We retrospectively evaluated 370 patients, aiming at assessing the interrelation between cardiac and brain SVD by using quantitative 82Rb PET/CT and a brain 1.5T or 3T MRI. Left-ventricle myocardial blood flow (LV-MBF) and flow reserve (LV-MFR) were recorded from 82Rb PET/CT, while Fazekas score, white matter lesion (WMab) volume, deep gray matter lesion (GMab) volume, and brain morphometry  using the MorphoBox research application were derived from MRI. Groups were compared with Kruskal–Wallis test, and the potential interrelation between heart and brain SVD markers was assessed using Pearson’s correlation coefficient. Patients with cardiac SVD had lower stress LV-MBF and MFR (P < 0.001) than patients with normal myocardial perfusion; Fazekas scores and WMab volumes were similar in those two groups (P > 0.45). In patients with cardiac SVD only, higher rest LV-MBF was associated with a lower left-putamen , right-thalamus , and right-pallidum  z-scores and with a higher GMab volume. Lower stress LV-MBF was associated with lower left-caudate z-score , while lower LV-MFR was associated with lower left - and right -putamen z-scores, as well as higher right-thalamus GMab volume .In our population of 370 patients, 176 had normal myocardial perfusion, 38 had pure cardiac SVD and 156 had obstructive coronary artery disease. All underwent both a cardiac Significant interrelations between cardiac and cerebral SVD markers were found, especially regarding deep gray matter alterations, which supports the hypothesis of SVD as a systemic disease. Ischemic heart disease, stroke, and dementia are the most frequent causes of mortality and disability worldwide, especially among the elderly population  Although the pathophysiology and impact of microvascular pathologies on the general population as well as their link with cardiovascular risk factors are clear, there are little data in the literature on the correlation of microvascular disease between different organs, particularly between the heart and the brain  and myocardial flow reserve (MFR) , which can manifest clinically as angina, myocardial infarction, and heart failure, can be quantitatively analyzed with cardiac Brain SVD, which is a substrate of stroke, dementia, cerebral atrophy, and gait disorders, can be evaluated using cerebral magnetic resonance imaging (MRI)  patients older than 18 years; and (2) who underwent a brain MRI. We excluded patients with large cerebral sequelae , bad image quality due to motion artifacts, or proved non-vascular leukoencephalopathy. From patients’ medical records, we collected the following clinical variables: sex, age, cardiovascular risk factors , coronary artery disease (CAD), history of myocardial infarct or stroke, history of peripheral arterial disease, current medications. For patients who were finally included in the analysis . Patients were asked to fast for at least 6 h and refrain from any caffeine intake for at least 24 h before examination. Cardiac PET/CT acquisition was performed at rest and at stress after intravenous infusion of adenosine, as previously described  were computed applying the 17-segment model of the American Heart Association  rest myocardial blood flow (MBF), stress MBF, and myocardial flow reserve (MFR) were obtained by processing data with the fully automated FlowQuant software  , left circumflex (LCx), and right coronary artery (RCA). A global LV MFR < 2 was considered abnormal, as previously documented ; III, normal SSS < 4 and LV MFR < 2. For this last group, an invasive coronary angiography was available to distinguish between flow-limiting epicardial lesions (presence of obstructive CAD) or SVD (absence of obstructive CAD) . Included patients had all at least an axial T2 spin echo (T2SE) and a 3D T1 magnetization-prepared rapid gradient-echo (MPRAGE) with acquisition parameters that follow the Alzheimer’s Disease Neuroimaging Initiative guidelines  in order to find brain sequelae due to non-lacunar stroke or to other pathologies . In the remaining patients, leukopathy was assessed on the T2SE images and divided into 4 categories by using the Fazekas score  collected by the ADNI and studies following the ADNI guidelines . All brain regions were automatically segmented from the 3D T1-MPRAGE sequences using the MorphoBox research application  and patients with cardiac SVD using the Kruskal–Wallis test. In patients with cardiac SVD (N = 38), multivariate regression analysis was performed to explore whether the same risk factors  are related to cardiac and brain SVD, using, respectively, the LV-MBF, MFR, and Fazekas score as predicted variables. Finally, potential interrelation between heart and brain SVD markers was assessed using Pearson’s correlation coefficient in these two groups only. A P value < 0.05 was considered statistically significant. The significance level was not corrected for multiple comparisons.Statistical analyses were performed with Stata 16.0 software . Continuous variables are presented as median with interquartile range (IQR) or mean with standard deviation (SD) when normally distributed. Categorical variables are reported as number or percentage. 82Rb PET/CT and brain MRI . The LVEF at rest, LVEF at stress, and TID ratio were not significantly different between the two groups (P > 0.22).All quantitative results are displayed in Table N = 38, β = 0.44, P = 0.012). There was no independent predictor of LV-MBF at rest or MFR.On multivariate regression analysis, active smoking was independently related to LV-MBF at stress in patients with cardiac SVD  and were excluded from the MRI quantitative analysis. Of the 300 remaining patients with MRI, 114 were excluded due to obstructive CAD without brain sequelae. One hundred and twenty-three could not be segmented because the 3D T1-MPRAGE that did not follow the ADNI guidelines . The 3D T1-MPRAGE was segmented in 63 subjects with normal myocardial perfusion or cardiac SVD  but lower z-score for right and left frontal WM volumes (P = 0.024 and P = 0.021) and higher z-score for left and third ventricles (P = 0.042 and P = 0.016). There was also a trend toward higher GMab volume and higher right ventricle z-score in SVD patients compared to patients with normal myocardial perfusion. The z-score for all segmented structures for patients with normal myocardial perfusion and SVD is reported in Table Compared to patients with normal myocardial perfusion, patients with SVD had similar Fazekas score .On multivariate analysis, only age independently predicted Fazekas score in patients with cardiac SVD (P = 0.72), at stress , and LV-MFR .Regarding the qualitative analysis, no correlation was found; indeed, there was no association between Fazekas score and LV-MBF at rest , rest LV-MBF was negatively correlated with z-score of total brain , right occipital GM , and left  and right  temporal WM volumes; LV-MFR was positively correlated with z-score of total brain , total GM , left  and right  parietal GM volumes, left  pallidum z-score, and negatively correlated with z-score of total CSF . There was no significant correlation between cardiac perfusion parameters and WMab or GMab volumes (P > 0.18).Taking into account all patients who had both brain morphometry and normal cardiac perfusion or patients with SVD (N = 12), we found that rest LV-MBF was negatively correlated with left-putamen z-score , stress LV-MBF was positively correlated with left-caudate z-score , and LV-MFR was positively correlated with left  and right  putamen z-score. Also, in SVD patients, we found a positive correlation between rest LV-MBF and right-thalamus  and right-pallidum  GMab volume. Moreover, we found a negative correlation between LV-MFR and right-thalamus GMab volume . On the other hand, no correlation was found between an abnormal cardiac perfusion and WMab volumes (P > 0.47). A graphical representation of these results is presented in Fig. When considering only patients with cardiac SVD and available brain morphometry N = 1, we founThis study focused on the potential association between cardiac and cerebral microvascular pathologies. The main results can be summarized as followed: (1) Patients with SVD have lower LV stress MBF and MFR; (2) SVD has lower frontal WM z-score and higher ventricular z-scores and tends to have higher GMab volume in deep nuclei; (3) in SVD patients, LV-MBF and MFR correlate with deep gray matter z-scores and deep nuclear GMab volumes; and (4) in patients with cardiac SVD, LV-MBF at stress is independently related to smoking, while Fazekas is independently related to age.N = 2175) with no significant perfusion defect on 82Rb cardiac PET had a MFR < 2, while other authors even reported higher SVD prevalence up to 54% in patients without perfusion defect , a NOTCH3 mutation-related SVD, reported that similar small-vessel alterations can be found on myocardial specimens and in the brain . In accordance, we did not find any significant interrelation between Fazekas score and MBF or MFR using 82Rb PET. However, these authors did not explore detailed brain morphometry, while we found that rest MBF, stress MBF, and MFR were significantly correlated with striatal volume z-score and abnormal deep nuclear gray matter volume in SVD patients. As lacunae of presumed vascular origin (GMab in our study) and brain atrophy (z-score in our study) are listed between signs of SVD on conventional MRI in the literature  (Rauf et al. In this retrospective study, we found significant interrelations between cardiac and cerebral small-vessel disease quantitative parameters, especially regarding deep gray matter alterations and cardiac perfusion. This finding supports the hypothesis of an association between cardiac and brain SVD as a systemic disorder. Further larger prospective studies are now needed to understand the pathophysiological mechanisms and respective or cumulative effects of congenital and acquired risk factors.


Lateral thoracotomy (LT) approach may preserve the right ventricular (RV) function after left ventricular assist device (LVAD) implantation. This study evaluated the short- and long-term RV function using echocardiography after LVAD implantation via LT or median sternotomy (sternotomy).The patients who underwent HeartMate 3 implantation were retrospectively reviewed. The RV function was assessed before and 1 month and 1 year after LVAD implantation. The primary and secondary outcomes were all-cause mortality and a composite of death or readmission due to RV failure, respectively.P = 0.003] and RV end-diastolic area  and a greater RV fractional area change  and peak systolic tissue velocity . Twenty-four patients died and 46 met the composite end point. Kaplan–Meier curve analysis did not reveal significant differences between LT and sternotomy in the 2-year survival  and adverse event rate .Of the 195 patients, 55 (28%) underwent LT and 140 (72%) underwent sternotomy. There were no significant differences in the preoperative RV geometry or function. One month after the LVAD implantation, the LT group had a smaller RV end-diastolic dimension . Minimally invasive cardiac surgery is employed in many cardiac surgical procedures , 2. RecePrevious studies have revealed potential benefits of the LT approach, such as the potentially decreased risk of postoperative right ventricular failure (RVF), presumably due to the preservation of pericardial integrity , 2.To our knowledge, no study has directly evaluated the right ventricular (RV) function and geometry in the patients undergoing HeartMate 3 implantation via either LT or sternotomy.This study aimed to compare between the 1-month and 1-year RV function and geometry using echocardiogram after HeartMate 3 implantation via LT or sternotomy.This retrospective study was approved by the Institutional Review Board of Columbia University Medical Center , and the requirement for individual consent was waived.The medical records of consecutive patients who underwent HeartMate 3 implantation  at Columbia University Medical Center between November 2014 and September 2021 were retrospectively reviewed. The exclusion criteria were the patients who: (1) received right ventricular assist devices (RVADs) intraoperatively; (ii) had a history of tricuspid valve (TV) surgery; or (iii) had undergone concomitant TV surgery at the time of LVAD implantation. Clinical, electrocardiographic, laboratory and haemodynamic data were collected from electronic medical records.The primary outcome was all-cause mortality. The secondary outcome was a composite of death or readmission due to worsening RVF within 2 years of implantation. RVF was defined according to the Interagency Registry for Mechanically Assisted Circulatory Support based on the signs and symptoms of RVF and elevated central venous pressure . If a paAll transthoracic echocardiograms (TTEs) were performed by a trained, registered cardiac sonographer before LVAD implantation and 1 