial to prevent sudden cardiac death ,4. The objective of this review article is to provide physicians with a practical, diagnostic step-by-step approach aiming at distinguishing between extreme physiology and structural cardiac disease during the cardiovascular evaluation of athletes.Clinical history, physical examination, and the standard 12-lead electrocardiogram (ECG) represent the first step of the athlete’s evaluation. Clinical history should be focused on the type and volume of physical activity practiced by the athlete: it is possible to hypothesize an “athlete’s heart” only if training loads are really heavy. Additionally, the use of performance-enhancing drugs should be investigated and taken into account during history collection.Athlete’s heart is commonly (up to 80%) associated with adaptative ECG changes ,6. SinusAccording to the current recommendation of the European Association of Preventive Cardiology (EAPC) and the European Association of Cardiovascular Imaging (EACVI), echocardiography is a second-line investigative tool for the differential diagnosis between the athlete’s physiological adaptation to exercise and underlying malignant cardiac conditions ,7,8. HowThe physiological hypertrophy of athlete’s heart is characterized by a harmonic and symmetric wall thickening that is homogeneously distributed and involves all the cardiac chambers . The exeExercise stress echocardiography (ESE) is a reliable, safe, non-invasive imaging test, well-tolerated by the athletes, which can be combined with clinical and electrocardiographic information to detect cardiac abnormalities .A typical indication of ESE is the detection of exercise-induced ischemia in athletes with chest pain and/or ECG anomalies, and suspicion of coronary artery disease or congenital coronary artery anomalies .In endurance athletes with LV and/or RV dilatation and mildly reduced ejection fraction at rest, ESE may be used to assess contractile reserve during exercise. A significant improvement in contractility during physical exertion  suggests a physiological cardiac remodeling; conversely, an absent or subnormal improvement is in favor of a pathological condition  ,31,32,33An LV outflow tract gradient >50 mmHg during or immediately after exercise in athletes with LV hypertrophy complaining symptoms  can be suggestive of hypertrophic cardiomyopathy ,32.Finally, ESE may be useful in athletes with valvular heart disease, where it provides information about exercise tolerance, biventricular contractile reserve, changes in hemodynamics , and in valvular functional parameters  .Speckle tracking echocardiography (STE) is a relatively recent echocardiographic technique of deformation imaging that has provided new insights into the characterization of the athletes’ myocardial properties . It is aLV global longitudinal strain (GLS) obtained by STE is the most used parameter in clinical practice, and it is not significantly different between athletes and healthy controls. Therefore, a reduction in longitudinal strain in athletes has to be considered as a subclinical sign of LV contractile dysfunction and should raise the suspicion of myocardial disease, particularly in the presence of doubtful LV hypertrophy or dilatation ,40,41,42Data regarding the interpretation of RV, STE-derived parameters in athletes are still controversial ,47,48,49During the last decades, STE has also been applied to the evaluation of left and right atrial function ,52,53,54Myocardial work (MW) is a novel, less load-dependent ultrasonographic index of LV contractile function, which corrects STE-derived parameters for afterload, by using systolic blood pressure . In diffColorDoppler flow mapping is an advanced echocardiographic tool that evaluates LV function through the analysis of intracardiac flows . LV vortFinally, three-dimensional (3D) echocardiography improves the diagnostic capability of cardiac ultrasound in evaluating cardiac anatomy, ventricular function, valvular disease, and blood flow velocity. It allows quantifying LV volume and mass, provides data on LV remodeling and function, and can show, in detail, the heart chambers’ morphological features .Cardiac magnetic resonance (CMR) is the second most valuable imaging method for the differential diagnosis between physiology and pathology in athletes. It can help discriminate health from disease where echocardiography leaves doubts.CMR is the gold standard for the definition of myocardial morphology, wall motion assessment, heart chambers size, and tissue characterization. It evaluates, with high accuracy and reproducibility, the heart chambers’ volume and mass, as well as global and regional contractile function ,59,60. ICMR represents the superior method to identify myocardial fibrosis and its distribution pattern, through the assessment of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) mapping ,63,64,65Myocardial fibrosis has also been observed in athletes with a higher prevalence than in non-athlete healthy populations. In healthy athletes, myocardial fibrosis involves less than 3% of the myocardium. It shows a large variation in quantity, location, and pattern, but it is generally found in the right ventricle (particularly in right ventricle insertion points) or in the interventricular septum. The prevalence of myocardial fibrosis in athlete’s heart appears greater when there is a long-standing history of exercise training, particularly of the endurance type . The proHeart valve morphology and function, and great vessel structure can be well evaluated by CMR. Coronary magnetic resonance angiography shows high accuracy for the non-invasive detection and definition of anomalous coronary arteries, thanks to its ability in identifying the proximal coronary course and generating tomographic images in any orientation . Stress CMR, usually with exercise, can be used to identify a reduced functional reserve and early-stage cardiomyopathy when resting functional assessment is mildly abnormal . HoweverFinally, the possible role of CMR-based deformation imaging in distinguishing athlete’s heart from pathological phenotypes is being studied in different disease settings ,74,75.Limitations of CMR include high cost, less availability than echocardiography, incompatibility with some metallic devices (though this is rarely an issue in athlete populations), the need for evaluation of renal function prior to administration of gadolinium, and claustrophobia.Cardiac computed tomography (CCT) shows high accuracy in the evaluation of coronary arteries’ origin, course , and termination  Figure . TherefoAll athletes with indeterminate, suspected, or confirmed anomalous coronary artery anatomy following echocardiography should undergo CTA or CMR, according to institutional preferences and expertise.In the case of suspected coronary atherosclerotic disease, CTA is a valuable tool for coronary artery calcium scoring and non-invasive coronary angiography.If dilatation of aortic root or ascending aorta is suspected or confirmed, at least one comprehensive aortic tomographic assessment  is indicated .Recent technological advances have extended the role of CCT beyond coronary and great vessels evaluation. Morphological and functional assessment of the left ventricle is performed using a retrospective ECG-gated scanning protocol. The evaluation of LV volumes, stroke volume, ejection fraction, and mass have shown excellent correlation with CMR assessment .LV functional evaluation by CCT is particularly useful in claustrophobic patients, unable to undergo CMR, or if contraindications to CMR exist . Otherwise, CCT cannot be recommended as a first-line imaging technique for functional evaluation of the LV in athletes, given the higher radiation exposure required ,77.The use of iodine contrast medium allows the evaluation of ECV and myocardial fibrosis  by CCT, even if not routinely used in clinical practice, with good agreement with the same evaluations performed by contrast-enhanced CMR .Nuclear scintigraphy can be used for the research of exercise-induced ischemia—as an alternative or integration to ESE—when coronary disease is suspected, with the same indications as in the non-athlete population. A broad spectrum of imaging modalities is available for pre-participation cardiovascular evaluation of the athletes. The clinician should adopt a step-by-step approach, with the aim to distinguish between the physiologic, exercise-induced remodeling and structural cardiac disease. This practical approach is based on the periodic use of first-line screening tools , possibly integrated by standard echocardiography, which is safe and not very time-consuming. Third-line imaging modalities  should be selected when the previous evaluation is still doubtful. Speckle tracking echocardiography provides new insights into the characterization of the athlete’s myocardial properties. However, further accumulation of evidence is needed to refine STE diagnostic performance and make it part of the standard diagnostic workup.


