To compare potential of ultrashort time-to-echo (UTE) T2* mapping and T2* values from T2*-weighted imaging for assessing lumbar intervertebral disc degeneration (IVDD),with Pfirrmann grading as a reference standard.UTE-T2* and T2* values of 366 lumbar discs (L1/2-L5/S1) in 76 subjects were measured in 3 segmented regions: anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus. Lumbar intervertebral discs were divided into 3 categories based on 5-level Pfirrmann grading: normal (Pfirrmann grade I),early disc degeneration (Pfirrmann grades II-III), and advanced disc degeneration (Pfirrmann grades IV-V). Regional differences between UTE-T2* and T2* relaxometry and correlation with degeneration were statistically analyzed.P < 0.001). In NP, correlations with Pfirrmann grade were high with UTE-T2* values  and moderate with T2* values . Diagnostic accuracy of detecting early IVDD was better with UTE-T2* mapping than T2* mapping (P < 0.05),with receiver operating characteristic analysis area under the curve of 0.715–0.876.UTE-T2* and T2*value correlated negatively with Pfirrmann grades (UTE-T2* relaxometry provides another promising magnetic resonance imaging sequence for quantitatively evaluate lumbar IVDD and was more accurate than T2*mapping in the earlier stage degenerative process. Low back pain (LBP) is a leading cause of disability worldwide, placing a great burden on the global health care system , 2. InteEarly stages of IVDD are mainly in the form of biochemical changes, including proteoglycan (PG) reduction, dehydration, and collagen degeneration. It will lead to a decrease in hydrostatic pressure, resulting in nucleus pulposus (NP) dehydration and loss of the structural and mechanical properties of the IVDs. In advanced stages of IVDD, along with loss of hydration and the subsequent drop in disc pressure, IVD height decreases under load –9. TheseConventional magnetic resonance imaging (MRI) is widely used for morphologic, qualitative assessment of IVDD in the clinical workup. Lumbar IVDD is commonly scored using the Pfirrmann grading system, which is based on the assessment of structure and loss of the signal intensity on T2-weighted imaging (T2WI). This grading system provides a standardized and reliable assessment of MRI disc morphology, but cannot detect early degeneration of IVDs characterized by a loss of PG quantitatively , 15.Several quantitative MRI techniques to evaluate IVD degeneration objectively have been reported, such as diffusion-weighted imaging, diffusion tensor imaging, glycosaminoglycan chemical exchange saturation transfer, sodium, delayed gadolinium-enhanced MRI, T2/T2*, and T1rho mapping. Previous studies have demonstrated that T2* mapping could be quantitative imaging biomarkers for evaluating the biochemical state of the discs and correlating that with histology, water content, and degeneration .Ultrashort time-to-echo (UTE) imaging as a novel MRI technique has the capacity to catch very short T2* signals (0.008 ~ 0. 50 ms) –20, It hThe present study aimed to assess whether lumbar IVDD can be evaluated using UTE-T2* mapping and to compare the potential of UTE-T2*and T2* values in the diagnosis of early IVDD.Ethics approval for this study was provided by the ethics commission of the Fudan University Affiliated Zhongshan Hospital Xiamen Branch. Written informed consent was obtained from all subjects. The inclusion criteria were patients with single or recurrent episodes of nonspecific LBP in the last 6 months and age ≥ 18 years. Exclusion criteria were contraindications for MRI and patients with other spine diseases, such as spinal infection, tumor, tuberculosis, and serious scoliosis.All data were acquired on a 3.0 T MRI scanner  equipped with an 8-channel spine-array coil covering the IVDs L1/L2 to L5/S1. All participants underwent MRI examinations, including sagittal T2WI, UTE-T2*, and T2* mapping. T2WI images were used for Pfirrmann grading. Detailed acquisition parameters were assigned to T2WI, UTE-T2* mapping, and T2* mapping.For T2WI, repetition time (TR)/echo time (TE) = 2500/120 ms, slice thickness/gap = 5/0.5 mm, field of view (FOV) = 300 × 300 mm, matrix = 256 × 192, and bandwidth = 41.7 kHz. For UTE-T2* mapping, TR = 112.4 ms, TE = 0.032/3.8/8.8/13.2 ms, slice thickness/gap = 3/0.5 mm, flip angle = 15, FOV = 300 × 300 mm, matrix = 300 × 256, and bandwidth = 62.5 kHz. Maps of the T2* was calculated using R2*(R2* = 1/T2*) , 27.For Table Fig. All lumbar IVDs were evaluated by 2 musculoskeletal radiologists each with more than six years of experience using T2WI and assigned a Pfirrmann grade  and Medcalc 20.022 . The Kruskal–Wallis test was performed to determine differences among the 5-level Pfirrmann grades. The differences between the two methods were expressed using the ± 95% confidence intervals (CIs) from the Bland–Altman analysis. Correlations of quantitative values with Pfirrmann grades were analyzed using Spearman's rank correlation. Receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC), sensitivity, specificities, positive likelihood ratio (+ LR), and negative likelihood ratio (− LR) were obtained to assess the diagnostic efficacy of each quantitative parameter for differentiating normal IVDs from early disc degeneration and to differentiate early disc degeneration from advanced disc degeneration. AUCs were compared using the DeLong method . A P valn = 2), collapsed disc space (Pfirrmann grade V) that made it impossible to measure the quantitative values (n = 9), and image quality problems (n = 3). A total of 366 IVDs were included in this study.Seventy-six subjects aged 54.4 ± 15.7 years  were recruited into this study. They included 29 males  and 47 females . Five intervertebral discs (L1/L2–L5/S1) per subject were examined, of which 14 discs were excluded due to previous vertebral fusion operation .UTE-T2* values showed high correlations with Pfirrmann grade in NP . Moderate correlations with Pfirrmann grade were observed in T2* value of NP . Comparing the Spearman correlation coefficient, the highest correlation value was seen in NP and the lowest was seen in AAF. Among those, the UTE-T2* value of NP showed the highest correlation values with Pfirrmann grades. Results of Spearman's correlation analysis are summarized in Fig. The Kruskal–Wallis test demonstrated that all quantitative values for all segments were significantly different among different Pfirrmann grades  and that AUCs for the assessment of the early disc degeneration (AUC 0.876) were significantly higher than those for T2*(AUC 0.763).Overall, the diagnostic efficacy of UTE T2* mapping was better than that of T2* mapping for evaluating IVDD, especially in NP. The results of this study demonstrated that the UTE-T2* value in NP showed high correlations with Pfirrmann grade  and ultrashort echo time range , 22. BecMultiple large general-population–based studies have proved that UTE-T2* mapping can detect cartilage subsurface matrix changes, which can be indicative of reduced cartilage health from injury or early degeneration noninvasively , 23, 25.In NP and PAF, UTE-T2* mapping showed significantly higher diagnostic accuracy in differentiating early disc degeneration from normal than did T2*. Theoretically, both UTE-T2* and T2* mapping measured the T2* value of the tissue. UTE MRI technique mitigates the rapid signal loss from short T2* by reducing the TE to the scale of 0–200 microseconds to sample the free induction decay as early as possible. With considerably shorter TEs (0.032 ms in this study) than T2*, UTE-T2*mapping allows signals from very short T2 components to be detected . Thus, UPrevious studies have reported that T2 relaxation time of Pfirrmann grades IV is significantly shorter than Pfirrmann grades III, and no significant differences were found between Pfirrmann grades IV and V, both of which show extremely low signal intensity . The resA previous report on healthy ovine IVDs demonstrated that the T2 values show regional variation in discs and reported that high T2 values were observed in NP and low T2 values in the AAF and PAF when histologically evaluated . Disc deThere were some limitations in this study. First, our study had no detailed histologic confirmation associated with IVDD changes. This is hard to achieve in humans. In addition, the relationship between T2* values and biochemical changes in IVDD has been previously established in human cadaveric lumbar discs . Second,We demonstrated that UTE-T2*mapping was more accurate than T2* mapping in quantitatively diagnosing early intervertebral disc degeneration. In particular, UTE-T2* mapping allowed for precisely distinguishing disc degeneration, potentially providing a promising imaging biomarker with potential applications in intervertebral disc degeneration for the emerging cell-based therapies.


