Purpose of this study is to evaluate the diagnostic accuracy of quantitative T2/ADC values in differentiating between PCa and lesions showing non-specific inflammatory infiltrates and atrophy, features of chronic prostatitis, as the most common histologically proven differential diagnosis.t tests. Receiver operating characteristic curves (ROCs) and cutoff were calculated to differentiate between PCa and chronic prostatitis.In this retrospective, single-center cohort study, we analyzed 55 patients suspected of PCa, who underwent mpMRI (3T) including quantitative T2 maps before robot-assisted mpMRI-TRUS fusion prostate biopsy. All prostate lesions were scored according to PI-RADS v2.1. Regions of interest (ROIs) were annotated in focal lesions and normal prostate tissue. Quantitative mpMRI values from T2 mapping and ADC were compared using two-tailed p < 0.001). PCa showed significantly lower ADC and T2 values than chronic prostatitis (p < 0.001). ROC analysis revealed areas under the receiver operating characteristic curves (AUCs) of 0.85 (95% CI 0.74–0.97) for quantitative ADC values and 0.84 (95% CI 0.73–0.96) for T2 mapping. A significant correlation between ADC and T2 values was observed .Focal lesions showed significantly lower ADC and T2 mapping values than normal prostate tissue (T2 mapping showed high diagnostic accuracy for differentiating between PCa and chronic prostatitis, comparable to the performance of ADC values.The online version contains supplementary material available at 10.1007/s00345-022-03991-8. Prostate cancer (PCa) is the most common non-cutaneous cancer among men with a lifetime risk of up to 37% . MultipaT2w fast spin-echo (FSE) sequences provide images with high spatial resolution of the prostate that allow the depiction of its zonal anatomy . Howevern = 4), (b) technical problems with postprocessing and export of MRI datasets (n = 2) and (c) two patients with elevated PSA levels  were excluded due to a high risk of prostate cancer, which was subsequently also confirmed by biopsy. Eventually, we included 55 patients in our analysis.This retrospective, single-center cohort study was approved by the institutional review board (359/2019BO2). Between January 2015 and March 2018, we enrolled a total of 63 patients meeting the following inclusion criteria (a) suspected for PCa; (b) mpMRI ; (c) PI-RADS v2.1 Score ≥ 3; (d) histopathological reference obtained by RA-TB and (e) available PSA value measured previously to the biopsy. Exclusion criteria were (a) relevant motion artifacts on MRI images .Standard T2w imaging was performed using fast spin-echo sequences. EPI-sequences were used for DWI. Additional to these standard sequences we routinely add a vendor provided prototype model-based accelerated T2 mapping sequence that uses voxel-wise measurements of tissue T2 relaxation time values . DetaileAll included patients underwent prostate biopsy with the iSR’obot Mona Lisa robot unit using the UroBiopsy™ 3D modelling software  with an ultrasound machine  and a multi-frequency ultrasound probe  in lithotomy position . First, To determine the quantitative T2 and ADC values from the lesions that were sampled through targeted biopsy, we defined regions of interest (ROI) in the suspicious solitary, circumscribed lesions previously identified for and histologically proven by the RA-TB. The ROI was annotated voxel-wise for a single slice with maximum extent of the suspicious lesion.Reference ROIs were annotated in the PZ of the prostate on the same slice as the lesion, if it was not suspicious (PI-RADS 1), or in the PZ on a neighboring slice in case of signal alterations (≥ PI-RADS 2).For all ROIs, the mean signal intensity of the ADC and T2 maps were calculated over all included voxels. NORA  was used to read the images and to annotate all ROIs.p < 0.05.Statistical analysis was performed using SPSS 26 . Characteristics and quantitative mpMRI values of subpopulations were compared using two-tailed t-tests. The results are given as mean ± standard deviation. ROC analysis was performed and Youden’s index was used to select the optimum cutoff point. The area under the receiver operating characteristic curve (AUC) and its 95% confidence interval (CI) were calculated. Correlation between mean T2 and mean ADC values was evaluated using Pearson’s correlation. Statistical significance was considered at p = 0.08).We included a total of 55 patients in our study (mean age 63.8 ± 7.4 years). PCa was detected in 29 patients, while the histopathological examination of the other 26 lesions showed non-specific inflammatory infiltrates and atrophy, features of chronic prostatitis (18 of 29 patients with PCa and 14 of 26 patients with prostatitis were biopsy-naive). There was no significant age difference between the two groups (p = 0.07).The mean PSA level of all patients combined was 8.6 ± 3.4 ng/ml. PSA was slightly higher in patients with PCa (9.3 ± 3.3 ng/ml vs. 7.7 ± 3.4 ng/ml). However, this difference was not statistically significant . Within those pathological lesions PCa showed significantly lower values than chronic prostatitis . ROC analysis revealed an AUC of 0.84; CI [0.73–0.96] and a T2 threshold of 84.98 ms (sensitivity 84.6%/specificity 79.3%) for the classification of PCa and chronic prostatitis  in general had significantly lower T2 values than control parenchyma . Within those pathological lesions PCa showed significantly lower values than chronic prostatitis . ROC analysis revealed an AUC of 0.85; CI [0.74–0.97] and a cutoff value of 0.85 × 10–3 mm2/s (sensitivity 84.6% / specificity 89.7%) to differentiate between PCa and chronic prostatitis  had a significantly lower value than the control parenchyma (0.88 ± 0.25 × 10p < 0.001) Below is the link to the electronic supplementary material.


Cardiogenic shock remains a deadly complication of acute on chronic decompensated heart failure (ADHF-CS). Despite its increasing prevalence, it is incompletely understood and therefore often misdiagnosed in the early phase. Precise diagnosis of the underlying cause of CS is fundamental for undertaking the correct therapeutic strategy. Temporary mechanical circulatory support (tMCS) is the mainstay of management: identifying and selecting optimal patients through understanding of the hemodynamics and a prompt profiling and timing, is key for success. A recent statement from the American Heart Association provided pragmatic suggestions on tMCS device selection, escalation, and weaning strategies. However, several areas of uncertainty still remain in clinical practice. Accordingly, we present an overview of the main pitfalls that can occur during patients’ management with tMCS through a clinical case. This case illustrates the strict interdependency between left ventricular unloading and right ventricular dysfunction in the case of low filling pressures. Moreover, it further illustrates the pivotal role of stepwise escalation of therapy in a patient with an ADHF-CS and its peculiarities as compared to other forms of acute heart failure. Cardiogenic shock (CS) is a heterogeneous clinical syndrome with increasing incidence and high mortality . The twoRecent consensus documents have highlighted that CS is defined by the presence of hypoperfusion although not necessarily requiring the presence of hypotension ,4,5,6. TA recent scientific statement from the American Heart Association provided pragmatic suggestions on temporary mechanical circulatory support (tMCS) device selection, escalation, and weaning strategies, suggesting invasive monitoring to drive the management . HoweverAccordingly, we decided to review these key points through a clinical case of a patient with acute on chronic heart failure, complicated by CS.This case describes, throughout a complete hemodynamic assessment, that right ventricular (RV) failure with pulmonary hypertension (PH) can occur because of ineffective unloading and would, paradoxically, dictate the need for LVAD implantation. The case description provides useful insights for clinicians managing ADHF-CS patients in an intensive cardiac care unit (ICCU).2). Mitral regurgitation (MR) and tricuspid regurgitation (TR) were respectively moderate and mild; tricuspid annular plane systolic excursion (TAPSE) was 16 mm, RV fractional area change (RVFAC) was 29%, and RV tissue Doppler S velocity of the tricuspid annulus was 8 cm/s. He was congested and normotensive with chronic Stage 3b kidney disease, .A 62-year-old man was admitted to the Intermediate Cardiac Care with a diagnosis of post ischemic ADHF . EjectioThe patient was started on furosemide, nitroprusside, and dopamine infusion. The patient deteriorated 5 days later  and was Hemodynamic stabilized with the device deployed at a support level of P8 (cardiac output-CO 3.4 L/min). Invasive monitoring showed CO 4.1 L/min, pulmonary pressures of 34/11/22 mmHg, PAWP of 9 mmHg, RAP of 0 mmHg, and indexed pulmonary vascular resistances (iPVR) of 1 Woods Units. Echocardiogram showed correct positioning of the Impella pump with a moderate MR, increased compared with previous days, and normal RV function.Soon after the hemodynamic assessment post=Impella implantation, a hypotension occurred, which promptly responded to fluid challenge. The patient was awake and there were no signs of respiratory failure.2/beat) to 8.5 g/m (mPAP 53 mmHg and SVi 13.11 mL/m2/beat). Moreover, there was a decrease of CO (from 3.2 to 2.9 L/min) despite an unchanged LVSWI [16 g/m (MAP 75 mmHg and SVi 15 mL/m2/beat) to 15.5 g/m (MAP 83 mmHg and SVi 13 mL/m2/beat)].Ninety minutes after Impella activation, the patient developed hemodynamic collapse , panel ASodium nitroprusside was discontinued due to hypotension. Intravenous fluids and red blood cell transfusions were delivered, and epinephrine was started at 0.12 mcg/kg/min.After fluid challenge with 1000 cc of sodium chloride and 3 units of packed red blood cells, echocardiography confirmed right-sided shift of IVS, but increased dimensions of RV with reduced contractility.The patient was intubated and inhalation of nitric oxide (20 ppm) was started, with a rapid normalization of pulmonary pressures and hemodynamic stabilization  appeared unlikely.The patient expired 24 h after Impella implantation.The present case illustrates the challenges in promptly identifying and managing high-risk ADHF-CS phenotypes from drugs to escalating tMCS.On admission, clinical evaluation was misled by normotension and as a consequence we overlooked the metabolic damage, missing the identification of CS phenotype III-cardiometabolic  and SCAIIn this regard, the IABP was able to stabilize the patient and might have effectively bridged the patient to LVAD. However, the lack of an immediate long-term strategy produced a significant delay in the process of care. Furthermore, if temporary mechanical support escalation from IABP is required, we envision the role of an axillary Impella 5.0/5.5 as a potentially superior escalation strategy to fully unload the left ventricle and provide a higher level of systemic perfusion while assessing the ability of the right ventricle to tolerate high-forward flow from the LV, as a tolerance test for a durable LVAD ,15.In our patient, the Impella CP device was chosen over Impella 5.0/5.5 because we thought it could provide full cardiac support and due to its ease of insertion, did not need surgical involvement . AdditioImpella CP was able to adequately unload, but could not provide sufficient support for biventricular failure. The patient likely needed a biventricular