P < 0.05). Left ventricular (LV) end-diastolic mass index increased significantly from 45 (38–51) to 65 (51–73) g/m2 (P =  < 0.01). Biventricular systolic function, NT-proBNP, high-sensitive troponin T, and native T1 time did not differ significantly from BL to FU. No patient experienced cardiac decompensation following TIPS. In conclusion, in patients without clinically significant prior heart disease, increased cardiac preload after TIPS resulted in increased volumes of all cardiac chambers and eccentric LV hypertrophy, without leading to cardiac impairment during follow-up in this selected patient population.Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension in patients with liver cirrhosis. The exact cardiac consequences of subsequent increase of central blood volume are unknown. Cardiovascular magnetic resonance (CMR) imaging is the method of choice for quantifying cardiac volumes and ventricular function. The aim of this study was to investigate effects of TIPS on the heart using CMR, laboratory, and imaging cardiac biomarkers. 34 consecutive patients with liver cirrhosis were evaluated for TIPS. Comprehensive CMR with native T1 mapping, transthoracic echocardiography, and laboratory biomarkers were assessed before and after TIPS insertion. Follow-up (FU) CMR was obtained in 16 patients (47%) 207 (170–245) days after TIPS. From baseline (BL) to FU, a significant increase of all indexed cardiac chamber volumes was observed (all  Insertion of a transjugular intrahepatic portosystemic shunt (TIPS) effectively alleviates portal hypertension and is indicated in patients with refractory ascites and/or risk of recurrent variceal bleeding2. Beside its beneficial effects, TIPS increases cardiac preload resulting from increased shunting of blood from the splanchnic vascular bed into the central vascular bed and thereby increases the central blood volume and aggravates the hyperdynamic circulation state3. These changes can lead to acute heart failure following TIPS implantation in 0.9 to 20%5. Therefore, transthoracic echocardiography is routinely performed in most centers before TIPS implantation in order to detect patients at highest risk for acute heart failure after TIPS. Congestive heart failure, severe tricuspid regurgitation and severe pulmonary hypertension are considered as cardiac contraindications for TIPS implantation2. However, despite a careful echocardiography-based patient selection, post-TIPS heart failure still occurs in some cases. Thus, there is uncertainty in clinical routine whether more subtle cardiac phenotypes are at risk for cardiac decompensation after TIPS implantation since diastolic dysfunction, left atrial dilation, and other findings have been detected as potential predictors for acute heart failure following TIPS implantation6. To date, little is known about cardiac stress and adaptive cardiac changes after TIPS.Portal hypertension is a major complication of advanced liver cirrhosis. It may lead to systemic and splanchnic vasodilatation as well as hyperdynamic circulation, which is characterized by increased cardiac output, low systemic vascular resistance, and low arterial blood pressure7. Moreover, CMR is also the major non-invasive tool for myocardial tissue characterization8. In particular, T1 mapping is a novel parametric technique that permits routine quantification of changes in myocardial tissue composition, based on changes in T1 relaxation times without the need of contrast agent8. Multiple lines of evidence suggest a central role for T1 mapping in detection of diffuse myocardial disease even in early stages of infiltrative diseases, acute myocardial injury as well as diffuse fibrosis, which is a common finding in many cardiomyopathies9. To the best of our knowledge, the medium- and long-term effects of TIPS on cardiac function and volumes have not been assessed so far using CMR.Cardiovascular magnetic resonance imaging (CMR) is currently the reference standard for determination of left and especially right ventricular volumes and function with high intraobserver, interobserver, and test–retest reproducibilityIn the present study, our aim was to characterize how TIPS insertion affects cardiac function in patients with liver cirrhosis in order to identify possible mechanisms leading to post-TIPS heart failure.Detailed patients’ characteristics and laboratory results of all 34 patients with CMR at baseline (BL) are displayed in Supplementary Table 14. Five patients showed an increase of NT-proBNP > 50% despite preserved LV function at BL and FU. Two of these five patients presented with diastolic dysfunction (DD) already at BL, and two patients showed a newly occurred DD or progression of initially existing DD, respectively. Following TIPS implantation, median portosystemic pressure gradient decreased from 21 ± 3 to 7 ± 3 mmHg, indicating adequate function of implanted stents.We prospectively screened 39 patients with liver cirrhosis and refractory ascites who were evaluated for TIPS implantation in our tertiary care center. The only exclusion criteria were contraindications for CMR. Three of 39 had to be excluded due to contraindication for CMR and in two patients CMR had to be interrupted due to unknown claustrophobia Fig. . Of 34 p2 (P = 0.01) and median left atrial volume index (LAVi) from 38 (32–45) to 53 (40–62) ml/m2 (P < 0.01). The median right ventricular end-diastolic volume (RVEDVi) increased from 52 (45–65) to 88 (73–94) ml/m2 (P < 0.01), median right ventricular end-systolic volume (RVESVi) from 17 (15–24) to 24 (19–37) ml/m2 (P < 0.01) and median right ventricular stroke volume (RVSVi) from 35 (31–45) to 56 (52–65) ml/m2 (P < 0.01). The median right ventricular ejection fraction (RVEF) showed no significant change from BL (67 (65–69) %) to FU (70 (63–76) %; P = 0.25).CMR results of all 34 cirrhotic patients at the time of TIPS evaluation are displayed in Supplementary Table 2 (P < 0.01), median left ventricular end-systolic volume (LVESVi) from 14 (12–19) to 25 (16–32) ml/m2 (P < 0.01) and median left ventricular stroke volume (LVSVi) from 47 (37–57) to 73 (62–80) ml/m2 (P < 0.01). The median left ventricular ejection fraction (LVEF) remained unchanged from BL (75 (67–81) %) to FU (76 (70–79) %; P = 0.73). Similar to the observed increase in cardiac volumes, median left ventricular myocardial mass (LVEDMi) increased from BL (45 (38–51) g/m2) to FU (65 (51–73) g/m2; P < 0.01).Concordant with the changes of RV volumes, median left ventricular end-diastolic volume (LVEDVi) significantly increased from 57 (48–73) to 96 (79–107) ml/mP = 0.50). Median high-sensitive Troponin T (hs-TnT) was 19 (13–28) pg/ml  at BL and showed no increase at FU (18 (11–40) pg/ml; P = 0.91). Global myocardial native T1 showed no significant difference from BL (1049 (1038–1067) ms) to FU (1042 (1015–1070) ms; P = 1.0) (Table Median NT-proBNP was slightly increased at BL (215 (174–497) ng/l; normal < 194) but showed no further increase at FU (218 (136–367) ng/l; P = 0.01), whereas median TAPSE did not differ significantly from BL to FU (25 (21–31) vs. 28 (26–34) mm; P = 0.12). Both, the median LAVi (23 (22–33) vs. 32 (28–44) ml/m2; P = 0.02) and the median RA area (16 (13–19) vs. 18 (15–23) cm2; P =  < 0.01) increased significantly from BL to FU  are shown in Supplementary Table 14.In this study, we investigated the medium-term cardiac effects resulting from hemodynamic changes after TIPS implantation using CMR and cardiovascular biomarkers. Our three major findings were: Firstly, TIPS implantation led to size increase of all four cardiac chambers. Secondly, this increase of cardiac chamber volumes was accompanied by an increase of LV myocardial mass in terms of an eccentric LV hypertrophy. Thirdly, stable right and left ventricular function as well as stable laboratory and imaging biomarkers such as NT-proBNP, hs-TnT, and myocardial native T1 time do not indicate that these cardiac adaptions caused severe myocardial injury with impairment of systolic function in patients with normal LV function, no relevant heart valve defects, and a maximum diastolic dysfunction of grade 2. None of the patients in our cohort experienced acute heart failure defined as rapid development or change of symptoms and signs of heart failure that requires urgent medical attention15. Interestingly, we found a significant increase of myocardial mass after TIPS. Both studies used different modalities for the evaluation of LV myocardial mass and the unequal observations may be explained by the longer FU period in our study, if LV hypertrophy only arises with greater latency, and different sensitivities of TTE and CMR to detect LV hypertrophy. Mechanical overload in general can lead to LV hypertrophy and can be classified into pressure overload and volume overload, causing concentric and eccentric cardiac hypertrophy, respectively16. Moreover, it has been shown that the physiological volume overload during pregnancy leads to reversible LV hypertrophy17. Our results demonstrate an adaptive eccentric LV hypertrophy as a medium-term effect possibly preventing cardiac decompensation after TIPS.In our cohort, the increased preload after TIPS induced a significant increase of all cardiac chamber volumes after a median FU of seven months. These results are in line with those of Busk et al. who evaluated 25 patients one week and four months after TIPS by assessment of systemic, cardiac, and splanchnic hemodynamics using catheterization, TTE, and cardiac biomarkers to evaluate cardiac function over time. 2D-TTE and M-Mode revealed an increase of LV internal diameter as well as an increase of LA volume from BL to FU, respectively9, was not increased at BL or FU. Thus, the observed hemodynamic changes and cardiac adaptions neither led to any impairment of systolic function, nor to myocardial injury or myocardial fibrosis and these observations are in line with those of Busk et al. who also found a preserved LVEF and TAPSE as well as stable values for proANP and hs-TnT four months after TIPS15. On the other hand, Jansen et al. have recently shown in a large retrospective study that even in patients with normal EF there may be subgroups with better contractility, as measured by LV global longitudinal strain using TTE, who experience better outcome after TIPS, with reduced rates of acute-on-chronic liver failure and mortality18.Despite these effects, the median right and left ventricular systolic function was preserved from BL to FU. Interestingly, median NT-proBNP was slightly increased at BL, but showed no further increase at FU, which could be related to an already existing hyperdynamic circulation at BL. Hs-TnT was not increased at BL or FU. The native T1 time, which has been shown to enable the detection of diffuse myocardial disease even in early stages of in many cardiomyopathies5. In contrast to this low incidence of heart failure, a current study found acute heart failure in 20% of patients following TIPS4. Identified risk factors for acute heart failure were prolonged QTc interval, elevated BNP or NT-proBNP, elevated E/A ratio and E/e' ratio, left atrial dilatation, and aortic stenosis. A level of BNP < 40 pg/mL and a NT-proBNP < 125 pg/mL as well the absence of DD criteria at echocardiography ruled out the risk of subsequent cardiac decompensation4. Especially the role of DD is under debate. Caused by stiffness of the myocardium, DD might impair the cardiac ability to handle an increased preload. Moreover, DD has been shown to be a possible predictor of