Echocardiography has been the choice for imaging modality for valvular heart disease. It is less invasive, widely available, and allows valvular structure visualization. Echocardiographic assessment often also determines the management. Left ventricular ejection fraction is the most commonly used indicator during echocardiography assessment. It shows signs of left ventricular dysfunction in patients with valve disease. However, most of the time, the ongoing process of cardiac damage may already occur even with preserved cardiac function; further deteriorated ejection fraction will show irreversible cardiac damage. There is a need for a more advanced diagnostic tool to detect early cardiac dysfunction, to prevent further damage.Advanced echocardiography imaging using strain imaging allows a physician to evaluate cardiac function more precisely. A more sensitive parameter than left ventricular ejection fraction, global longitudinal strain, can evaluate subclinical myocardial dysfunction before the symptoms occur by evaluating complex cardiac mechanisms. Global longitudinal strain evaluation provides the chance for physicians to determine the intervention needed to prevent further deterioration and permanent cardiac dysfunction. Global longitudinal strain is proven to be beneficial in many types of valvular heart diseases, especially in mitral and aortic valve diseases. It has an excellent diagnostic and prognostic value for patients with valve disease. This review aims to present the superiority of global longitudinal strain compared to left ventricular ejection fraction in assessing cardiac function in patients with valvular heart disease. Clinical usage of global longitudinal strain in several valvular heart diseases is also presented in this review.The superiority of global longitudinal strain to left ventricular ejection fraction relies on the mechanism where other strains would compensate for the deterioration of longitudinal strain, which is more vulnerable to damage, so the cardiac function is preserved. Therefore, examination of longitudinal strain would give the physician early signs of cardiac function impairment, and prompt management can be conducted. Valvular heart diseases (VHD) remain a health burden. In Europe, the prevalence of VHD is around 13.3 million, with aortic stenosis and mitral regurgitation becoming the most common types of VHD . In the p = 0.037) . This study also found that of all asymptomatic patients, some of the patients who were indicated for surgery had more impaired LV GLS values [GLS measurement in aortic regurgitation is less studied. However, several studies were able to show the role of GLS in aortic regurgitation patients. A study by Alashi et al. showed that lower LV GLS had a prognostic value for mortality in the long term. The study was conducted on asymptomatic patients with aortic regurgitation and preserved cardiac function. The mortality risk at 5 years was also increased if the LV GLS value was lower than − 19.5%. In addition, according to the findings of this study, LV GLS has both incremental and additive prognostic value. Using LV GLS might provide a synergistic improvement in risk reclassification in individuals with severe MR prior to the development of overt LV systolic failure or symptoms. As a result, LV GLS might assist as basis for further optimizing treatments in asymptomatic individuals before to the development of atrial fibrillation or pulmonary hypertension . AnotherS values .p < 0.01). However, the preoperative LVEF measurement showed no differences [Mitral regurgitation is a common valvular disease globally and can be classified into primary and secondary mitral regurgitation . In primferences . A studyferences .In secondary mitral regurgitation, GLS is also superior to LVEF in showing cardiac function. Kamperidis et al. showed that patients with severe secondary mitral regurgitation had more impaired GLS than the 'none or less than mild' secondary mitral regurgitation patients with comparable LVEF . The stuThere are very limited studies about GLS application in tricuspid and pulmonary valve disease. However, several studies were able to show the benefit of GLS measurement. Right ventricular (RV) longitudinal strain was superior to other echocardiographic measurements and was related to outcome in patients with tricuspid regurgitation . In pulmThere is no consensus on the standard GLS value used as a benchmark for determining left ventricular dysfunction in patients with VHD. However, Dahl et al. proposed a new algorithm for asymptomatic patients with severe aortic stenosis Fig. . FurtherAssessment of global longitudinal strain in valvular heart disease is beneficial and superior to LVEF because of the ability to detect cardiac dysfunction in asymptomatic patients due to compensation by other groups of strain. This advantage of GLS can be further used to determine the therapeutic strategy for the patients. GLS has been studied in many mitral and aortic valve diseases. Further studies are needed to establish the role of GLS in various tricuspid and pulmonary valve diseases.


To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM).Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized.In this single‐centre, observational, cross‐sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme‐linked immunosorbent sandwich assay (ELISA).After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern.Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM. The anthropometric assessment was illustrated in the 2.3®; Siemens Healthcare GmbH, Erlangen, Germany); white blood cell (WBC) count and neutrophils were measured using an automated particle counter ; and HbA1c was determined with high‐performance liquid chromatography using a National Glycohemoglobin Standardization Program (NGSP)‐certified automated analyser .Venous blood was withdrawn in the morning after at least 8‐hour fasting. Blood specimens were immediately centrifuged to separate sera and then frozen at −80°C for storage. Alongside serum levels of C‐reactive protein (CRP), considered a generic biomarker of inflammation in several classes of disease including metabolic ones,2.4All measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Echocardiographic measures were collected according to literature, as reported in the No dysfunction (Grade 0): E/A ratio between 0.8 and 1.9 + E/e’ ratio <8.0 or left atrial diameter (LAD) ≤4.2 cm, if E/e’ ratio between 8.0 and 15.0;Mild dysfunction (Grade 1): E/A ratio <0.8;Moderate dysfunction (Grade 2): E/A ratio between 0.8 and 1.9 + E/e’ ratio >15 or LAD >4.2 cm, if E/e’ ratio between 8.0 and 15.0;Severe dysfunction (Grade 3): E/A ratio ≥2.0.The definition and grading of left ventricular (LV) diastolic dysfunction were adapted from the recommendations of the EACVI,No dysfunction (Grade 0): LVEF ≥55% and LV s’ ≥0.075 m/s;Mild dysfunction (Grade 1): LVEF between 40% and 55% or LV s’ between 0.03 and 0.075 m/s;Severe dysfunction (Grade 2): LVEF <40% or LV s’ <0.03 m/s;The definition and grading of LV systolic dysfunction were based on values of LV ejection fraction (LVEF) measured through Simpson's biplane formula2;No dilation (Grade 0): ≤75 mL/m2;Mild dilation (Grade 1): 76‐86 mL/m2;Moderate dilation (Grade 2): 87‐96 mL/m2.Severe dilation (Grade 3): ≥97 mL/mThe presence and severity of LV dilation were assessed according to the indexed LV end‐diastolic volume (LVEDDi)2No hypertrophy (Grade 0): ≤115 g/m2Mild hypertrophy (Grade 1): 116‐131 g/m2Moderate hypertrophy (Grade 2): 132‐148 g/m2Severe hypertrophy (Grade 3): ≥149 g/mThe presence and severity of LV hypertrophy were assessed according to the indexed LV mass (LVMi) Dilative pattern with systolic dysfunction (dilative/SD): the presence of any LV systolic dysfunction and/or severe LV dilation;Restrictive pattern with diastolic dysfunction (restrictive/DD): the presence of any diastolic dysfunction in a subject not meeting the criteria of dilative/ SD;Normal pattern: the absence of criteria for either dilative/ SD or restrictive/ DD.Echocardiographic patterns in patients with diabetes mellitus were defined according to Seferović and colleagues2.5The primary endpoint of the study was the detection of whether surrogate biomarkers of neutrophil degranulation correlate with at least two echocardiographic patterns of myocardial dysfunction. The secondary endpoint was a significant correlation between the over‐mentioned biomarkers and the ultrasonographic parameters of myocardial dysfunction.The adequacy of sample size was assessed assuming a 60% prevalence of subclinical myocardial dysfunction in patients with T2DM, with an equal prevalence of dilative/SD and restrictive/DD pattern.2.6U test or univariate logistic regression, after log transformation of non‐normally distributed variables. The correction for potential confounders was performed using multiple logistic regression analysis. The analysis was performed using the SPSS software package 23.0 (IBM Inc.).Continuous variables are expressed as median and interquartile range (IQR) or mean ± standard deviation (SD) according to their distribution assessed with the Kolmogorov‐Smirnov test. Categorical variables are instead presented as number (%). A probability of type 1 error <0.05 is considered significant under the assumption of null hypothesis. Overall significance of differences between groups was assessed by the Kruskal‐Wallis test and the chi‐square test for continuous and categorical parameters, respectively. The significance of pairwise differences was assessed through the Mann‐Whitney 33.12) with a good glycometabolic control (median HbA1c: 6.9%). As reported in Demographic, physical and laboratory characteristics of the enrolled population are reported in Table Complete echocardiographic parameters were available for 451 patients. Median values and IQR of parameters analysed in the present study are reported in 3.2As expected, inflammatory parameters belonging to neutrophil degranulation were positively correlated with neutrophils and white blood cell counts, with CRP levels and with each other Table  It is no3.3Comparing the average values of neutrophil degranulation biomarkers among echocardiographic patterns , a significant difference between normal and restrictive patterns was observed for resistin, MPO, MMP‐8, MMP‐9/TIMP‐1 complex, TIMP‐1 and TIMP‐2 Figure . Those v4The main finding of the present study is the association between neutrophil degranulation, evaluated through surrogate serum biomarkers, and the restrictive/DD pattern of myocardial dysfunction, evaluated through echocardiography, in patients with T2DM. This association is confirmed also after adjustment for potential confounders. Specifically, measured biomarkers are significantly higher in patients with restrictive/DD pattern than in those with normal pattern. Such difference has not been observed between patients with dilative/SD pattern and normal pattern, with the exception of MPO, showing significantly elevated values also in the dilative/SD pattern group. Notably, resistin values were significantly higher in the restrictive/DD pattern group than in the dilative/SD pattern group, whereas CRP failed to show any difference across the patterns of myocardial dysfunction. Overall, these findings might suggest some specific role for neutrophil degranulation in the pathophysiology of diabetic cardiomyopathy. This would not be surprising as the involvement of leucocyte in diabetic cardiomyopathy has been well established.Equally interesting is the evidence about the potential involvement of resistin in diabetic cardiomyopathy. Traditionally known as is cysteine‐rich adipokine with downregulating effect of insulin signalling,Instead, why MPO, MMP‐8, TIMP‐1, ‐2, and MMP‐9/TIMP‐1 as well are significantly associated with restrictive/DD, whereas only MPO is associated with dilative/SD still remains a controversial point. Although speculative, the development of restrictive/DD pattern can be assumed as a more complex process involving the deposition of extracellular matrix. This could be linked to a different neutrophil activation/degranulation pattern. In particular, MMP‐8, and MMP‐9—when balanced with TIMPs—exert pro‐fibrotic effects.As an additional limitation, we should acknowledge that this study is composed of patients with a relatively recent diagnosis of diabetes. This may somewhat limit the generalization of results, but it may also point out how neutrophil degranulation contributes earlier to the development of diabetic cardiomyopathy.Finally, the prevalence of hypertension, obesity and metabolic syndrome was quite homogeneous among the three groups. Although model adjustments for these potential confounders were adopted, a relevant contribution of these comorbidities to myocardial dysfunction cannot be excluded. In particular, the adjustment for hypertension only concerns the presence of disease and the number of anti‐hypertensive drugs, but not the duration of hypertension. The latter is often difficult to estimate as it often occurs asymptomatically but undoubtedly represents a missing confounder that should be acknowledged as a further study limitation.In conclusion, the results of the present study suggest that neutrophil degranulation characterizes the restrictive/DD echocardiographic pattern in patients with T2DM, compared with the normal pattern and the dilative/SD pattern as well. This result is consistent with previous observations in animal models but not in human beings. Future studies are needed to assess whether serum biomarkers could help in stratifying the risk of myocardial dysfunction in subjects with T2DM and normal myocardial function, as well as investigating the potential pharmacological strategies targeting neutrophil activity (eg inhibitors of MMPs) to prevent the progression of myocardial dysfunction to overt heart failure.The authors declare they have no conflict of interest.Supplementary MaterialClick here for additional data file.


