Mass COVID-19 vaccination campaigns have helped impede the COVID-19 pandemic. In rare cases, some vaccines have led to vaccine associated myocarditis in a specific subset of the population, usually young males. Cardiac magnetic resonance (CMR) can reliably diagnose vaccine associated myocarditis, but follow-up data of CMR proven acute myocarditis is scarce.Nine patients with acute vaccine associated myocarditis underwent baseline and follow-up CMR examinations and were compared to baseline parameters at initial presentation and to a group of 20 healthy controls. CMR protocol included functional assessment, T1 and T2 mapping, T2 signal intensity ratio, strain feature tracking, and late gadolinium enhancement (LGE).n = 9, aged 24 ± 6 years, 8 males) underwent CMR follow-up after an average of 5.8 ± 4.3 months. All patients showed a complete resolution of visual myocardial edema while also demonstrating a reduction in overall LGE extent from baseline to follow-up , although visual LGE was still noted in all patients. Left ventricular ejection fraction was normal at baseline and at follow-up  as well as compared to a healthy control group . T1  and T2 relaxations times  normalized at follow-up. Most patients reported a resolution of clinical symptoms, while two (22%) reported new onset of exertional dyspnea.Myocarditis patients (Patients with COVID-19 vaccine associated acute myocarditis showed a complete, uncomplicated resolution of myocardial inflammation on follow-up CMR, which was associated with a near complete resolution of symptoms. Minor, residual myocardial scarring was present on follow-up LGE imaging. The long-term implications of the remaining myocardial scar-tissue after vaccine associated myocarditis remain unknown warranting further studies. The start of the coronavirus disease-19 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 prompted a world-wide effort to curtail the spread of the pandemic. One possible way to achieve this was the development of safe and effective vaccines. This effort cumulated in a rapid deployment of a few COVID-19 vaccines, most commonly and notably the Ad26.COV2-S [recombinant] (Janssen) vaccine, the mRNA-1273 (Moderna) vaccine, the BNT162b2 (Pfizer/BioNTech) vaccine, and the ChAdOx1-S [recombinant] (AstraZeneca) vaccine. Shortly after mass immunization programs began, reports of vaccine associated adverse reactions, such as fever, deep venous thrombosis, and myocarditis, started to emerge. Myocarditis and pericarditis are rare cardiovascular adverse vaccine reactions with an estimated incidence of approximately 0.48 cases per 100,000 administered vaccines . In accoThis retrospective study was approved by the appropriate institutional ethics committee and performed in concordance with the Declaration of Helsinki and International Conference on Harmonization of Good Clinical Practice. The requirement for written informed consent was waived. Patients who underwent initial CMR with diagnosis of acute vaccine-associated myocarditis and subsequent follow-up CMR at the Department of Diagnostic and Interventional Radiology from September 2021 to August 2022 were retrospectively identified.Initial symptoms for referral for CMR included exertional dyspnea, chest pain, fever, or palpitations with associated elevated troponin T, within hours or days of receiving a COVID-19 vaccine. All patients received at least one dose of a COVID-19 vaccine approved for use in the European Union. Initial CMR results were positive for myocarditis as defined by the 2018 Lake Louise criteria . ReasonsThe control group consisted of healthy subjects without previous myocarditis and no cardiovascular disease history who underwent CMR for study control reasons. Controls were age-matched to the myocarditis cohort and had normal CMR results without structural abnormalities.All CMR examinations were performed using clinical whole-body MRI systems . Signal reception was achieved by a 16-channel torso coil using a digital interface. A signal intensity correction algorithm  was utilized to correct for torso-coil related signal inhomogeneities. Short-axis, 2-chamber, 3-chamber, and 4-chamber cine views were acquired using electrocardiogram gated, breath-hold steady state free precession sequences for functional analysis. A transversal respiratory-gated fat-suppressed T2-weighted fast spin echo sequence  was acquired for the assessment of axillary and mediastinal lymphadenopathy, which was also included in the follow-up protocol. Myocardial edema was visualized using T2-weighted short-tau inversion-recovery sequences in short axis and transversal views. T2 STIR images were also used to calculate T2 signal intensity ratio. Myocardial T1 and T2 mapping was performed in end-diastolic short axis views with acquisition of apical, midventricular, and basal sections. A six-echo gradient spin-echo sequence (GraSE) was applied for myocardial T2 mapping . MyocardImage analysis was performed by a board-certified cardiovascular radiologist (J.A.L with 10 years of experience in CMR) and a radiology resident (D.K. with 4 years of experience in CMR) using dedicated software . Papillary muscles were included for the volumetric quantification of the left ventricle. Global systolic radial, longitudinal, and circumferential strain were calculated by using feature tracking strain analysis software  using short-axis, 2-chamber, and 4-chamber balanced steady state free precession cine imaging.Focal areas of regional high signal intensities in a non-ischemic distribution pattern on T2 short-tau inversion-recovery and on LGE images were visually assessed by consensus agreement of the two readers. Quantitative markers of myocardial edema  and myocardial injury and fibrosis  were calculated as previously reported –13. MotiT-test was used. A paired T-Test was used for the comparison of means in variables recorded at baseline and at follow-up. Mann–Whitney-U test was used for non-normal distributed data. Dichotomous variables were compared by using the χ2 test. One-way analysis of variance (ANOVA) followed by Tukey post-hoc multiple comparison tests was performed to compare variables in three groups. The level of statistical significance was set to P < 0.05.Prism  and Jamovi  were used for statistical analysis. Data are given as means ± standard deviation or as percent to absolute frequency. Continuous variables were summarized as median with interquartile range (IQR) or as mean ± standard deviation, as appropriate. Normal distribution was checked using the Shapiro–Wilk test. For comparison of continuous variables and inter-individual variables the Student’s n = 7, 78%) of which one was a first dose, four were the second dose, and two were a booster dose (third vaccination); Moderna  of which it was a second dose; Janssen  first dose (only one dose required). Highly sensitive troponin T levels were elevated in all nine patients (median 644 ng/l [IQR: 159–930 ng/l]). All patients were treated with either cardioprotective or anticoagulative medication: 6 out of 9 (67%) were treated with beta-blockers, 4 (44%) with ACE-inhibitors, 2 (22%) with low molecular weight heparin, and one (11%) with a diuretic.In total, nine patient datasets with baseline and follow-up CMR  were available for retrospective analysis. A detailed comparison with 20 age-/and gender-matched controls  is given in All nine had clinical symptoms of acute myocarditis at initial scan: 8 out of 9 (89%) presented with chest pain, 3 (33%) with exertional dyspnea, and 2 (22%) with occasional fever. At follow up, only 1 out of 9 (11%) patients reported persistent chest pain, 2 patients reported new onset of exertional dyspnea (22%), and none reported fever. Patients did not report signs of infection prior to vaccination. Median number of days to symptom onset after vaccination was 0 days , median time to initial CMR was 6.5 days , and median time to follow-up was 3.0 months .n = 9, 100%), followed by midwall  or diffuse transmural involvement . LGE distribution according to the American Heart Association 17-segment heart model at baseline and at follow-up is depicted in p-values within the text are derived from a paired t-test analysis between baseline and follow-up data unless otherwise noted. All patients demonstrated a significant reduction of overall LGE extent from baseline to follow-up , although persistent LGE was noted in all patients at follow-up, consistent with post-inflammatory scar tissue. In two cases (22%) visual LGE on follow-up was barely discernable, and in all cases visual LGE demonstrated a reduction in signal intensity. Septal LGE sparring was noted in most patients and only 2 patients demonstrated septal LGE. T2 relaxation times were noted to be significantly higher at baseline compared to follow-up . T1 relaxation times were also higher at baseline, although not statistically significant .T1 and T2 relaxation times from the same scanner at the same field strength (1.5T) were available for 8 patients while one patient received both, baseline and follow-up scans using a 3.0T MRI scanner. T1 and T2 maps from this patient were excluded from consecutive analysis. All patients demonstrated positive LGE findings typical for acute myocarditis. The most common LGE distribution pattern was subepicardial (p = 0.10), left ventricular end diastolic volume , or left ventricular end diastolic volume index . A significant reduction in axillary lymph node size was noted between baseline and follow-up . A slightly significant improvement in systolic global circumferential strain (GCS) was noted from baseline to follow-up . No such statistically significant difference was noted for systolic global radial strain  or global longitudinal strain  between baseline and follow-up. No significant differences between baseline and follow-up investigation were noted for left ventricular ejection fraction . The number of received doses also seems to play a role as vaccine associated myocarditis is less likely to be noted after the first dose, usually causing symptoms after the second or third booster dose, suggesting that prior exposure is necessary for the development of vaccine associated myocarditis. However, the exact pathomechanism of vaccine associated myocarditis remains unknown. Current theories focus on a hypersensitivity reaction or cross reactions of spike proteins with myocardial contractile proteins , 34.Collaborating previously published findings, we found vaccine associated myocarditis to predominantly affect younger males , 3, 35. Our study suffers from limitations, including the small patient cohort and variable follow-up times. Most statistical comparisons were not corrected for multiple testing due to the small data set. As of date, there are no published consensus criteria for the diagnosis of vaccine associated myocarditis after COVID-19 vaccination. We therefore defined it as myocarditis like symptoms after COVID-19 vaccination with abnormal CMR findings in previously healthy people accompanied with elevated troponin T levels within a reasonable number of days of COVID-19 vaccination. Not all CMR examinations were performed on the same machine or at the same field strength, diminishing data sets available for statistical analysis. Furthermore, the reference standard for diagnosis of myocarditis, endomyocardial biopsy, was not performed as it is not part of the best standard of care practice at our institution. Further studies comparing CMR findings in vaccine associated myocarditis with other causes of myocarditis akin to data published by Fronza et al. offer an outlook for potential future research .Vaccine associated myocarditis tends to affect younger, predominantly male patients and shows abnormal CMR findings such as focal or diffuse edema, elevated T1 and T2 relaxation times, and LGE. While the overall prognosis seems to be favorable and a rapid resolution of symptoms is observed, reduced, yet persistent LGE findings indicative of myocardial fibrosis in light of complete resolution of edema have been noted. Further studies are needed to examine the long-term effects of the remaining scar-tissue and develop recommendations for patients with a history of vaccine associated myocarditis regarding booster doses.The raw data supporting the conclusions of this article can be provided upon reasonable request by the authors, without reservation.The studies involving human participants were reviewed and approved by Ethikkommission der Medizinischen Fakultät Bonn, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn. Written informed consent from the participants or their legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.JL and DKr contributed to the conception and design of the study and performed the statistical analysis. DKr organized the database and wrote the first draft of the manuscript. JL, AI, DKu, DKr, CP, and SZ wrote sections of the manuscript. All authors contributed to the manuscript revision, read, and approved the submitted version.