month and 1 year after LVAD implantation. TTEs were interpreted by experienced attending physicians at our institution according to the American Society of Echocardiography guidelines under a rigid quality-control regimen. Device speed optimization studies were routinely performed at least 2 weeks after LVAD implantation and before hospital discharge. The device speed was determined based on the TTE findings . The optRV geometry was assessed via the RV end-diastolic dimension (RVEDD) and RV end-diastolic area (RVEDA) using modified apical four-chamber views encompassing the entire RV  Fig. 1)1). RV fuBetween 2014 and 2019, full sternotomy was the standard approach for HeartMate 3 implantation. Since 2020, LT has become the standard approach for HeartMate 3 implantation. LT was performed via an upper J-hemisternotomy in the third right intercostal space or right anterior thoracotomy in the second or third intercostal space with left thoracotomy in the fifth or sixth intercostal space. Computed tomography scans were routinely obtained before surgery to evaluate the access to the ascending aorta and LV apex . During t-test  or Mann–Whitney test  was used to compare the continuous variables between the LT and sternotomy groups. Paired t-test or Wilcoxon signed-rank test was used to compare the parameters of the preoperative and 1-month and 1-year follow-up TTE, as appropriate. Chi-squared test or Fisher’s exact test was used to compare the difference in dichotomous variables depending on the size (>5). The Kaplan–Meier method was used to estimate the overall survival and event-free survival, and groups were compared using the log-rank test.Normality of all continuous variables was examined using the Shapiro–Wilk test. Continuous variables are presented as means with standard deviations if normally distributed or otherwise as medians with interquartile ranges. Categorical variables are presented as numbers and proportions. Student’s Propensity score matching was performed with the surgical approach as the dependent variable and selected variables from Table All statistical analyses were performed using MedCalc  and R statistical software .A total of 253 patients underwent HeartMate 3 implantation during the 7-year study period. A flowchart of the study population is shown in Fig. P = 0.004], there were no significant baseline differences in age, sex, body size, Interagency Registry for Mechanically Assisted Circulatory Support profile level or treatment strategy between the 2 groups  vs 83 (59%); ps Table . RegardiPreoperative TTEs were performed at a median of 7 3–15) days preoperatively, whereas short-term and long-term follow-up TTEs were performed at 35 27–47) and 360 (304–392) days postoperatively, respectively. The TTE findings are summarized in Table 7–47 and –15 days P = 0.37 and RVEDA, 27 (23–32) vs 28 (24–34) cm2; P = 0.29], RV function  and peak systolic tissue velocity  between the LT and the sternotomy groups.There were no significant differences in the preoperative RV geometry  and RVEDA  and greater RV fractional area change  and peak systolic tissue velocity . Moreover, 1 month after the LVAD implantation, the LVAD speed was similar between the 2 groups .One month after the LVAD implantation, the LT group had a smaller RVEDD , RV function  or peak systolic tissue velocity  between the 2 groups.One year after the LVAD placement, there were no significant differences in the RV geometry  at preoperative TTE  vs 30 (22%); TE Table .n = 1, sternotomy: n = 10)], quality of life concerns [3 patients ], device failure [3 patients ], stroke [3 patients ], withdrawal of care due to advanced cancer [2 patients ], bleeding [1 patient ] and unknown [1 patient ].In our cohort, 24 patients died and 46 met the composite end point with a 100% follow-up rate at 2 years. Twenty-five patients were hospitalized during the study period due to RVF. The causes of death were sepsis and/or multiorgan dysfunction [11 patients (LT: P = 0.28) .Kaplan–Meier curve analysis demonstrated a 2‐year survival of 93% and 83% in the LT and sternotomy groups, respectively  Fig. . Curve aAfter matching the patients’ baseline characteristics and operative details, there were 36 patients in each group . Short-tThe LT Group preserved better RV function and geometry 1 month after LVAD implantation than those of the sternotomy group. However, these differences were not observed at the 1-year follow-up, and there were no significant differences in the 2-year survival and RVF rates.Our findings suggest that LT may confer a short-term RV protective strategy , 2. PoteTherefore, the mechanism underlying the differences in short-term RV function likely involves excess RV preload and significant TR.Haemodynamically, the LVAD therapy causes dramatic changes as the cardiac output is restored and LV filling pressures are relieved. This can in turn lead to decreased RV afterload and increased RV preload , 20. ComA recent expert consensus declared that patients requiring concomitant TV surgery should not be considered for LT . In our Short-term better RV function and geometry were also observed in the matching cohort, which had no significant differences in the baseline TR grade and concomitant surgery. Consistent with the previous study, LT decreased the RV preload and blood product requirements compared with sternotomy in the matching cohort .Ultimately, our study may suggest that the LT approach should be considered for selected patients undergoing LVAD placement to take advantage of its potential short-term beneficial effects with respect to the RV function and geometry. Long-term surveillance and monitoring will help determine the impact of significant TR on the clinical outcomes in this cohort.This study has some limitations. The design was retrospective, single centre and observational with a small sample size, particularly for the LT group and events. Echocardiographic RV assessment may be hindered by anatomical complexity, presence of devices and severe manifestations of end-stage heart failure . AdditioOur preliminary data suggest that after 1 month from LVAD implantation, the RV function was better preserved in patients who underwent LT than in those who underwent sternotomy. At the 1-year postoperative evaluation, this difference was no longer present, and there were no significant differences in the 2-year survival and adverse event rates.ivad168_Supplementary_DataClick here for additional data file.