The objective of this review article is to discuss how cardiovascular magnetic resonance (CMR) imaging measures left ventricular (LV) function, characterizes tissue, and identifies myocardial fibrosis in patients receiving anthracycline-based chemotherapy (Anth-bC). Specifically, CMR can measure LV ejection fraction (EF), volumes at end-diastole (LVEDV), and end-systole (LVESV), LV strain, and LV mass. Tissue characterization is accomplished through T1/T2-mapping, late gadolinium enhancement (LGE), and CMR perfusion imaging. Despite CMR’s accuracy and efficiency in collecting data about the myocardium, there are challenges that persist while monitoring a cardio-oncology patient undergoing Anth-bC, such as the presence of other cardiovascular risk factors and utility controversies. Furthermore, CMR can be a useful adjunct during cardiopulmonary exercise testing to pinpoint cardiovascular mediated exercise limitations, as well as to assess myocardial microcirculatory damage in patients undergoing Anth-bC. Cardiovascular magnetic resonance (CMR) is a non-invasive imaging method that produces 3-dimensional images without using ionizing radiation and may accurately assess left ventricular (LV) myocardial structure, function , perfusion, and tissue characteristics across a variety of disease processes including heart failure, ischemic heart disease, non-ischemic cardiomyopathy, myocarditis, pericardial disease, and congenital heart disease .Recently, CMR has been used to assess LV myocardial injury and identify cardiotoxicity in patients receiving anthracycline-based chemotherapy (Anth-bC) for the treatment of various cancers including breast, leukemia, lymphoma, bladder, and ovarian cancer . Cardiotvia CMR, address challenges, and finally, consider recent breakthroughs and new frontiers of research.This article will review the utilization of CMR for identifying cardiotoxicity in patients receiving Anth-bC, discuss recent clinical data and parameters that can be detected p = 0.0004)  .Although effective in eradicating tumors in breast, lymphoma, and soft tissue sarcoma cancers, anthracycline-related treatments may have a negative impact on LV function and promote heart failure (HF) , 9, 10. Mechanistically, CMRs are based on the detection of signals from hydrogen nuclei . When a 2 for males and 24 ±5 mL/m2 for females, whereas LVEDV is the LV volume at the end of diastole, with an average indexed value of 81 ± 12 mL/m2 for males and 76 ± 10 mL/m2 for females  at 351–700 days after anthracycline therapy of 240 mg/m2 , and cardiac troponin T significantly increased (p < 0.001). Therefore, based on these studies, patients being treated with Anth-bC obtained CMRs before, 6, 12, and/or 24 months after anthracycline treatment.In 53 men and women with breast cancer, leukemia, or lymphoma, LVEF decreased within 6 months after low to moderate doses of Anth-bC  Table 1Table 1. 40 mg/m2 . AdditioFurthermore, a study by Melendez et al.  used CMR2 for males and 36–72 g/m2 for females  and LVEF (p < 0.0001) but did not observe this decline in patients receiving non-Anth-bC (n = 15) or control patients (n = 24). Additionally, patients receiving Anth-bC experienced a decline in Minnesota Living with Heart Failure Questionnaire scores over the 6-month period, which was associated with LV mass declines , yet not with LVEF declines , thus indicating that patients with declining LV mass while undergoing treatment with Anth-bC may experience worsening heart failure symptomatology that’s independent of LVEF . The researchers also determined if patients experienced a major adverse cardiovascular event (MACE), which was defined as cardiovascular death, implantable cardioverter defibrillator therapy, and admission for heart failure (p < 0.001) in a multivariable model , and the 3-month changes in each measurement also correlated   . Moreove 0.0001) , the aut 0.0001) .LV strain can also be quantified and tracked with post-processing semi-automated methods, such as tissue tracking. Specifically, LV strain can be tracked over time with CMR feature tracking (CMR-FT), as CMR-FT follows myocardial boundaries and automates strain calculation. The tracked features are anatomic elements along the cavity-myocardial interface and throughout the cardiac cycle, and each feature is tracked by algorithms . Tissue via CMR-FT, and LVEF of 20 patients undergoing cardiotoxic chemotherapy, and among these patients, LV strain was negatively correlated with LVEF   .The reproducibility and validity of CMR-FT have been assessed extensively . For exaBecause cine loops can be acquired during breath holding from nearly any tomographic plane, CMR also allows for visualization of LV wall motion . MoreovePeak radial, longitudinal, and circumferential velocities are some of the parameters of LV wall motion . Typicalp < 0.01; In a study by de Barros et al. , the LV 2 and exhibited normal systolic function, post contrast T1 values were significantly lower than control patients  , such as T1 and T2 mapping. Longitudinal relaxation time (T1) and transverse relaxation time (T2) are properties determined by a tissue’s molecular composition . Thus, c = 0.01) .One CMR technique that assesses myocardial fibrosis using gadolinium contrast is LGE, and inversion recovery (IR) with magnitude reconstruction is the pulse sequence most widely used for LGE . Roughlymyocardium vs. 1/T1blood, and then using the following formula: When T1-maps are collected both with and without contrast in a patient, the extracellular volume fraction (ECVF) can be calculated by first determining the partition coefficient from the slope of 1/Tloodpre) . A blindloodpre) . Figure loodpre)  shows T1loodpre)    and ECVFloodpre)    remain ep < 0.001; 60). Perfusion imaging may also allow for assessment of myocardial perfusion reserve (MPR), which is the maximum increase in myocardial blood flow above baseline conditions, by quantifying myocardial blood flow at rest and during stress. Changes in MPR may elucidate the underlying pathophysiology of cardiomyopathies, such as coronary microvascular dysfunction and CAD, which increases risk of cardiotoxicity for patients undergoing potentially cardiotoxic chemotherapy.CMR perfusion imaging can further characterize tissue . PerfusiCMR accurately assesses LV function and structure, and this allows for physicians to use findings in clinical decision-making. Cardiotoxicity is defined as a decline in LVEF by > 10% to a value < 50% while undergoing cancer treatment . ProbablAlthough CMR is the gold standard for assessing myocardial function, challenges persist. CMR availability and portability are limited, which may contribute to less widespread use of CMR. A CMR scanner is 4–10 times the cost of a standard 3D echocardiography system . HoweverFeasibility to perform CMR on all patients must also be considered. Specifically, some patients require anxiolytics for claustrophobia while undergoing CMR, which may lower their heart rate and blood pressure during the exam, and thus affect findings. Additionally, patients with certain implants may not undergo magnetic resonance imaging, as artifacts can affect imaging outcome.As CMR continues to serve as a robust and reliable tool for monitoring a patient’s progression through cardiotoxic treatment, as well as other myocardial injuries, the imaging modality continues to improve. Artificial intelligence (AI) and machine learning (ML) have become increasingly prominent in the field of CMR, improving the efficiency and accuracy of assessing cardiac function . A deep p = 0.0001); ; . Thus, aMoreover, CMR can be used to assess cardiac function during exercise testing  and has ex vivo found that among adult human coronary microvessels treated with doxorubicin, flow-mediated dilation (FMD) and coronary arteriolar function were significantly impaired  CMR, advances are also being made in CMR efficiency. By allowing for high spatial and temporal resolution during free breathing and without ECG synchronization, RT CMR reduces the total exam time from 12 to 15 min for SSFP to evaluate LV function in under 2 min. Although there have not been many studies assessing the accuracy of SSFP vs. RT CMR among cancer patients, the RT CMR technique may be useful in improving efficient resource utilization.As a non-invasive cardiac imaging technique, CMR assesses LV function, tissue characterization, and myocardial injury. LV function is accurately assessed through determination of LVEF, volumes at end-diastole (LVEDV), and end-systole (LVESV), strain, mass, and wall motion. Various techniques may be used for tissue characterization, some of which use gadolinium contrast (LGE and T1-mapping), and some of which are non-contrast methods (T1/T2 mapping). Significant clinical changes in LV function may correlate with cardiotoxicity, and CMR is especially useful in monitoring cardiac function throughout treatment with potentially cardiotoxic chemotherapy.When compared to other modalities, CMR provides a variety of information while being non-ionizing, non-invasive, and accurate, thus making it advantageous for routine cardiac monitoring among oncology patients in a clinical setting. Additionally, CMR assesses LV volumes and can characterize tissue to assess myocardial fibrosis. Challenges persist, however, while using CMR in cancer patients, such as cost, efficiency, and accessibility. As new frontiers of research with CMR are constantly discovered, its applications and techniques continue to expand and improve, respectively.LM drafted the initial manuscript. WH, WB, and JJ critically reviewed the manuscript. All authors approved the final manuscript.