The carbohydrate antigen 125 (CA125) was proven as a robust biomarker for risk stratification in adults with heart failure. This is the first study analyzing CA125 in a cohort of infants with congenital diaphragmatic hernia (CDH).Sixty-eight infants with CDH, treated at the University Children’s Hospital Bonn (Germany), between January 2018 and February 2021, were prospectively enrolled for analysis. CA125 values were measured at the following timepoints: 6,12, 24, 48 h, and during ECMO daily from day 1 to day 7.In infants not surviving to discharge, CA125 values were significantly higher at day 1 . Infants with subsequent need for ECMO presented significantly higher CA125 values at 12 h of life. During ECMO, CA125 values measured at day 1 were significantly higher in infants not surviving to discharge. In the ROC analysis, a CA125 value of ≥10 U/ml was calculated as optimal cut-off for the prediction of ECMO and in-hospital mortality. CA125 values correlated significantly with the severity of PH and ventricular dysfunction.CA125 values correlate significantly with echocardiographic markers of PH and ventricular dysfunction and correlate significantly with parameters of disease severity .CA125 was proven as robust cardiac biomarker in adult cohorts.Information about the utility as a biomarker in neonatal cohorts is lacking.This is the first study analyzing CA125 as a cardiac biomarker in a cohort of infants with congenital diaphragmatic hernia (CDH).CA125 correlates significantly with markers of echocardiographic assessment (PH and ventricular dysfunction) in infants with CDH and helps to identify infants at high risk for ECMO and in-hospital mortality.The results underline the need for the inclusion of cardiac biomarkers in the clinical routine in neonates at risk for cardiopulmonary failure. The identification of early cardiac biomarkers is essential, as an optimization of initial drug therapy, the fast implementation of extracorporeal membrane oxygenation (ECMO), or transition to ECMO centers can improve care and outcome of infants with CDH. Several studies focused on the evaluation of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) as cardiac biomarker in infants with CDH.7 However, studies concerning biomarkers with alternative pathophysiological pathways are needed, because of inconsistent data regarding natriuretic peptides in CDH and possible intra- and inter-individual fluctuations in the first days of life.4Despite decades of investigation and novel therapeutic approaches in the management of infants with congenital diaphragmatic hernia (CDH), mortality rates remain high for those with severe defects.9 The high molecular weight glycoprotein CA125 is synthesized by epithelial serous cells. CA125 presents a complex molecular structure with an intracytoplasmic transmembrane domain and an extracellular domain consisting of oligosaccharide chains.10 As a tumor marker, CA125 is well established to monitor therapeutic effects in ovarian cancer.11 The mechanism of CA125 elevation in heart failure and PH can be explained by different mechanisms. As CA125 is a soluble glycoprotein, it can be released from tissue surfaces or produced by epithelial cells in response to stimuli as mechanical stress and inflammation.13 Patients with heart failure and signs of congestion are at risk for serosal effusion of the pleura, pericardium, or peritoneum, which potentially stimulates CA125 release from epithelial cells.15 Furthermore, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were found to correlate significantly with CA125 levels in patients with heart failure.12 It is well established that cytokines have a potential role in the pathophysiology of heart failure and cytokines can have negative inotropic effects on cardiac function.17 The link between inflammatory cytokines and disease severity in infants with CDH was recently evaluated.18 Studies in adults revealed that CA125 correlates significantly with mortality in patients with acute heart failure and is associated with the hemodynamic status and echocardiographic parameters.23 However, research in the pediatric field is scarce.8 CA125 seems to be an ideal candidate as biomarker in infants with CDH because it is widely available at economic costs and due to its potential to mirror both cardiac function and patient’s outcome. The aim of this study was to identify CA125 as a useful predictor for PH and ventricular dysfunction in infants with CDH. Furthermore, the study aimed to evaluate CA125 as a predictor for ECMO and mortality in these infants.The plasma carbohydrate antigen 125 (CA125) demonstrates an increased expression in adult and pediatric patients suffering from heart failure and PH.Infants with CDH admitted to the NICU at the University Children’s Hospital of Bonn, Germany in the study period from 06/2018 to 02/2021 were eligible for study participation. Patients were prospectively enrolled in the study after informed written consent was obtained from the parents or legal representative. The study was approved by the local ethics committee of the Medical Center of the University of Bonn . Infants with an underlying congenital heart defect or primary palliative care were not included in the study.1Prenatal assessment and risk stratification included estimation of the lung size using the observed-to-expected lung-to-head ratio and liver position on ultrasound ). Right- and left-sided CDH and infants with intrauterine fetal endoluminal tracheal occlusion procedure were included in the analysis. Postnatal CDH management was performed according to the recommendations of the CDH Euro Consortium group. Treatment consisted of the following key strategies: (I) lung-protective ventilation, (II) treatment of PH and right-ventricular, left-ventricular, or biventricular dysfunction (RVD/LVD/BVD), (III) in case of oxygenation failure implementation of veno-venous extracorporeal membrane oxygenation (ECMO), and (IV) delayed surgical repair.2 > 70 mmHg with pH <7.15, (d) peak inspiratory pressure ≥28 cmH2O or mean airway pressure ≥17 cmH2O, (e) systemic hypotension resistant to fluid and inotropic therapy.1Criteria for ECMO therapy were defined as follows: (a) preductal oxygen saturation <85% or postductal saturation <70%, (b) oxygenation index (OI) ≥ 40 consistently present, (c) PaCOBlood samples for CA125 analysis were collected at the following timepoints after birth: 6, 12, 24, and 48 h. In cases where ECMO was required, additional blood samples were collected daily from day 1 to day 7 during veno-venous ECMO. Blood samples were collected via an indwelling arterial catheter. CA125 serum levels (unit: U/ml) were measured using the electrochemiluminescence immunoassay (Elecsys CA 125 II Assay) on cobas e 801 analyzer .Echocardiography was performed using a Philips CX50 Compact Extreme Ultrasound system with a S12‐4 sector array transducer . For echocardiographic assessment of PH and RVD/LVD/BVD, standardized measurements at 1–4 h after birth  and 48 h after birth were analyzed. All echocardiographic data were reviewed independently by two neonatal echocardiographers blinded to the clinical course of the respective infants.25 Ventricular systolic function was graded based on the subsequent quantitative information, if available: fraction shortening, S’ velocity on tissue Doppler imaging, mitral or tricuspid annular plane systolic excursion (TAPSE), or ventricular size, and output.PH was graded as following: (I) none, (II) <2/3 systemic pressure (mild), (III) 2/3 to systemic systolic pressure (moderate), and (IV) suprasystemic systolic pressure (severe). Echocardiographic PH evaluation included: (a) ductus arteriosus flow direction, (b) the intraventricular septum position, and (c) the tricuspid valve regurgitation. RVD, LVD, and BVD was assessed separately using a combination of qualitative and quantitative measures based on international guidelines.Patients were allocated to one of the two subgroups according to the primary endpoint: (group A) need for ECMO or early death within 48 h after birth (despite fulfilling ECMO criteria); (group B) no need for ECMO. Secondary endpoints included in-hospital mortality and length of mechanical ventilation (MV).n) with percentage. Using receiver operating characteristic (ROC) curve analysis, a CA125 cut-off value was evaluated to predict the secondary clinical endpoint . For comparison of continuous variables, Mann–Whitney U-test was used. For categorical variables, Fisher’s exact test and chi-square test was applied. Correlations between variables were evaluated by Pearson correlation coefficients and were only applied if any two measurements were taken at the same point in time. A p value <0.05 was considered significant. The statistical analysis was performed using the statistical software .Demographic data and baseline characteristics are presented as median with interquartile range or absolute number (p = 0.013) as compared to infants allocated to group B. When analyzing the secondary endpoint in-hospital mortality separately, CA125 values were