support strategy early on, but this was not easily identified due to the RA pressure of zero. In fact, the residual LV function was overestimated due to the low filling pressures obtained with diuretics.The following key points can be drawn from this clinical case.QUESTION 1: What is the role of filling pressures in patients with ADHF-CS?Patients with ADHF usually present with congestion and clinicians are usually prone to quickly start diuretics iv in order to reduce filling pressures and improve splanchnic congestion ,17. HoweThe pharmacological strategies with diuretics and nitroprusside may have sub-optimal effect in the case of tight biventricular pre/afterload balance and delay the MCS implantation, leading to advanced stages of end-organ failure. In other terms, manipulating the hemodynamics with diuretics and nitroprusside might further delay mechanical support.The ‘cold and dry’ ADHF-CS patients is an extremely challenging cohort since they play off the Starling curve with profoundly low cardiac output that is likely to worsen after volume resuscitation.Additionally, the assessment of the right heart hemodynamic is particularly challenging since the RA pressure and RV function remains normal but highly susceptible to volume loading, which may precipitate RV failure.QUESTION 2: Which is the optimal mechanical circulatory support in ADHF?Among MCS, intra-aortic balloon counterpulsation (IABP) provides a modest hemodynamic support, potentially acting on ventricuo-arterial coupling (VAC) by reducing pre-systolic (end–diastolic) aortic pressure, left ventricular wall tension, and the rate of left ventricular pressure rise (dp/dt), and favouring coronary perfusion . At the In contrast, there are limited data exploring the efficacy of IABP in patients with CS due to ADHF.Recent studies and one review ,22,23 shPersistence of elevated LV filling pressures, pulmonary congestion, metabolic deterioration, and end-organ damage during IABP support should be criteria to promptly escalate the support.2). This aspect was certainly a drawback that should always be considered in the diagnostic/therapeutic pathway for the escalation or choice of Impella device, in particular if diameter is greater than 60 mm. In this case, it could be more appropriate to go directly to Impella 5.5 and, if not available, to VA-ECMO with CP as an unloading strategy , but recently para-corporeal LVAD/biventricular assist device (BiVAD) have been taken into consideration more often.ECMO has the advantage of being readily implanted in most patients and different clinical scenarios. However, high-dose inotropic support is often necessary, alongside IABP and/or LV venting, with the result of increasing the risk of local or systemic complications .Para-corporeal VADs could have a role in selected adult patients, in particular in the case of biventricular failure . The absWe can assert that there were multiple levels of failure that may have been precipitated by the challenging assessment of biventricular function and pathophysiology, finally leading to an irreversible CS vicious cycle.After the deterioration following IABP weaning, we should have immediately upgraded to a further hemodynamic supportas Impella and chosen a most powerful pump, Impella 5.0/5.5, with an upper body approach . This coQUESTION 3: How much unloading is necessary to protect the right ventricle?Increased LV filling pressures in the setting of chronic LV failure increase RV afterload, which promotes RV remodeling. A recent study  describeIn this context, the thoughtful monitoring of RV hemodynamic with pulmonary catheter and function with, at least daily, echocardiography during mechanical unloading of the LV, is paramount. Among clinical predictors of RV failure, PAPI could be of clinical utility, but it may be challenging to interpret if the RAP is less than 10 or the PASP is >50 and with extremely severe RV/biventricular failure (stage E SCAI), as in our case.QUESTION 4: Should patients on temporary MCS receive inotropes?The use of adrenergic drugs is supported by a low level of evidence ,32,33. TTherefore, weaning from adrenergic agents is strongly suggested soon after the MCS is in place and failure to achieve it should prompt re-evaluation for ineffective unloading. The usual setting where the inotropes are maintained is in the absence of an ejecting pulse pressure  when a patient is on a continuous flow pump. However, this should be interpreted as ineffective offloading in the presence of increased afterload and, therefore, treated with flow titration and eventually MCS step-up approach.Inotropes cut-off values are extremely valuable for clinical purposes, for example an inotropic score > 20 should warrant evaluation for device escalation .According to recent data , the ADHRV modulates LV structure and function through diastolic and systolic interdependence in conditions of pressure and/or volume overload, and may be in turn affected by the induced changes in the left ventricle .Moreover, RV contractility response to increased PAP is closely associated to its preserved systolic function/size: There is some ability of RV to increase its contractility with increases in afterload through homeometric autoregulation . Our patWhen choosing a tMCS device, clinicians should take into account the etiology of shock (acute versus acute on chronic pathologies), the stage of shock (including the extent of end-organ failure), and the patient’s age and beliefs along with the goals of care.In this context, a specific timeline for “early phenotypization”, “prompt management”, and “exit strategies” should always be implemented in these patients devoid of chances for native heart recovery.


Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal–Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM . DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration  and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C,  Diabetes mellitus (DM) is a chronic worldwide pandemic . PatientSeveral mechanisms are involved in diabetic cardiomyopathy . HyperglCurrently, there is no specific treatment to prevent or treat diabetic cardiomyopathy. A new class of antidiabetic drug, selective sodium-glucose co-transporter 2 (SGLT2) inhibitors, has been introduced in clinical practice in the last decade . SGLT2 iMost studies have evaluated the effect of SGLT2 inhibitors on Type 2 DM but few have assessed their effects on Type 1 DM ,17,18,19Most studies have evaluated the effect of SGLT2 inhibitors on Type 2 DM, but few have assessed their effects on Type 1 DM ,17,18,19Male Wistar rats weighing approximately 450 g were purchased from the Central Animal House at Botucatu Medical School, Sao Paulo State University, UNESP. All animals were housed in individual cages in a room under temperature control at 23 °C and kept on a 12-h light/dark cycle. Water and food were supplied ad libitum. All experiments and procedures were approved by the Ethics Committee of Botucatu Medical School, UNESP.n = 14); control treated with dapagliflozin ; diabetes ; and diabetes treated with dapagliflozin .The rats were assigned into four groups: control  was used to measure blood glucose seven days after streptozotocin administration. Rats with glycemia higher than 220 mg/dL were included in the study  × 1.04. LV relative wall thickness (RWT) was calculated by the formula 2 × LVPWT/LVDD. LV systolic function was analyzed by the following parameters: ejection fraction, endocardial fractional shortening (EFS), and posterior wall shortening velocity (PWSV). LV diastolic function was assessed by the variables of early and late diastolic mitral inflow velocities , E/A ratio, isovolumetric relaxation time (IVRT), and E-wave deceleration time (EDT). A combined evaluation of systolic and diastolic LV function was made using the myocardial performance index (Tei index).At the end of the experiment, an echocardiogram was performed with an echocardiograph  using a 5–11.5 MHz multifrequency probe, as described in our laboratory ,30,31. RTissue Doppler imaging (TDI) was used to assess systolic (S’) and early (E’) and late (A’) diastolic velocity of the mitral annulus, and E/E’ ratio .Transverse sections of LV were fixed in formalin and immersed in paraffin. Hematoxylin–eosin-stained sections  were useThe concentration of hydroxyproline (HOP) was evaluated in LV to estimate the myocardial collagen content using a colorimetric assay .The expression of lysil oxidase  and Type I  and Type III collagen  was assessed by Western blot . After pg for 15 min at 4 °C. The supernatant was used to measure total protein, lipid hydroperoxide, and anti-oxidant enzyme activities as previously described .DM had higher myocardial lipid hydroperoxide concentration and lower anti-oxidant enzyme activities than C. DM + DAPA had lower lipid hydroperoxide concentration and higher superoxide dismutase and glutathione peroxidase activity than DM . AdvanceStreptozotocin doses between 50 and 80 mg/kg  have been used to induce Type 1 DM ,44,45,462 [As expected, the DM + DAPA group had lower glycemia than DM. SGLT2 inhibitors were first introduced in clinical practice to reduce renal glucose reabsorption and decrease plasma glucose levels. Therefore, clinicians were concerned that loss of urinary glucose could reduce body weight and impair physical status in lean patients with Type 1 DM ,50. In f2 . Thus, i2 . The redSystolic blood pressure was higher in DM than C and DM + DAPA. Reduced blood pressure has been observed in DM patients after SGLT2 inhibition and attributed to several mechanisms, such as increased natriuresis and decreased plasma volume, arterial stiffness, and sympathetic tone ,54,55.In this study, the streptozotocin-induced diabetic cardiomyopathy was well characterized. We have previously showed that this is a good experimental model to assess diabetic cardiomyopathy ,22,23,24+/H+-exchanger, and SGLT1; and prevention of ischemia/reperfusion injury [Different mechanisms have been proposed to explain the cardioprotective effects of SGLT2 inhibitors, such as an increase in diuresis/natriuresis, autophagy, lysosomal degradation, circulating pro-vascular progenitor cells, erythropoiesis and erythropoietin levels; decrease in blood pressure, oxidative stress, hyperuricemia, inflammation, myocardial fibrosis, and epicardial fat mass; improvement in energy metabolism and vascular function; inhibition of sympathetic nervous system, Nan injury ,56,57. IMyocardial collagen content evaluated by interstitial collagen fraction and hydroxyproline did not differ between groups, suggesting that myocardial fibrosis is not an important mechanism of cardiac function impairment in this relatively short-term cardiomyopathy model. In accordance with our results, changes in cardiac function were observed before overt myocardial structure alterations in Type 1 diabetes rats . EmpagliMechanical myocardial properties are influenced by both the collagen amount and collagen crosslinking. Fibrillar collagen Types I and III are the predominant forms in cardiac extracellular matrix . Type I Hyperglycemia increases reactive oxygen species, which are a major mechanism in the pathophysiology of diabetic cardiomyopathy ,64,65. DHyperglycemia and oxidative stress increase AGEs. AGEs per se increase oxidative stress and impair ventricular stiffness ,7,68. InIn conclusion, dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental model of Type 1 diabetes mellitus. In healthy rats, dapagliflozin increases protein expression of Type 1 collagen.