Field Strength/Sequence: a 3.0T MR, Steady state free precession (SSFP), Phase-sensitive inversion recovery (PSIR). Assessment: infarct location and size were assigned and quantified by late-gadolinium enhancement (LGE) imaging. LA performance was analyzed using CMR-FT in 2- and 4-chamber cine images, including LA reservoir, conduit and booster pump function. Statistics: descriptive statistics, ANOVA with post Bonferroni correction, Kruskal–Wallis H, Spearman’s correlation, intraclass correlation coefficient. Results: Anterior MI patients had impaired LA reservoir function , conduit function  and booster pump function  compared with controls (p < 0.05). Non-anterior MI patients had impaired LA strain  but preserved LAEFs (p > 0.05). After adjusting the area of MI, there was no significant difference in the LA morphology and function between the anterior and non-anterior wall groups. Stratification analysis by MI size revealed that LA volumes and LAEFs were unchanged in patients with MI size ≤ 15% compared with controls (p > 0.05); only εs and εe were decreased (p < 0.05). Increased LAVIpre-a, LAVImin and decreased LATEF, and LAAEF were found in patients with MI size > 15% compared with the MI size ≤ 15% group (p < 0.05). LVSVI, εs and MI size were significant correlated with LAVI pre-a in multiple stepwise regression analysis. Data conclusions: The location of myocardial infarction is not a major factor affecting the morphology and function of the left atrium. Patients with MI size > 15% experience more pronounced post-infarction LA remodeling and dysfunction than MI size ≤ 15% patients.Background: LA function has been recognized as a significant prognostic marker in many cardiovascular diseases. Cardiovascular magnetic resonance feature tracking (CMR-FT) represents a promising technique for left atrial function evaluation. The size and location of myocardial infarction are important factors in the cause of adverse left ventricular remodeling, but the effect on the left atriam is unclear. Purpose: to investigate the effect of location and size of previous myocardial infarction (MI) on LA function using CMR-FT. Study type: retrospective. Population: patients formerly diagnosed with anterior MI ( Left ventricular systolic and diastolic function is impaired after acute myocardial infarction (MI) and left atrial (LA) function also undergo changes. Impaired LA function is related to myocardial fibrosis in the left ventricular infarction and diastolic filling transferring stress from the left ventricle (LV) to LA . The lefPercutaneous coronary intervention (PCI) has improved MI patient outcomes, but some patients still suffer adverse cardiovascular events, such as arrhythmias and heart failure, resulting in poor prognosis . During A total of 101 consecutive patients who had previously suffered MI and received cardiac magnetic resonance imaging (MRI) between April 2017 and June 2021 were retrospectively enrolled. MI was diagnosed according to the criteria of The 2018 Fourth Universal Definition of Myocardial Infarction [Scans were performed on a 3.0-T MRI  and retrospective cardiac gating was used. Balanced SSFP sequence with breath-hold generated cine CMR images comprising a stack of contiguous parallel short-axis slices covering the entire LV from base to apex plus three LV long-axis slice . Slice thickness/spacings were 5 mm/1 mm for the long axis and 8 mm/2 mm for the short axis, repetition time (TR)/echo time (TE) was 3.8/1.3 ms and temporal resolution = 35 m. LGE imaging covered the entire heart: TR/TE = 750/1.6 ms, flip angle = 12°, bandwidth = 465 Hz/pixel and phase-sensitive inversion recovery (PSIR) occurred about 10 min after gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) injection. The total acquisition time ranged from 30 to 40 min.CMR image analysis was conducted by two radiologists with more than 3 years’ experience in cardiovascular imaging. The first observer (Z.H.) performed LA analysis while the second (JSQ) performed LV analysis. MRI examinations with reduced image quality or with suboptimal tracking were reviewed by a third experienced observer  and a consensus decision was reached. All the MR images were processed by CVI 4.2  over a time period of 20 min per case.LAVI) was calculated by dividing LA volume by body surface area (BSA). The total left atrial (LATEF), passive atrial (LAPEF) and active atrial (LAAEF) emptying fractions were calculated according to the following formula:LV cardiac function and volume, including the volume of papillary muscles, were calculated from short-axis cine images . LA voluLA strain analysis was performed by a feature-tracking algorithm, and the borders of LA were manually delineated, excluding pulmonary veins, and then the curve of strain and strain rate changing with cardiac cycle were generated automatically by CMR-FTmodule of CVI 4.2 . All conLGE cardiac MRI is best used to detect replacement fibrosis  . The loct test was performed for comparisons of two groups and Chi2 and Fischer’s exact tests for proportions. One-way analysis of variance (ANOVA) with Bonferroni test was used for comparisons of multiple groups. Non-normally distributed variables were compared using the Mann–Whitney U test (comparisons of two groups) or Kruskal–Wallis H test (comparisons of multiple groups).Statistical analyses were performed by SPSS software . Continuous variables were first tested for normality using Shapiro–Wilk’s test. Data are presented as percentage, means ± standard deviation (SD) or median , as appropriate. For normally distributed variables, Student’s Intra- and inter-observer agreements of LA strain and strain rate were evaluated by intraclass correlation coefficient (ICC) and mean differences. Intraclass correlation coefficients (ICC) were assessed to evaluate intra- and inter-observer reproducibility as follows: ICC > 0.75: excellent; ICC = 0.60~0.74: good; ICC = 0.40~0.59: fair and ICC < 0.4: poor .Pearson’s correlation analyses were used for continuous variables after verification of normality. The correlation coefficient, r, was interpreted as follows: 0.00 to 0.10: negligible correlation; 0.10 to 0.39: weak correlation; 0.40 to 0.69: moderate correlation: 0.70 to 0.90: good correlation and 0.90 to 1: strong correlation . Multivap value < 0.05 was considered statistically significant.All tests were two-tailed and a n = 42, 51%) or non-anterior MI  groups based on the location of LGE on post-contrast imaging. Controls were 47 gender-matched asymptomatic healthy participants with a similar age range . There was no significant difference in gender, BMI or BSA among the three groups (p > 0.05). No difference in N-terminal pro-B-type natriuretic peptide (NT-proBNP) between anterior MI and non-anterior MI patients was detected (p > 0.05). Demographic and clinical characteristics of participants are shown in A total of 82 patients with previous myocardial infarction, consisting of 73 males (89%) and 9 females (11%) with mean age of 60 ± 10 years (range:32–80), were enrolled. Patients were assigned to anterior MI (p < 0.001) and LVESVI, LVSVI and LVMI were increased . LVEDVI was elevated in anterior MI patients relative to controls  but no difference was found for non-anterior MI patients. Infarct size and transmurality were both significantly increased in the anterior MI group compared with the non-anterior MI group .LVEF, Mitral annular plane systolic excursion (MAPSE)-inferior and MAPSE-anterior were significantly decreased in the anterior MI and non-anterior MI groups compared with controls . However, after adjusting MI size, there were no differences in LAVImax, LAVIpre-a and LAVImin between anterior MI and non-anterior MI patients . However, impairments of only LA strain and strain rate  were found in the non-anterior MI group with LATEF, LAPEF and LAAEF being well preserved. After adjusting MI size, there were no differences in LA functions between anterior MI and non-anterior MI patients , conduit function  and booster pump function  were found in anterior MI patients , LA conduit function  and booster pump function , between εe and LAPEF  and between εa and LAAEF  were all moderate  After adjusting the area of MI, there was no significant difference in the LA morphology and function between the anterior and non-anterior wall groups. These indicated that the location of myocardial infarction is not a major factor affecting the morphology and function of the left atrium. Patients with MI size > 15% experienced more pronounced post-infarction LA remodeling and dysfunction than patients with MI size ≤ 15%. (2) Furthermore, LA booster pump function was impaired, which may represent late stage left ventricular dysfunction and heart failure in the left atrium. LVSVI, εs and MI size were significantly associated with LA contractile function itself in post-MI patients.The repair of myocardial infarction can be divided into three intersecting periods: inflammation, proliferation and maturation. The degree of post-myocardial infarction LV remodeling depends on infarct size and quality of repair . An incrIn terms of LA function, the reservoir and conduit functions contribute the most during early diastole while the booster pump function is the basis for LV filling during late diastole . TherefoIn terms of LA volume, left atrial size has been considered a biomarker of cardiovascular disease and a risk factor for heart failure, atrial fibrillation, myocardial infarction, stroke and sudden death . The curFurthermore, LA strain and strain rate were analyzed from 2- and 4-chamber cine images, including εs, εe, εa and their corresponding strain rates . These parameters have been employed and validated in previous LA CMR-FT studies ,34. The We acknowledge several limitations to the current study. Firstly, this is a retrospective single-center study with a relatively small number of patients. Strict inclusion and exclusion criteria were necessary to minimize the effect of confounding factors on LA function, which limited the sample size. Secondly, CMR-FT faces several challenges due to the variable anatomical shape of the left atrium, and differences in strain measurements caused by different CMR-FT models cannot be excluded. Standardization of postprocessing methods would be desirable to facilitate comparative analysis of LA deformation and reduce inter-model variability. Thirdly, little data relating to the impact of changes in LA function on cardiovascular events and long-term survival were available, and a substantial follow-up period would allow further validation of the predictive value of LA function in patients with previous MI.During the recovery period from myocardial infarction after PCI, the location of myocardial infarction is not a major factor affecting the morphology and function of the left atrium. Detected by CMR-FT-derived LA parameters, patients with MI size >15% experience more pronounced post-infarction LA remodeling and dysfunction than MI size ≤15% patients.