significantly higher at day 1  in those patients who died.Sixty-eight infants (6 infants outborn) with CDH were prospectively enrolled in this study. Demographic data are summarized in Table p = 0.046) compared to ECMO survivors. At later timepoints, CA125 values did not differ significantly between subgroups.For 24 patients, daily CA125 measurements during ECMO are displayed in Fig. Correlation analysis of outcome parameter, baseline characteristics, and cardiac assessment are illustrated in Table p = 0.004) compared to infants with none–severe PH (mild or moderate). This trend was not seen in PH assessment at 48 h. When analyzing infants presenting an isolated PH (without RVD) on admission (23 infants), PH did not correlate significantly with mean CA125 values at 6 and 12 h. RVD on admission showed significant correlation with CA125 values at 24 h, without significant findings at the other timepoints of CA125 measurement. In contrast, the presence of LVD on admission was found to correlate significantly with mean CA125 values at 48 h. Mean CA125 values measured at 6 and 12 h were significantly correlated with BVD.Prevalence and course of PH severity and ventricular dysfunction on admission and at 48 h are displayed in Fig. p = 0.001). Additionally, 86% of the infants with a CA125 value ≥10 U/ml at 6 h did not survive to discharge (p = 0.001). The ROC curves of CA125 measurement at 6, 12, 24, and 48 h to predict ECMO/early death and in-hospital mortality are displayed in Fig. In all, 100% of the infants presenting a CA125 value ≥10 U/ml at 6 h of life had subsequent need for ECMO  with secondary PH and demonstrated that a CA125 cut-off >35 U/ml was highly sensitive and specific for the presence of PH.8 Children without heart disease and PH findings  presented with significantly lower CA125 levels with a mean value of 13.8 U/ml. CA125 values were found to correlate significantly with echocardiographic markers of RVD . Similarly, we could demonstrate a significant correlation between CA125 values and echocardiographic markers of PH as well as ventricular dysfunction. But this association was not evident in infants with CDH presenting PH without signs of ventricular dysfunction, assuming that ventricular dysfunction seems to be the major determinant for CA125 release. Infants with PH without ventricular dysfunction presented overall a mild course of PH and CA125 seems to be ineffective as a biomarker in this subgroup.This is the first study evaluating serial measurements of the biomarker CA125 in the first 48 h of life and during ECMO in infants with CDH. A major aim of this study was to evaluate the glycoprotein CA125 as a biomarker of the cardiac status in infants with CDH. According to our data, CA125 values correlated significantly with both PH severity and ventricular dysfunction. In the past decade, the potential of CA125 as a prognostic biomarker in adults with acute and chronic heart failure was evaluated.The second aim of this study was to prove CA125 as a predictor of patient’s outcome. Our data revealed that CA125 seems to be useful as an early predictor for the need of future ECMO in CDH infants and to identify infants at risk for in-hospital mortality. In most infants, ECMO was initiated after 12 h of life (median 18 h). Therefore, the early measurement of CA125 could be a relevant tool for guidance of vasoactive therapy, the decision to evaluate ECMO indication, or to transfer infants to an ECMO center when ECMO is not available. Further studies aiming to analyze CA125 for risk stratification of ECMO are lacking. In our cohort, infants with a need for ECMO had a lower GA than infants not requiring ECMO. As CA125 values seems to correlate negatively with GA, data regarding CA125 measurements during ECMO need to be interpreted carefully.Longitudinal CA125 measurement during ECMO in our study were intended to early identify infants with CDH who can be successfully weaned from ECMO and infants who will fail to wean from ECMO. In our cohort, CA125 values measured during ECMO tended to increase over time from day 1 to day 7, which is a contrary finding to the observed improvement of PH and ventricular dysfunction during ECMO. Only values measured on day 1 during ECMO differed significantly between ECMO survivors and non-survivors, with significantly higher CA125 values in infants who failed to wean from ECMO. Therefore, only early CA125 measurements at the beginning of ECMO rather than longitudinal CA125 measurements during ECMO seems reasonable. Infants during ECMO are likely to present a systemic inflammatory response syndrome, with capillary leak and fluid overload, causing pleural effusions and ascites. Additionally, blood flow via the return cannula during ECMO lead to increased right atrial and central venous pressures, inducing changes in the blood distribution of the central venous system and splanchnic veins. These changes potentially influence the CA125 release from epithelial cells and lead to an increase of CA125 values seen during ECMO.31 Preterm infants aged 24–32 weeks’ GA presented mean CA125 values of 68 U/ml, infants aged 33–37 weeks’ GA presented mean CA125 values of 34 U/ml, and term infants (>37 weeks’ of GA) presented mean values of 10 U/ml. These findings are in line with our data, presenting a negative correlation of the GA and CA125. Two explanations are possible. First, CA125 is highly expressed by fetal/placental tissues  and levels are high during rapid fetal growth in early phases of GA, with a decreasing expression to later phases of gestation.32 Second, immaturity of the fetal hepatic clearance of glycoproteins (as CA125) is leading to higher CA125 concentrations in earlier stages of gestation.31 CA125 between the first year of life seems to remain at low levels in comparison to cord blood samples of term infants. Data of this Finnish cohort are not comparable one to one with our data, because all blood samples were taken in infants with CDH and cord blood samples were not analyzed. But the data emphasize that a CA125 value ≥10 U/ml in newborn infants with CDH is a reasonable cut-off when comparing both data sets.Standardized reference values for CA125 in infants are available from one study, with 105 cord blood samples from preterm and 28 samples from term infants.CA125 levels at 12 h were found to correlate significantly with liver herniation in our cohort. As liver herniation is a marker of disease severity and is associated with higher incidences of ventricular dysfunction and PH, these infants potentially express higher CA125 values due to right-ventricular fluid overload, causing central venous congestion and ascites. In case of LVD with high postcapillary pressures, infants tend to produce more pleural effusions, leading to CA125 elevation.21 CA125 seems to outperform natriuretic peptides in patients with combined left and right heart failure. Additionally, CA125 values are not altered in patients with renal impairment and therefore provide better information in cases of acute or chronic renal failure, as recently shown in large adult populations.34 Other data suggest that the risk stratification in acute heart failure can be optimized when combining CA125 with natriuretic peptides.19 A combination of both parameters might be a reasonable approach in a neonatal cohort for future studies.When comparing CA125 with established biomarker such as natriuretic peptides, CA125 seems to have potential advantages in prognosing long-term mortality and RVD in patients with acute heart failure.In summary, CA125 seems to be an ideal biomarker to monitor the clinical course of infants with CDH, as it correlates significantly with PH severity and ventricular dysfunction. Additionally, a CA125 cut-off value of ≥10 U/ml at 6 and 12 h is highly predictive for ECMO and in-hospital mortality. Future prospective trials are required to further analyze CA125 as a biomarker, because it could potentially help to optimize initial treatment and could be a helpful clinical tool for low-volume as well as high-volume CDH treatment centers.Due to study design, this study has some limitations. A comparative cohort is missing, because multiple laboratory assessments and at least two echocardiographic assessments in 48 h were performed, which raises problems of ethical and parental approval in a healthy control group. Nevertheless, a comparison group would facilitate the interpretation of results and statistical effects. The echocardiographic assessment of PH and ventricular dysfunction was based to some extent on a qualitative grading, with the risk of observer-related bias. We tried to minimize this bias by reviewing the echocardiographic data independently by two neonatal echocardiographers, blinded to the clinical course of the respective subject.This is the first prospective study evaluating CA125 as a cardiac biomarker in a cohort of infants with CDH. Our data demonstrate a correlation of CA125 with PH and ventricular dysfunction and an increased expression in infants with a more complicated hospital course or poor outcome .