Epicardial adipose tissue (EAT) can play an important role in the occurrence and development of atrial fibrillation and stroke. In this study, we explored the relationship between left atrial epicardial adipose tissue (LA-EAT) and left atrial appendage flow velocity (LAA-FV) in patients with nonvalvular atrial fibrillation (NV-AF). A total of 145 patients with NV-AF who underwent their first radiofrequency ablation were enrolled. They underwent left aortopulmonary vein computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before AF ablation. Left atrial (LA) electroanatomical mapping was performed intraoperatively to assess left atrial voltage. Univariate regression analysis showed that LAA-FV was lower in patients with a low voltage zone . A multiple linear regression model showed that the left atrial low voltage zone (β = − 0.311 P < 0.001), LA-EAT volume (β = − 0.256 P < 0.001), left atrial appendage shape (β = − 0.216 P = 0.041), LAVI (β = − 0.153 P = 0.041), and type of atrial fibrillation  (β = − 0.146 P < 0.048) were independent predictors of LAA-FV. In NV-AF patients, the increase in LA-EAT volume is related to the decrease in LAA-FV. Although the management of atrial fibrillation has been continuously improved, there are obvious limitations of antiarrhythmic drug therapy and radiofrequency ablation3, and the long-term maintenance of sinus rhythm in patients with atrial fibrillation is challenging. Therefore, anticoagulation therapy is very important.Atrial fibrillation (AF) is the most common arrhythmia4. Many studies have shown that a decrease in left atrial appendage velocity (LAA-FV) is closely related to left atrial appendage mural thrombosis6. At present, the main measurement method for LAA-FV is transesophageal ultrasound7, but this is a semi-invasive approach, and its accuracy is related to the skill level of the operator. During the COVID-19 pandemic, noninvasive tests were recommended to reduce the risk of exposure to the virus9. Epicardial adipose tissue (EAT) is in direct contact with the surface of the atrium and pulmonary vein and, like the myocardium, is supplied by the coronary artery10, which can play an important role in the occurrence and development of atrial fibrillation and stroke through a variety of mechanisms, such as fat infiltration, fibrosis and inflammation12. Previous studies have shown that myocardial fibrosis is closely related to the velocity of the left atrial appendage14. However, the relationship between epicardial adipose tissue and left atrial appendage velocity is rarely reported.The most important source of embolic stroke in patients with nonvalvular atrial fibrillation (NV-AF) is the left atrial appendage16, it is generally accepted that atrial fibrosis can be shown by mapping the low voltage zone through electrophysiological intracavitary voltage mapping18. In this study, we identified atrial fibrosis by left atrial voltage mapping during radiofrequency ablation to explore the relationship between LA-EAT and left atrial appendage velocity in patients with nonvalvular atrial fibrillation. We hope to find a safe and reliable index to evaluate left atrial appendage function.With the popularization and development of electrophysiological technology in recent yearsA total of 145 patients with nonvalvular atrial fibrillation who underwent their first radiofrequency ablation at the Affiliated Hospital of Xuzhou Medical University between 2020 and 2021 were selected. All patients underwent CTA and TEE examinations of the left atrium and pulmonary vein before the operation. There were 76 patients with paroxysmal atrial fibrillation and 69 patients with nonparoxysmal atrial fibrillation. All patients were diagnosed with atrial fibrillation by electrocardiogram and/or dynamic electrocardiogram. Paroxysmal atrial fibrillation is defined as atrial fibrillation that lasts less than 7 days and terminates spontaneously, while persistent atrial fibrillation is defined as atrial fibrillation that lasts more than 7 days or requires electrical cardioversion and/or drug cardioversion to terminate. Exclusion criteria: (1) previous catheter ablation of atrial fibrillation or other cardiac surgery; (2) hyperthyroidism; (3) rheumatism and other cardiac valvular diseases; (4) active connective tissue disease; and (5) inability to undergo CTA or CT imaging or inability to obtain complete left atrial appendage data because of contrast medium allergy. This study was reviewed by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, and all patients signed informed consent forms.Transthoracic echocardiography (TTE) was performed with a Philips EPIQ7c ultrasonic diagnostic instrument, S5-1 probe and probe frequency 1–5 MHz. Parameters such as left ventricular ejection fraction (measured by the biplane Simpson's method) were recorded in detail in the left recumbent position. TEE was examined by PhilipsiE33 color Doppler ultrasonography with an X7-2t transesophageal matrix real-time three-dimensional probe with a frequency of 2–7 MHz. Before fasting for 6–8 h, the ECG was recorded synchronously, the pulsed Doppler sampling volume was placed within 1 pulse near the opening of the left atrial appendage, and the blood flow spectrum of the left atrial appendage was obtained. The left atrial appendage blood flow spectrum was a regular two-way wave in sinus rhythm and an irregular zigzag waveform in atrial fibrillation rhythm. The peak value of the positive wave, that is, the maximum emptying velocity of the left atrial appendage, was recorded in 3 and 10 cardiac cycles, respectively, and the average value was taken as the velocity of the left atrial appendage (LAA-FV)  was used to obtain CT imaging data. Iohexol (60–80 ml) was injected into the elbow vein at a flow rate of 5 ml/s, and then saline (50 ml) was injected at a speed of 5 ml/s. The contrast agent tracking technique triggered the enhanced scan. Image processing and measurement: All images were reconstructed by retrospective ECG gated reconstruction, slice thickness 0.5 mm, overlapping 0.3 mm, and image postprocessing was performed by an Advantage Workstation 3.2  workstation. The CT threshold range of the adipose tissue was set to − 50 HU ~ − 200 HU. The left atrial epicardial adipose tissue (LA-EAT) was manually segmented, and the LA-EAT was calculated . Left atrial voltage mapping was performed directly in patients with paroxysmal atrial fibrillation after PVI. Patients with persistent atrial fibrillation underwent synchronous electrocardioversion if they were still in atrial fibrillation after isolation, and voltage mapping was performed after cardioversion. Voltage mapping was carried out with an ST ablation catheter , and contact force values of > 5 g for mapping electrograms confirmed adequate endocardial contact. We used ≥ 3 adjacent peak-to-peak bipolar voltage cutoffs of 0.2–0.5 mV to define the low-voltage region to more accurately delineate the LAVI19 Fig. .Figure 4If the measurement data were normally distributed, they were expressed as the mean ± SD. If they do not conform to a normal distribution, they are expressed by the median (quartile spacing), that is, M (Q25 Q75), and the counting data are expressed by the number (percentage). The counting data were compared by Student’s t test or Wilcoxon's singed rank-sum tests , and the classified variables were compared by chi-square tests or Fisher’s exact test. Pearson or Spearman correlation tests were used to evaluate the relationship between LAA-FV and various parameters. In addition, to evaluate the independent predictors of LAA-FV, multiple regression analysis was carried out. P < 0.05 was considered to be statistically significant. All statistical analyses were carried out using SPSS version 24.0 software .Patient studies were approved by the Ethics Committee of Affiliated Hospital of Xuzhou Medical University. All methods were implemented in accordance with relevant guidelines and regulations, and all enrolled patients signed informed consent forms.2, the left atrial volume index (LAVI) was 68.26 ± 23.97 ml/m2, the left atrial epicardial adipose tissue volume (LA-EAT) was 30.72 ± 11.81 ml, and the left atrial appendage flow rate (LAA-FV) was 47.59 ± 13.38 cm/s.The characteristics of the patients are shown in Table CARTO3 voltage mapping of the left atrium was performed in all cases under sinus rhythm, and an average of 864 marker points were obtained in each case. No complications occurred during the process of LA mapping. The voltage mapping results were used to divide the patients into a low voltage zone group (LVZ group) and a nonlow voltage group (non-LVZ group). Among them, 28 patients (19.31%) had left atrial LVZ. The clinical features, epicardial adipose tissue and echocardiographic parameters of the LVZ group and non-LVZ group were compared, and the results are shown in Table There were significant negative correlations between LAA-FV and left atrial volume index (LAVI)  and nonchicken wing type . The LAA-FV of the persistent AF group was lower than that of the paroxysmal AF group . In addition, a lower LAA-FV was significantly correlated with the left atrial volume index (LAVI) and the LA-EAT volume (p ≤ 0.001). In a multiple linear regression model, the left atrial LVZ , LA-EAT volume , left atrial appendage shape , LAVI , and type of atrial fibrillation   were independent predictors of LAA-FV (Table 20 reported that human adventitia adipose tissue (EAT) caused fibrosis of atrial cardiomyocytes in rats and promoted fibroblasts to differentiate into