death in patients with cirrhosis who are treated with TIPS6. In our cohort, only five of 34 patients presented with any DD at BL. None of these patients, even one patient with DD grade 2, experienced acute heart failure after TIPS. Nonetheless, we observed a significant increase of median E/e′ in our cohort in line with the observations of other groups6. However, the diagnosis of acute heart failure in patients with liver cirrhosis is challenging due to an overlap of clinical symptoms , reflected by substantially varying incidence in previous studies5. Finally, we were not able to identify possible predictors for cardiac decompensation in our small cohort of patients due to a lack of heart failure events. Our results underline that the probability of systolic heart failure after TIPS is very low in patients with preserved ejection fraction and no relevant heart valve defects or severe diastolic dysfunction. Whether CMR in addition to routinely performed TTE may add prognostic information about acute heart failure after TIPS cannot be answered. Since more possible laboratory and echocardiographic risk factors for cardiac decompensation have recently been found by Billey et al.4, a correlation of these findings with CMR parameters would be highly interesting. Therefore, future studies with higher numbers of patients and precise definition of acute heart failure in patients with liver cirrhosis are warranted to identify predictors of insufficient cardiac adaption as risk factor of post-TIPS heart failure.Until recently there was a lack of data regarding incidence and predictors of acute heart failure after TIPS. Modha et al. found symptomatic heart failure after TIPS in eight of 883 patients (0.9%). Patients with acute heart failure showed higher pre-TIPS right atrial and portal vein pressures, higher albumin, and higher prothrombin timeThought as a pilot study, the sample size is small. Many patients were referred for TIPS implantation from secondary care centers so that FU of patients was hindered, which is reflected by a relatively high rate of patients who were lost to FU. We also cannot exclude that a selection bias has influenced our findings. Patients considered for TIPS in secondary care centers could have been not referred due to external assessment of cardiac function with detection of severe systolic or diastolic impairment.In conclusion, in patients without clinically significant prior heart disease, the increased cardiac preload after TIPS insertion resulted in increased volumes of all cardiac chambers and eccentric LV hypertrophy. However, in this highly selected patient cohort the morphologic adaptions did not lead to cardiac impairment which is reflected by a stable biventricular systolic function and stable laboratory and imaging biomarkers for heart failure, myocardial injury, and fibrosis during the follow-up period.10. 16 of these 34 patients received a FU CMR after a median interval of 7.4 (5.3–8.6) months from BL CMR.This study has been approved by the licensing ethics committee  and all patients gave their written informed consent. Methods were carried out in accordance with relevant guidelines and regulations. Planned as an observational pilot-study, 39 patients with liver cirrhosis and refractory ascites who were evaluated for TIPS implantation in the Department of Gastroenterology and Hepatology at University Medical Center Hamburg-Eppendorf (UKE) from March 2016 until December 2017. Exclusion criteria were contraindications for CMR. 34 patients were scanned at BL. Median time from BL CMR to TIPS implantation was 1.5 (1.0–6.3) days. TIPS implantation was carried out as described in detail previously3, echo time = 0.7 ms, time to repetition = 2.3 ms, partial echo factor = 0.8, flip angle = 35°, SENSE factor = 2, linear phase encoding, ten start-up cycles to approach steady-state prior to imaging, effective inversion times between 134 and 5627 ms. The CMR protocol with typical imaging parameters is presented in Fig. CMR was performed on a 1.5T scanner . The CMR protocol consisted of a standard cine-CMR with long-  and short-axis views as well as one axial stack for the assessment of cardiac volumes, mass, and function using a standard steady-state free-precession (SSFP) sequence. T1 mapping was performed using a 5s3s)3s-MOLLI on 3 representative short axis slices . Imaging parameters of T1 mapping were as follows: Voxel size 2 × 2 × 10 mms3s-MOLLI11. LV end-diastolic and end-systolic volumes were obtained from cine-CMR short-axes to calculate LV stroke volume index (LVSVi) as well as LV ejection fraction (LVEF). LV end-diastolic mass index (LVEDMi) was obtained including papillary muscles. RV end-diastolic and end-systolic volumes were obtained from axial cine-CMR short-axes to calculate RV stroke volume index (RVSVi) as well as RV ejection fraction (RVEF). For the analysis of global native T1, endo- and epicardial contours were drawn, manually corrected for motion and carefully aligned with the contours in one basal, midventricular, and apical slice.All CMR scans were analyzed using the commercially available software cvi42 (Circle Cardiovascular Imaging Inc.). CMR measurements were performed according current guidelines13.All patients were examined using two-dimensional transthoracic echocardiography (TTE) before and after TIPS. Echocardiography was obtained with a Philips iE33 and EPIQ 7  and analyzed by two experienced cardiologists using TOMTEC ARENA Version 4.6 (TOMTEC Imaging Systems GmbH). All measurements for the assessment of RV and LV systolic function, LA and LV volumes as well as measurements for diastolic function were performed and graded according to current guidelinesP values were calculated and statistical significance was defined as P < 0.05.Statistical analysis was performed using GraphPad Prism version 6.00 . Descriptive statistics were presented as median and interquartile range (Q1–Q3) and compared by Mann–Whitney U test for continuous data. Categorical data are presented as numbers and percentage and compared using Fisher’s exact test. BL and FU data was compared using paired t-test or Wilcoxon matched pairs test when the variables were not normally distributed. Two-sided Supplementary Information.


Background: Cardiac pacing in patients with bradyarrhythmia may employ variable pacing sites, which may have different effects on cardiac function. Left bundle branch pacing (LBBP) is a new physiological pacing modality, and the acute outcomes on cardiac mechanical synchrony during LBBP remain uncertain. We evaluated the acute effects of four pacing sites on cardiac synchrony and contraction using speckle-tracking echocardiography, and comparisons among four different pacing sites were rare.Methods: We enrolled 21 patients with atrioventricular block or sick sinus syndrome who each sequentially underwent acute pacing protocols, including right ventricular apical pacing (RVAP), right ventricular outflow tract pacing (RVOP), His bundle pacing (HBP), and left bundle branch pacing (LBBP). Electrocardiograms and echocardiograms were recorded at baseline and during pacing. The interventricular mechanical delay (IVMD), the standard deviation of the times to longitudinal peak strain during 17 segments (PSD), and the Yu index were used to evaluate ventricular mechanical synchrony. Layer-specific strain was computed using two-dimensional speckle tracking technique to provide in-depth details about ventricular synchrony and function.Results: Left ventricular ejection fraction (LVEF) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased during RVAP and RVOP but were not significantly different during HBP and LBBP compared with baseline. RVAP and RVOP significantly prolonged QRS duration, whereas HBP and LBBP showed non-significant effects. IVMD and PSD were significantly increased during RVAP but were not significantly different during RVOP, HBP, or LBBP. LBBP resulted in a significant improvement in the IVMD and Yu index compared with RVAP. No significant differences in mechanical synchrony were found between HBP and LBBP.Conclusion: Among these pacing modalities, RVAP has a negative acute impact on cardiac synchrony and contraction. HBP and LBBP best preserve physiological cardiac synchrony and function. Cardiac pacing, an effective therapy for patients with bradyarrhythmia, has multiple modalities, including right ventricular apical pacing (RVAP) , right vThis study evaluated the acute effects of different pacing sites on cardiac synchrony and contraction in patients with atrioventricular block (AVB) or sick sinus syndrome (SSS) using echocardiography.Between March and June 2018, we prospectively enrolled consecutive patients with AVB or SSS who were scheduled for pacemaker implantation. The inclusion criteria were: (1) no history of pacemaker implantation, (2) no pregnancy, (3) at least 18 years of age, (4) New York Heart Association (NYHA) classification I or II. Patients were excluded for the following conditions: (1) severe valvular regurgitation, (2) recent acute myocardial infarction, (3) a history of cardiac surgery or atrioventricular node ablation, (4) poor acoustic window condition, (5) confirmed infra-His bundle block, or (6) the presence of severe chronic diseases. The study conformed with the 1975 Declaration of Helsinki, and the protocol was approved by the Zhongshan Hospital Ethics Committee. All patients provided their written informed consent to participate in the study.via the right external jugular vein; the electrodes were positioned within the right ventricular (RV) apex (RVA) and RV outflow tract (RVOT)  was delivered along the sheath with its distal part beyond the tip of the sheath for HBP recording (The pacing procedures were performed in a cardiac catheterization laboratory. Twelve-lead electrocardiogram (ECG) and intracardiac electrograms were simultaneously displayed and continuously recorded during all pacing interventions on a multichannel Bard Electrophysiology Lab System recorder . A catheter with a 6-Fr quadripolar electrode was inserted t (RVOT) . For HBPecording . For LBBecording . AccordiEach pacing mode was separated by a 10-min washing-out interval. In all patients, the pacing sequence ended with LBBP, and the lead was left in place after LBBP. During each procedure, the atrial lead was implanted in the right atrium appendage. Both the atrial and ventricular leads at the four pacing sites were connected to the programmer (Medtronic 2290) in DDD mode, with an AV delay of 150 ms and a pacing output of 3.5 V/0.5 ms during unipolar configuration.ECGs and echocardiography were performed at baseline and during each pacing modality. During each session, patients were kept in the left lateral decubitus position with the ECG connected. Two-dimensional echocardiography was performed, according to current guidelines, using a Vivid E95 scanner  equipped with an M5S probe (4.0-MHz transducer) having frame rates higher than 40 fps . LV end-The apical triplane-mode data were analyzed offline using an EchoPAC 203 workstation (GE Vingmed Ultrasound). The best cardiac cycle with good quality or clear endocardial boundaries was chosen, and the endocardial borders were automatically identified and tracked throughout the cardiac cycle. If the images were not optimal, manual adjustments were made. The LV wall of each apical view was divided into six segments. The global longitudinal peak strain (GLPS)  and the post-hoc analysis. Otherwise, the Friedman test was performed, and Dunn's post-hoc test was used