Skopi software package provides tools to generate realistic simulations of coherent X-ray diffractive imaging of noncrystalline biological samples, which in turn will aid algorithm development for a range of experiments at X-ray free-electron laser sources.The  Skopi is a simulation package that can generate single-hit diffraction images for reconstruction algorithms, multi-hit diffraction images of aggregated particles for training machine learning classifiers using labeled data, diffraction images of randomly distributed particles for fluctuation X-ray scattering algorithms, and diffraction images of reference and target particles for holographic reconstruction algorithms. Skopi is a resource to aid feasibility studies and advance the development of algorithms for noncrystalline experiments at XFEL facilities.X-ray free-electron lasers (XFELs) have the ability to produce ultra-bright femtosecond X-ray pulses for coherent diffraction imaging of biomolecules. While the development of methods and algorithms for macromolecular crystallography is now mature, XFEL experiments involving aerosolized or solvated biomolecular samples offer new challenges in terms of both experimental design and data processing.  Although unsuitable for certain types of dynamics like side-chain flips and local unfolding, normal modes analysis offers a general way of modeling large-scale collective motions Fig. S1. Noise can be added by modeling spatial variation of the fluence in the plane of the beam to follow a Gaussian profile and by introducing jitter, in which shot-to-shot changes in total fluence are Gaussian distributed.The beam object contains information about the beam’s dimensions, fluence and wavelength spectrum. The simplest case models a single monochromatic spike with spatially uniform fluence. A more advanced option accounts for self-amplified spontaneous emission (SASE), which produces ultra-bright pulses but broadens the beam’s energy spectrum (Geloni a)Fig. S4Fig. S4Fig. S5Fig. S5Fig. S5]. For each shot, the particle or set of particles is randomly displaced and oriented in the volume intersected by the sample-delivery jet and beam, and the coherent diffraction pattern is computed [Fig. 2b)]. The incorporation of random displacements accounts for the variable distance between the particles and detector that can result from aerosol injection. To facilitate incremental testing of reconstruction algorithms, either the ideal intensities or quantized photons can be saved, in addition to the number of particles, particle orientations and particle positions at each shot. Beyond Poisson error, the additional sources of noise described above can be defined in configuring the experiment and individually tuned to achieve the desired signal-to-noise ratio  acceleration and parallelization using a message passing interface (MPI). For a reciprocal-space grid of fixed dimensions, the diffraction calculation is performed by direct summation over each atom’s contribution to the intensity and thus scales linearly with the number of atoms in the particle. Consequently, the full 3D diffraction volume for each particle is computed when an experiment is first configured and thus represents a one-time cost. Diffraction images are then efficiently calculated by slicing through this pre-computed volume at a rate independent of the number of atoms . The resolution of this volume is determined by the detector distance and the X-ray wavelength, while its default dimensions are sufficiently large that interpolation error during slicing is negligible. The disadvantage of this approach is the inability to account for the stochastic effects of radiation damage during each interaction between the sample and beam . We then validated Skopi by recovering the protein structure from simulated diffraction images of a chaperonin (PDB 3iyf). SPI data sets consisting of 5000 images each were generated in the absence or presence of Poisson noise on a PnCCD detector positioned for a resolution limit of 14 Å at the edge of the detector. On average, the noisy data sets featured 0.0076 photons per pixel at the edge. The theoretical number of snapshots required for reconstructing a 70 Å particle at 14 Å resolution at this signal level is 3380  algorithm  at https://pypi.org/project/skopi/. The version referenced in this work is 0.5.1. More information about installation can be found at https://github.com/chuckie82/skopi/blob/main/docs/installation.md and additional example usage scripts at https://github.com/chuckie82/skopi/tree/main/examples/scripts.10.1107/S1600576722005994/yr5084sup1.pdfAdditional figures. DOI:


In such instances, it can be challenging to remove the LAAC device. Here, we present two cases in which patients with atrial fibrillation experienced LAAC device exposure at an inappropriate site because of interventional operator error and device mismatch: (a) the LAAC device was dislodged into the aortic arch and retrieved percutaneously from the femoral artery route, and (b) in the left atrium, which was dislodged into the left atrium and retrieved  We also analyzed the possible treatment strategies following a review of the available literature.Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Patients with AF are at high risk of ischemic stroke and require long-term or even life-long anticoagulation therapy. The left atrial appendage (LAA) is the site most prone to thrombosis in patients with AF. LAA occluders are not only an alternative method of anticoagulation therapy, but also a contraindication for oral anticoagulation, and several occluders, including those made in China, have been used in clinical practice . The devCase 1 involved a 69-year-old male patient with a history of persistent AF, hypertension, diabetes, cerebral embolism, and transient ischemic attack for > 10 years. The patient had a history of taking warfarin but had self-discontinued the medication. Transthoracic echocardiography revealed the following findings: left atrium (LA), 44 mm; left ventricle (LV) end-systole, 46 mm; LV end-diastolic, 55 mm; LV ejection fraction, 58%; mitral calcification with minimal regurgitation; and minimal aortic regurgitation. Both the CHA2DS2-VASc and HAS-BLED scores were 6 points. LA computed tomography angiography (CTA) excluded LA thrombus. The patient underwent a combination of catheter ablation and LAAC in a single procedure. Transesophageal echocardiography (TEE) measured an LAA ostial of 25–30 mm and an effective depth of 28 mm , or 27-Fr sheath used for wireless pacemaker . The capture devices include the gooseneck snare, Ensnare , a self-made capture device, or Raptor grasping device. It should be noted that the iatrogenic patent foramen ovale was caused by percutaneous retrieval of the occluder through the fossa ovalis.via a femoral artery or femoral vein route, respectively. The causes, characteristics, and removal methods of the LAA occluder were summarized by combining our cases with those reported previously.In conclusion, we herein reported two case studies of LAA occluder detachment where the occluder dislodged and drifted in the aortic arch in one case and the LA in the other. Both occluders were successfully retrieved The original contributions presented in this study are included in the article/The studies involving human participants were reviewed and approved by the China Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.ZZ participated in research design and data acquisition and analysis. SH, SW, JZ, and ZZ participated in the writing of the manuscript. JZ, LZ, and ZN participated in the performance of the research. All authors have read and approved the manuscript.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.


Analysis of the R‐R interval coefficient of variation (CVR‐R) is a noninvasive method to measure parasympathetic activity. We aimed to assess autonomic dysfunction of ATTRwt and determine the utility of CVR‐R for the detection of ATTRwt in other cardiac diseases.An autonomic nervous disorder is an important characteristic of cardiac amyloidosis; however, the prevalence of autonomic dysfunction in wild‐type transthyretin amyloidosis , n = 20; and left ventricular hypertrophy (LVH) due to other disease processes , n = 20. We measured the CVR‐R at rest (CVR‐Rrest), CVR‐R with deep breaths (CVR‐Rbreath), and the change rate (CVR‐Rdiff rate). The relative change formula is as follows: CVR‐Rdiff rate = (CVR‐Rbreath − CVR‐Rrest)/CVR‐Rrest× 100 (%).This is a single‐center, retrospective, case‐control study. Fifty patients with heart failure (HF) were studied. The etiologies of HF were as follows: ATTRrest levels among the three groups. The CVR‐Rdiff rate levels in the ATTRwt group were significantly lower . Based on the receiver operative characteristic curve analysis to identify ATTRwt in HF, the best cut‐off value for the CVR‐Rdiff rate was 19.7 (area under the curve: 0.848).There was no difference in the CVR‐Rwt. Measurement of the CVR‐R in HF patients may be a convenient support tool for the detection of ATTRwt.Our data suggested autonomic dysfunction in patients with ATTR The major findings of CA are left ventricular hypertrophy (LVH) and a cardiac conduction disorder. An autonomic nervous system disorder is one of the important features.v and AL amyloidosis. Reduction of the standard deviation of beat‐to‐beat or NN intervals (SDNN) ≤ 50 ms is a strong predictor of 1‐year mortality in patients with AL amyloidosiswt has not been established. The coefficient of variation in R‐R intervals (CVR‐R) is a measure of HRV that mainly reflects the parasympathetic nervous system. The aims of this study were: (1) to assess autonomic dysfunction of ATTRwt using the CVR‐R and (2) to determine the utility of the CVR‐R for detecting ATTRwt in patients with other cardiac conditions of LVH or myocardial infarction.Cardiac amyloidosis (CA) is a progressive disease caused by myocardial deposition of amyloid fibrils.2wt (70–90 years of age) attending to our hospital between April 2019 and March 2021. ATTRwt was diagnosed by endomyocardial biopsy and/or 99mTc‐PYP scintigraphy. Amyloid deposition was identified by Congo red staining in combination with polarization microscopy and classified by immunohistochemistry. The presence of global transmural or subendocardial late gadolinium enhancement on cardiac magnetic resonance added support to the diagnosis of ATTRwt. As a comparison with ATTRwt group, we subsequently enrolled the consecutive HF patients (70–90 years of age) with LVH or previous myocardial infarction (MI), who underwent CVR‐R test during the same period. These patients were assessed using New York Heart Association (NYHA) classification. The LVH group included patients with hypertrophic cardiomyopathy (HCM), aortic stenosis, and hypertensive heart disease. The clinical diagnosis of HCM was made based on echocardiographic demonstration of LVH with an end‐diastolic wall thickness ≥15 mm in more than 1 segment in the absence of any disease which causes LVH. A history of MI was confirmed with the patient's medical record. The HF subtypes were defined according to European Society of Cardiology guidelines: HF with preserved ejection fraction as LVEF ≥ 50%, HF with midrange ejection fraction as 40%–49%, and HF with reduced ejection fraction as LVEF < 40%.This is a single‐center, retrospective, case‐control study. First, we enrolled the consecutive patients with ATTRv, and a history of a MI that occurred 1 year before enrollment. In the absence of a genetic diagnosis, ATTRv was ruled out based on the family medical history. A small number of registrations was expected because of the rarity of the disease, strict eligibility criteria, and the single‐center study. Study sample size was referenced from previous studies.Patients with arrhythmias  were excluded. We also excluded patients with NYHA classification IV, AL amyloidosis, AA amyloidosis, ATTRBlood samples were collected from patients who were clinically stable. Serum cardiac troponin I and plasma brain natriuretic peptide (BNP) levels were measured in all patients. The chronic kidney disease (CKD) stage was based on the estimated glomerular filtration rate (e‐GFR), which was calculated using the Modification of Diet in Renal Disease (MDRD) equation. Anemia was defined as a hemoglobin level < 13.0 g/dl in men and <11.5 g/dl in women. Hypertension, dyslipidemia and diabetes mellitus were diagnosed according to their guidelines, respectively.Echocardiographic parameters included chamber size, wall thickness, left ventricular ejection fraction (LVEF), and left ventricular mass. LVEF was calculated using Simpson's method. The peak early and late diastolic velocity of left ventricular inflow  and the deceleration time of the E wave were determined. The peak diastolic velocity on the septal and lateral corner of the mitral annules was measured in the apical four‐chamber view and the E/e’ ratio was calculated. The left ventricular mass index (LVMI) was calculated based on the following formula: {0.8 × (1.04[(LVDd + PWT + IVST)3 – (LVDd)3]) + 0.6}/body surface area, where LVDd = left ventricular end‐diastolic dimension, IVSTd = interventricular septal thickness at end‐diastole, and PWTd = posterior wall thickness at end‐diastole. The relative apical sparing and right ventricular (RV) free wall thickness were evaluated.