myofibroblasts. At present, the clinical detection methods for myocardial fibrosis are limited. Myocardial fibrosis is mainly detected through endocardial biopsy, late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) and intracardiac voltage mapping. In this study, left atrial voltage mapping was performed during radiofrequency ablation, and patients with atrial fibrillation were divided into an LVZ group and a non-LVZ group. Compared with the non-LVZ group, the LAA-FV in the LVZ group was lower. This is consistent with the results of previous studies that show that there may be a correlation between atrial fibrosis and left atrial appendage velocity14. At present, TEE is the most widely used method to measure the function of the LAA, and it is considered the gold standard, but it is semi-invasive. We hope to find a non-invasive and reliable index to evaluate left atrial appendage function. In this study, it was found that left atrial LVZ, LA-EAT volume, left atrial appendage shape, left atrial volume index and type of atrial fibrillation  were independent predictors of LAA-FV.In recent years, increasing attention has been given to the relationship between epicardial adipose tissue and atrial fibrillation (AF). Venteclef et al.21 found that patients with low LAA-FV (20 cm/s) were characterized by the presence of left anterior wall LVZ and high CHA2DS2VASc scores. SHIH-HSIENSUNG et al.22 found that the larger the left atrium was, the larger the LVZ of the left atrium, and there was a significant correlation between the LVZ of the left atrium and the emptying velocity of the LAA. These results are consistent with our research. A possible reason is that atrial structural remodeling characterized by atrial fibrosis is the core of the maintenance mechanism of atrial fibrillation23. Left atrial electrical remodeling and fibrosis cause greater left atrial pressure, which is more likely to increase the afterload of the left atrial appendage and cause systolic dysfunction, therefore resulting in a decrease in LAA-FV. Another possible reason is that this structural remodeling also occurs in the left atrial appendage24. LAA-FV can reflect changes in left atrial function, including contraction, stunning, fibrosis, etc., so the LAA-FV may represent the severity of the left atrial remodeling25.Yuichi Hori et al.26. The results of this study are consistent with the above studies, and the mechanism may be as follows: first, during TEE, the heart rhythm of patients with paroxysmal atrial fibrillation shows a sinus rhythm, while that of patients with persistent atrial fibrillation shows an atrial fibrillation rhythm. Thus, the emptying time of the left atrium and left atrial appendage is shortened, and rapid irregular electrical activity can significantly affect the active contractile force of the left atrial appendage muscle and decrease the velocity of the left atrial appendage.In a previous study, the types of atrial fibrillation were divided into paroxysmal atrial fibrillation, persistent atrial fibrillation and long-term persistent atrial fibrillation, and the results showed that LAA-FV decreased gradually28found that the LAA orifice enlargement or a chicken wing type was closly related with the decreased flow velocity of LAA. The results of this study are consistent with the above studies. This may be because the chicken wing-type LAA has a higher muscle mass to contract the left atrial appendage29. Previous studies have shown that there is a significant negative correlation between the left atrial diameter and LAA-FV31. LAVI was used in this study because the use of the LA volume can more accurately identify structural atrial remodeling that involves the left atrial low-voltage matrix than the LA diameter. The results showed that LAVI was negatively correlated with LAA-FV and was an independent predictor of LAA-FV. The left atrial appendage is thought to act as a decompression chamber during left ventricular contraction and other increases in left atrial pressure32. LAA-FV may represent the full functionality of LA and indicate the severity of LA refactoring33. Therefore, dilatation of the left atrium and an increase in LAVI leads to remodeling of the left atrial appendage and a decrease in LAA-FV. This may also explain why some scholars believe that the risk of stroke increases with increasing left atrial size34.Previous studies have shown that LAAFV and LAA morphology are closely related. Lee JM et al.35 reported that the capacity of EAT may be related to the function of the left atrial appendage. However, that study did not investigate echocardiographic parameters. Yamaguchi et al.36 evaluated the thickness of EAT by TTE. The results showed that the thickness of the EAT was negatively correlated with the filling and emptying velocity of the left atrial appendage. Because the thickness of the EAT varies greatly in different parts and the measurement repeatability is poor, this study improves the accuracy by measuring the EAT volume. It was found that the adipose tissue volume of the left atrium was an independent predictor of LAA-FV. The explanation may be as follows: First, EAT can cause atrial myocardial fibrosis through various pathways. Haemers et al.37proposed that EAT could lead to progressive fibrosis of the adjacent atrial myocardium through fatty infiltration. Venteclef et al.20 found that EAT is the main source of activin A, and activin A may be the main factor mediating the pro-fibrotic effect of EAT. A recent study by Patel et al.38 found that EAT can induce myocardial fibrosis by activating the renin–angiotensin–aldosterone system (RAAS), especially angiotensin II (Ang II). Previous studies41have confirmed that EAT can secrete inflammatory factors including interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF) and other inflammatory factors through endocrine and paracrine pathways. Under the action of these factors, myocardial inflammatory response is caused, which leads to myocardial fibrosis. As mentioned above, atrial fibrosis can lead to decreased LAAFV. Second, EAT is also closely related to oxidative stress. Salgado-Somoza et al.42 obtained EAT from 55 patients undergoing cardiac surgery and detected oxidative stress indicators such as reactive oxygen species (ROS) in EAT tissue. The results suggest that EAT has higher levels of oxidative stress in patients with cardiovascular disease compared to other adipose tissues. Dudley et al.43 established an atrial fibrillation model by rapid atrial pacing in pigs. The results showed that the level of oxidative stress in LAA tissues was significantly increased. Therefore, we speculate that the effect of EAT on LAA function may be related to oxidative stress. Oxidative stress can lead to cellular damage, impair myofibril energetics, and lead to myocardial contractile dysfunction, resulting in a decrease in LAAFV44.A previous studyThere are some limitations in this study. First, this study is a retrospective, single-center, small sample study, so it is necessary to conduct a prospective study on a larger cohort. Second, when measuring LA-EAT, semiautomatic methods are used to manually outline the epicardium, which may lead to differences in LA-EAT evaluation. In this study, two experienced imaging physicians separately performed the LA-AT measurement to reduce this measurement artifact. Third, the specific mechanisms of LA-EAT and LAA-FV are still unclear, such as EAT-induced fibrosis, inflammation, and fat infiltration, which need to be studied further.In NV-AF patients, the increase in LA-EAT is related to the decrease in LAA-FV. Currently, there are some limitations to CHA2DS2-VASc score to assess stroke risk in patients with NV-AF, which may be related to the fact that the score does not reflect the effect of cardiac structure and function on thrombosis. EAT may be able to compensate for the shortcomings of the CHA2DS2-VASc score.


Left ventricular rupture following prosthetic mitral valve replacement might be avoided by valve-sparing techniques and vigilance at the time of debridement to maintain or support annular integrity.See Article page 48.,DavidAlthough performing prosthetic MVR is not usual, few surgeons have had the misfortune of having to deal with LV rupture. Bright red blood emanating from the posterior pericardium upon separation from cardiopulmonary bypass following MVR is universally accompanied by a sinking feeling in the operator. Should an ill-prepared surgeon attempt lifting the heart to locate the bleeding source in this setting, the maneuver may prove fatal. As outlined by David,,Predispositions to this complication include female patients, a small LV cavity, advanced age, severe mitral annular calcification, and implantation of higher-profile bioprosthetic valves. Vigilance and patch correction at the time of annular debridement may avoid type 1 LV disruption, whereas avoiding deep debridement involving the papillary muscles can mitigate type 2 LV disruption. Posterior leaflet and total leaflet sparing MVR operations have nearly eliminated this complication.Greek mythological reference to Achilles' heel symbolizes that despite overall strength, a focal vulnerability may lead to downfall. Surgeons are well versed in the reproducible techniques of prosthetic MVR. Valve-sparing methods and adaptive strategies to address mitral annular calcification are the established necessary standards to avoid this potential vulnerability and circumvent this pitfall. Vigilance can often save patients from this often fatal problem.