Regression analysis showed that a combination of other structural abnormalities at diagnosis of PA represented the principal risk factor for chromosomal imbalances (OR = 2.672). A combination of other structural abnormalities and a high maternal age increased the risk of adverse pregnancy outcomes in PA cases, including intrauterine fetal death (IUFD), termination of pregnancy (TOP), and preterm delivery. (4) Conclusions: The value of CMA for locating imbalanced genetic variations in fetuses with PA was highlighted by this study, particularly when combined with additional structural abnormalities.(1) Objective: To evaluate the application of chromosomal microarray analysis (CMA) in fetuses with pulmonary atresia (PA) and to explore the risk factors for predicting chromosomal imbalances and adverse perinatal outcomes. (2) Methods: This study investigated 428 cases of PA singleton pregnancies that were tested using CMA and quantitative fluorescent polymerase chain reaction (QF-PCR) as first-line genetic testing. The PA cases were divided into two groups: an isolated group and a non-isolated group. (3) Results: CMA revealed clinically relevant copy number variations (CNVs) in 9/139 (6.47%) PA fetuses, i.e., pathogenic copy number variations (pCNVs) in 8/139 (5.76%) fetuses and likely pathogenic CNVs in 1/139 (0.72%) fetuses. Stratified analysis showed that the incidence of clinically significant variants was higher in non-isolated PA fetuses than in isolated PA fetuses (12.50%, 6/48 vs. 3.30%, 3/91,  Congenital heart defects (CHDs) are among the most common congenital malformations worldwide, having an impact on 3–11 out of every 1000 live births and being the main cause of newborn death ,3. AccorA chromosomal microarray (CMA) is a technique that detects chromosomal imbalances known as copy number variations (CNVs) ,8,9. TheIn this study, we used genome-wide high-resolution CMA technology to perform genomic analyses on PA fetuses to investigate the genetic etiology of PA and the application value of CMA technology in PA fetal cases.This was a retrospective cohort study of 146 fetuses with or without other abnormalities that were diagnosed with PA by prenatal ultrasound or fetal echocardiography at the Guangzhou Women and Children’s Medical Center from January 2017 to January 2022. The study protocol was approved by the Guangzhou Women and Children’s Medical Center’s ethics committee. All patients agreed that their data could be used in the study. The survey was carried out in accordance with relevant guidelines and regulations. Inclusion criteria were (I) PA diagnosed by echocardiography; (II) accurate gestational ages based on the mother’s menstrual history and the results of her first-trimester scan; (III) all enrolled cases subjected to invasive prenatal genetic testing. Exclusion criteria were (I) multiple pregnancies; (II) maternal age (MA) < 18 years old; (III) suspected TORCH infection .Fetal echocardiography, using grayscale and color Doppler ultrasound, was performed by ultrasound experts to assess the fetal heart. Each patient underwent standard echocardiography for 30–40 min to review the fetal cardiac anatomy and to record any abnormalities. If there was no direct connection between the right fetal ventricle and the pulmonary artery, fetal PA was diagnosed according to this ultrasound scan. PA fetuses were divided into two groups based on whether they were combined with other structural abnormalities: an isolated group, and a non-isolated group.An electronic ultrasound database and patient records were used to gather information about maternal and fetal clinical characteristics and perinatal outcomes. These included maternal age (MA), pregnancy history, gestational age (GA) at PA diagnosis, gestational age at invasive prenatal diagnosis, karyotype and CMA results, the outcome of pregnancy, GA at birth, mode of delivery, physical examination of newborns, and postnatal therapy if necessary. Patients were routinely contacted by phone for follow-up interviews to collect information. Clinical postnatal follow-up evaluations were scheduled from birth to one year.Fetal DNA was extracted from amniocytes and umbilical blood samples using QIAamp DNA Blood Mini Kit  to screen for aneuploidy on chromosomes 13, 18, 21, X, and Y and to rule out maternal cell contamination by quantitative fluorescence polymerase chain reaction (QF-PCR) [https://www.ncbi.nlm.nih.gov/clinvar/, accessed on 23 January 2020), OMIM , DECIPHER , ClinGen resource , University of California Santa Cruz , and ISCA .CNVs ≥ 100 kb in size were selected for comparative analysis. CNVs are categorized into five categories in accordance with the joint consensus guidelines of the American College of Medical Genetics (ACMG) and Clinical Genome Resource (ClinGen): pathogenic, likely pathogenic, variations of unknown significance (VOUS), likely benign, and benign. Following GRCh37/hg19 genome construction, genomic locations were assessed. With the use of the International System for Human Cytogenomic Nomenclature, the CMA and karyotype findings were recorded (ISCN 2020). In addition, as part of the CMA results for heritability evaluation or trios’ analysis, DNA collected from mother and paternal blood samples was also analyzed. VOUS, likely pathogenic CNVs, and pathogenic CNVs were recorded, but likely benign variants were not considered. Two authors (R.L. and F.F.) reviewed all reported CNVs to ensure that the classifications were fully updated based on the knowledge and experience described in public databases. The public databases interrogated in the process of variant classification included ClinVar (All CNVs were further confirmed by fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction (RT-PCR). Verification was performed not only on fetal samples but also on parental samples.Pregnancy outcomes included live birth, termination of pregnancy (TOP), or neonatal death. We conducted clinical follow-up assessments by means of electronic medical records or telephone enquiry one year after birth, and routine follow-up assessments were performed annually. If other cardiac structural abnormalities are found during the screening of newborns, we recommended that the physicians at the Heart Center perform a further evaluation.p value < 0.05 was considered statistically significant.Statistical analysis was performed using Pearson’s chi-square or Fisher’s exact test and SPSS software version 25.0 (IBM); a PA was identified in 148 singleton pregnancies in total, and the prenatal diagnoses were performed by invasive methods at Guangzhou Women and Children’s Medical Center from January 2017 to January 2022. Amniocentesis for genetic diagnosis was performed in 