× 100(%). In healthy persons, CVR‐R values are higher during deep breaths than at rest. The CVR‐R values in normal control subjects were not examined in this study. According to the previous reports, the CVR‐R values in normal elderly subjects were about 2.0%–3.0%.rest) and the CVR‐R with deep breathing (CVR‐Rbreath), the difference rate (CVR‐Rdiff rate) was calculated using the following formula: CVR‐Rdiff rate = (CVR‐Rbreath – CVR‐Rrest)/CVR‐Rrest × 100 (%).After at least 5 min at rest, a standard 12‐lead ECG was recorded in the spine position , and the R‐R interval was analyzed for 1 min. Drugs with anticholinergic effects were discontinued before testing. Following measurement of the R‐R interval with normal breathing, the R‐R interval with deep breaths at a rate of six times/min was analyzed. Based on the mean R‐R interval (mRR) and the R‐R standard deviation (RR‐SD), the CVR‐R was calculated as follows: RR‐SD/mRR χ² or Fisher's exact test. After the Bonferroni correction for multiple comparisons, a p‐value < 0.05 was considered significant in all statistical analyses. Receiver‐operating characteristic (ROC) curve analysis was performed to identify CA in HF patients and to calculate sensitivity, specificity, area under the ROC curve (AUC), and the optimal cut‐off value. Cardiac troponin is a sensitive marker of CA.diff rate were compared using DeLong's method. All statistical analyses were carried out with the EZR on R‐commander , which is a graphical user interface for R .Continuous data are summarized by the mean ± SD or median (interquartile range) if the distribution was skewed. Categorical data are reported as numbers and percentages. Multiple group comparisons of continuous data were performed with one‐way analysis of variance (ANOVA) or the Kruskal–Wallis test. Categorical variables are presented as percentages and compared with a http://www.amed.jp/mc/index.php) and gave patients the opportunity to withdraw from the study.All procedures were performed in accordance with the Declaration of Helsinki and its amendments. The study protocol was approved by the Institutional Review Board of the Amakusa Medical Center . The requirement for informed consent was waived because of the low‐risk nature of this retrospective study. We announced this study protocol at the Amakusa Medical Center and on our website . The clinical characteristics of the patients are shown in Table wt group. Based on the echocardiography findings, the left ventricular mass index, and mitral E/A and E/e’ were significantly higher in the ATTRwt group; however, the E wave deceleration time was significantly lower in the ATTRwt group. Apical sparing and right ventricular hypertrophy were also observed in the ATTRwt group. The prevalence of beta blocker prescription was lower in the ATTRwt group, although the difference was not significant. The use of ACE/ARB was most frequent in the MI group.Forty‐two patients were diagnosed as having CA between April 2019 and March 2021, and consecutive 10 patients with ATTRrest levels among the three groups. In the LVH and MI groups, the CVR‐Rbreath was higher than the CVR‐Rrest; this change was not observed in the ATTRwt group. The CVRRdiff rate levels in the ATTRwt group were significantly lower than those in the other two groups . Furthermore, at this cut‐off value the sensitivity and specificity for predicting ATTRwt were 97.5% and 80%, respectively. There were no statistically differences in the AUC values between CVR‐Rdiff rate and troponin I. Analysis of interplay between CVR‐R values and MRI could not be performed due to the small number. There was no significant correlation between CVR‐R and LVMI (data not shown).There was no difference in the CVR‐Rwt. Electrocardiogram findings  and elevation of high‐sensitive troponin I (162.52 pg/ml) were compatible with ATTRwt. Based on echocardiographic data, LVEF, LVMI, E/A, and E wave deceleration time were 37%, 124.5 g/m2, 1.53 and 180 ms, respectively; however, apical sparing and RV free wall thickness were not observed. The R‐R histogram showed poor fluctuation of R–R intervals under deep breathing . The quantitative value of myocardial‐to‐contralateral lung uptake ratio at 3 h was 1.175  were excluded due to difficulties in interpreting their data. Our study sample size was too small for multivariate analysis. The combination of elevation of high‐sensitivity cardiac troponin T, left ventricular posterior wall thickness, and wide QRS has been reported to raise the pretest probability of wt makes it difficult to investigate the association CVR‐R values with the stage of ATTRwt.The association cardiac amyloid load with CVR‐R values was not evaluated because some patients were diagnosed with endomyocardial biopsy, only. The progression of cardiac amyloid load can affect CVR‐R values as well as echocardiographic findings.wt and non‐ATTRwt groups. Genetic testing for ATTRv was not performed for all patients. Finally, late‐onset ATTRv is a possibility that we considered.CVR‐R values can be influenced by etiologies of LVH. HCM has been reported to affect autonomic function.5wt. Treatment options for ATTRwt are expanding rapidly. Early ATTRwt diagnosis is necessary for treatment optimization. Measurement of the CVR‐R in HF patients may be a convenient support tool for the detection of ATTRwt.In this study, decreased CVR‐R levels under deep breathing are highly suggestive of ATTRYasuhiro Nagayoshi: Conceptualization; data curation; formal analysis; investigation; methodology; project administration; writing – original draft; writing – review and editing. Hiroaki Kawano: Conceptualization; supervision; writing – original draft; writing – review and editing. Taiki Nishihara: Investigation. Kei Morikawa: Investigation. Haruka Nagano: Investigation. Shinsuke Hanatani: Investigation. Naritsugu Sakaino: Investigation. Kenichi Tsujita: Supervision.The authors declare no conflict of interest.All procedures were performed in accordance with the Declaration of Helsinki and its amendments. The study protocol was approved by the Institutional Review Board of the Amakusa Medical Center .The lead author Yasuhiro Nagayoshi affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.


This study aimed to investigate the diagnostic performance of non-invasive resting myocardial deformation indices in identifying functional significance of intermediate stenosis of the left anterior descending (LAD) artery. Patients with 50–70% LAD stenosis upon coronary angiography were enrolled and divided into group I with fractional flow reserve (FFR) > 0.8 and group II with FFR ≤ 0.8. Patients were subjected to conventional and speckle tracking echocardiography with measurement of myocardial deformation indices including regional peak longitudinal strain (PLS), global longitudinal strain (GLS), Post-systolic strain index (PSI), and time interval between Aortic valve closure (AVC) and PLS. The current study included 200 patients. Group II patients had significantly lower absolute mean values of regional (PLS) and (GLS) compared to group I . The FFR values of LAD correlated significantly and negatively with the time interval between AVC and regional PLS  as well as PSI . For identifying cases with FFR ≤ 0.8, the optimal cut-off value of the time interval between AVC and PLS was 76 ms with 77.8% sensitivity and 93.8% specificity. The best cut-off value of PSI was 13%, yielding 50% sensitivity and 87.5% specificity. In patients with intermediate 50–70% LAD coronary artery stenotic lesions, the PSI and the duration between AVC and regional PLS enabled the identification of functionally significant lesions with reasonable diagnostic accuracy.Trial registration ZU-IRB#3199-20-11-2015 Registered 20 November 2015, IRB_123@medicine.zu.edu.eg. Coronary angiography has been considered as a standard for assessment of coronary artery stenosis inspite of having few restrictions particularly in assessment of functional significance of intermediate stenotic lesions . The accCurrently, the gold standard for diagnosing hemodynamically significant intermediate stenoses in CAD patients is the fractional flow reserve (FFR). An FFR equals or less than 0.80 is used as a cut-off for identifying significant stenosis that will benefit if treated by revascularization. –6.The new non-invasive measurement of myocardial deformation using speckle tracking echocardiography (STE) provides an objective reproducible evaluation of regional systolic left ventricular function and hence detection of myocardial ischemia .Longitudinal strain (LS) as a myocardial deformation parameter was found to predict subtle concealed ischemia in asymptomatic patient even in absence of regional wall motion abnormalities . MoreoveTherefore, this study was conducted to explore the clinical application of non-invasive resting myocardial deformation indices  in predicting the functional severity of intermediate left anterior descending (LAD) coronary artery stenosis.The current study protocol has been evaluated and approved by our university's Institutional Review Board (IRB). The IRB guaranteed that all methods were carried out in conformity with the 1975 Declaration of Helsinki's ethical norms for human research. Informed written consent was obtained from all participants.This cross-sectional study was conducted at cardiology department of our university between June, 2016 and May, 2021.https://www.medcalc.org; 2015). Assuming an area under the receiver operating characteristic curve (AUC) of at least 0.7, type I error of 0.01, 90% power of the test, and a ratio of cases with FFR > 0.8 to FFR ≤ 0.8 of 2.5 based on the prevalence of 29% of FFR ≤ 0.8 that was reported by Hoole et al.  − [end-systolic strain])/(maximum strain change during the cardiac cycle) × 100. The greatest (least absolute) value in the analyzed LAD distribution segment was adopted as a representative value for LAD .The duration between AVC and regional PLS was calculated manually as follows: [the time between regional PLS and R-wave on ECG]—[the time between AVC and R-wave on ECG] .The Statistical Package for Social Sciences (IBM SPSS Statistics) for Windows, version 26 was used to analyze the data . The distribution of continuous numerical data was assessed using the Shapiro–Wilk test for normality. Variables which were distributed normally and summarized as mean and standard deviation SD. The correlations between two numerical variables were assessed using Pearson's correlation  and group comparisons were done using the unpaired student t-test. Frequencies and percentages were used to summarize categorical variables. Pearson's Chi-square and Fisher's exact tests were used to examine the relationships between the groups. The diagnostic performance of the researched indices was evaluated using a Receiver Operating Characteristic (ROC) curve analysis. The AUC was used to measure the indices' discriminating strength . To illustrate statistical significance, a p-value of less than 0.05 was used.The current study included 200 patients who had functionally suspicious intermediate LAD stenosis (50–70%) by coronary angiography. The patients were divided into two groups according to their FFR values. Group I included 117 patients with functionally non-significant LAD lesions (FFR > 0.8), while group II included 83 patients with functionally significant LAD lesions (FFR ≤ 0.8). While patients with significant stenosis in vessels other than LAD were excluded from our study, non-significant stenotic lesions in vessels other than LAD was documented in 57 (48.7%) cases in group I, 35 (42.2%) cases in group II with no statistical difference between the two groups .The baseline characteristics were comparable between the two groups Table . As regaTable As regard The Post systolic strain index (PSI), it was 9.93 ± 6.4 in group I vs 13.08 ± 6.78 in group II, with statistically significant difference between the studied groups (P = 0.001). While, duration between AVC & regional PLS was 50.97 ± 28.14 in group I, 53.05 ± 28.43 in group II, with statistically significant difference between the studied groups (P = 0.02).We found a significant negative correlation between the value of LAD FFR and each of the time interval between AVC and regional PLS on admission  and the best-detected cut-off value was 76 ms, with 77.8% sensitivity and 93.8% specificity (Fig. Assessment of the functional significance of intermediate coronary lesions is challenging; however, it is crucial for clinical decision-making. Invasive FFR was considered the gold standard to differentiate between functionally significant and non-significant lesions using a cut-off value of 0.8 , 16–18.The resting TTE is a rapid, non-invasive test compared to the gold standard FFR which is an invasive procedure that requires a hospital stay and carries a risk of radiation and contrast exposure , 20. TheFew studies investigated the relationship between the functional significance of intermediate LAD coronary stenosis measured by invasive FFR in stable CAD patients and the regional LS. Therefore, the present study aimed to assess the diagnostic accuracy of resting myocardial deformation indices in detecting the functional significance of intermediate LAD coronary artery lesions. To the best of the authors’ knowledge, this is the first study with an adequate sample size to investigate the correlation between FFR values and PSS parameters including PSI and the duration between AVC and regional PLS obtained from the territory of LV segments supplied by LAD coronary artery.In the current study, the resting conventional TEE parameters revealed no significant differences between the studied groups. On the contrary, the regional PLS and GLS showed significantly lower absolute values in patients with FFR ≤ 0.8 than those with FFR values > 0.8. This finding supports the hypothesis that myocardial strain is a more sensitive alternative to standard echocardiographic parameters, which are not always sensitive enough to detect subtle changes in myocardial function . Also, sThese findings are supported by the results of previous studies. Gaibazzi et al.  investigDobrowolski et al.  evaluateNishi et al.  examinedXing and colleagues  used twoThe present study also investigated the PSI and the duration between AVC and PLS as parameters for the assessment of PSS. The PSS was proposed as an ischemia marker and was linked to a degree of coronary flow reduction. The PSS was also found to be negatively correlated with measures of LV systolic function in ischemic areas . The ROCThe diagnostic utility of PSS measures to detect the ischemic segments supplied by stenotic LAD lesions with an FFR value ≤ 0. 