Such drugs are thought to be omecamtiv mecarbil (OME) and mavacamten (MYK-461), respectively. Their function in contracting human muscle is not fully understood and was the focus of the present study. OME from 1 nM to 10 µM cumulatively applied failed to raise force of contraction in human right atrial preparations strips (HAP) or mouse left atrial preparations (LA). However, OME prolonged time to peak tension and time of relaxation in HAP and LA but did not alter the beating rate in right atrial preparations from mice (RA). In contrast, MYK-461 (10 nM to 10 µM) reduced concentration- and time-dependently force of contraction in HAP and LA. MYK-461 (10 µM) did not affect the beating rate in RA. In summary, the present data failed to detect an increase in force of contraction for OME, in human and mouse atrium. In contrast, a Ca2+ desensitizer studied for comparison was able to reduce force of contraction in HAP and LA. We conclude that putative beneficial effects of OME in dilated cardiomyopathy cannot be explained by positive inotropic effects in the HAP, whereas beneficial functional effects of MYK-461 in HOCOM can be explained by negative inotropic effects in HAP.Heart failure is a syndrome that can result from impaired heart muscle contractions like in dilative cardiomyopathy but also from hypertrophic obstructive cardiomyopathy (HOCOM). A pharmacological therapy might lie in CaThe online version contains supplementary material available at 10.1007/s00210-022-02333-0. Like OME, also MYK-461 was also found by using an in vitro screen of myosin function, by the same company  parts of the inimical muscle mass in the ventricle. A less invasive treatment option is the use of negative inotropic drugs. The assumption being that negative inotropic drugs like propranolol or verapamil thereby reduce muscular mechanical obstruction in the outflow tract of the left ventricle and thus facilitate left ventricular ejection of blood. Here, the opposite approach to OME has entered the clinic: a compound named mavacamten MYK-461) 2+ sensitivity of myofilaments and used already in study patients with heart failure. One was presumably a negative inotropic drug (MYK-461) and the other a putative positive inotropic drug (OME). We wanted to know how they affect beating rate in mouse atrium and force of contraction in mouse atrium and human atrium in the organ bath. These studies were hoped to lead us to better clinical use of such drugs acting on Ca2+ sensitivity in syndromes of human heart failure.Hence, we wanted to compare two drugs acting oppositely on cardiac myosin function/CaIn brief, wild-type mice were sacrificed, the thorax was opened, and the heart was mobilized and cut from the ascending aorta to make sure the right atrium was not damaged. Then the whole heart was transferred to a dissection chamber filled with gassed Tyrode’s solution at room temperature. Right or left atrial preparations were isolated and mounted in organ baths as described by Gergs et al. , 2019a aThese experiments were performed as reported repeatedly . All other statistical analyses were performed as indicated in the figures and tables.Data were treated as in most our previous studies -1-phenylethyl]amino]-3-propan-2-yl-1H-pyrimidine-2,4-dione or MYK-461) were purchased from Cayman Chemical . Omecamtiv mecarbil (methyl 4-[(2-fluoro-3-{[N-(6-methylpyridin-3-yl)-carbamoyl]-amino}-phenyl)methyl]piperazine-1-carboxylate or CK-1827452)) was purchased from Selleck Chemicals, Berlin, Germany. (-)-Isoprenaline ( +)-bitartrate was purchased from Sigma-Aldrich . All other chemicals were of the highest purity grade commercially available. Deionized water was used throughout the experiments.OME effects on force of contraction of spontaneously beating mouse right atrial preparations (RA) were qualitatively similar as in left atrial preparations . Cumulatively applied OME (10 nM–10 µM) did not increase force of contraction in isolated spontaneously beating RA (data not shown). Moreover, under conditions where OME (10 nM–10 µM) prolonged time parameters and reduced the rate of tension development in LA, OME failed to alter the spontaneous beating rate in RA  increased force, but additionally and subsequently applied OME did not increase force of contraction, but clearly at 10 µM, OME reduced force of contraction  for isoprenaline in human atrium. This was done to ensure that a positive inotropic effect of OME would still be measurable as isoprenaline at 10 nM did not stimulate force maximally. This finding may have a clinical bearing. It might indicate that at the beginning of heart failure when noradrenaline levels in patient plasma are high and β-adrenergic stimulation is presumably elevated, OME might be especially detrimental for cardiac force generation.Moreover, we wanted to know whether in the presence of isoprenaline  left atrial preparations under isometric conditions which is a novelty of this work.2+ to raise force of contraction. We have noted such prolongation of contraction duration with a pure Ca2+ sensitizer called CGP 48,506 in guinea pig, but this was accompanied by clear positive inotropic effect in human atrial preparations , MYK-461 reduced the maximal response to CaSome explanatory words on the interpretation of the data on force in right atrium seem to be in order. Physiologically the mouse atrium exhibits a negative staircase or “treppe” phenomenon: that is, in mouse atrial preparations, an increase in the beating rate leads to a negative inotropic effect, and a reduction of the beating rate leads to a positive inotropic effect. Thus, when reporting force of contraction in spontaneously beating right atrial preparations, one always has to keep in mind the accompanying changes in beating rate. However, this possible complication does not apply to the present data: we did not observe changes in beating rate due to OME or MYK-461. Hence, the negative inotropic effects of MYK-461 in right atrium and the contraction prolonging effects of OME in right atrium are very likely direct effects on the cardiomyocytes and not secondary effects due to changed beating rates. Thus, from these data, force of contraction responded in left and right atrium similarly to OME or MYK-461, at least in the mouse atrium.2+ concentration response curves in mouse left atria gave functional evidence for Ca2+-desensitizing effect of MYK-461 and support the data in skinned mouse cardiac fibers by other groups. However, we did not observe evidence for a sensitizing effect of OME to increasing concentrations of Ca2+ in contracting mouse left atrial preparations. This is in line with a lack of any positive inotropic effects of OME alone in mouse atrium. One might argue that this might be due to different isoforms of myosin in rat and mouse heart. This interpretation is hardly convincing: in rat and mouse, the alpha myosin isoform of myosin is predominant. Moreover, in rat heart itself based on experimental conditions, a positive inotropic  that sensitized skinned human cardiac fibers  that this compound increased force of contraction in human ventricular muscle strips under conditions that were identical to that of this study  that cancel the positive inotropic effect of OME on the myofilaments. Using radioactive OME, one could try to identify OME binding proteins in human hearts as a first experimental step in this direction. From a practical clinical perspective, our data and those of others  preparations. Hence, our data support a clinical utility of MYK-461 in the rare cases where heart failure results from a hyperdynamic contraction of the heart . Thus, MYK-461 is a small step forward towards a personalized drug therapy of heart failure. It still remains to be shown that mavacamten reduces mortality in any group of patients before it can be widely prescribed.In contrast, our contractile data make it easy to understand clinical benefits of MYK-461. It is well established that in HOCOM, the symptoms of the patient are improved if negative inotropic compounds are given. Such compounds included in the past verapamil, a drug that can block cardiac L-type CaAn apparent limitation of our work lies in the fact that we investigated drugs intended for heart failure therapy in human atrial preparations and not in ventricular preparations. Unfortunately, in our institution, we do not have access to human ventricular tissue. Likewise, we do rarely get atrial tissue from failing hearts. Usually, we only receive atrial tissue from bypass surgery of patients who are not (yet) in heart failure. Therefore, we have restricted our efforts to that tissue that was available to us.In summary, the present work confirms that OME does not increase force of contraction but prolongs duration of single contractions in isolated human atrial preparations. We extend these results for OME to left atrial preparations from wild-type mice. We noticed a negative inotropic effect of MYK-461 in isolated left atrial preparations from wild-type mice and in isolated human atrial preparations.Supplementary file1 (PZF 201 kb)Supplementary file2 (PZF 202 kb)Supplementary file3 (PZF 191 kb)Supplementary file4 (PZF 221 kb)Supplementary file5 (PZF 174 kb)Supplementary file6 (PZF 182 kb)Supplementary file7 (PZF 176 kb)Supplementary file8 (PZF 184 kb)Below is the link to the electronic supplementary material.