to adjust the P-value. Statistical significance was defined as a two-sided P < 0.05. All statistical analyses were performed using GraphPad Prism 7.0 .Continuous variables are described as means ± standard deviations; categorical variables are described as counts or percentages. When the data were or approximated normal distributions, comparisons among three or more conditions were evaluated using repeated measures one-way analysis of variance tests followed by the Tukey A total of 21 patients (15 men and 6 women) were enrolled in the study, with a mean age of 66.1 ± 13.0 years. All procedures were successfully performed in these patients. Of these, 19 patients were diagnosed with AVB, including one with first-degree AVB, 10 with second-degree AVB, and eight with third-degree AVB, and two with SSS. The mean heart rate was 53.8 ± 16.2 beats/min and the mean QRS duration was 118.8 ± 24.6 ms at the baseline ECG .To compare the acute changes in cardiac contraction between the different pacing sites, we measured the LVEDV, LVESV, LVEF, and TAPSE. We also evaluated the GLPS and the longitudinal layer-specific myocardial strains of the LV and RV  in the apical four-chamber view using EchoPAC 203 . LVEDV, p < 0.01, p < 0.05)] and RVOP [58.8 ± 9.4% (p < 0.01)] than at baseline (65.6 ± 7.0%) (p < 0.001) and RVOP (p < 0.01) were significantly reduced  . Compare reduced ; howeverp < 0.001, At all pacing sites, the absolute values of GLPS  and QRS duration using ECG; IVMD, PSD, and the Yu index were analyzed by echocardiography. Moreover, we also measured the Ts of the apical, middle, and basal segments of the lateral wall of left ventricle  or right ventricle  in the four-chamber view, as well as the difference in Ts between the basal, middle, and apical segments of left and right ventricle lateral walls  in the same patients (each with AVB or SSS), to evaluate the effect of the His-Purkinje system pacing on ventricular electrical and mechanical synchrony. Echocardiographic parameters including LVEF, GLPS, TAPSE, IVMD, PSD, and Yu index, provided more detailed evaluations of ventricular synchrony and contraction at different pacing sites than QRS duration. HBP and LBBP demonstrated similar added value in preserving physiological hemodynamics and cardiac function, implying their interchangeability under some conditions. Our results showed that LBBP could maintain cardiac hemodynamics similar to or better than HBP, providing more evidence for this alternative of physiological pacing modality. In conclusion, our study suggests that LBBP is an effective physiological pacing mode as HBP, which preserved normal cardiac contraction and synchrony.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University. The patients/participants provided their written informed consent to participate in this study.XS and HC contributed to the research design, analyzed the data, and critically revised the manuscript. XC contributed to the research design. HX contributed to the data collection, analyzed the data, and drafted the paper. YW contributed to the collection and analyzed the data. YC, YZ, and YaL contributed to the data interpretation. YuL and ZG contributed to critically revised the manuscript. All authors read and approved the final manuscript.This study was funded by National Natural Science Foundation of China (No. 82071933) and Shanghai Science, Technology Commission Science and technology innovation plan (No. 20JC1418400), 2018 Clinical Trial Funding of Zhongshan Hospital, Fudan University (No. 2018ZSLC14), and Youth Foundation of Shanghai Municipal Health Commission (No. 20194Y0272).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In multivariable analyses, lower MEEi was associated with lower LV myocardial function by MFS and GLS independent of higher LV mass and clinical variables, including older age, male sex, presence of hypertension and a higher triglycerides level . In conclusion, in subjects with increased BMI without known cardiovascular disease participating in the FATCOR study, reduced MEEi was associated with lower LV myocardial function both in the circumferential and longitudinal direction, independent of cardiometabolic factors.Lower myocardial mechanic-energetic efficiency (MEEi), expressed as stroke volume/heart rate ratio (SV/HR) in mL/s/g of the left ventricular (LV) mass, is associated with the incidence of heart failure in subjects with cardiometabolic disorders. We explored the association of MEEi with LV systolic circumferential and longitudinal myocardial function in 480 subjects with increased body mass index (BMI) without known cardiovascular disease  participating in the fat-associated cardiovascular dysfunction (FATCOR) study. Insulin resistance was assessed by the homeostasis model assessment insulin-resistance index (HOMA-IR). SV was calculated by Doppler echocardiography. The LV systolic circumferential myocardial function was evaluated by midwall fractional shortening (MFS) and longitudinal function by global longitudinal strain (GLS). Patients were grouped into MEEi quartiles. The lowest MEEi quartile (<0.41 mL/s per g) was considered low MEEi. The association of MEEi with MFS and GLS were tested in multivariable linear regression analyses. Patients with low MEEi were more frequently men, with obesity and hypertension, dyslipidemia and higher HOMA-IR index (all  Obesity is linked to the full spectrum of cardiac dysfunction, from subclinical left ventricular (LV) diastolic dysfunction to decompensated systolic heart failure . Cardiac2 free from clinical cardiovascular disease were enrolled from 2009 to 2017 at Haukeland University Hospital, Bergen, Norway. The exclusion criteria were previous myocardial infarction, gastrointestinal disorder, severe psychiatric illness or the inability to communicate in the Norwegian language. The FATCOR study was conducted in accordance with the Declaration of Helsinki and with approval from the Regional Ethics Committee. Written informed consent was obtained from all participants. A total of 127 participants were excluded due to incomplete echocardiographic data (n = 51), insufficient echocardiographic image quality (n = 49) or hardware mismatch for the analysis of global longitudinal strain , missing information on Doppler stroke volume  or withdrawal of informed consent (n = 2). All participants completed a standardized questionnaire reporting their medical history and use of any medication. Clinic blood pressure (BP) was measured in accordance with guidelines using an Omron M4 sphygmomanometer  with an appropriately sized cuff [2. In accordance with the criteria from the American Diabetes Association [2.7 as recommended in obesity [2.7 (>46.7 g/m2.7 in women and >49.2 g/m2.7 in men). The relative wall thickness (RWT) was calculated from the posterior wall thickness/LV internal radius ratio and considered increased if ≥0.43 (concentric LV geometry). The SV was calculated by PW-Doppler at the aortic valve hinging points. Midwall fractional shortening (MFS) was calculated using a previously reported formula [The current study used data from the fat-associated cardiovascular dysfunction (FATCOR) study. The characteristics of the study population have been previously reported . A total SV, n =  or withdociation . The imaociation . LV mass formula . To estiThus, MEE could be measured as the ideal amount of blood pumped by one single heartbeat in one second. Since this quantity is related to the amount of myocardium available for pump performance , MEE was2 distribution was used to compare categorical variables and Kendall’s t–b was used for trend analysis. Univariable and multivariable regression analyses were used to identify the association of MEEi with circumferential and longitudinal LV myocardial systolic function (MFS and GLS) after adjusting for age, sex, BMI, the presence of hypertension, HOMA index, serum triglycerides, LV mass and concentric geometry. The odds ratio (OR) and associated 95% confidence intervals (CI) were reported. A p-value of <0.05 was considered statistically significant. All variables used in the multivariable models were analyzed for multicollinearity, by computing the linear variance inflation factor (VIF). VIF was always less than 1.5.Data were analyzed using SPSS . The study cohort was divided into MEEi quartiles. The lowest MEEi quartile was considered as low MEEi (<0.41 mL/s/g). Analysis of variance was used to compare continuous variables among MEEi quartiles, using polynomial linear contrast for trend analysis. The χp for trend <0.05). The lower MEEi quartile was also associated with a worse lipid profile and higher HOMA-IR index  . The lower MEEi quartile was confirmed to be associated with a greater proportion of men, as well as obesity and hypertension  . Ejectiod <0.05) .In univariable analyses, the lower MEEi quartile was paralleled by increasing serum triglycerides level and LV mass, and by lower LV systolic myocardial function assessed by MFS and GLS .p < 0.05). After adjusting for these factors as well as for LV geometry, lower MEEi remained independently associated with lower LV myocardial function by MFS and GLS   .The present study advances our understanding of the association of obesity with heart failure. Our study demonstrates that LV systolic function, assessed by MFS and GLS, is independently related to MEEi among adults with increased BMI and free from CV disease in parallel. Low MEEi also parallels worse metabolic profile and higher prevalence of abnormal LV geometry, as also shown in previous studies in different populations, expanding previous results on metabolic and hemodynamic correlates of reduced myocardial efficiency ,8.Reduced GLS has been reported in arterial hypertension, in particular when obesity or LV hypertrophy is present . IncreasIn obesity, an excess in circulating triglycerides is associated with increased fat storage in the epicardium, fat infiltration in the myocardium and subsequent impaired myocardial function . In the Our results demonstrate that in some patients with increased BMI but free from CV disease, at a given level of LV mass, the left ventricle works inefficiently with high energy-wasting, a condition associated with high CV risk phenotype. We demonstrate that systolic myocardial dysfunction is also part of this adverse cardiometabolic phenotype. Interestingly, low MEE is associated with both reduced MFS and GLS, strongly suggesting that both longitudinally and circumferentially, dysfunction contributes to determining reduced efficiency in obese/overweight individuals as previously reported .Compared to the directly invasive PET measures of myocardial metabolism, our indirect approach is more feasible in larger studies and potentially clinically applicable to the daily care of patients. This approach has a strong rationale. The calculation of stroke work has been invasively validated and largely adopted , and shoDue to the cross sectional dataset available in our study, the prognostic impact of MEEi cannot be assessed in this particular subset of patients. Future prospective studies are needed in obese/overweight subjects without prevalent CV disease.In conclusion, our study demonstrates that reduced MEEi in subjects with increased BMI is associated with lower LV myocardial function both in the circumferential and longitudinal direction, independent of cardio metabolic factors even in subjects without prevalent CV disease. An increased serum level of triglycerides was a main metabolic characteristic of reduced MEEi.