8 was evaluated in a prior study by Ozawa et al. . The resOur findings indicate that the thresholds of PSI as well as the duration between AVC and regional PLS, as measures of PSS, can help the detection of LV myocardial ischemic segments in functionally significant intermediate LAD lesions.Moreover, the cut-off points for the detection of the myocardial ischemic segments can be used as adjunctive to the standard diagnostic tools to differentiate functionally significant from non-functionally significant intermediate LAD lesions in patients with stable CAD.Although this study was powered to test the diagnostic performance of the tested measures using ROC curve analysis, the results may be limited by non-testing of the agreement between the echocardiographic operators. In addition, stress echocardiography was not performed in the current study. Further studies need to be conducted using stress echocardiography to reveal the effect of exercise or medications on the same parameters for the detection of ischemic segments confirmed by FFR.The current study was single centered. Although this study was powered to test the diagnostic performance of the tested measures using ROC curve analysis, the results may be limited by non-testing of the agreement between the echocardiographic operators. In addition, stress echocardiography was not performed in the current study, using stress echocardiography may reveal the effect of exercise or medications on the same parameters for the detection of ischemic segments confirmed by FFR.Resting myocardial deformation indices including regional PLS and GLS can be used as non-invasive tool to aid in assessment of intermediate coronary artery stenosis. Also, using the appropriate cut-off values of PSI and duration between AVC and regional PLS can identify functionally significant LAD stenotic lesions.In patients with stable CAD having 50–70% LAD coronary artery stenotic lesions, the 2-D speckle tracking regional PLS and GLS had significant correlations with FFR values. The PSS measures, including PSI and the duration between AVC and regional PLS, enabled the identification of segments with FFR values ≤ 0. 8 using the appropriate threshold with reasonable diagnostic accuracy.Future studies can test significance of measures on larger cohort. As well as, further studies can be conducted using stress echocardiography to reveal the effect of exercise or medications on the same parameters for the detection of ischemic segments confirmed by FFR.


The therapeutic application of carnosine in myocardial tissue is promising, with carnosine playing a potentially beneficial role in both healthy and diseased myocardial models. This narrative review discusses the role of carnosine in myocardial function and health, including an overview of the metabolic pathway of carnosine in the myocardial tissue, the roles carnosine may play in the myocardium, and a critical analysis of the literature, focusing on the effect of exogenous carnosine and its precursors on myocardial function. By so doing, we aim to identify current gaps in the literature, thereby identifying considerations for future research.Carnosine is a pleiotropic histidine-containing dipeptide synthesized from β-alanine and  Statement of Significance: Carnosine could perform important, yet different, roles within healthy and/or diseased hearts. Findings suggest that carnosine could improve calcium handling and, therefore, muscle contractility in a healthy model and oxidative stress, myocardial injury markers, and morphological and histological parameters in a diseased model. The translation of these findings into humans is, however, lacking, and considerable future work is required in this regard to determine whether carnosine has therapeutic potential. AlthougAs mentioned previously, β-alanine is produced in the liver through the degradation of uracil and released into the bloodstream . The demCarnosine is degraded into its constituent amino acids by two isoforms of carnosinase: CN1 and CN2. CN1 is primarily expressed in human plasma with high specificity for carnosine and homocarnosine, whereas CN2, known initially as tissue carnosinase, has a broad substrate specificity and is ubiquitously expressed throughout central and peripheral human tissues . CN1 is Alanine-glyoxylate aminotransferase 2  and 4-aminobutyrate-2-oxoglutarate transaminase  have been reported to be responsible for catalyzing the degradation of excess exogenous β-alanine into keto-acid malonate semi-aldehyde (MSA). MSA may be converted into acetyl-coenzyme A and subsequently enter the citric acid cycle , althougProton-coupled amino acid transporter (PAT1) and sodium and chloride-dependent taurine transporter (TauT) are likely to facilitate β-alanine transportation, and the proton-coupled oligopeptide transporter family (peptide transporter 1 (PEPT1), peptide transporter 2 (PEPT2), peptide-histidine transporter 1 (PHT1) and peptide-histidine transporter 2 (PHT2); collectively known as the solute carrier family 15) are responsible for nonspecific cellular transportation of peptides . The degThe proposed physiological roles of carnosine include intramuscular pH buffer, the regulation of intramuscular calcium handling and improved contractile apparatus sensitivity to calcium, improvements in histopathological and hemodynamic parameters, the quenching of ROS, metal ion chelation, and protection against lipid peroxidation and AGEs  Figure ]. The fiCARNS1-knockout (–/–CARNS1) rats, the absence of endogenous HCDs (such as carnosine) did not impair mitochondrial function or oxygen consumption and hydrogen peroxide release was not different between the –/–CARNS1 rats and wild-type controls  resulted in reduced lactate content and increased oxygen consumption  on myocardial function. In isolated cardiomyocytes, the lack of carnosine and HCDs reduced sarcomere's maximal shortening, re-lengthening, and velocity measurements, affecting the overall contractility of the cardiomyocytes. These results, alongside impairments shown in in vivo functional data , indicate that the absence of carnosine in these animals could result in impairments to calcium handling. In addition, decreased calcium amplitude was shown, although there was no change in calcium release or sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) expression. The study showed increased isovolumetric contraction time and reduced left ventricular ejection fraction and shortening fraction in –/–CARNS1 rats, indicating an impairment in systolic function, whereby the left ventricle has difficulty pumping blood out of the heart, increasing the volume of blood remaining in the ventricle at the end of the contraction. Despite this, cardiac output was unaffected, suggesting that the heart might be able to compensate. –/–CARNS1 rats display a reduced e′ wave and an increased E:e′ ratio, suggesting left ventricular relaxation impairments and a diminished diastolic function. This indicates that endogenous HCDs  are essential for myocardial calcium handling and contractility under healthy conditions , given that the myocardium was unable to function as well in these rats when compared with wild-type controls.Carnosine has been suggested to influence intracellular calcium concentrations and myocardial contractility. Gonçalves et al.  recentlyl-histidine  attenuated detrimental ECG changes in rats exposed to adriamycin , preventing the metal ions from contributing to the production of free radicals through the Fenton reaction, and thus reducing oxidative stress ; non-histidine-containing amino acids had limited interaction with the aldehydes  were shown in the left ventricular myocardial tissue of hypertensive rats compared with normotensive rats . This maThere are contradictory findings regarding the vasodilatory properties of exogenous carnosine. The dose-dependent, vasodilatory effect of exogenous carnosine was demonstrated on isolated rat aortic rings . CarnosiA summary of the literature investigating the effect of carnosine and β-alanine supplementation on myocardial injury markers and morphological and histological characteristics are displayed in l-histidine, is absent in non-primate mammals . Many of the studies in the literature have exposed animal myocardial tissue to either a healthy or diseased environment. The cumulative findings from these studies indicate that carnosine improves calcium handling and, therefore, muscle contractility in a healthy model and improves oxidative stress, myocardial injury markers, and morphological and histological parameters in a diseased model. Future research should include supplementation protocols in both healthy and diseased myocardial models to determine the specific roles of carnosine in both of these conditions.β-alanine supplementation is commonly used to increase myocardial carnosine concentrations; however, it could also be implemented to potentially decrease myocardial taurine concentration. A concentration of >3% β-alanine supplementation has been suggested to be required to reduce myocardial taurine concentration . There il-carnosine supplementation in patients with stable chronic heart failure and impaired left ventricular function. The participants were supplemented with 500 mg/d l-carnosine in an open-label approach. The control group received their regular, routine treatment. l-carnosine improved quality of life and exercise capacity, but no improvements were shown in myocardial function measurements. The authors suggested that the buffering effect of l-carnosine improved exercise capacity, although this was not directly measured. The potential underlying mechanisms that might support a role for carnosine in the myocardium were not measured. The supplementation protocol contains several limitations. The lack of blinding and placebo supplement in the control group means that the study is at a high risk of bias. Participants were supplemented with intact l-carnosine, which has low bioavailability and stability in circulation due to the presence of CN1 and, in turn, will limit the uptake of carnosine into myocardial tissue. In addition, it is uncertain, and highly unlikely, that carnosine can be directly taken up intact by the myocardium. Intact carnosine is likely to be hydrolyzed into β-alanine and l-histidine, with these constituent amino acids being taken up into the tissue and re-synthesized to carnosine. An appropriate supplementation dose would be required to ensure adequate metabolite is available to the myocardium. Harris et al. (l-carnosine (13 g/d) is required to be able to obtain a similar increase in skeletal muscle carnosine content to that shown with 6.4 g/d of β-alanine. This suggests that the level of substrate available to the myocardium from a dose of 500 mg of l-carnosine may not be sufficient to have an overall effect on myocardial function. The recommended daily amount of β-alanine is 3.2 to 6.4 g/d for improvements in exercise capacity and performance . Practical recommendations for β-alanine supplementation cannot yet be given concerning myocardial function and health.