Mitral annular disjunction (MAD) is an abnormal displacement of the mitral valve leaflet onto the left atrial wall and is commonly found in patients with mitral valve prolapse (MVP). The diagnosis is usually made by transthoracic echocardiography (TTE) although findings can be subtle and further cardiac imaging may be necessary. MAD has been associated with a risk of malignant ventricular arrhythmias and sudden cardiac death, therefore recognition of this diagnosis and risk stratification are highly important. In this review, we will discuss the diagnosis, clinical implications, risk stratification and management of MAD based upon currently available literature, as well as provide a series of cases showing the heterogeneity in presentation and our experience with management of this rare but potentially fatal entity. Mitral valve prolapse (MVP) is a common condition that affects up to 3% of the population and is the most frequent cause of primary or degenerative mitral regurgitation (MR) , 2. The MAD is a common finding in patients with concomitant MV disease, and has been reported in over 30% of patients with MVP, although this rate varies based upon different populations and imaging modalities , 11, 12.In this review, we summarize the diagnosis, clinical implications, risk stratification and management of MAD and provide a case series to show the heterogeneity in presentation of MAD.The mitral annulus is a complex D-shaped structure with an anterior straight component and a posterior curved component. The anterior annulus is composed of the anterior mitral leaflet which inserts onto a band of connective tissue called the mitral-aortic curtain. The posterior mitral annulus is composed of the left atrial wall, the leaflet hinge line, the LV free wall and epicardial adipose tissue, held together by a fibrous cord. The posterior mitral leaflet hinges to the junction of the atrial and ventricular myocardium , 16. In Barlow's disease is a form of degenerative MV disease characterized by myxomatous thickening, billowing and prolapse of the mitral leaflets and pronounced annular dilation, often leading to significant MR . The assThe diagnosis of MAD is made with cardiac imaging which can be done by transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), cardiac computed tomography (CT) or cardiac magnetic resonance imaging (CMR). It is defined as the absence of myocardium during systole between the MV annulus and the adjacent segment of the left ventricular wall, although MAD has not been consistently defined in prior studies or guidelines and a reference standard imaging technique has not yet been established . Carmo eAlthough MAD can be detected by TTE and TEE, it is only visualized during ventricular systole and may be missed and underreported especially in the absence of concomitant mitral valve disease. Recognition of MAD is particularly important given its association with life-threatening arrhythmic events and should especially be investigated in those with concomitant MVP or myxomatous MV disease with arrhythmias or symptoms of arrhythmias, therefore a multi-imaging modality approach may be necessary to improve detection. Imaging tools with superior spatial resolution such as cardiac CT or CMR may serve as complementary diagnostic tools for those with a lesser degree of MAD , 26. DetThe clinical outcome of MVP is variable and related to complications such as mitral regurgitation, congestive heart failure, infective endocarditis and stroke. The risk of malignant arrhythmias and SCD is low, occurring in ~0.2–0.4% of patients with MVP per year, and MVP is not routinely considered as a major cause of SCD , 31. SevDejgaard et al. showed a high prevalence of life-threatening arrhythmic events occurred in patients with MAD, with or without MVP, suggesting that the arrhythmogenesis of MAD may be independent of MVP . In a loA 34 year old female with no past medical history who presented with sudden cardiac arrest due to ventricular fibrillation. While return of spontaneous circulation was obtained, patient developed significant cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation. A transthoracic echocardiogram (TTE) on presentation showed severely depressed left ventricular ejection fraction (LVEF) and coronary angiography excluded obstructive coronary artery disease (CAD). Her LVEF improved over time and she was taken off mechanical circulatory support. Repeat TTE showed improved LV function and evidence of bileaflet MVP, moderate mitral regurgitation (MR) and MAD, not clearly visualized on initial imaging. CMR confirmed these findings and additionally showed diffuse myocardial fibrosis and late gadolinium enhancement (LGE) in the inferolateral wall. Patient was discharged after receiving a secondary prevention implantable cardioverter defibrillator (ICD).47 year old female with a history of MVP who presented with a syncopal episode. Ischemic work-up was negative for CAD by coronary CT angiography and TTE showed normal LVEF with bileaflet MVP, moderate MR and MAD , with mi49 year old female with MVP and myxomatous mitral valve disease, MAD and palpitations who presented for outpatient evaluation valvular disease. A TEE and stress echocardiogram were performed which confirmed severe MR and showed a lack of contractile reserve with peak exercise . CMR sho35 year old female with a history of MVP and MR who presented for outpatient follow-up of her valvular disease. A TTE performed showed severe bileaflet prolapse and MAD with mild-moderate MR and no fibrosis or LGE was seen on CMR. Cardiac event monitoring showed rare VE with no ventricular arrhythmias. Patient has remained asymptomatic without palpitations and has been followed annually in clinic without need for intervention at this time.A 34 year old female with MVP with MR and palpitations who presented for evaluation of her valvular disease. TTE showed normal LVEF, moderate bileaflet MVP with MAD, and moderate MR. No LGE was seen on CMR however ECV was elevated consistent with myocardial fibrosis. Cardiac event monitoring showed 1 run of non-sustained VT and 8.1% VE burden. Patient was referred for an electrophysiology consult, and was started on a low dose beta-blocker with recommendations for annual cardiac event monitoring in addition to TTE monitoring.Our experience with MAD highlights the highly variable clinical course that patients may present with, from asymptomatic MVP to sudden cardiac arrest requiring mechanical circulatory support . Case 1 In asymptomatic patients with MVP and MAD, risk stratification is important. Cases 3-5 reflect our routine use of ambulatory cardiac rhythm monitoring and CMR in symptomatic and asymptomatic patients. Basso et al. and Chakrabarti et al. provide clinical approaches to risk stratifying patients based upon clinical, imaging, electrocardiogram and cardiac event monitor factors . In patiPatients with significant valvular disease, heart failure or arrhythmias should be treated according to standard AHA/ACC guidelines, however there is little data studying the use of medical therapy such as beta-blockers or antiarrhythmics in patients with MVP and MAD. One small study looking at 112 patients with MVP showed that antiarrhythmic therapy  was not effective in decreasing burden of VE .Although there are no guidelines regarding catheter ablation in MVP and MAD, this can be performed in patients with symptomatic, drug refractory ventricular arrhythmias. Syed et al. showed that catheter ablation of clinically dominant VE foci in patients with bileaflet MVP is effective at reducing symptomatic VE and reducing ICD shocks in patients with prior cardiac arrest . In contThe role of primary prevention ICD in MVP and MAD is unclear. As mentioned above, risk stratification with cardiac rhythm monitoring, electrophysiology study or CMR may be useful, however there is no data at this time to support primary prevention ICD and decisions should be made on an individual basis. Secondary prevention ICD is generally indicated in patients experiencing out-of-hospital cardiac arrest after reversible causes are excluded .Surgical mitral valve repair or replacement is indicated in patients with MVP and severe MR who are symptomatic or asymptomatic who meet certain echocardiographic criteria . While tMitral transcatheter edge-to-edge repair (TEER) with the MitraClip device was approved in the United States in 2013 for the treatment of primary MR. Surgical mitral valve repair can repair MAD in almost all patients likely due to the annuloplasty ring suture joining the mitral annulus to the LV myocardium and bridging the MAD gap, however this structural correction does not occur with TEER , 13, 22.Mitral valve prolapse and mitral annular disjunction are becoming increasingly recognized as important phenomena that can lead to malignant ventricular arrhythmias and sudden cardiac death. While much remains to be elucidated, the importance of awareness and detection of these entities is highlighted in this article, especially in patients presenting with syncope, ventricular arrhythmias, and cardiac arrest. MAD is a common finding in patients with MVP and most of the prior studies have been done in MVP populations. Given that MAD has been recently shown to be arrhythmogenic even in the absence of MVP, future research may need to focus on populations with MAD with and without MVP. Additionally, larger prospective studies are needed to optimize risk stratification and management.Both authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


Coronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF).This study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes.P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery.Short-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090–1.702); Pre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG. Coronary atherosclerotic disease (CAD) is the most common heart disease and it remains a leading cause of death worldwide . CAD patThe European System for Cardiac Operative Risk Evaluation (EuroSCORE) and its updated version EuroSCORE II are widely accepted risk models for cardiac surgery –10. In bLeft ventricular systolic dyssynchrony, which reflects the mechanical effects of asynchronous LV contraction, has been shown to be a prognostic indicator for some cardiovascular diseases and it also occurs in CAD patients –16. LV sTherefore, the main purpose of this study was to evaluate the predictive value of LV dyssynchrony parameters obtained from RT-3DE for short-term adverse outcomes after CABG in 3VD patients with preserved or mildly reduced LVEF. By documenting the advantages of this technology over conventional echocardiography, we hope that this study will find additional indexes besides LVEF and help to improve the standard of echocardiography care for 3VD patients before CABG in the future.2); (3) moderate to severe valvular heart disease including stenosis, prolapse, and regurgitation; (4) cardiomyopathy; (5) previous pacemaker implantation; (6) prosthetic valve; (7) the presence of chronic or acute kidney disease; and (8) poor echocardiographic image quality. This study was registered at clinicaltrials.gov (NCT03235323) and was performed in accordance with the ethical standards of the Institutional Ethics Committee. Written