In our study, we retrospectively analyzed cardiac examinations in a large number of warmblood horses conducted over a period of almost 20 years. We compared the results of the cardiac auscultation as the character and grade of a heart murmur with the results of the echocardiographic examination. We found that auscultation works very well to identify the valve affected, if following the general clinical guidelines on which kind of murmur is usually caused by specific valvular regurgitations. Auscultation is less specific in determining the grade of the regurgitation based on the loudness of the murmur. Only low-grade murmurs are usually caused by mild regurgitations, while differentiation between moderate and severe regurgitations based on the loudness of the murmur is not reliable. Moreover, we could not find that enlargement of one or more compartments of the heart generally leads to a higher-grade murmur.Heart murmurs are detected frequently when auscultating horses and certain murmurs can usually be linked to specific valvular regurgitations. Limited information exists about the accuracy of these broad rules in warmblood horses and the influence of grade of the regurgitation and dimensional changes on murmur intensity. This study aims to clarify the accuracy of cardiac auscultation in warmblood horses and the influence of the grade of regurgitation and dimensional changes on the loudness of the murmur. In this retrospective study, 822 warmblood horses presented for cardiac examination in a large equine referral center in northern Germany underwent a thorough cardiac auscultation. In total, 653 of these revealed one or more heart murmurs. Most common auscultatory findings were left-sided systolic murmurs (68%) or left-sided diastolic murmurs (15%). On 635 of these horses, an echocardiographic examination was performed, revealing regurgitations of the mitral valve as the most common valvular regurgitation (77%) followed by regurgitations of the aortic valve (23%). Thirty-one percent of horses that underwent echocardiographic examination displayed dimensional changes of one or more compartments of the heart, with the left atrium being most affected (21%), followed by the left ventricle (13%). The main goal of this study was to link certain auscultatory findings with results of the echocardiographic examinations, trying to determine whether auscultation and echocardiography agreed on the valve affected, as well as to find out if loudness of the murmur coincided with grade of regurgitation and presence of dimensional changes. Agreement between auscultation and cardiac ultrasound was substantial (Kappa 0.74) if one or more murmurs and regurgitations were present and almost perfect (Kappa 0.94) if only one murmur and one regurgitation were found. Auscultation was particularly well suited for detection of left-sided systolic and diastolic murmurs, with 87% of left-sided systolic murmurs being caused by a mitral valve regurgitation and 81% of left-sided diastolic murmurs originating from an aortic valve regurgitation. We found a fair agreement between the grade of regurgitation and the respective murmur. Association was particularly good between mild regurgitations and low-grade murmurs, while differentiation between moderate to severe regurgitation based upon the loudness of the murmur was less reliable. Dimensional changes were usually linked to more severe regurgitations and higher-grade murmurs. However, a direct correlation between murmur intensity and the presence or severity of dimensional changes, independent of the grade of valvular regurgitation, could not be established in this cohort of horses. Heart murmurs are a common auscultatory finding in horses of all breeds, ages and disciplines and can be of a physiological or pathological nature ,2. WhileHorses—Warmblood horses that were presented for initial cardiac work-up in a large equine referral center in northern Germany between January 2000 and May 2020 were included in the study. Results from follow-up examinations were not included; therefore, each horse appears only once in the study. The horses were presented because of either a clinical complaint such as poor performance or collapse or because of a heart murmur or arrhythmia detected as an accidental finding. A detailed report of the examination was saved in the patient file for all horses, including information about the clinical examination, the auscultatory findings and, if conducted, the results of the echocardiography.Auscultation—After a general clinical examination with a special focus on the cardiovascular system, the horses presented were auscultated by one of five experienced veterinary practitioners upon arrival in the clinic. Auscultation was performed in a quiet environment on the left and right hemithorax with a conventional stethoscope placed in the third, fourth and fifth intercostal space. Frequency, intensity and rhythm of the heartbeats, and audible murmurs were noted. All auscultated heart murmurs were described as audible loudest on the left, right or on both sides of the thorax. Moreover, they were characterized depending on their timing as systolic, diastolic or continuous murmurs and were graded from Grade 1 to Grade 6  2]..2].Echocardiography—An echocardiographic examination was performed if a murmur was present upon auscultation. This included an examination in B-Mode, M-Mode and a color Doppler-echocardiography of all four valves ,11. If rData Analysis—The auscultatory and echocardiographic findings were collected retrospectively from the reports saved in the electronic patient files and the video archive. Horses were classified in different groups for the statistical analysis. Criteria were the presence of a murmur at the time of the examination, grade, phase and point of maximal intensity of that murmur, and the findings of the echocardiographic examination, such as the presence and grade of valvular regurgitation and dimensional changes.® Version 2016, Microsoft Corporation, Redmont, WA, USA) and analyzed using IBM SPSS statistical software version 25 . Descriptive statistics are presented in terms of frequency tables as well as means, median, standard deviations, 95% confidence intervals and boxplots.Data were stored in an Excel sheet  were calculated to determine whether specific cardiac findings lead to an increased risk of the development of other cardiological pathologies. Risk is enhanced if the OR is above 1.00.p was above 0.05 (p = 0.543). Hochberg’s post hoc test was then used for multiple comparisons. Model diagnostics included a visual inspection of normality and homoscedasticity of residuals. The level of significance was set at 0.05.An analysis of variances (ANOVA) was carried out to test how the different grades of regurgitation and the different grades of dimensional changes influenced the murmur intensity. The target variable was the loudness of the murmur. Input variables were the different grades  of MVI, AVI and TVI, the different grades  of left atrial and left ventricular dimensions, and the different grades  of right atrial and right ventricular dimensions. All two-way interactions were also included in the model. The homogeneity of the different variances was determined using Levene’s test. Equal variances could be assumed, as n = 264), followed by Holsteins (n = 229), Trakehners (n = 98), Oldenburgs (n = 85) and German Riding Horses (n = 78). A total of 242 (29%) of the horses were mares, 72 (9%) were stallions and 509 (62%) were geldings.Horses—822 warmblood horses were included in the study. They were between 3.5 months and 29.6 years of age. The mean age was 9.17 years, while the median age was 7.67 years. Most horses were Hanoverians (n = 528) with a left-sided systolic murmur being the most common with a total of 445 cases (68%). A right-sided systolic murmur was present in 46 cases (7%) and the systolic murmur was of a bilateral nature in 37 cases (5.5%). Diastolic murmurs were less frequent findings with a total of 109 cases (17%). A total of 95  of the diastolic murmurs were left-sided, 1 (0.2%) was right-sided and 13 (2%) both-sided , a combined MVI and AVI (n = 29/4%) and an isolated TVI (n = 25/3.5%)  examined. The most common finding was an isolated MVI, which was found in 372 horses (45%), followed by an isolated AVI, which was present in 87 horses (11%). Further common findings were a combined MVI and TVI (25/3.5%) . An MVI 25/3.5%) . A VSD wNo underlying regurgitation could be detected in 46 cases (7%) of all cases, even though a murmur was present upon auscultation. These murmurs were left-sided systolic in 23 cases, left-sided diastolic in 12 cases and right-sided systolic in 6 cases.Dimensional changes of one or more departments of the heart were present in 228 (31%) of the 735 horses examined echocardiographically. Left atrial enlargement was the most common