Methods and Results: Preoperative and postoperative Doppler echocardiography data were evaluated for 120 patients after AVR. The patients’ mean age was 67.7 years; 55% of the patients were male. Forty-four (37%) patients suffered from MACCE during a mean follow-up period of 3.6 ± 2 years. The following hemodynamic parameters at follow-up were associated with lower relative indexed LV mass (LVMI) regression: lower postoperative indexed effective orifice area, greater mean transvalvular pressure gradient (MPG), greater stroke work loss (SWL), and concentric or eccentric LV remodeling mode. The following hemodynamic parameters at follow-up were associated with a higher risk of MACCE: higher valvuloarterial impedance (ZVA), greater SWL, greater MPG, greater relative wall thickness, greater LVMI, and hypertrophic LV remodeling mode. Lower relative LVMI regression was associated with a higher risk of MACCE . The corresponding cutoff of relative LVMI regression was −14%. Conclusions: Changes in hemodynamic parameters were independently associated with relative LVMI regression. Impaired reverse remodeling and persistent residual LV hypertrophy were independent risk predictors of MACCE. An LVMI regression lower than 14% indicated higher MACCE. A postoperative ZVA greater than 3.5 mmHg/mL/m2 was an independent risk predictor of cardiac events and mortality after AVR. Preventive strategies should be used at the time of the operation to avoid PPM.Patient-prosthesis mismatch (PPM) causes a high transvalvular pressure gradient and residual left ventricular (LV) hypertrophy, consequently influencing long-term results. This study aimed to find the relationships between hemodynamic parameters and LV mass regression and determine the risk predictors of major adverse cardiovascular and cerebral events (MACCE) after aortic valve replacement (AVR) for aortic stenosis.  Degenerative aortic stenosis (AS) is the most prevalent heart valve disorder in developed countries . Hypertr2/m2. PPM has the hemodynamic consequence of an elevated transvalvular pressure gradient with normally functioning aortic valves  = 10.2 years) and 55% of the patients were male. Only eight patients (6.7%) had received previous AVR surgery. Approximately two-thirds 82 (68.3%) of the patients received mini-invasive AVR surgery. The most prevalent comorbidity was hypertension 91 (75.8%), followed by hyperlipidemia 79 (65.8%), coronary artery disease 51 (42.5%), and diabetes 48 (40%). Small annulus size <21 mm 71 (59.2%). At pre-operation, 22 patients (18.3%) showed systolic dysfunction and 26 (21.7%) had dilated LVEDD. Most of the patients . All hemodynamic function parameters changed significantly after AVR, except for the RWT ratio .The preoperative and postoperative values of geometry and hemodynamic function are shown in p < 0.05). In addition, preoperative LVMI was significantly negatively associated with relative LVMI regression during follow-up . The relationships between preoperative LVMI and postoperative LVMI and relative LVMI regression are illustrated in The results of the analysis of the association between hemodynamic parameters at follow-up and relative LVMI regression are shown in VA , SWL , the presence of PPM , RWT , postoperative LVMI , and concentric or eccentric LV remodeling mode were significantly positively associated with the risk of MACCE. The cumulative rates of MACCE for patients with higher (>3.5 mmHg/mL/m2) and lower (≤3.5 mmHg/mL/m2) postoperative ZVA are shown in Over the mean follow-up period of 3.6 years (SD = 2.0 years), 19 patients suffered from stroke, 31 patients were hospitalized for heart failure, 7 patients underwent a redo-AVR operation, and 13 patients died. This means that 44 patients (36.7%) experienced a MACCE. The results of the analysis of the association between hemodynamic parameters at follow-up and the risk of MACCE are shown in VA, and SWL) and relative LVMI regression and the risk of MACCE were analyzed. The results showed that a smaller improvement in MPG  and SWL  was significantly associated with lower relative LVMI regression , and SWL  were significantly associated with higher risk of MACCE. Furthermore, lower relative LVM regression was significantly associated with a higher risk of subsequent MACCE . The corresponding optimal cutoff of relative LVMI regression was −14%; the cumulative event rates against the cutoff are shown in The associations between changes in hemodynamic parameters  received bioprosthetic valves, of which 48 were porcine valves, 44 were bovine valves, and 25 were sutureless valves. Because of the generally short stature of Taiwanese people, the aortic annuli were less than 21 mm in the majority of cases (71 [59.2%]) in this study. This was the reason for the severe PPM occurring in 5% and moderate PPM in 44.2% of all cases, with PPM observed in almost half of our study population , higher SWL , the presence of PPM , higher RWT , greater postoperative LVMI , and a concentric or eccentric LV remodeling mode were significantly associated with a greater risk of MACCE. The cumulative event rates of MACCE for patients with higher (>3.5 mmHg/mL/m2) and lower (≤3.5 mmHg/mL/m2) postoperative ZVA are shown in VA of >3.5 mmHg/mL/m2 was an independent risk predictor of clinical MACCE. Although SWL decreased after AVR, a higher persistent postoperative SWL or MPG also caused a higher number of MACCE. ZVA and RWT ratio were not correlated with relative LVMI regression but had strong relationships with postoperative MACCE.Greater relative LVMI regression was associated with fewer MACCE. Lower relative LVMI regression after AVR was correlated with inferior hemodynamic function and more MACCE. During the mean follow-up period of 3.6 ± 2 years, 19 patients suffered from stroke, 31 patients were hospitalized for heart failure, 7 patients underwent a redo-AVR operation, and 13 patients died, i.e., 44 patients (36.7%) experienced MACCE. The associations between hemodynamic parameters at follow-up and the risk of MACCE are shown in B, 0.46; 95% CI, 0.26–0.67) and SWL  were significantly associated with higher relative LVMI regression. In addition, greater changes in MPG , ZVA , and SWL  were also significantly associated with a lower risk of MACCE. Furthermore, lower relative LVMI regression was significantly associated with a higher risk of subsequent MACCE . The corresponding optimal cutoff of relative LVM regression was −14%; the cumulative event rates against the cutoff are shown in VA alteration and relative LVMI regression.We evaluated the association between changes in hemodynamic parameters and relative LVMI regression and the risk of MACCE . The resVA was correlated with higher MACCE, and higher relative LVMI regression was associated with fewer MACCE.Higher Z2/m2 to avoid PPM, lower the risks of MACCE, and obtain better long-term results. The EOAI, which reflects the severity of PPM, is an independent predictor of LVM regression [VA can be calculated using the projected EOA following AVR, but the extent of LVMI regression is obtained using echocardiography a few months after the operation. ZVA may be used to predict prognosis in advance and earlier than prediction with the extent of LV mass regression.The preventive strategy is to preserve EOAI at >0.85 cmgression . Survivagression ,54. Persgression ,34,58. Ggression . In our VA, SWL, EOAI, MPG, LVMI regression, and remodeling mode. Hypertension was the common comorbidity in AS; therefore, postoperative blood pressure control is important to preserve the benefits of AVR. The preventive strategy should involve choosing newer-generation prostheses, supra-annular implantation, or aortic root augmentation. Preventive strategy is a critical issue for long-term surveillance in Taiwanese people.The Asian is generally short in stature and has a small aortic annulus, so most small-sized valves were implanted. We revealed the results of post-aortic valve replacement, patient-prosthesis mismatch after AVR, is not an uncommon occurrence. PPM affects LVMI regression; it is an obstacle to reverse remodeling and leads to residual hypertrophy. We found preoperative LVMI to be a predictor of LVMI regression; hemodynamic parameters, including EOAI, MPG, SWL, LVMI, and remodeling mode, were also predictors too. We also found that the risk predictors of MACCE included the hemodynamic parameters ZFirstly, this study was a nonrandomized retrospective investigation with a small number of patients. Secondly, nearly half of the prostheses were 19 and 21 mm for the relatively small annulus in the population studied. Thirdly, the quality of echocardiographic assessment is observer dependent. Finally, the surveillance interval of the echocardiographic data of the 120 patients varied. LV mass regression is a complex phenomenon that is influenced by patient-related and prosthesis-related factors. Residual hypertrophy after an unload of LV pressure overload may be due to irreversible changes in interstitial fibrosis owing to long-term disease, and could affect the results.VA, and remodeling mode. The reduction in global LV afterload following AVR has an important role in decreasing LV mass and enhancing LV reverse remodeling. Values of ZVA >3.5 mmHg/mL/m2 predict MACCE earlier than LVMI regression. Attention should be paid to providing adequate blood pressure control with antihypertensive agents after AVR. Strategies to prevent PPM include preoperative planning with projected EOA reference tables, aggressive valve sizing, adjunctive intraoperative procedures (aortic root augmentation), and using newer-generation valve designs , new-generation bi-leaflet mechanical valves, and sutureless bioprosthetic valves. Earlier valve replacement should be scheduled before irreversible maladaptive LV hypertrophy and predictors of myocardial fibrosis should be identified with echocardiography.This study confirmed that the relationship between PPM and increased cardiac events can be observed at any degree of PPM. Variation in LVMI regression was observed after AVR and was predicted by EOAI, MPG, SWL, remodeling mode, and preoperative and postoperative LVMI. Risk predictors for postoperative MACCE were EOAI, MPG, SWL, RWT, Z


LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months.Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor  for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability  for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%.The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.[The online version contains supplementary material available at 10.1007/s00259-022-06015-0. Heart failure after acute ST-segment elevated myocardial infarction (STEMI) causes complex and long-term structural cardiac changes known as left ventricular (LV) remodeling, and may be associated with poor prognosis. Myocardial fibrosis after acute myocardial infarction (AMI) plays a key role in LV remodeling . FibroblFibroblast activation protein (FAP) is a membrane-bound serine protease highly expressed in activated fibroblasts in the infarcted myocardium . Positro68Ga-labeled FAP inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) aimed to quantitatively assess the longitudinal changes in the intensity and extent of myocardial fibroblasts activation, and explore its predictive value for late LV remodeling at average 12 months after AMI.Our prospective study using hybrid PET/MR with 68Ga]Ga-DOTA-FAPI-04 PET/MR scans at average 4.5 ± 1.5 days (3 ~ 8 days) after STEMI. Clinical symptom rating of the patients with AMI in this study was based on the Killip class Ga-DOTA-FAPI-04 PET/MR scans at average 12 months (11.5 ± 1.4 months) after AMI. Other three patients refused 12-months follow-up [68Ga]Ga-DOTA-FAPI-04 PET/MR, but performed follow-up echocardiography at the same time. The study flow chart is shown in Fig. Twenty-six patients with STEMI were consecutively recruited from August 2020 to September 2021 and underwent primary percutaneous coronary intervention (PCI) within 12 h of symptom onset. All patients underwent baseline cardiac [ip class . Blood bClinicalTrials.gov (NCT04723953). All patients gave written informed consent.All procedures involving human participants were conducted in accordance with the ethical guidelines of the Declaration of Helsinki and national regulations. The study was approved by the Research Ethics Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (2020CER152) and was registered at 68Ga]Ga-DOTA-FAPI-04 PET on Biograph mMR system , and no preparation was required. The FAPI precursor DOTA-FAPI-04 was purchased from CSBio Ltd.  and radiolabeled as previously described [68Ga]Ga-DOTA-FAPI-04. Images were reconstructed using the point-spread function algorithm with 172 × 172 pixels, four iterations, 21 subsets, and a filter with a full width at half maximum of 2 mm.All patients underwent Ga-DOTA-FAPI-04 on the infarcted myocardium. The uptake volume (UV) of enhanced [68Ga]Ga-DOTA-FAPI-04, defined as the extent of activated myocardial fibroblasts, was automatically calculated using a threshold above mean SUV (SUVmean) + 2 standard deviations in the reference tissue (left ventricular blood pool). The SUVmean of the infarcted myocardium was obtained by calculating the average activity within the UV. The intensity of myocardial fibroblasts activation was quantified using the maximum and mean target-to-background ratio (TBRmax and TBRmean), which were equal to the SUVmax and SUVmean of the infarcted myocardium divided by the SUVmax and SUVmean in the reference tissue, respectively.A volume of interest (VOI) was placed on the left ventricle to obtain the maximum standardized uptake value (SUVhttp://segment.heiberg.se) Ga-DOTA-FAPI-04 PET and blood biomarkers as well as cardiac function parameters were analyzed using 2-tailed Pearson correlation analysis. Univariate logistic regression was used to analyze the predictability of clinical risk factors, cardiac function and imaging parameters at baseline on LV remodeling occurrence at one year after AMI. A linear regression analysis was performed for the relationship between [68Ga]Ga-DOTA-FAPI-04 uptake and LV remodeling using the changes in LVESV or LVEDV as continuous dependent variable. The incremental predictive ability of 68Ga-FAPI-04 UV to conventional parameters was assessed by Harrell’s C-statistics calculated from a Cox proportional hazards regression model and integrated discrimination improvement (IDI) index based on logistic model [68Ga]Ga-DOTA-FAPI-04 UV at baseline between patients in the LV remodeling and non-LV remodeling groups as well as comparison of the change in LV volumes between patients with [68Ga]Ga-DOTA-FAPI-04 UV < 134.8 cm3 and [68Ga]Ga-DOTA-FAPI-04 UV ≥ 134.80 cm3 was performed using independent samples t-test. Receiver operating characteristic (ROC) analysis was used to assess the predicting accuracy of baseline [68Ga]Ga-DOTA-FAPI-04 UV for LV remodeling. P-values smaller than 0.05 were considered statistically significant.All statistical analyses were performed using SPSS version 20.0 , MedCalc version 20.027  and GraphPad PRISM version 7.0 . Data were expressed as mean ± standard deviation or number (%). Correlations between Ga-DOTA-FAPI-04 UV and NT-pro-BNPpeak, hsCRPpeak, CK-MBpeak, and TnIpeak at baseline either.As shown in Table 68Ga]Ga-DOTA-FAPI-04 uptake at baseline varied considerably between individuals , LVESV  and LVEF  at baseline  and LVESV  and a decrease in LVEF  during 12 months. Meanwhile, [68Ga]Ga-DOTA-FAPI-04 UV  and TBRmax  showed a negative correlation with LVEF at the time of 12-month follow-up  and the group with [68Ga]Ga-DOTA-FAPI-04 UV ≥ 134.80 cm3 (n = 13) according to the median of [68Ga]Ga-DOTA-FAPI-04 UV at baseline. The changes in cardiac function parameters between the two groups were compared. As shown in Fig. p = 0.003) and LVEDV (p = 0.007) as well as a tendency in difference of LVEF (p = 0.052) between the two groups indicating a potential association between baseline [68Ga]Ga-DOTA-FAPI-04 UV and late increased LV volume and decreased LVEF.Based on the above observed association between longitudinal [N = 10) and non-LV remodeling (N = 16) groups. We found that the LV remodeling group demonstrated higher baseline [68Ga]Ga-DOTA-FAPI-04 UV compared to the non-LV remodeling group (p < 0.001), as shown in Fig. 68Ga]Ga-DOTA-FAPI-04 PET for late LV remodeling. Univariate logistic regression analysis showed that besides baseline cardiac function parameters, [68Ga]Ga-DOTA-FAPI-04 UV , LGE volume , LGE% , and the extent of transmural infarction  were significant predictors for LV remodeling at 12 months after STEMI  using the change in LVESV as a dependent variable, but it only showed a predictive trend without statistical significance  using the change in LVEDV as a dependent variable  and LGE%  significantly increased predictive accuracy compared to MR parameter alone , LGE% , LVEDV , LVESV , LVEF , and the extent of transmural infarction , [68Ga]Ga-DOTA-FAPI-04 UV at baseline showed the highest diagnostic performance  for predicting late LV remodeling, with optimal sensitivity of 100.0% and specificity of 81.3% , characterized by robust immune cell infiltration and tissue digestion, and reparative (lasting 10–14 days), manifested by myofibroblast conversion and proliferation and tissue repair [68Ga]Ga-DOTA-FAPI-04 uptake at baseline was correlated with the level of acute inflammation or myocardial damage-related markers in the present study. Recent studies also showed that there was no correlation between FAPI uptake and the level of TGF-β1, TNF-α, IL-6, hsCRP Ga-DOTA-FAPI-04 uptake in the myocardial tissue. This hypothesis needs to be further validated in future studies by dynamic assessment at different time points.Longitudinal Ga-DOTA-FAPI-04 uptake in the animal model of myocardial infarction declined to background levels within 2 weeks due to decreased number of activated myofibroblasts and increased apoptosis of myofibroblasts during the healing phase , [68Ga]Ga-DOTA-FAPI-04 uptake of infarcted myocardium in the patients of our study could be observed as long as 12 months after AMI, suggesting that activated myocardial fibroblasts involved in human cardiac repair or LV remodeling exist much longer than that in the animal model. Furthermore, [68Ga]Ga-DOTA-FAPI-04 uptake that persisted at the 12-month follow-up may be correlated to the adverse LV remodeling that has already occurred in the past, and to a possible further LV remodeling in the future.Different from [68Ga]Ga-DOTA-FAPI-04 UV at baseline seems demonstrate better prediction of late LV remodeling compared to LGE volume, LGE %, and the extent of transmural infarction in our study. In fact, previous studies showed uncertain predictive power of myocardial LGE for late LV remodeling because of high individual variability, i.e., a portion of patients with large infarct size might not incur late LV remodeling on follow-up, while those with a limited infarct size might unexpectedly suffer late LV remodeling [68Ga]Ga-DOTA-FAPI-04 UV may not only correlate with infarct size, but also indirectly reflect the extent of cardiac inflammatory response, which may be the reason why [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive power for late LV remodeling than conventional LGE MR. A recent study from Hannover medical school, Germany also suggested that there was a significant inverse correlation between FAPI volume and LVEF obtained at later follow-up Ga-DOTA-FAPI-04 UV was a significant predictor of late LV remodeling, there was partial overlap in [68Ga]Ga-DOTA-FAPI-04 UV between the LV remodeling and non-LV remodeling groups. Previous studies have indicated that late LV remodeling occurrence may be also associated with other factors such as neurohormonal activations Ga-DOTA-FAPI-04 uptake intensity within 2 weeks after AMI. As fibroblasts with increase of FAP expression level is gradually activated by inflammatory factors after PCI revascularization, myocardial [68Ga]Ga-DOTA-FAPI-04 uptake intensity seems to be dependent on time. In contrast, as fibroblasts at the border of infarct zone are the first to be activated [68Ga]Ga-DOTA-FAPI-04 UV correlates mainly with infarct size, which may change less in the early period after AMI, and thus [68Ga]Ga-DOTA-FAPI-04 UV may have less time-dependent variability. Therefore, [68Ga]Ga-DOTA-FAPI-04 UV but not its intensity at baseline may be a promising predictive imaging indicator for late LV remodeling, which will likely make [68Ga]Ga-DOTA-FAPI-04 PET/MR an important workflow in the future for monitoring the efficacy of related drugs that act directing on the myocardial fibrosis process Ga-DOTA-FAPI-04 UV to predict LV remodeling. Therefore, although [68Ga]Ga-DOTA-FAPI-04 UV have shown to be potentially valuable in predicting LV remodeling, strong conclusions still require larger samples to be obtained.The present study has the following limitations: (1) Only patients with relatively mild symptoms (Killip class I and II) who could tolerate long scan time of PET/MR were enrolled in the present study; therefore, data on patients with severe symptoms (Killip III and IV ), who ar68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV in the early stage of STEMI may have potential predictive value for late LV remodeling at 12 months follow-up.Overall, [ESM 1(DOCX 73 kb)


RV dysfunction occurs in patients without ECG evidence of RV STEMI. RV dysfunction is worse in anterior than inferior MI. Moreover, RV systolic functions were affected by declined LV ejection fraction irrespective of the infarction site, which clinically implies prognostic, treatment, survival rate, and outcome improvement between both conditions. . This study hypothesized that imaging provides information indicating the right ventricular (RV) involvement after anterior or inferior ST-elevation myocardial infarction (STEMI), beyond standard electrocardiogram (ECG) due to the increasing interest in RV function and assessment techniques. This study aimed to compare RV function between anterior and inferior MI without RV involvement using different echocardiographic modalities. This study included 100 patients with anterior (50 patients) and inferior (50 patients) STEMI, who underwent primary percutaneous coronary intervention (PPCI) and two-dimensional echocardiographic imaging within 24 h after PPCI with RV function analysis by left ventricular (LV) infarct size, LV filling pressure, and RV strain rate. Our primary endpoint was the subclinical RV dysfunction in anterior or inferior MI using tissue Doppler and speckle tracking (STE). The study population included 80 (80%) males and 20 (20%) females. Patients with the anterior STEMI had higher mean creatine kinase-MB (CKMB) and troponin than those with inferior STEMI. This study revealed worse RV dysfunction in patients with anterior than those with inferior STEMI, as reflected by significantly lower RV systolic function, tricuspid annular plane systolic excursion ( Inferior and anterior myocardial infarctions (MIs) lead to different right ventricular (RV) hemodynamic responses .Two-dimensional 2D) strain and strain rate analyses are novel Doppler-independent approaches to obtain myocardial mobility and deformation measures that are widely employed to assess left ventricular (LV) functions [D strain The quantitative assessment of RV function remained difficult and is not routinely used in clinical practice because of its