informed consent was obtained from each patient. The enrolled patients underwent assessment consisting of demographic features, medical history, laboratory parameters, QRS duration, and echocardiographic imaging workup. Calculation of EuroSCORE II was done with the interactive calculator at www.euroscore.org.Patients meeting the inclusion and exclusion criteria were enrolled from April 2018 to December 2021. The inclusion criteria were as follows: (1) CAD patients with 3VD confirmed by coronary angiography, waiting elective on-pump CABG; (2) LVEF >45% (Simpson’s method) , 18; andEchocardiography imaging was recorded in DICOM format using EPIQ7 Philips Ultrasound systems  and X5-1 transducer and 3.5-mHz probe were used. The standard examination was completed per the guidelines of the American Society of Echocardiography . LVEF waThe RT-3DE full-volume datasets were acquired from the apical window of the entire LV. HeartModel acquisition (HMQ) mode, as a specific one-beat acquisition, was used to acquire 3DE datasets. At least three full-volume datasets throughout one cardiac cycle were obtained using this acquisition model. Gain and compression controls and time-gain compensation settings were optimized to ensure image quality. Data sets were acquired using a wide-angle acquisition (93 × 80 degrees) mode. Four wedge-shaped subvolumes (93 × 20 degrees each) were obtained from five consecutive cardiac cycles. Then, the digital echocardiographic videos were analyzed using fully automated quantification software . The performed analytical procedure was described in detail in our previous study . The timThe standard procedure was described in our previous study . BrieflyThe clinical endpoints comprised 30-day mortality and/or postoperative complications, defined as death within 30 days and/or the occurrence of at least one of the following complications within 7 days after surgery: (a) cardiac ; (b) respiratory ; (c) neurological ; (d) surgical (reoperation for any reason); (e) infectious (sepsis and deep wound infection); and (f) acute renal failure requiring dialysis –23.After the surgical procedure, all the patients were transferred to a cardiac surgical intensive care unit (ICU). The duration in ICU and length of postoperative hospital stays were recorded.t-test was used for variables with a normal distribution, and the Mann–Whitney’s U-test was used for variables not satisfying the normal distribution. The chi-square test was used to compare categorical variables. The correlation of the Tmsv16-SD% and QRS duration and the relationship among dyssynchrony parameters were assessed using Spearman’ correlation analysis. Univariate logistic regression analysis was used to assess risk factors for post-CABG short-term adverse outcomes. Variables with P < 0.10 were included in the multivariate logistic regression model. The odds ratio (OR) from the regression were reported with 95% confidence interval (CI). The area under the receiver-operator characteristic (ROC) curve was calculated. The value closest to the upper left corner of the ROC curve determined the optimal sensitivity and specificity. The best cutoff value for predicting adverse outcome occurrence was determined using the Youden index according to the optimal sensitivity and specificity. The value was carried out to evaluate the prognostic performance of Tmsv16-SD% regarding the short-term clinical outcome. For all tests, P-value < 0.05 was significant. All analyses were conducted using SPSS 22.0 software .Continuous variables were expressed as means ± SD, or as median and interquartile range (IQR). Categorical variables were expressed as numbers and percentages. For comparing the mean values between the groups, the Student’s P = 0.021). However, there were no significant differences in the other characteristics.A total of ninety-five 3VD patients were enrolled. Twelve patients (12.6%) showed adverse postoperative short-term outcomes. Some patients had more than one complication. The details about postoperative adverse outcomes were shown in Two-dimensional echocardiography echocardiographic parameters are summarized in P < 0.001), Tmsv12-SD% (P = 0.014), Tmsv16-Dif% (P < 0.001), and Tmsv12-Dif% (P = 0.024).A mathematical full-volume model of the LV was obtained through RT-3DE . PatientP = 0.010).The myocardial perfusion index, CSI, was different between the two groups (P < 0.001). However, there was no correlation between Tmsv16-SD% and QRS duration  (The correlations among the dyssynchrony parameters were significant (= 0.500) .P-value < 0.10: NT-proBNP (P = 0.045), LVDd (P = 0.012), Tmsv16-SD% (P = 0.002), Tmsv12-SD% (P = 0.015), Tmsv6-SD% (P = 0.028), Tmsv16-Dif% (P = 0.015), Tmsv12-Dif% (P = 0.060), Tmsv6-Dif% (P = 0.017), and CSI (P = 0.014) (P = 0.006) was independently associated with the occurrence of postoperative short-term adverse outcomes  . Due to = 0.014)  and the outcomes .The ROC curve analysis of Tmsv16-SD% as a predictor of adverse short-term outcome occurrence is shown in n = 24) before CABG had a longer postoperative stay in ICU (P < 0.001) and hospital (P = 0.043).As shown in This study revealed that 3VD patients with preserved or mildly reduced LVEF undergoing CABG who experienced postoperative short-term adverse outcomes had a higher preoperative LV systolic dyssynchrony. The parameter Tmsv16-SD% obtained from RT-3DE was identified as an independent risk factor. Thus, RT-3DE was a useful additional method for the risk classification in 3VD patients with preserved or mildly reduced LVEF before CABG. To our knowledge, this is the first study which focus on predicting adverse postoperative short-term outcomes occurrence of 3VD patients with preserved or mildly reduced LVEF, based on RT-3DE measurement.It is crucial to identify individuals at high risk before undergoing CABG surgery. Accordingly, the modified EuroSCORE II has been developed for risk assessment and treatment guidance. However, it still shows defective discrimination ability in terms of sensitivity and accuracy . A similvia the specialized conduction system, while the early impaired myocardial perfusion in CAD patients may damage the synchronization of LV mechanical activity by reducing electromechanical coupling and LV coordination, resulting in a change of LV myocardial mechanics (Patients with preserved or mildly reduced LVEF were included in our study, and the measured LVEF in both groups with different outcomes was comparable. This volumetric approach mainly reflecting the change in LV morphology was not able to adequately describe the early change of myocardial dysfunction. It is important to identify additional indicators that can supplement risk stratification. The impairment of LV systolic synchrony is prevalent among CAD patients, and it can also occur in those patients with preserved or mildly reduced LVEF –28. In oechanics , 32.Moreover, preoperative LV systolic dyssynchrony appeared to play an important role in the occurrence of post-CABG short-term adverse outcomes. The most representative parameter, Tmsv16-SD%, was significantly associated with the occurrence of short-term adverse outcomes, according to the multivariate regression analysis. This indicated the significance of LVMD in CAD patients with preserved or mildly reduced LVEF. Fudim et al.  also fouThe LV dyssynchrony parameters for different segments in this study were higher than those in a community-based population,  but loweEchocardiography is one of the cornerstones of cardiac function assessment. Previous studies have reported that conventional echocardiography has some inherent limitations, including the inability to image the whole structure simultaneously, geometric assumptions, and the possibility of imperfect alignment , 36. ForOur study had several limitations. First, the limited size of the present study population may have affected the power of the present analysis. The presented study was designed as a single-center study; thus, validation from multiple centers could not be obtained. Therefore, to support the viewpoint from this study, larger studies are needed with a higher number of patients and with multiple centers. Second, although patients with poor image quality were excluded as much as possible, RT-3DE imaging could also have led to some errors in the volume measurement due to its definition of the endocardial border.The current study demonstrated an independent association between pre-operative Tmsv16-SD% and the occurrence of short-term adverse outcomes after CABG in 3VD patients with preserved or mildly reduced LVEF. Tmsv16-SD% obtained by RT-3DE may be useful for additional evaluation of LV systolic function and can improve echocardiographic evaluation levels in pre-operative risk classification.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University. The patients/participants provided their written informed consent to participate in this study.F-JY, WL, and JL contributed towards the conception and design of the study. JL collected data of clinical trials and drafted the manuscript together with RF and C-LL. Y-QL and D-HL revised and edited the final version of the manuscript for important intellectual content and gave the technical support. JL and RF contributed equally to the acquisition of data, e.g., RF contributed in examination, and JL contributed towards the to patient collection and gave technical support. JL and RF performed data analysis together, including imaging, computation and statistical analysis, and edited the manuscript together. All authors read and approved the final manuscript.


The A2BAR mRNA expression were measured. A mouse AMI model was established by left anterior descending coronary artery (LADCA) ligation. MDSCs were analysed by FACS and immunofluorescence staining (of heart tissue). A2BAR mRNA expression was assessed by qRT-PCR. Myocardial injury was detected by HE staining. Myocardial cell apoptosis was analysed by immunohistochemistry. Cardiac systolic function was evaluated by transthoracic echocardiography.In AMI patients, the circulating MDSC ratio and A2BAR mRNA expression . In AMI model mice, the percentage of MDSCs was increased in the circulation and infarcted heart and decreased in the spleen. MRS-1754-mediated A2BAR inhibition decreased the MDSC ratio in the circulation and infarcted heart and prevented the decrease in MDSC number in the spleens of mice with AMI. A2BAR blockade inhibited myocardial cell apoptosis, alleviated myocardial inflammatory injury, and improved myocardial systolic function in the AMI mouse model. Similar results were found in mice after splenectomy. Additionally, spleen-derived MDSC injection increased the MDSC ratio in the infarcted heart, increased myocardial cell apoptosis, aggravated myocardial injury, and decreased cardiac systolic function in mice with AMI.In AMI patients, the circulating MDSC ratio was increased and positively correlated with A2BAR alleviates myocardial damage and improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation after AMI.Spleen-derived MDSC mobilisation aggravates myocardial inflammatory injury within 24 h of AMI.2BAR promotes spleen-derived MDSC mobilisation within 24 h of AMI.A2BAR improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation.Blocking ABlocking A Recent + and Gr-1+, while human