finding, being present in 154 horses (21%), followed by left ventricular enlargement found in 95 (13%) of the horses examined. RA enlargement was present in 21 (3%) of the horses and 19 horses (2%) were diagnosed with dimensional changes of the RV.Association between different echocardiographic findings—Dimensional changes and valvular insufficiencies were a combined finding in 200 cases. This means that 88% of all horses with dimensional changes also had one or more valvular regurgitations and 34% of all horses with valvular regurgitation could also be diagnosed with dimensional changes of one or more compartments of the heart.The risk for horses with valvular regurgitations to also have dimensional changes was more than twice as high as for horses without regurgitations (OR = 2.12). Moreover, a higher-grade regurgitation leads to a higher risk of dimensional changes, with the risk being six times higher in moderate to severe MVI (OR = 5.92) and seven times higher in moderate to severe AVI (OR = 6.72) than in mild regurgitation of these valves.n = 458) between auscultation and echocardiography in these horses. If horses with more than one murmur and more than one regurgitation were taken into consideration (n = 547), agreement was slightly less but still substantial . A total of 430 of 447 (87%) left-sided systolic murmurs were due to an MVI. This means, in return, that 96% of all MVIs were accompanied by a left-sided systolic murmur. Therefore, agreement between auscultation and echocardiography was substantial  in this case. A total of 99 of 123 (81%) left-sided diastolic murmurs were linked to an AVI, ergo 74% of all AVIs presented as left-sided diastolic murmurs on auscultation. There is substantial agreement  between these two diagnostic tests. Right-sided systolic murmurs were due to a TVI in 22 (48%) and/or due to VSD in 13 (29%) out of 46 cases. This means a murmur of that kind was due to one of these two conditions in 76% of cases. Agreement  was moderate in this case. However, while 65% (n = 13) of all VSDs were right-sided systolic murmurs on auscultation, only 26% (n = 22) of TVIs presented themselves as right-sided systolic murmurs  between the grade of the murmur and the severity of the valvular regurgitation. Agreement was particularly good for low-grade murmurs, meaning that 236 of 276 (86%) low-grade murmurs also presented as mild regurgitations in echocardiography. Only 13% (n = 37) of these low-grade murmurs were linked to moderate regurgitations and only 1% (n = 3) to a severe regurgitation. Agreement was less for moderate murmurs. Of the 257 moderate murmurs detected on auscultation, only 40% (n = 102) could be linked to a moderate regurgitation in the ultrasonographic examination of the heart, while 48% (n = 122) of moderate murmurs were related to a mild and 22% (n = 33) to a severe regurgitation. Concerning high-grade murmurs, 13 of 29 (45%) could be linked to a moderate and only 11 (40%) to a severe regurgitation. However, only 5 (17%) high-grade murmurs were associated with a mild insufficiency  upon auscultation. On the other hand, the most frequent finding in horses without dimensional changes was a low-grade murmur (n = 278/47%) (p < 0.001). ANOVA showed that grades of MVI, TVI, AVI, and VSD as well as dimensional changes of the LA and of the RA and RV were significantly associated with murmur intensity (p < 0.001), VSD (p < 0.001), and dimensional changes of the RA (p = 0.010) influenced the murmur intensity directly, the other factors had significant interactions: AVI interacted significantly with MVI (p = 0.009) and with TVI (p = 0.010). Changes in the dimension of the LA showed significant interactions with dimensional changes of the RA (p = 0.016), with MVI (p = 0.001) and with VSD (p = 0.015). The MVI also interacted with the dimensional changes of the left ventricle (p = 0.008).Horses with an enlargement of one of the compartments of the heart most frequently had a murmur of a moderate grade (278/47%) . The mea278/47%) . This fintensity . While Tp < 0.05), with no and mild MVI causing systolic murmurs of lower intensities than moderate and severe MVI. This test revealed for TVI that only severe regurgitation differed significantly in loudness from the other grades of regurgitation (p < 0.001). No significant difference could be detected between mild and moderate regurgitation (p = 0.963). No and mild insufficiencies differed significantly from moderate and high-grade regurgitations in loudness in regurgitations of the aortic valve according to Hochberg’s post hoc test (p < 0.001). Moderate insufficiencies were considerably louder than mild regurgitations (p < 0.001) and quieter than severe regurgitations (p = 0.006), which were markedly louder than mild and moderate regurgitations . Concerning the LA, hearts without dimensional changes (<135 mm) differed significantly from all other groups (p ≤ 0.001). The larger the LA, the higher the murmur intensity. Dimensional changes of the LV always led to significant changes of the murmur (p < 0.001). However, there was no significant difference between mild (136–140 mm) and moderate (141–150 cm) changes (p = 0.951), with the murmur intensity being lower the larger the ventricle. The categories of the dimensional changes of the RA did not differ significantly, except that the group of no changes (<80 mm) had a significantly higher murmur intensity than the group of severe (>91 mm) changes (p = 0.013). The same situation applied to the RV: only no (<80 mm) changes were associated with a lower murmur intensity than severe (>91 mm) changes (p = 0.031).Following Hochberg’s post hoc test, all categories of MVI differed significantly from each other (Finally, in Equine veterinarians are frequently asked to evaluate heart murmurs upon special request, due to clinical concerns such as poor performance or an accidental finding on a prepurchase or a routine examination. As severe cardiac disease can be a safety risk for the horse and rider, it is crucial to find out the etiology of auscultatory findings and, consequently, judge the horse’s prognosis . MoreoveHowever, the accuracy of auscultation is widely discussed in the literature and different studies have come to very different conclusions regarding the significance and exactness of auscultatory findings . Naylor Studies in human medicine have shown that a significant correlation exists between the severity of regurgitations of the aortic valve and the intensity of diastolic murmurs, and between the loudness of systolic murmurs and the intensity of MVI . The samFinally, we wondered whether a higher-grade murmur may also be an indicator of dimensional changes of one or more compartments of the heart. It has been found in dogs that animals with murmurs of a low grade did not show structural changes of the heart in 90% of cases and that the probability of congestive heart failure increased with murmur intensity . The samUltimately, we can say that cardiac auscultation is an integral part of any cardiac examination and very well suited to identify the cause of a murmur in case of left-sided isolated murmurs and MVI and AVI, which show an almost perfect agreement between auscultation and ultrasonography. If right-sided murmurs and more than one regurgitation are present, agreement is lower and the technique is less suited to identify the valvular regurgitation as being the cause of the murmur. The limiting factor in this case is that only the grade, timing and location were used to describe the murmur. If character could have been taken into account, a higher agreement may have been achieved.We could determine a fair agreement between the grade of the murmur and the severity of the regurgitation. This is particularly true for mild regurgitations. Accuracy is lower for moderate- to high-grade regurgitations, with the murmur often being less loud than the severity of the corresponding valvular regurgitation may suggest, possibly introducing the risk of underestimating the risk of a grade 3 or 4 murmur. We also found that horses with cardiac dimensional changes have, on average, louder murmurs; however, this could also be due to the fact that dimensional changes are often accompanied by more severe regurgitations. In the case of AVI and left ventricular enlargement, we can even say that there is no direct correlation between the grade of enlargement and the murmur intensity.To sum up, we can say that auscultation is very well suited for an approximate assessment of a cardiac disease, especially in rural equine practice or when transportation to an equine referral center is not possible or not wanted. However, if further sporting activities are desired, further diagnostics should be performed, especially in a moderate to loud murmur, a right-sided murmur, or multiple murmurs, as auscultation may be inaccurate in these cases.