101 (72.66%) cases, and percutaneous umbilical cord blood collection was performed in the remaining 38 cases (27.34%). Chromosomal microarrays discovered clinically significant variants in 9/139 (6.47%) fetuses, including pathogenic copy number variations in 8/139 (5.76%) fetuses and likely pathogenic CNVs in 1/139 (0.72%) fetuses. VOUS were discovered in 18/139 (12.95%) fetuses. Parental CMA results were available in seven cases with P/LP or VOUS, but the remaining patients refused the test due to economic reasons. The results of prenatal diagnosis and the details of follow-up are recorded in the flowchart in +2 (21+5–27+4) weeks. In all instances, 103/139 (74.10%) were diagnosed in the late second trimester (19+6–27+5 weeks of pregnancy), and the remaining 36/139 (25.90%) were diagnosed in the third trimester. Among all cases, 85 (61.15%) were live births, 52 (37.41%) chose to have the pregnancy terminated, and a diagnosis of spontaneous intrauterine fetal death was made in 2 (1.44%) cases. n = 8) and likely pathogenic CNVs (n = 1)). Of these nine cases with clinically significant variation, eight had CNV fragments <10 Mb, and only one had CNV fragments >10 Mb. Of the nine clinically significant CNVs, eight were copy-number losses, and one was a duplication. The molecular diagnoses were 22q11.2 microdeletion syndrome (n = 4), Williams–Beuren syndrome (n = 1), mosaic chromosome 21 monosomy (n = 1), 8q24.3 duplication with 21q22.2q22.3 deletion (n = 1), 16p13.11 microdeletion syndrome (n = 1), and 7q36.1 microdeletion (n = 1).The mean maternal age (MA) (at the time of reporting) was 30.1 ± 3.8 years old, and the median gestational age (GA) at diagnosis of PA was 23p = 0.019) was the main risk factor for the prediction of chromosomal imbalances in PA fetuses. Regression analysis showed that a combination of other structural abnormalities at diagnosis of PA . The logistic analysis showed that a combination with other malformations represented the main risk factor for chromosomal imbalances when diagnosing PA. In combination with other structural malformations, maternal age of >35 years was a positive predictor of abnormal CMA results in PA fetuses. In summary, MA, GA in diagnosing PA, and the presence of other structural abnormalities all increase the risk of adverse pregnancy outcomes in PA fetuses. In providing patients with prenatally identified PA counseling, these objective data may be useful.With this study, we identified the prevalence and distribution of genetic variations in PA fetuses, whether or not they had other structural defects. We also explored and described the clinical outcomes of the PA fetuses, as well as the factors affecting prognosis. Most importantly, our study confirmed the value of CMA in detecting genomic imbalances in PA fetuses, particularly fetuses suspected of having PA in combination with other structural abnormalities. Overall, CMA had a clinically significant variant detection rate of 6.47% in PA fetuses. However, the detection rate of clinically important variants in the non-isolated PA group was higher than that in the isolated group  may be involved in developing the sixth arched artery; it may also be involved in the junction between the peripheral and central pulmonary arteries. Notably, in 80% of cases, the causative imbalance of 22q11.2 microdeletion syndrome is not inherited and is defined as de novo. However, regardless of their sex, affected individuals, in common with patients with an autosomal dominant condition, face a 50% chance of having an affected child in each pregnancy. For this reason, 22q11.2 microdeletion syndrome is a focus of current research [Considering our results relating to chromosomal imbalances, we found that 22q11.2 microdeletions are particularly common in PA fetuses. Among the nine pathogenic CNVs detected in our cohort, four (44.44%) involved 22q11.2 microdeletion syndrome. In addition to this, 22q11.2 microdeletion syndrome; trisomy 21, 18, and 13; and Turner’s syndrome are chromosomal imbalances commonly found in clinical practice and are common chromosomal imbalances in CHDs. Furthermore, 22q11.2 microdeletion syndrome is the most common microdeletion syndrome, although its gene-fragment deletion size is about 1.5–3.0 Mbp [Turner syndrome, 22q11.2 microdeletion syndrome, 21-trisomy syndrome, 18-trisomy syndrome, and 13-trisomy syndrome are common chromosomal defects in the clinic and are also common chromosomal defects in congenital heart disease. In 1998, Hofbeck et al.  used theIt is worth noting that PA/VSD has a more significant correlation with 22q11 microdeletion than PA/IVS, especially in fetuses with MAPCAs and/or right aortic arch or thymus dysplasia, which increases the risk of 22q11 microdeletion. Therefore, fetal craniofacial and thymic development should be observed when PA/VSD is detected on prenatal ultrasound of the fetal heart. In this study, both fetuses showed thymus dysplasia, facial morphological abnormalities, and PA/VSD, and their genetic testing results showed 22q11 microdeletion. To sum up, when prenatal ultrasound finds that the fetus has the above developmental abnormalities, pregnant women should be recommended to undergo genetic testing to determine whether the PA fetus is combined with 22q11 microdeletion.In about 40% of reported cases, trisomy 21 is associated with CHDs, such as complete atrioventricular canal defect (CAVC), VSD, ASD, and TOF; however, PA is rarely reported . Using aIn recent years, with the development of high-resolution ultrasound instruments and the improvement of the technical level of sonographers, the application of transabdominal ultrasound, transvaginal ultrasound, or a combination of the two can better display the fetal heart structure in early and late pregnancy. Several studies have shown that the combination of fetal nuchal translucency (NT) and ductus venosus blood flow spectrum abnormalities can improve the specificity and accuracy of screening for congenital heart defects ,27,28,29p < 0.05). Overall, a definitive genetic diagnosis and a good prognosis help to increase the confidence of patients to continue a pregnancy, especially those who carry fetuses with isolated PA and have negative genetic testing results.It is essential to carry out postnatal follow-ups of children with a prenatal diagnosis of fetal PA. To this end, we collected data on the pregnancy outcomes and postpartum treatment of the live-birth PA cases described above. A total of 59 (69.4%) of the 85 live births in our study cohort underwent postpartum surgery and had a good prognosis. Our data revealed that non-isolated PA is a powerful predictor of adverse outcomes in cases of PA pregnancy, including termination of