complex structure and it is nearly often considered as a reservoir . Cabin eThe quantification of velocity gradients between two sites is possible with strain rate (SR) imaging. The resulting contraction variable does not affect passive tethering effects from other regions; thus, it is a suitable candidate for quantifying regional myocardial function .This study hypothesized that imaging provides RV involvement information after anterior or inferior MI, beyond standard electrocardiogram (ECG). This is linked with the increasing interest in RV function and assessment techniques of what was once often considered a forgotten ventricle.This study aimed to compare RV function between patients with anterior and inferior MIs without RV involvement using different echocardiographic modalities.Results may lead to treatment changes and a better understanding of the varying survival rate and different outcomes between both conditions regarding mortality, cardiogenic shock prevalence, and the need for mechanical or inotropic support .This single-center comparative cross-sectional study was conducted from January 2018 to January 2020 at the Cardiology Department of our university. The protocol was approved by our University Institutional Review Board which confirmed that all methods were performed following the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research. Informed written consent was obtained from all participants.Patients were prospectively recruited. The study group comprised a convenience sample of 100 consecutive age, sex, RV systolic pressure, and pharmacological therapies administered before the percutaneous coronary intervention (PCI)-matched subjects admitted to our critical care unit with the first episode of acute STEMI according to the STEMI guidelines  and refeThis study included 100 patients with first anterior and inferior STEMI who underwent PPCI. Acute STEMI was defined as evidence of ischemic chest pain for > 30 min and new ST-segment elevation in two or more contiguous ECG leads and elevated cardiac troponin. Anterior MI was defined as ST-segment elevation of at least 1 mm in anterior leads . Inferior MI was defined as ST-segment elevation of at least 1 mm in inferior leads  .3R, V4R (RV infarction), bundle branch block, or any other interventricular conduction delay, MI history, previous revascularization, rheumatic heart disease, cardiomyopathy, cardiogenic shock, acute pulmonary congestion, heart failure, previous documented abnormal LV function, rhythm disturbance, pulmonary hypertension, pulmonary embolism, liver cell failure, chronic renal failure, hemodynamic instability, and poor echogenic window.ST-elevation in Vhistory taking and a thorough physical examination, including pulse and systolic and diastolic blood pressure measurements.All patients were subjected to upon admission and ST-segment elevation were analyzed according to the joint European Society of Cardiology, American College of Cardiology (ACC), American Heart Association (AHA), and World Heart Federation task force for the universal MI definition . Dispropwith special emphasis on cardiac markers (troponin and CKMB) and creatinine.Left ventricular assessment included LV ejection fraction (EF%) measurement by modified Simpson’s method and LV fractional shortening (FS%) to evaluate LV systolic function and LV volume. Pulsed wave Doppler (PW) echocardiography was used to evaluate LV diastolic function. The peak E wave velocity, the peak A wave velocity, and the E/A ratio were measured by conventional PW Doppler. The peak e′ wave velocity, the peak a′ wave velocity, and E/e′ ratio were measured by tissue Doppler imaging (TDI); the assessment of LV infarct size depends on EF and LV filling pressure parameters. RV assessment included 2D and tissue Doppler; RV minor dimension at the basal ventricular level measured in end-diastole; right atrial (RA) minor dimension measured in end-systole; tricuspid annular plane systolic excursion (TAPSE); myocardial performance index (MPI) by pulsed wave Doppler method; pulsed wave tissue Doppler imaging (PW-TDI); pulsed wave Doppler imaging (PW); and strain, SR, and speckle tracking . Data acquisition was done by 2 independent operators and the mean values were interpreted to avoid LAB inter- and intra-observer variability. Data acquisition was performed at a depth of 16 cm in the parasternal long axis, apical 4 and apical 2 chamber views, using a 1.5–4.3-MHz M4S transducer. During hold-breath, M-mode and 2-D images were obtained in 3 consecutive beats and were saved. The reference limits of all recorded and calculated parameters were defined according to the American Society of Echocardiography Guidelines . Left veCoronary angiography was performed using the percutaneous radial approach by the Sildenger technique. Right and left coronary angiography was performed using multiple projections, and analysis was done by professional interventionists who were blind to the cases. Drug-eluting stents, or more specifically everolimus-eluting stents, were implanted using a routine method, and procedure success indicated residual stenosis of < 20%, thrombolysis in MI (TIMI) flow grade III, and no in-hospital acute complications , and no major adverse cardiac events  . All patOur primary endpoint was to assess the subclinical RV dysfunction in anterior or inferior MI using tissue Doppler and speckle tracking.X2) for qualitative variable, t-test for quantitative independent groups, and correlation coefficient for testing association between two variables. A p-value of ≤ 0.05 was considered a significant difference for all statistical analyses.All data were analyzed using IBM Statistical Package for the Social Sciences software version 23 for windows . The statistical analysis was conducted following the principles as specified in the International Council for Harmonization Topic E9 (ICH1998). Results were presented as mean value ± standard deviation for continuous variables and as frequency (%) for categorical variables. Data were tested for normality using the Kolmogorov–Smirnov test. The following tests were used to test differences for significance: chi-square test (p = 0.793). Our study showed no statistically significant differences between both groups regarding demographic data (Table Our study population included 80 (80%) males and 20 (20%) females divided into 2 groups. There was no significant difference in the median age between the anterior and inferior STEMI groups (ta Table .Table 1Cp = 0.012).Patients with anterior STEMI had significantly higher mean CKMB and troponin than those with inferior STEMI  and higher MPI of the RV by pulsed (RMPI-PD) and tissue Doppler (RMPI-TDI), as well as worse diastolic function in the form of lower lateral E′ velocity, compared to those with inferior MI .The anterior MI group was significantly associated with the left anterior descending artery (LAD) as the culprit in contrast to the inferior MI group, which was significantly associated with the right coronary artery (RCA) as the culprit  patients, left circumflex artery (LCX) in 12 (24%), and RCA in 5 (10%). In the inferior MI group, LAD was affected in 4 (8%) patients, LCX in 6 (12%), and RCA in 50% of patients. Regarding the number of vessels, the anterior MI group had 34 (68%) patients with single-vessel disease, 15 (30%) had two-vessel diseases, and 1 (2%) had three-vessel diseases, whereas the inferior MI group had 42 (84%) patients with single-vessel diseases, 7 (14%) two-vessel diseases, and 1 (2%) with three-vessel diseases. No statistically significant differences were found between both groups regarding the number of affected vessels (Table Table p < 0.0001), which may be a confounding factor in RV function evaluation.From the physiological point of view, given the distribution of the perfusion territories of the major epicardial coronary arteries, inferior MI in most cases is due to RCA stenosis, which supplies both the RV free wall and the base of the interventricular septum and would thus affect most RV functional measurements while anterior MI is usually due to LAD artery stenosis, which does not significantly contribute to RV perfusion other than the RV apex when the LAD artery wraps around the apex . Hence, p < 0.0001). Additionally, LV filling pressure was significantly higher in the anterior MI group (p < 0.001). This data was concordant with Abtahi et al. [LV systolic function and LVEF by Simpson’s method were highly significantly lower in the anterior MI group compared to the inferior MI group . These data were concordant with Korup et al. [LVEDD was significantly higher in the anterior MI group compared to the inferior MI group although both were within the normal range . RV diameter was significantly higher in the anterior MI group compared to the inferior MI group although RV diameter was higher than the normal range in both groups (p < 0.05). These data were discordant with Abtahi et al. [p < 0.0001).RA and RV dimensions and RA diameter were significantly higher in the anterior MI group compared to the inferior MI group . TAPSE was below the normal value in the anterior MI group while within the normal range in the inferior MI group. These data are concordant with Keskin et al. [RV systolic function and TAPSE were significantly lower in the anterior MI group compared to the inferior MI group . These data are concordant with Ozturk et al. [MPI of RV (RMPI) by pulsed and tissue Doppler was significantly higher in the anterior MI group and normal in the inferior MI group with a significant difference between both groups  was significantly lower in the anterior MI group compared to the inferior MI group (p = 0.008). These data are concordant with Hsu et al. [S′ in the anterior STEMI group compared to the inferior STEMI group. Hsu et al. [The systolic velocity of the lateral wall of RV by tissue Doppler . However, lateral E′ was significantly lower in the anterior MI group compared to the inferior MI group (p = 0.005) while no significant difference between both groups regarding lateral E/e′ (p = 0.185). This data is in disconcordant with the findings of Hsu et al. [RV diastolic function and tricuspid u et al. , where Ru et al.  reportedE/E′ ratio and diastolic SR are commonly utilized to assess RV diastolic function.The tricuspid E/e′ ratio, RA volume, and hemodynamic parameters in the tricuspid valve. The tricuspid E/E′ ratio predicts cardiac events and increased mean arterial pressure as a reliable measure of RV filling pressure. An E/e′ ratio of > 6 exhibited good sensitivity and specificity in identifying the mean RA pressure of 10 mmHg.Demirkol et al.  revealedS′), was significantly lower in the anterior MI group compared to the inferior MI group (p = 0.008). These data are concordant with Hsu et al. [S′ in the anterior STEMI group compared to the inferior STEMI group. Hsu et al. [The systolic velocity of the lateral wall of RV, as assessed by tissue Doppler . However, lateral E′ was significantly lower in the anterior MI group compared to the inferior MI group (p = 0.005) while no significant difference between both groups regarding lateral E/e′ (p = 0.185). These data are discordant with the findings of Hsu et al. [p < 0.0001).Concerning the RV diastolic function, the tricuspid u et al. , where Ru et al.  reportedp < 0.001). RV septal strain was significantly lower in the anterior MI group compared to the inferior MI group , as well as the RV free wall strain (p < 0.001). RV-GLS was significantly lower in the anterior MI group compared to the inferior MI group (p = 0.009).RV free wall tissue velocity was lower than the average with no significant difference between both groups. RV strain was significantly lower in the anterior MI group compared to the inferior MI group  and inferior MI groups . Antoni et al. [Our results showed a significant positive correlation between EF and TAPSE in the anterior  is important to improve prognosis, treatment, and outcomes.RV dysfunction can occur in patients with no ECG evidence of RV STEMI. RV dysfunction is worse in patients with anterior compared to those with inferior MI. Moreover, RV systolic functions were affected by declined LVEF irrespective of the infarction site. This had potential clinical implications to improve prognosis, treatment, survival rate, and outcomes between both conditions.We recommend a follow-up of a large sample study with the change in studied parameters to include RV infarction which requires more studies for its implication.Future larger multicenter studies are needed to demonstrate clinical outcome data, such as mortality, cardiogenic shock prevalence, and the need for mechanical or inotropic support.Future mid- and long-term longitudinal studies will need to investigate RV dysfunction as a predictor of outcome in patients with STEMI.