To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB).We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy.In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment.Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony.The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure.Trial registration: This study was retrospectively registered.The online version contains supplementary material available at 10.1186/s12968-021-00731-6. Left bundle-branch block (LBBB) is considered to exaggerate or even cause ventricular dysfunction and myocardial remodeling resulting in increased mortality in patients with cardiovascular disease –3. LBBB First, we hypothesized that ventricular conduction delay, expressed by the electrocardiogram (ECG) QRS duration, correlates with cardiac dysfunction, ventricular enlargement, myocardial fibrosis and septal flash volume. Second, we aimed to enhance the understanding of functional impairment in idiopathic LBBB and hypothesized that effects of asynchrony caused by septal flash volume and a contractile impairment are two different mechanisms contributing to structural remodeling in patients with idiopathic LBBB. To investigate the hypothesis, we used a novel method to calculate the septal flash volume in order to differentiate between LBBB patients with ventricular asynchrony and superimposed contractile impairment.Potential patients with idiopathic LBBB were retrospectively identified from our local CMR and echocardiography database at the Department of Cardiology, Angiology and Pneumology, University Heidelberg during May 2009 and August 2019.Patients with greater than mild valvular disease, myocardial infarction, obstructive CAD (major artery diameter stenosis > 75%), cardiomyopathy, arrhythmia, prior cerebrovascular events and history of potential cardiotoxic chemotherapy exposure were excluded Fig. a. All paLBBB has been confirmed by 12-lead ECG before or immediately after CMR. LBBB was defined as QRS duration > 120 ms as previously described [Age-, sex-, body-surface area (BSA)- and CVD risk factor -matched individuals free of evident CVD or any conduction delay (control group A) were selected from our CMR database. These individuals were patients who underwent CMR due to a high risk for CAD or a family history of cardiomyopathy, but without any pathological findings on CMR. Exclusion criteria of controls were the same as for our study group.Additionally, we compared our study group with healthy individuals without any CVD risk factors or history of heart disease (control group B). This cohort was also age-, sex-, BSA-matched.42 software . CMR parameters were indexed to body-surface area.Standard CMR was performed supine in a CMR system , with a commercial cardiac phased array receiver coil as previously described , 14. Det42 software (Circle Cardiovascular Imaging). Regional T1 times were measured using 16-segment American Heart Association model. T1 times of the segments antero-septal and infero-septal were combined and labelled “septal”, while segments antero-lateral and infero-lateral were combined and labelled “lateral”.”Myocardial tissue characterization was assessed by measuring the longitudinal relaxation time constant of the myocardium  using a Modified Look-Locker Inversion recovery (MOLLI) sequence, 5 s(3 s)3 s variant in a midventricular SAx during breath-hold in end-expiration in the end-diastolic phase of the cardiac circle . LV endo42 (Circle Cardiovascular Imaging) software and defined as areas with a signal intensity more than 5 standard deviations higher than the mean signal intensity of remote myocardium in the same short-axis Sect. [T2 mapping was performed using multiecho Gradient-Spin-Echo (GraSE) sequence on the same ventricular short-axis slice as T1 mapping. Late gadolinium enhancement (LGE) images were acquired 10 min after administration of gadolinium diethylenetriamine pentaacetic acid /DTPA  (before February 2016) or Gadobutol  (after February 2016) and analysis was performed as previously described [By assuming a homogenous circumferential wall thickening, the corrected LV end-systolic volume (corrected ESV) was assessed. Hereby, all SAx slices were used from the anulus of the atrioventricular valves to the apex at end-systole.Septal flash volume was calculated accordingly as the difference of uncorrected LVESV and corrected ESV Fig. b. Intra-The corrected LVESV was used to calculate the corrected LVEF. Corrected LVEF values of idiopathic LBBB patients were compared to LVEF reference values from our center  were expressed as mean ± standard deviation (SD). Group differences for continuous variables were tested using independent t-test or 2-way ANOVA for more than two groups followed up by Bonferroni post-hoc pairwise group comparisons. Continuous variables without normal distribution were stated as median and interquartile range, group differences were tested using nonparametric Mann–Whitney U test or Kruskal–Wallis test for more than two groups followed up by Bonferroni post-hoc pairwise group comparisons. Categorical variables were compared using chi-squared test. Pearson correlation was used to assess linear relationships between variables.Statistical analysis was performed using SPSS  and MedCalc , with 2). Intraobserver variability of the septal flash volume was 0.96 (CI: 0.91–0.99) and interobserver variability 0.93 (CI: 0.81–0.97). NT-proBNP and high-sensitive Troponin T were within normal range in the idiopathic LBBB group.Baseline characteristics of patients and controls are presented in Table Three patients revealed a mild stenosis on coronary angiography, but stress CMR examination was negative for ischemia. The median time between coronary angiography and CMR was 1 (0–13.5) month. Five patients underwent CMR more than 12 months after exclusion of CAD using coronary angiography, however stress CMR examination revealed no myocardial ischemia.p < 0.001; sMAPSE: p < 0.01; Table LVEF, septal mitral annular plane systolic excursion (sMAPSE), GCS and GLS were significantly reduced in idiopathic LBBB compared to control groups A and B  and indexed LVEDV (LVEDVI) were significantly enlarged in idiopathic LBBB patients compared to control group A and B  and a positive correlation between RVEDVI and QRS duration   EDV (RVEDVI), RVEF, tricuspid annular plane systolic excursion (TAPSE) and LV mass between the idiopathic LBBB and control group A or B . The time between first documented LBBB in ECG and the CMR examination was similar between both groups (LBBB with isolated asynchrony = 83 (18–112) days; LBBB with superimposed hypocontractility = 78 (47–617) days; p = 0.777). However, significant differences between the groups were found:Thirty-three patients with idiopathic LBBB were identified having a normal LVEF after correction of septal flash volume, revealing systolic dysfunction solely due to isolated ventricular asynchrony (LBBB with isolated asynchrony). However, 22 patients had a reduced LVEF after correction of septal flash volume, indicating a superimposed contractile impairment (LBBB with superimposed hypocontractility). Indexed septal flash volume was similar in both groups : p < 0.05, Table 4. Additionally, LGE was significantly more present in the group with superimposed hypocontractility compared to the one with isolated asynchrony : p < 0.05, Table 5. RVEDVI was significantly increased and RVEF decreased in the subgroup with superimposed contractile impairment compared to one with isolated ventricular asynchrony (th percentile), indicating increased chronic myocardial damage.This study suggests two separate mechanisms in patients with idiopathic LBBB that are both contributing in a differing extent to systolic impairment and structural remodeling. To our knowledge no data are available in the literature demonstrating this mechanism. First, the isolated ventricular asynchrony results in functional impairment, because septal flash volume, as the volume displaced from the lateral wall to the septum, does not contribute to the global stroke volume resulting in a reduced ejection fraction. Hence, LV dysfunction can be attributed solely to the effect of septal flash volume in a portion of patients. However, in close to a half of the studied individuals septal flash volume alone did not explain the apparent systolic impairment sufficiently. In this fraction of patients with idiopathic LBBB we assume an additional superimposed contractile impairment and could demonstrate an increased structural remodeling compared to those with isolated ventricular asynchrony Fig. . These pThese findings demonstrate the pathophysiologic heterogeneity of idiopathic LBBB. The evidence for a superimposed hypocontractility in addition to effects solely due to septal flash volume and therefore isolated ventricular asynchrony suggests a LBBB-associated cardiomyopathy Fig. . HoweverIn addition to these findings, we demonstrated that CMR does allow a quantification of septal flash volume with a high intra- and interobserver variability, which was previously only assessed visually by blinded physicians in echocardiographic studies , 25. SepExercise intolerant patients with idiopathic LBBB and systolic impairment caused by septal flash volume effects alone might benefit more extensively from CRT than patients with a leading cause of reduced global contractile function. This hypothesis is supported by Vaillant et al., who demonstrated the development of heart failure in idiopathic LBBB patients and the recovering of LVEF after CRT implantation . Even thThe present study has some limitations, such as the retrospective design. It is possible that patients with isolated ventricular dyssynchrony develop LBBB-cardiomyopathy with fibrosis and superimposed hypocontractility over time. However, in order to proof a sequential cascade of this pathology, knowledge about the onset and duration of LBBB is necessary. The onset of LBBB was similar in both groups, indicating that the development of a superimposed hypocontractility is independent of the duration of LBBB. However, due to the retrospective nature of this study, the onset point of LBBB was not available in all patients and the large interquartile range in the LBBB group with superimposed hypocontractility indicates a heterogeneity in this group. Therefore, longitudinal prospective follow-up studies are required to investigate the development of myocardial fibrosis in patients with idiopathic LBBB. Also, prospective follow-up studies would be necessary to evaluate if patients may develop clinically relevant heart failure with reduced ejection fraction or a cardiomyopathy.Additionally, due to incomplete data of native T1 maps, LGE and T2 measurements, the degree of fibrosis could not be investigated in all patients. Only about 2% of patients with a documented LBBB or dyscoordinated contraction had an isolated LBBB, indicating that it is difficult even in a tertiary referral hospital to identify suitable individuals. However, the present study consists, to our knowledge, of the largest population with idiopathic LBBB studied using CMR.Coronary angiography was not performed in all patients in order to exclude CAD. Even though the rest of the cohort had a negative stress CMR or echo and none of the LBBB patients had cine CMR evidence for regional dysfunction other than the septum, invasive coronary angiography or coronary computed tomography angiography should be performed to rule out CAD in future studies. The high prevalence of female patients (70%) is most likely a result of the retrospective nature of the study. Our study consists of a relatively small sample size. However, it needs to be emphasized that among 2356 patients with a documented LBBB, only 53 fulfilled the criteria for our study. Therefore, additional prospective studies are required in order to exclude a sex-specific functional impairment in patients with idiopathic LBBB. Additionally,  the measurements of T1 values with three different vendors including a 1.5 T and 3 T scanner resulted in different T1 times. This limits the number of individuals that can be compared between the patient group and the control group as well as between the subgroups. In future studies, the same vendor should be used for the study and the control group. Also, extracellular volume fraction (ECV) would be useful for quantification of myocardial fibrosis in further detail. Furthermore, to our knowledge this is the first study that measured septal flash volume using CMR. Additional studies are necessary to confirm that septal flash volume influences cardiac dysfunction and structural remodeling using CMR. Patients with idiopathic LBBB and controls had similar prevalence of hypertension, however we do not know the exact blood pressure during CMR examination. Moderate elevation of blood pressure can reduce LVEF and GLS in patients with LBBB . TherefoIn addition, genetic data are missing in this study, which might help to distinguish global hypocontractility and fibrosis caused by LBBB from other underlying cardiomyopathies such as dilated cardiomyopathy. While our data demonstrate that idiopathic LBBB induces cardiac dysfunction and structural remodeling, prospective studies are required to investigate potential risk factors, time of onset and development of myocardial fibrosis and finally prognosis of these patients.There is heterogeneity of cardiac remodeling in patients with idiopathic LBBB suggesting two separate pathophysiologic mechanisms that are both contributing in a differing extent to systolic impairment and structural remodeling. Besides isolated ventricular asynchrony, patients with hypocontractility have been identified indicative for the presence of an LBBB-associated cardiomyopathy.Additional file 1. Additional tables.