pregnancy (TOP), intrauterine fetal death (IUFD), and preterm birth. We also found that cases of isolated PA have a better prenatal and postnatal prognosis than cases of non-isolated PA and that fetal PA associated with other anomalies correlates with increased rates of pregnancy termination and postnatal surgery. Furthermore, our statistical analysis showed that the prognosis of PA fetuses without genetic conditions was better than that of PA fetuses with genetic conditions  and that non-isolated PA led to an increase in the pregnancy termination rate and the postpartum surgery rate. Our study data revealed that CMA produced a genetic etiology diagnosis rate of 6.47% for prenatal PA and that the detection rate in non-isolated PA cases was higher than that of the isolated group . Finally, we found that CNVs were identified in a substantial proportion of PA cases. In conclusion, we recommend that CMA should be offered in all pregnancies with fetal PA, regardless of whether other ultrasound anomalies are present or absent.To our knowledge, this is the first largest prenatal study using CMA for fetal PA chromosome detection. This study emphasized the importance of chromosome detection for PA fetuses and found that non-isolated PA fetuses had a higher rate of chromosomal imbalances. In this study, we found that cases of isolated PA had better prenatal and postpartum prognosis compared with non-isolated PA cases (73.62% vs. 37.50%,


Fucoidan is synthesized through the condensation of a key substance, guanosine 5′‑diphosphate (GDP)‑l‑fucose. Therefore, a more direct approach for biomanufacturing l‑fucose could be the enzymatic degradation of GDP‑l‑fucose. However, no native enzyme is known to efficiently catalyze this reaction. Therefore, it would be a feasible solution to engineering an enzyme with similar function to hydrolyze GDP‑l‑fucose.l‑fucose synthetic route in Bacillus subtilis by introducing heterologous GDP‑l‑fucose synthesis pathway and engineering GDP‑mannose mannosyl hydrolase (WcaH). WcaH displays a high binding affinity but low catalytic activity for GDP‑l‑fucose, therefore, a substrate simulation‑based structural analysis of the catalytic center was employed for the rational design and mutagenesis of selected positions on WcaH to enhance its GDP‑l‑fucose‑splitting efficiency. Enzyme mutants were evaluated in vivo by inserting them into an artificial metabolic pathway that enabled B. subtilis to yield l‑fucose. WcaHR36Y/N38R was found to produce 1.6 g/L l‑fucose during shake‑flask growth, which was 67.3% higher than that achieved by wild‑type WcaH. The accumulated l‑fucose concentration in a 5 L bioreactor reached 6.4 g/L.Herein, we constructed a de novo l‑fucose. Additionally, we found an efficient GDP‑mannose mannosyl hydrolase mutant for L‑fucose biosynthesis that directly hydrolyzes GDP‑l‑fucose. The engineered strain system established in this study is expected to provide new solutions for l‑fucose or its high value‑added derivatives production.In this study, we established a novel microbial engineering platform for the fermentation production of The online version contains supplementary material available at 10.1186/s12934-023-02060-y. It has been reported that l‑fucose decreased fat accumulation and hepatic triglycerides in mice fed a high‑fat diet, helping to restore healthy intestinal composition and function [l‑Fucose is known to suppress pathogen virulence, protecting the host against infection and inflammation [l‑fucose‑containing glycan motifs alter pro‑ and anti‑inflammatory immunoglobulin G activities, which indicates their potential application in immunotherapy [l‑fucose have led to its application in the treatment of human diseases. Research has found that ∼20% of the population has a Fut2 defect, which is linked to diseases with potential connections to the gut microbiota [l‑fucose enhances fitness by supporting beneficial gut bacteria [l‑fucose is also a common constituent of extracellular polysaccharide (EPS) secreted by many gram‑negative pathogens [l‑fucose supplementation has been reported as a promising therapy for congenital glycosylation disorders, improving growth and cognitive skills in children with GFUS‑CDG  [l‑Fucose can also be applied as the substrate for producing 2′‑fucosyllactose (2′‑FL) and 3‑fucosyllactose (3‑FL), two key oligosaccharides in human milk [l‑fucose‑containing colanic acid hexasaccharide [l‑fucose.l‑Fucose exists in the form of sulfated l‑fucose‑rich polysaccharides called fucoidans in brown algae, seaweeds and echinoderms [l‑fucose production is achieved by laborious and costly extraction and purification processes using brown algae as the crude material [l‑fucose have been developed to meet the increasing demand for this chemical. For example, l‑fucose can be chemically converted from d‑mannose [l‑fucose‐rich microbial EPS [l‑fuculose [L‑Fucose  . l‑Fucosman milk , 11. A rccharide , and it inoderms . Industrmaterial . Other r‑mannose , and it bial EPS  or bio cfuculose .l‑fucose bioproduction from sustainable carbon sources seems to be a more promising approach. Previously engineered Escherichia coli was developed to produce l‑fucose from in situ synthesized 2′‐fucosyllactose (2′‐FL) by recombinant 2′‐fucosyltransferase and α‐l‑fucosidase [l‑fucose synthetic route, involving the addition and discharge of a lactose molecule, would be redundant if guanosine 5′‑diphosphate (GDP)‑l‑fucose could be directly degraded into GDP and L‑fucose; however, no enzyme has been identified as being capable of such a catalytic reaction. A known enzyme with a similar function is E. coli GDP‑mannose mannosyl hydrolase . wcaH is part of an operon encoding enzymes for the synthesis of colanic acid, a l‑fucose‑rich extracellular polysaccharide. WcaH is speculated to regulate the cellular level of GDP‑d‑mannose by catalyzing the hydrolysis of GDP‑D‑mannose to GDP and d‑mannose in the presence of Mg2+ to limit the carbon flux channeled toward GDP‑l‑fucose formation [d‑mannose, GDP‑d‑glucose and GDP‑l‑fucose, all of which bind to the catalytic center of the enzyme through 12 hydrogen bonds [l‑fucose, the kcat of WcaH is low, with a high Km, suggesting that GDP‑l‑fucose might be a potent competitive inhibitor of GDP‑d‑mannose hydrolysis [l‑fucose to yield l‑fucose  that can trigger aberrant inflammation. B. subtilis is regarded as generally recognized as safe (GRAS) and has become a model chassis host cell for industrial applications due to its robustness and metabolic versatility [B. subtilis microbial platforms [B. subtilis lacks the GDP‑l‑fucose generation pathway that E. coli naturally possesses. To achieve enzymatic l‑fucose production from GDP‑l‑fucose, an E. coli‑derived