Echocardiography is frequently used to evaluate cardiac function in rodent models of cardiovascular disease. Whereas methods to acquire the commonly used echocardiography parameters are well-described in published protocols or manuals, many important parameters are ill-defined and often open to subjective interpretation. Such lack of uniformity has engendered conflicting interpretations of the same parameters in published literature. In particular, parameters such as mitral regurgitation, mitral stenosis, pulmonary regurgitation, and aortic regurgitation that are required to define more esoteric etiologies in rarer mouse models often remain equivocal. The aim of this methods paper is to provide a practical guide to the acquisition and interpretation of infrequently used echocardiography parameters and set a framework for comprehensive analyses of right ventricle (RV), pulmonary artery (PA) pulmonary valve (PV), left atrium (LA), mitral valve (MV), and aortic valve (AoV) structure and function. The remaining ∼70% of parameters that are often essential for comprehensive and accurate characterization of murine cardiovascular pathology have not to our knowledge been formally standardized and the relevant procedures are absent from current protocols and manuals of rodent echocardiographic imaging technology. While there are examples of uncommon parameters being acquired to expand on a pathology, details of the acquisition procedures used for such parameter is often lacking. Here we provide an easily accessible protocol of infrequently used views and parameters that will allow for more complete analyses of the right ventricle (RV), pulmonary artery (PA), pulmonary valve (PV), left atrium (LA), mitral valve (MV), and aortic valve (AoV).Echocardiography is a non-invasive imaging modality and a pillar of preclinical cardiovascular research. Rodent models for human disease are routinely analyzed The images acquired in this paper were captured using Vevo 2100 and 3100 imaging systems and analysis with Vevo Lab, however, the methods described may be applicable to other multi-modal imaging systems.Cardiac function and morphology were assessed using either Vevo 2100 or 3100 imaging systems with a high frequency transducer probe MS400 . The anterior chest and abdomen of mice were depilated using Nair depilatory cream  1 day before experiments  views, the mouse is placed in a supine position with the right side of the platform inclined at 45° counterclockwise , and theThe parasternal short axis view (PSAX) is derived from the PLAX view by rotating the transducer probe in the rail system to approximately 90° clockwise .To obtain apical views, the platform is placed slightly lateral with the head of the mouse pointing to the left, and the right upper side of the platform positioned 30° counterclockwise. The transducer probe is placed diagonally oriented toward the head .With the anterior portion of the platform tilted 45° superiorly and slightly to the left, the transducer probe is shifted from the PSAX view cranially to the level of the aortic valve .Right-sided heart assessment is important for evaluating right heart failure (RHF) and pulmonary hypertension in rodent models, but the possible methodologies are underused in mice despite the availability of clinical guidelines for such imaging . Higher Right ventricular internal diameter (RVID) provides metric dimensions of the right ventricle during systole and diastole. To obtain this parameter, a PSAX or PLAX M-mode image should be captured with the M-mode line positioned over the RV. Obtaining the correct view may require repositioning the platform 45° to the right. Furthermore, skin reverberation artifacts can easily be confused with the RV, therefore flow on Doppler or movement in a B-mode image should be used to confirm that the RV is correctly identified. In PSAX or PLAX M-mode, RVID;s and RVID;d should be selected  to measure the diameter of the right ventricle . This paRight ventricular outflow tract (RVOT) length is the measurement of the right ventricular outflow tract at end diastole. It can be measured by selecting “RVOT” in a PLAX B-mode image containing the RV . The RVORight ventricular outflow tract velocity time integral (RVOT VTI) is a measurement of blood flow through the RVOT. It can be measured as the area under the curve in a pulsed wave (PW) Doppler image of PLAX with the yellow marker on the flow of the RVOT . Mean vePulmonary and right ventricular parameters are more informative when applied concurrently. RV dysfunction in the absence of elevated PA pressures indicates isolated RHF, while RV dysfunction concurrent with elevated PA pressures could indicate pulmonary hypertension leading to RHF or LHF leading to RHF. PA and PV measures may be incorrectly assumed to be interchangeable; however, the PA is anatomically distal to the PV in mice, and images should be captured accordingly. Measurements are made of PW Doppler mode images with the marker overlying either the PA or PV , 5.Pulmonary artery velocity time integral (PA VTI) is a direct measure of blood flow through the pulmonary artery. It is calculated as the area under the curve in a PW Doppler image of the PA . Mean vePulmonary regurgitation peak velocity (PR Peak Vel) relates to degrees of pulmonic regurgitation in mouse models. PR Peak Vel is the maximum velocity of the regurgitant stream. Like most other pulmonary measures it is performed with a PW Doppler mode image of pulmonary artery flow . This mePulmonic valve diameter (PV diameter) measures, in millimeters, the length of the pulmonic valve. This measurement can be performed using a PLAX or PSAX view of the pulmonic valve; however, visualization is typically easier in PLAX . PV diamLeft atrial size is rarely evaluated in small animal echocardiography despite the reciprocity between LA reservoir function and LV systolic function and thus cardiac output . In otheLeft atrial depth can be measured vertically at end diastole. To perform this parameter, a PLAX M-mode image should be captured with the yellow line positioned over the LA, which is located inferior to the aorta .Although extensively characterized because of the accessibility of imaging the LV, many parameters are inadequately described in literature.Left ventricular outflow tract length (LVOT) measures, in millimeters, the left ventricular outflow tract, just proximal to the aortic valve, at end diastole. It is measured by selecting “LVOT” under “AoV Flow” in a PLAX B-mode image containing the left ventricular outflow tract . LVOT woLeft ventricular outflow tract velocity time integral (LVOT VTI) is defined as a measurement of blood flow out of the ascending aorta. It can be measured as the area under the curve in a PLAX PW Doppler mode image with the cursor over the flow of the ascending aorta . LVOT VTMitral regurgitation (MR) has not been well-described in mice because of their resistance to developing mitral valve prolapse . HoweverMitral stenosis is another disease that is not well-replicated in mice. However, mitral valve pressure half time (MV PHT) is a potentially useful parameter in the setting of mitral stenosis . MV PHT Mitral valve ejection time (MV ET) is equal to the duration of diastolic filling of the LV; therefore, can be used to further characterize diastolic dysfunction. MV ET is measured at the end of IVRT to the beginning of IVCT on a PW Doppler of the mitral valve .Aortic regurgitation has been seen in existing mouse models; however, methods for analysis beyond visual recognition have not been well-established.Aortic insufficiency pressure half time (AI PHT) is the rate of deceleration of Doppler signal, indicating the degree of regurgitation and LVEDP . The samAortic acceleration time (AAT) has been validated by Perez et al. to assess LV contractility in mice. It is measured in PW Doppler mode as the time to peak aortic velocity . StudiesNormalizing the acquisition and analysis of infrequently used parameters coupled with commonly used values will provide further insight into both left and right-sided cardiac function. In recent years, the importance of the right heart has become more evident but a complete understanding remains elusive. Implementing the additional parameters described here will generate a more comprehensive picture of cardiovascular disease in mouse models that can be applied to parallel human conditions.All analyses are limited by human error in image acquisition. The RV must be captured in PLAX M-mode in order to measure RV parameters, however, as noted by Brittain et al., sometimes the RV is only visible when dilated. If the transducer is misaligned with blood flow for Doppler modes, blood velocity will be decreased for LVOT VTI and RVOT VTI measurements and SV and CO will be falsely low . To obtaIn our quest to improve resources, expand and optimize echocardiography parameters in rodent models, we realized a need for protocols and information to define and facilitate infrequently used parameters. Here, we present multiple parameters that are rarely used and provide a thorough description of echocardiography acquisition and analysis of these parameters. Although VisualSonics Vevo imaging systems were used to obtain these images and derive parameters, the same approaches should be applicable to other comparable imaging systems such as S-Sharp , 16. In Previously, the importance of the right heart was underestimated . Within In contrast, left-sided parameters are frequently characterized due to ease of accessibility to the left ventricle during echocardiography acquisition. Despite accessibility, some left-sided parameters including, LA size and depth, LVOT, LVOT VTI, visual assessment of MR and AR, MV PHT, MV ET, AI PHT, and AAT are rarely acquired and analyzed. These values, coupled with frequently used left and right heart parameters, may provide further insight into cardiac function.This manuscript serves as a guide to understanding the acquisition and analysis of infrequently used echocardiography parameters. With the continued development of mouse models that mimic human cardiac disease it is imperative to define and integrate a complete repertoire of echocardiography parameters to maximize data yields and avoid overlooking elements of unique pathologies.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by IACUC.ET, MW, and LS perceived the project. MW and AK acquired the images. ET, MW, AK, and MR analyzed the images. ET and MW drafted the manuscript. All authors revised the manuscript, approved the final version of the manuscript, and agreed to be accountable for all aspects of the work.