This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group . The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 μm SW is generated as propagating wave by pushing pulse of ultrasound beam, which deforms a part of the tissue. SW velocity within the tissue is detected by tracking pulse. SW imaging provides information regarding tissue elasticity, which is calculated by SW velocity.Shear wave (SW) imaging is a novel ultrasound technique for assessing characteristics of tissues based on SW propagation velocity9. SW elasticity has been reported to be correlated with tissue stiffness in liver diseases5. In the field of cardiac diseases, some studies reported that SW elasticity could be used to measure myocardial stiffness in animal models12. In a clinical setting, one study reported that SW elasticity was higher in patients with hypertrophic cardiomyopathy13. However, hypertrophic cardiomyopathy has remarkable left ventricular (LV) hypertrophy. It remains unclear whether SW elasticity can assess the severity of hypertensive LV hypertrophy.SW imaging has been used for evaluating several organs, including the liver, breast, and thyroid14. The assessment of LV hypertrophy is beneficial for diagnosing disease severity and considering therapeutic strategies. We hypothesized that SW elasticity reflects the degree of myocardial hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing myocardial hypertrophy of left ventricle using hypertensive model rats.Hypertensive LV hypertrophy is a common cause of heart failure, leading to adverse clinical outcomesDahl salt-sensitive rats develop hypertension due to a high-salt diet. Adult male Dahl salt-sensitive rats  were purchased and housed under conditions of constant temperature (22 ℃) and humidity (60%), exposed to a 12-h light/dark cycle, and offered tap water to drink. Rats were divided into two groups: hypertension group (n = 6), which were fed a high-salt (8% NaCl) diet for 9 weeks to develop LV hypertrophy, and control group (n = 6), which were fed a normal diet. Systolic blood pressure was measured at 9 weeks by tail-cuff plethysmography , and the average value of three measurements was calculated. All surgery was performed under inhalation of 2% isoflurane anesthesia, and all efforts were made to minimize suffering. All protocols for animal experiments were approved in accordance with the recommendations of the Okayama University Animal Care and Use Committee, and all methods were performed in accordance with the relevant guidelines and regulations. This study was reported in accordance with the ARRIVE guidelines.Transthoracic echocardiography was performed with Aplio ver. 6.0 with a 10-MHz sector probe  using gel for ultrasound. The rats were anesthetized from inhalation of 2% isoflurane while lying in a left recumbent position, and were warmed to their body temperature. LV end-diastolic and end-systolic diameters were measured in the short-axis view, and fractional shortening was calculated. Interventricular septum and LV free wall thicknesses were measured  with 20 mmol/L butanedione monoxime, an inhibitor of actin-myosin interaction, and 10 μmol/L blebbistatin, a specific myosin II inhibitor. The ascending aorta was cannulated with an 18-gauge blunted needle connected to a retrograde perfusion system. The heart was perfused with the Tyrode solution with butanedione monoxime and blebbistatin to induce complete relaxation. The heart was set in a water tank of agar phantom.SW imaging was performed by ex vivo experiment. A retrograde perfusion system was used to maintain the rat’s heart in a completely relaxed stateρc2 . Each measurement was repeated five times, and the average value was calculated.SW elasticity was measured with Aplio i900 with an 18-MHz linear probe . B-mode image was obtained in the long-axis view. A rectangular region of interest was placed on LV free wall. SW was generated by pushing pulse, and SW velocity was obtained based on the tissue Doppler technique . Samples were immersed in xylene and alcohol, stained with phosphomolybdic acid for 2 min, stained with Picrosirius Red F3BA Stain solution for 1 h, stained with hydrochloride acid for 2 min, and re-immersed in alcohol and xylene. The sections were examined with light microscopy. The cross-sectional area of 50 individual cardiomyocytes on LV free wall in five sections within the heart was measured in the regions containing cellular nucleus using Image J software  , and significance was defined as a value of P < 0.05.Baseline characteristics are shown in Table Representative cases in hypertension group and control group are shown in Fig. 2 vs. 243 ± 14 μm2, P < 0.01). Picrosirius red staining of left ventricle in hypertension group and control group is shown in Fig. Hematoxylin–eosin staining of left ventricle in hypertension group and control group is shown in Fig. SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes  Fig. . There wFor the intra-observer variability for the measurements of SW elasticity, Bland–Altman method showed the mean difference of − 0.05 kPa . For the inter-observer variability, Bland–Altman method showed the mean difference of 0.02 kPa .The major findings of the present study were: (1) SW elasticity was higher in hypertensive rats; and (2) SW elasticity was positively correlated with myocardial hypertrophy. To the best of our knowledge, this is the first study to show the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy of left ventricle.14. LV hypertrophy is a common cause of heart failure with preserved LV ejection fraction, resulting in hospitalization. LV hypertrophy involves changes in myocardial tissue. Assessing the degree of myocardial hypertrophy can be useful for identifying the disease severity in the hypertensive population.The severity of LV hypertrophy is associated with adverse outcomes in the clinical setting18. Although SW elasticity has been recognized as a useful tool for characterization of liver diseases21, the efficacy is limited in cardiac diseases. Regarding the heart, the utility of SW elasticity was investigated in animal models12. Pernot et al. reported that SW elasticity could be used to measure myocardial stiffness in isolated rat hearts10. They also reported that SW elasticity differentiated between stiff, noncompliant infarcted myocardial walls and softer walls containing stunned myocardium in ischemic hearts of an ovine model, showing that SW elasticity was higher in infarcted myocardium12. In recent years, the feasibility of SW elasticity was investigated in human subjects23. Villemain et al. reported that SW elasticity could assess myocardial stiffness quantitatively, showing that SW elasticity was higher in patients with hypertrophic cardiomyopathy than in healthy volunteers13. Pislaru et al. reported that higher SW elasticity was observed in patients with cardiac amyloidosis22. Therefore, SW elasticity could be useful in evaluating cardiomyopathy. However, the utility of SW elasticity for assessing the severity of hypertensive LV hypertrophy remains unclear. The relationship of SW elasticity with myocardial histological tissue has not been well investigated.SW imaging is a novel technique for characterizing tissue structures by ultrasound beam. SW elasticity clarifies the contrast of anatomical structures consisting of tissues with different shear coefficients, thereby enabling tissue identification5, whereas the present study found that SW elasticity was related to myocardial hypertrophy in the myocardium with less fibrosis.To clarify these findings, we used hypertensive model rats and evaluated the efficacy of SW elasticity for histologically assessing myocardial hypertrophy. In the present study, SW elasticity was higher in hypertensive rats. Larger cross-sectional area of cardiomyocytes was observed in hypertensive rats, and SW elasticity was correlated with the cross-sectional area of cardiomyocytes. Our findings suggest that SW elasticity can evaluate the severity of hypertensive LV hypertrophy. SW elasticity may be able to detect early changes in hypertensive heart disease. Additionally, in the myocardium of hypertensive rats, myocardial fibrosis was slight, which was similar to that in control rats. SW elasticity has been reported to be correlated with fibrosis24. Animal experiments suggest that LV hypertrophy alone cannot explain myocardial stiffening, but that the deposition of collagen fibres and qualitative changes of the collagen are major determinants26. SW elasticity may be influenced not only by myocardial hypertrophy but also by these myocardial properties.Cvijic et al. demonstrated that SW velocity—as measure of myocardial stiffness—was higher in patients with concentric hypertrophy than in those with concentric remodelling or healthy controls, indicating that the differences in SW velocity reflected intrinsic material properties28. Villemain et al. have shown that SW imaging can quantify myocardial stiffness in human subjects13. Petrescu et al. also suggest that SW imaging has the potential to become a valuable method for the assessment of myocardial properties in human subjects28. The application seems to be possible.SW imaging is a non-invasive and quantitative method. The present study suggests that SW elasticity can provide valuable information for assessing the severity of LV hypertrophy. Additionally, SW elasticity may be useful as a clinical tool for assessing treatment effects for LV hypertrophy. SW elasticity may have the potential for identifying myocardial tissue characteristics, leading to the differentiation of cardiac diseases. Further studies are needed to determine the usefulness of SW elasticity. For clinical application of SW imaging, it is necessary to remove the influence of the beating of heart on SW velocity. A few recent studies have reported the feasibility of SW imaging under the beating heartsThere are limitations in the present study. First, this study evaluated SW elasticity in non-beating hearts, because the heart rate of rats is too rapid to obtain SW imaging. This study evaluated SW elasticity under a retrograde perfusion system to make the heart fully relaxed for simulating the end-diastolic phase. Second, SW elasticity was measured in the long-axis view, whereas myocardial histology was assessed in the short-axis view. Third, the myocardial stiffness and the structural properties are not homogenous in the left ventricle. It was not clear if SW elasticity was measured in the same area as histological evaluation. Fourth, histological evaluation, such as the cross-sectional area of cardiomyocytes and the extent of fibrosis, might not be exactly. However, the cross-sectional area of cardiomyocytes was measured at many locations, and interstitial fibrosis was automatically measured using computer-assisted image analysis. Fifth, the amount of interstitial fibrosis was small in hypertension rats. It was difficult to assess the correlation of SW elasticity with myocardial fibrosis. Finally, this study evaluated SW elasticity in the left ventricle. The effects of SW elasticity in the right ventricle were not assessed.SW elasticity was higher in hypertensive rats. SW elasticity was closely correlated with the degree of myocardial hypertrophy of left ventricle. Our findings suggest that SW elasticity has the potential for estimating the severity of hypertensive LV hypertrophy.Supplementary Legends.Supplementary Figure S1.Supplementary Figure S2.Supplementary Figure S3.