GDP‑l‑fucose generation pathway has to be transferred into B. subtilis ATCC 6051a, and similar work has been accomplished for microbial 2’‑FL production [l‑fucose with engineered B. subtilis, this work began with rationally designing WcaH mutants based on the docking model of wild‑type WcaH, followed by expressing the GDP‑l‑fucose synthetic pathway together with WcaH or its mutants. This is the first report of microbial l‑fucose production through GDP‑l‑fucose hydrolysis.Regarding the main applications of satility . A varielatforms –27. Howeoduction . To prodB. subtilis 6051a  used in this study is a well‑studied chassis strain with a clear genetic background and is easy to cultivate at a high density [B. subtilis is generally recognized as safe (GRAS) by the FDA and is suitable for the production of food processing enzymes or food additives [B. subtilis also offers advantages in product separation and purification. To assess whether B. subtilis was able to accumulate l‑fucose during cultivation, a B. subtilis growth experiment was performed. As shown in Additional file l‑fucose as the sole carbon source, indicating that B. subtilis 164 lacks the capability to catabolize l‑fucose. Next, to facilitate the convenient genetic manipulation of B. subtilis 164, we improved the transformation efficiency by integrating comk (B. subtilis endogenous gene for the regulation of genetic competence and DNA uptake) into the genome of host cells under the control of a mannitol‑inducible PmtlA promoter, and the generated strain was designated 164 M. However, there are no efficient expression kits for B. subtilis 164 M. To facilitate the efficient expression of target pathway, we attempted to transplant a T7 expression system into the 164 M genome at the aprE locus by integrating a DNA cassette expressing T7 RNA polymerase (T7 RNAP), which generated 164MT.The host  density . In addidditives , 30–32. l‑fucose is used as the l‑fucose donor to synthesize extracellular polysaccharides or lipopolysaccharides. For example, colanic acid (M‑antigen EPS) produced by E. coli has a specialized operon for expressing the enzymes required to perform glycosyl‑transferring reactions and generate GDP‑l‑fucose from d‑mannose, including WcaH. However, l‑fucose accumulation has not been reported, probably due to the low catalytic efficiency of WcaH for GDP‑l‑fucose. In addition, endogenous fucI, rhaA, and araA may also metabolize trace l‑fucose even if it is accidentally produced. Nevertheless, the E. coli pathway that enables GDP‑l‑fucose production together with WcaH or its mutants was transferred into B. subtilis. In contrast with E. coli, there is no known l‑fucose metabolizing pathway in B. subtilis, which would be a major advantage for l‑fucose accumulation.In some gram‑negative intestinal bacteria, GDP‑l‑fucose formation pathway was cumulatively expressed by two artificial operons that were then engineered into 164MT. The first operon consisted of manA, manB and manC. manA encodes a native mannose‑6‑phosphate (M6P) isomerase that transforms fructose‑6‑phosphate (F6P) to M6P, which is then used as the substrate of phosphomannomutase (ManB) and catalyzed to mannose‑1‑phosphate (M1P). M1P is further converted into GDP‑D‑mannose (GDP‑Man) through the catalysis of mannose‑1‑phosphate guanyltransferase (ManC). The second operon contained coding sequences of GDP‑mannose 4, 6‑dehydratase (Gmd) and GDP‑fucose synthetase (WcaG). Gmd and WcaG convert GDP‑Man to GDP‑L‑fucose. Both operons were cloned behind the T7 promoter, and manA/manB/manC cassette was inserted at the manA locus in 164MT, resulting in 164MTM. Next, gmd/wcaG cassette was integrated at the xylA locus in the 164MTM genome, leading to 164GF, which was then transformed by the WcaH‑expressing plasmid pMK4‑T7wcaH. The transformant bearing pMK4‑T7wcaH was designated 164GFpWT. As the control, pMK4‑T7 was transformed into 164GF, generating 164GFpC  analysis, with m/z values of 164.10 (l‑fucose), 182.16 (l‑fucose·H2O), and 147.08 (l‑fucose‑OH‑), corresponding to the molecular ion of l‑fucose  and enter glycolysis pathway; second, l‑fucose produced competitively inhibit the native catalytic reaction that should have yield d‑mannose. Herein, a de novo l‑fucose synthetic pathway was successfully constructed in a B. subtilis strain that was capable of l‑fucose production during growth. In contrast to the reported l‑fucose‑producing E. coli system [B. subtilis bypassed 2′‑FL formation and breakage. It is interesting that there has never been any report demonstrating that E. coli was able to synthesize l‑fucose utilizing its native GDP‑l‑fucose‑forming pathway and wild‑type (WT) WcaH, indicating that in addition to the l‑fucose metabolizing enzymes, sophisticated regulation mechanisms may also exist to guide GDP‑l‑fucose only toward polysaccharide synthesis, suggesting that the delicate engineering of E. coli native pathways is another feasible way to produce l‑fucose.Both 164GFpC and 164GFpWT were cultivated in shake flasks containing Luria‑Bertani (LB) medium for 96 h, with glycerol supplemented as an extra carbon source. The cell‑free broth was collected as a sample for high‑performance liquid chromatography (HPLC) analysis during growth. As shown in Fig. i system , the eng2+/Mn2+ and the triphosphate moiety of the substrate in a novel loop‑helix‑loop motif that is conserved in the MutT family of proteins, and its homology modeling has been established by using published X‑ray structures as templates [d‑mannose is the inclusion of a methyl group on the C6 of L‑fucose instead of a hydroxymethyl group in d-mannose  or leucine (R36L), which might provide a more hydrophobic microenvironment for the methyl group on the C6 of l‑fucose.WcaH is a type of MutT nucleoside triphosphate pyrophosphohydrolase belonging to a protein family of Nudix hydrolases. WcaH binds with Mgemplates . The cheose Fig. A. StructR36Y, WcaHR36F, WcaHR36L, WcaHR36I, and WcaHR36W were constructed and tested for L‑fucose production with growth experiments. As shown in Fig. l-fucose accumulated gradually and reached its maximum level after 96 h of fermentation. The highest titers of l-fucose during 96 h cultivation by WcaHR36Y, WcaHR36F, WcaHR36L, WcaHR36I, and WcaHR36W reached 609.3 mg/L, 514.5 mg/L, 310.7 mg/L, 357.7 mg/L, and 425.3 mg/L, respectively, compared to 436.1 mg/L achieved by WT WcaH. Thus, 39.7% and 18.0% increases in l-fucose were achieved by WcaHR36Y and WcaHR36F, respectively  method was used to calculate the binding free energy to evaluate the thermodynamic stability. As shown in Fig. l-fucose, except for Y102R performed on R36Y or R36F  and used for genetic manipulation in this study. E. coli DH5α was used for vector