MDSCs are mostly CD11b+ and CD14- [Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cell progenitors and precursors and are generated during biological stress, including tissue damage and inflammation . Mouse Mnd CD14- . These cnd CD14- , and incnd CD14- , acute cnd CD14- . A recennd CD14- . Our prend CD14- . Therefo2B adenosine receptor (A2BAR), a member of the adenosine receptor family, plays critical roles in tumours and cardiovascular diseases through its proangiogenic effects [2BAR attenuates cardiac remodelling, ameliorates left ventricular dysfunction, and improves cardiac outcomes after AMI in animal models [2BAR blockade or knockout reduces tumour-associated MDSC accumulation and leads to a significant delay in tumour growth [2BAR can regulate MDSC mobilisation in AMI remains unclear.A effects . Blockadl models . In manyr growth . HoweverTherefore, this study was designed to confirm whether MDSCs infiltrate myocardial tissue and further lead to myocardial injury during AMI. Furthermore, we aimed to investigate the origin of MDSCs. Moreover, a preliminary mechanism of and possible strategies for intervening in MDSC mobilisation are discussed.2.2.1.Supplementary Table 1). All participants agreed to participate in the study and provided written informed consent. The study protocol was approved by the Ethics Committee of Yi Ji Shan Hospital.Blood samples were collected from the peripheral veins of 10 AMI patients who underwent emergency coronary angiography (CAG) and were hospitalised in the cardiology ward of Yi Ji Shan Hospital affiliated to Wan Nan Medical College. Ten age- and sex-matched patients without coronary artery disease, as confirmed by CAG, were included as controls. There was no significant difference in the basic data between the 2 groups (2.2.n = 5): mice did not receive any operations. Sham group (n = 5): mice underwent control operation without coronary artery ligation. AMI group (n = 10): mice underwent LADCA ligation. A2BAR blocking group (n = 10): mice received A2BAR antagonist MRS1784 (1 mg/kg) [n = 10): mice underwent splenectomy before LAD ligation. MDSCs injection group (n = 10): the splenectomy mice immediately received isolated MDSCs (2 × 105/ml) injection via the medial canthus vein before LADCA ligated.Male C57BL6 mice  were used according to the guidelines of the Animal Ethics Committee of Yi Ji Shan Hospital affiliated to Wan Nan Medical College. Mice were randomly divided into 6 groups. Control group (1 mg/kg)  intraperAMI was induced by ligation of the left anterior descending artery (LADCA) . BrieflySplenectomy was performed as previous described . A skin 2.3.g for 20 min. White blood cells were isolated from the peripheral blood of mice by using erythrocyte lysate . Mononuclear cells were obtained from the mouse spleen and heart with a gentleMACS Dissociator.Mononuclear cells were isolated from the peripheral venous blood of patients on hydroxypropyl methylcellulose by centrifugation at 500×8 nucleated cells/mL in medium. Add FcR blocker, isolation cocktai and RapidSpheres™ to the resuspended cells suspension in turn, mix and incubate for 5 min at room temperature. Subsequently, MDSCs were isolated through a magnet. FACS was used to evaluate the separation efficiency of MDSCs isolated from the spleen. We found that the isolation efficiency was approximately 59.4%  according to the manufacturer's instructions. Disrupt spleen in PBS containing 2% foetal bovine serum (FBS). Then, the cell suspension was filtered through a 70 μm mesh nylon strainer to removed aggregates and debris. After centrifugation (300 × g for 10 min), the cells were resuspended at 1 × 102.4.+ CD14–) and mouse MDSCs (CD11b+ Gr-1+). All antibodies and the FACScan flow cytometer were purchased from BD Biosciences.Isolated cells were fixed in 1% paraformaldehyde  and incubated with PE-conjugated antihuman CD14, FITC-conjugated antihuman CD11b, PE-conjugated antimouse CD11b, and FITC-conjugated antimouse Gr-1 antibodies for 1 h on ice. After washing three times with 1% BSA in PBS, the cells were analysed with a FACScan flow cytometer to detect human MDSCs (CD11b2.5.+ Gr-1+) were detected by inverted phase contrast fluorescence microscopy .Twenty-four hours later, the mice were sacrificed by intraperitoneal injection of sodium pentobarbital (130 mg/kg). Heart tissue specimens were harvested and prepared for immunofluorescence staining . Heart t2.6.TM RT reagent kit  with gDNA Eraser. A2BAR  and GAPDH  primers were used. A2BAR expression was normalised to GAPDH expression and calculated by the 2−ΔΔCt method.Total RNA was isolated from mononuclear cells using the TRIzol method according to the manufacturer’s protocol. The concentration and purity of RNA were assessed by determining the relative absorbance ratio at 260/280 with a NanoDrop 2000 spectrophotometer . cDNA was synthesised using a PrimeScript2.7.Hematoxylin–eosin (HE) staining was performed to evaluate heart tissue damage. Paraffin heart tissue sections were stained with HE by using a HE staining kit  according to the manufacturer’s protocol. Morphological changes in myocardial tissue were assessed using an optical microscope. Cardiac muscle structure, myocardial cell fibrils swelling and arrangement, and granulocytes infiltration in heart specimens were observed and measured . A semiqTetrazolium chloride (TTC) staining was performed to detect the area of myocardial infarction . FollowiImmunohistochemical staining was performed to detect the nuclei of apoptotic myocardial cells by using a TUNEL staining kit  according to the manufacturer’s protocol. The number of apoptotic cells with TUNEL-positive nuclei was counted.2.8.Twenty-four hours after MI model establishment, the cardiac systolic function of the mice was evaluated by transthoracic echocardiography. The ejection fraction (EF), left ventricular shortening (LVFS), left ventricular end diastolic diameter (LVIDd), and left ventricular systolic inner diameter (LVIDs) were calculated.2.9.t test (2 groups) or one-way ANOVA (≥3 groups) was used to assess differences among groups. Pearson correlation analysis was used to assess the correlation between the circulating MDSC ratio and A2BAR mRNA expression. p < 0.05 was considered statistically significant.Statistical analyses were performed with GraphPad Prism version 9.0. All continuous variables are expressed as the mean ± SD. Student’s 3.3.1.2BAR mRNA expression in mononuclear cells by qRT-PCR. The results showed that A2BAR mRNA expression was also increased in AMI patients compared to controls   was injected intraperitoneally into mice before LADCA ligation  and that A2BAR blockade improved cardiac systolic function after MI.Further TUNEL staining showed that After AMI . Moreove2BAR blockade effectively alleviates myocardial injury and improves cardiac systolic function after AMI.These results suggested that A3.4.2BAR blockade, splenectomy significantly decreased the MDSC ratio in the circulation  were isolated and injected into mice that underwent splenectomy via the medial canthus vein before LADCA ligation (2BAR blockade and splenectomy, MDSC injection significantly increased the MDSC ratio in the circulation (2BAR blockade and splenectomy (To further verify that spleen-derived MDSC mobilisation led to myocardial injury after AMI, spleen-derived MDSCs (2 × 10ligation . We founculation . The MDSenectomy .2BAR blockade and splenectomy decreased the MDSC ratio and that MDSC injection increased the ratio of MDSCs in the infarcted hearts of mice with AMI (Immunofluorescence also revealed that both A3.5.2BAR blockade, splenectomy alleviated myocardial injury (We examined whether splenectomy affects myocardial injury and function in mice with AMI. We found that similar to Al injury  in the il injury .2BAR blockade and splenectomy, MDSC injection aggravated myocardial injury (Further study showed that compared to Al injury , and decl injury . These r4.2BAR blockade can inhibit myocardial cell apoptosis, alleviate myocardial inflammatory injury, and improve myocardial systolic function, mainly via prevention of spleen-derived MDSC mobilisation after AMI.In the present study, we revealed that spleen-derived MDSCs mobilise into the circulation and infarcted heart tissue, leading to myocardial cell apoptosis and tissue inflammatory damage and ultimately impairing cardiac systolic function. A2BAR prevented spleen-derived MDSC mobilisation, alleviated myocardial injury, and improved the cardiac systolic function of mice subjected to LADCA ligation. This suggests that preventing the mobilisation of spleen-derived MDSCs is a potential strategy for AMI treatment.AMI is an acute fatal disease characterised by massive immune cell infiltration into the myocardium following ischaemia and reperfusion . ExploriMDSCs, including immature granulocytes, macrophages, and dendritic cells at different stages of differentiation, are well-known immunosuppressive cells that play a decisive role in many disease states . A widel+ Gr-1+ cells are the major contributors to inflammatory reactions and organ damage [The spleen is an easily accessible peripheral immune organ and is thought to be the source of large quantities of immunocytes, including MDSCs, lymphocytes and macrophages ,39. Varin damage ,16,40. I2BAR is a G-protein coupled adenosine receptor that is widely expressed in haematopoietic cells and plays an important role in many pathophysiologic conditions [2BAR is expressed in Gr1+ cells, and evidence has revealed that A2BAR promotes the accumulation of intratumoral CD11b+ Gr1+ cells in many tumour models and that pharmacological blockade of A2BAR significantly reduces tumour growth [29Anditions . A2BAR ivia A2BAR signalling . Some biomolecules and synthetic drugs protect organs, including the heart, liver, and brain, against ischaemic–reperfusion injury gnalling .2BAR mRNA was highly expressed in the mononuclear cells of AMI patients. This result indicates that A2BAR may be involved in MDSC mobilisation during AMI. To further explore this issue, MRS-1754, a selective A2BAR antagonist [2BAR with MRS-1754 prevented spleen-derived MDSC mobilisation and improved the cardiac systolic function of mice with LADCA ligation.In this study, we found that Atagonist ,49, was 5.2BAR plays a pivotal role in myocardial injury by facilitating spleen-derived MDSC mobilisation during the acute phase of AMI. Blocking A2BAR with MRS-1754 improves cardiac systolic function. This effect is, at least in part, dependent on impaired spleen-derived MDSC mobilisation. Therefore, our study suggested that A2BAR-mediated spleen-derived MDSC mobilisation is a potential therapeutic target for AMI.In our study, we first revealed that A6.2BAR signalling pathway in MDSCs need to be further studied. Furthermore, we only explored the mechanism of MDSC mobilisation within 24 h after AMI. Third, small number of patients were included in this study. It may affect the credibility of the results. Therefore, we would conduct a larger sample size study to verify the results. Therefore, the mechanism of MDSC mobilisation during the recovery period after AMI needs to be further explored.There are two major limitations to this study. First, we did not explore the role of MDSC subtypes in AMI. Changes in the AClick here for additional data file.