The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators  from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637–0.781;  Heart disease and cancer are the two leading causes of global mortality . WorldwiIn recent years, researchers have paid increasing attention to the new field of cardio-oncology , 7. StudThis study aimed to investigate baseline cardiac function and risk of CVDs in patients with new-onset AL, explore CVD risk factors present before treatment and their association with prognostic survival, and provide data on cardiac management strategies for patients with AL.9/L , red blood cells , hemoglobin , platelets , alanine aminotransferase , aspartate transaminase , blood urea nitrogen , creatinine , D-dimer , biochemical blood indicators: creatine kinase , creatine kinase myocardial band , hydroxybutyrate dehydrogenase , lactate dehydrogenase , highly sensitive troponin-I , B-type natriuretic peptide  and echocardiography parameters: left atrial internal diameter , left ventricular internal diameter , interventricular septal , left ventricular posterior wall , end-diastolic volume , end-systolic volume , stroke volume  and ejection fraction .Collected the data in the medical records of patients at the first visit: age (years), sex, cardiovascular risk factors , AL type, routine blood tests: white blood cells  analysis was conducted between the AL and control groups. The log-rank test was used to perform univariate analysis through Kaplan-Meier curves, and meaningful values were screened for multivariate Cox regression analysis. Odd ratios (ORs) and hazard ratios (HRs) were expressed with 95% confidence intervals (CIs). Statistical analysis was conducted using SPSS version 25.0  and GraphPad Prism version 7.0 . A value of p < 0.05 was considered statistically significant.We performed linear regression analysis of biochemical blood indicators, myocardial enzymes, and echocardiographic indicators after logarithmic conversion. Normally distributed samples were compared using independent sample A total of 408 individuals participated in this study, including 200 newly diagnosed AL patients (including 15 HAL patients), 103 patients with confirmed CAD, and 105 control patients. We eliminated patients who did not meet the study requirements. The screening flowchart is shown in p < 0.05). In the comparison between the control and CAD groups, it could be found that the CAD group had more severe myocardial damage. The average values of echocardiography parameters LAID, LVID, EDV, and ESV were significantly higher, and EF value was significantly lower, in the CAD group compared with the control group; the average values of cardiac function and myocardial enzyme indexes increased significantly. Comparing the AL and the CAD groups, the average values of LAID, IVS, EDV, CK, CK-MB, and hs-cTnI in the CAD group were significantly higher, while only the values of DD and BNP were higher in the AL group.A comparison of cardiac damage index results among the three groups is shown in R2 = 0.603) for whether the AL group had damage from heart disease. Using multiple linear stepwise regression analysis, the final factors entering the equation were CK-MB, LDH, BNP, DD, and LVID  were matched for age, sex, cardiovascular risk factors , and hemoglobin concentration. The indexes with significant differences between the matched AL and control group were included in the multiple linear regression analysis. Using multiple linear stepwise regression analysis, the final factors entering the equation were BNP, HBDH, and LVID (p < 0.05). There were no significant differences between the two groups in terms of other serological indicators or echocardiogram-related indicators , LDH (p = 0.038), EF (p = 0.025), and the number of myocardial enzyme abnormalities (p = 0.002). The meaningful survival curve is shown in p < 0.1) in the previous single-factor analysis were subjected to multi-factor Cox regression analysis. The results showed that age  and EF  were independent factors related to the prognosis of AL patients . We analyzed the relationship among age, sex, cardiovascular risk factors , biochemical blood indicators, myocardial enzyme indexes, echocardiography indexes, and the number of abnormal myocardial enzyme indexes and survival, to screen for risk factors related to the prognosis of the disease. Variables with statistically significant effect measurement values included age . The ROC curve is shown in Classification based on the echocardiography clinical diagnosis in newly diagnosed AL patients include significant differences in myocardial enzymes and related echocardiographic indicators; the three indicators with the highest results for the ROC area under the curve (AUC) were LVID (0.709), EDV (0.675), and HBDH (0.591). This result revealed that the best predictor of leukemic myocardial damage was LVID. It showed the predictive ability of LVID (≥43.5 cm) , CK (r = 0.361), hs-cTnI (r = 0.433), and BNP (r = 0.379), while negatively correlated with EF (r = −0.257). Furthermore, WBC count was positively correlated with HBDH, LDH, and LDH1. LVID was positively correlated with age, CK, LDH, LDH1, EDV, ESV, and SV and negatively correlated with HGB and EF , and most commonly involve the pericardium, followed by myocardium, epicardium, and endocardium , 47, 48.Our analysis of cardiac-related parameters in newly diagnosed AL patients showed that compared with controls, AL patients did experience some cardiac-related lesions, both in myocardial enzymes and echocardiographic parameters. These clinical manifestations are similar to existing reports and recommendations for cardiac management monitoring in cancer patients –62. HoweAcute leukemia disease itself may be associated with cardiac damage because it shares systemic pathogenic pathways and mechanisms with CVDs: inflammation, metabolic alterations, clonal hematopoiesis, angiogenesis alterations, and extracellular matrix and stroboscopic cells , 65. CanFor the reasons described above, clinicians should comprehensively evaluate patients’ cardiac function before chemotherapy. Echocardiography can be used to observe changes in LVEF . ConditiThere were several limitations in this study. First, in order to eliminate confounding factors, we used PSM analysis, but the sample size after PSM analysis was small, which may cause some data bias and be different from the real-world situation. Second, we focused on the systolic function of the ventricle, and did not collect related indicators of ventricular diastolic function, thus possibly missing some correlations. Finally, this was a single-center observational study and the sample size was small. Larger sample size validation and prospective studies are needed to confirm the degree of cardiac damage in patients with leukemia. Nonetheless, our study provides important information about the relationship between cardiac damage and leukemia.In summary, we identified significant differences in cardiac function between patients with primary AL and control patients, and these differences could have an impact on patient prognosis. Our findings provide new insights into the complex etiology and molecular events leading to cardiac injury in patients with AL, and how they can alert clinicians to the presence of cardiac injury in AL patients. In addition, more research is still needed to confirm and explore the specific mechanism between leukemia and cardiac lesions.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Research Committee of Wuhan University in Wuhan, China. The patients/participants provided their written informed consent to participate in this study.WX, LM, YT, and FZ conceived and designed this research. LM, FY, GC, and JW were responsible for collecting the clinical outcome data of the patients included in the study. YL and TR re-checked the data. WX, YS, QW, and NZ performed the statistical analysis. WX, LM, and FZ wrote the manuscripts and created figures and tables. All authors strictly reviewed the manuscript and approved the final submitted 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.