Dynamic obstruction of the left ventricular outflow tract resulting from systolic anterior motion of the mitral valve can be an unexpected cause of acute and severe perioperative hypotension in noncardiac surgery. We report a patient undergoing spinal anesthesia for transurethral resection of the prostate who experienced sudden hypoxemia caused by systolic anterior motion-induced mitral regurgitation but with a clinically picture simulating fluid overload.An 83-year-old man with a history of hypertension was scheduled for transurethral resection of the prostate. One hour after spinal anesthesia, he developed acute restlessness and dyspnea, with pink frothy sputum and progressive hypoxemia. Slight hypertension was noted, and an electrocardiogram showed atrial fibrillation with a rapid ventricular response. Furosemide and nitroglycerin were thus administered for suspected fluid overload or transurethral resection of the prostate syndrome; however, he then became severely hypotensive. After tracheal intubation, intraoperative transesophageal echocardiography was promptly performed, which revealed an empty hypercontractile left ventricle, significant mitral regurgitation and mosaic flow signal in the left ventricular outflow tract. Following aggressive fluid therapy, his hemodynamic changes stabilized. Repeat echocardiography in intensive care unit confirmed the presence of systolic anterior motion of the anterior mitral leaflet obstructing the left ventricular outflow tract. We speculate that pulmonary edema was induced by systolic anterior motion-associated mitral regurgitation and rapid atrial fibrillation, and the initial management had worsened his hypovolemia and provoked left ventricular outflow tract obstruction and hemodynamic instability.Pulmonary edema caused by systolic anterior motion of the mitral valve can be difficult to clinically differentiate from that induced by fluid overload. Therefore, bedside echocardiography is paramount for timely diagnosis and prompt initiation of appropriate therapy in the perioperative care setting.The online version contains supplementary material available at 10.1186/s12871-022-01754-x. Systolic anterior motion (SAM) of the mitral valve is defined as the anterior displacement of a mitral leaflet toward the left ventricular outflow tract (LVOT) during systole, causing LVOT obstruction and mitral regurgitation (MR) . The typAn 83-year-old man  was admitted to our hospital for laser TURP due to recurrent prostate adenoma. Past medical history included hypertension, peptic ulcer bleeding and C6–C7 disc herniation.2 46 mmHg, pO2 83 mmHg, with severe metabolic acidosis, but no hyponatremia. He remained hypotensive and significant ST depression was noted. Thus, a titrated infusion of fluid and dopamine 5 μg/kg/min was initiated on suspicion of acute myocardial infarction. Unfortunately, his hypotension worsened and atrial fibrillation ventricular response rate increased to 160 beats per minute. Bedside TEE was promptly performed, which revealed a small hypercontractile left ventricle (LV), mosaic flow signal in the LVOT and a significant jet of MR  revealed a normal cardiac silhouette and no pulmonary lesions. Electrocardiogram (ECG) showed normal sinus rhythm without left ventricular hypertrophy or left atrial enlargement. Laboratory studies, including blood chemistry and coagulation profile, were within acceptable limits. In the operating room, initial routine monitoring showed sinus rhythm with a heart rate (HR) of 76 beats per minute, blood pressure (BP) of 140/63 mmHg, respiratory rate of 15 per minute, and 94% pulse oxygen saturation on room air. After adequate hydration with intravenous administration of 5% dextrose and 0.45% sodium chloride, spinal anesthesia was achieved with an injection of 0.5% hyperbaric bupivacaine 9.5 mg and fentanyl 15 μg into the subarachnoid space via a 26-gauge spinal needle at the L3/L4 level. Surgery commenced when the sensory block reached the T10 dermatome (assessed by pinprick sensation). With spinal anesthesia, his BP was still relatively stable around at 120/60 mmHg, while his HR gradually increased to 90 beats per minute. One hour after anesthesia, the patient became uncomfortable and restless. His cardiac rhythm changed to atrial fibrillation with a moderate ventricular response of 100 beats per minute. He therefore received intravenous midazolam 0.5 mg and fentanyl 25 μg in an attempt to alleviate his distress, and intravenous digoxin 0.125 mg was administered for rhythm control. However, his condition did not improve, and he became acutely dyspneic with pink frothy secretions. 100% oxygen was administered via the face mask, but his oxygen saturation decreased to 88%, while his BP increased to 145/65 mmHg. Crackles were heard on chest auscultation. The impression at this stage was acute pulmonary edema or TURP syndrome. Therefore, intravenous furosemide 5 mg and sublingual nitroglycerin 0.6 mg were given. However, his systolic BP dropped to 87/50 mmHg, and he became less alert. Surgery was discontinued and general anesthesia was conducted with tracheal intubation. An arterial line was inserted and with a fraction of inspired oxygen at 50%, his arterial blood gas showed pH 7.21, pCOUpon arrival at ICU, CXR showed pulmonary infiltrates, and his serum troponin I level was elevated at 2.338 ng/mL (reference range < 0.1 ng/mL), suggesting mild myocardial injury. After he became hemodynamically stable, a repeat TEE showed mild concentric left ventricular hypertrophy, SAM of the anterior mitral leaflet into the LVOT with subaortic obstruction and resultant severe eccentric dynamic MR on color-flow Doppler mapping  and the assumption of excessive irrigation fluid absorption following TURP. In fact, TEE showed that this patient was hypovolemic, but he developed pulmonary edema from the combination of atrial fibrillation with tachycardia, reduced hypertrophic LV compliance, and MR secondary to SAM. We speculate that spinal anesthesia, which can substantially decrease peripheral vascular resistance and ventricular preload, may have predisposed him to develop SAM, when he became volume depleted. However, our patient’s presentation was not typical of SAM, as he was initially mildly hypertensive, but this may have been an adrenergic response to his dyspnea. The paradoxical clinical features contributed to the initial misconception that his hypoxemia was a result of pulmonary edema from fluid overload during TURP. The administration of furosemide and nitroglycerin, used for treatment of cardiogenic pulmonary edema, likely aggravated the severity of his hypoxemia caused by SAM-induced MR and worsened his hemodynamics.Our case demonstrates that SAM may represent a potential cause of unexpected hypoxia and/or refractory hypotension in patients undergoing spinal anesthesia in the context of hypovolemia and adrenergic stimulation. In the critical care setting, echocardiography may be an important first-line diagnostic approach of SAM as it provides direct visualization of the underlying mechanic pathology, and can help differentiate this from other causes of severe cardiopulmonary events , 12. DiaBedside TEE plays an essential role not only for timely diagnosis of SAM but also in facilitating early treatment of underlying causative factors and thus preventing the development of SAM. The principles of medical therapy for SAM are to increase LV preload and reduce the hypercontractile state , 9. OptiIn conclusion, SAM may result in unexpected perioperative cardiopulmonary deterioration, particularly in the presence of myocardial hypertrophy or in vulnerable situations such as hypovolemia and anesthesia-mediated vasodilatation. Our case highlights that SAM can be easily overlooked and may clinically resemble cardiogenic pulmonary edema when actually in the hypovolemic state, which might lead to incorrect treatment. Prompt echocardiography plays an essential role in making a timely diagnosis and guiding appropriate management.Additional file 1. (intraoperative TEE.mov): Intraoperative transesophageal echocardiography with color-flow Doppler mapping  showed a significant MR jet and mosaic flow signals in the left ventricular outflow tract.Additional file 2. (postoperative TEE in the ICU.mp4): Postoperative transesophageal echocardiography in the intensive care unit  revealed systolic anterior motion of the anterior mitral leaflet into the left ventricular outflow tract.