construction, propagation and preservation, and its genomic DNA was applied as the template for the polymerase chain reaction (PCR) preparation of DNA fragments derived from E. coli. pMK4, a gift from the Bacillus Genetic Stock Center (BGSC), was used as the backbone to construct B. subtilis expression vectors. For recombinant expression, wcaH  was cloned behind a T7 promoter on pMK4‑T7.The strains and plasmids used in this study are listed in Additional file E. coli and B. subtilis. Routine growth experiments were performed at 37 ℃ with shaking rotors at 200 rpm, and chloramphenicol (10 mg/L), ampicillin (100 mg/L) and erythromycin (10 mg/L) were added to the medium as needed.LB medium  was used for the cultivation of B. subtilis single colony was inoculated into 5 mL of liquid LB and incubated at 37 ℃ overnight with shaking at 200 rpm. Then, 1 mL of grown culture was transferred to 50 mL of modified LB  in a 250/500 mL shake flask and grown at 37 ℃ with shaking at 200 rpm. Samples were collected at regular time intervals for HPLC and LC–MS analyses. For fed‑batch fermentation, an overnight culture of 50 mL LB grown in a 500 mL shake flask was transferred to a 5 L bioreactor with 3.0 L of fermentation medium that contained 20 g/L glycerol, 5 g/L yeast extract, 20 g/L tryptone, 2 g/L MgSO4·6H2O, 10 g/L (NH4)2HPO4, and 5 g/L KCl. The medium pH was maintained at 6.5 using aqueous ammonia as an alkali supplement and 500 g/L glycerol as a carbon source supplement. The growth temperature was set at 37 °C, with the ventilation volume set at 3.0 vvm and an initial stirring speed of 500 rpm.For shake‑flask growth, a mtlA‑comk cassette contained a copy of comk assembled behind the mtlA promoter, homologous arms (UnprE and DnprE) for recombination and an erythromycin resistance gene (ermC) for selection  was prepared by two rounds of PCR. First, PCR with 2 × Phanta Flash Master Mix  was performed to prepare each fragment component. For preparation of the flanking fragments (UnprE and DnprE) of approximately 1000 bp each, PmtlA and comk, the B. subtilis 6051a genome was used as the template, while the ermC fragment was obtained by PCR using the plasmid pMD19T‑aea as the template [mtlA‑comk cassette. Other linear DNAs, such as P43‑T7P, PxylA‑T7P, PrpsF‑T7P, PT7‑manC‑manB‑manA, or PT7‑gmd‑wcaG, were all prepared by similar strategies.Vector DNA construction was mostly accomplished by using the ClonExpress II One Step Cloning Kit . Linear DNA fragments for homologous recombination were constructed via the overlapping PCR technique. For instance, the Pion Fig. . Such a template . Next, a B. subtilis competent cells, which was prepared as described by Ji et al., with the modification of 1% mannitol being used as the inducer instead of xylose [ermC from the genome.Recombination‑mediated genetic manipulations were performed by incubation of linear DNAs with correspondingf xylose . Usuallyhttps://www.schrodinger.com/) using PDB structures 2I8T [2+ and GDP‑mannose from the templates were kept in the WT WcaH model. Glide XP [l-fucose and GDP‑mannose to the WT WcaH model. Modeling of WcaH mutants docked with GDP‑l-fucose was performed according to the conformation of WT WcaH bound with GDP‑l-fucose. Prime MM‑GBSA [The WT WcaH model was built through Prime in Cite Schrodinger 2020‑3  equipped with an RID‑10A refractive index detector. To prepare cell‑free samples, cultures were centrifuged at 12,000 ×g for 10 min and filtered using PTFE filters with an aperture span of 0.22 µm. The samples were then loaded into an Aminex HPX‑87H column (300 × 7.8 mm)  and separated by 5 mM H2SO4 solution as the mobile phase at a flow rate of 0.6 mL/min at 65 ℃. The L‑fucose concentration was calculated according to the calibrated standard curve. All data are representative of parallel independent experiments and presented as the means ± standard deviations (SDs). Statistical differences among the means of two or more groups (p < 0.05) were determined using one‑way analysis of variance.The cell biomass was monitored by measuring the ODAdditional file 1: Figure S1.B. subtilis growth experiment when supplied with A glucose B xylose C fucose D glycerol as the sole carbon source. Figure S2. L-Fucose standard A and fermentation supernatant B were analyzed by LC-MS. Table S1. The strains and plasmids used in this study. Table S2. The primers used in this study.


Right ventricular failure (RVF) is often caused by increased afterload and disrupted coupling between the right ventricle (RV) and the pulmonary arteries (PAs). After a phase of adaptive hypertrophy, pressure-overloaded RVs evolve towards maladaptive hypertrophy and finally ventricular dilatation, with reduced stroke volume and systemic congestion. In this article, we review the concept of RV-PA coupling, which depicts the interaction between RV contractility and afterload, as well as the invasive and non-invasive techniques for its assessment. The current principles of RVF management based on pathophysiology and underlying etiology are subsequently discussed. Treatment strategies remain a challenge and range from fluid management and afterload reduction in moderate RVF to vasopressor therapy, inotropic support and, occasionally, mechanical circulatory support in severe RVF. The function of the right ventricle (RV) remained enigmatic for medicine and science for centuries. In 1628, Sir William Harvey wondered why nature provided human bodies with a ventricle dedicated to the sole purpose of nourishing the lungs, whereas all other organs receive blood from the left ventricle (LV). The conundrum persisted during the first half of the 20th century after experiments in dogs showed almost unchanged blood pressure and cardiac output after complete RV-free wall cauterization ..16].es). On a single beat, Ees, however, also depends on the actual preload and afterload conditions and cannot be considered an independent surrogate of contractility. Nevertheless, as Ees is the only elastance value to be shared by multiple ejecting beats at variable preloads and fixed afterloads, linear regression connecting these pressure–volume points  can be performed to assess contractility as a relatively load-independent measurement. ESPVR can thus be measured over multiple beats (PV loops family) recorded during slow balloon inflation in the inferior vena cava or during a progressive Valsalva maneuver , that occurs at the end of ejection . Ea accounts for net vascular stiffness, is independent of preload and contractility, and can be approximated by the ratio between the end-systolic pressure and stroke volume on pressure–volume loops (es (mmHg/mL), Ea offers the possibility to assess how RV contractility may be adapted or not to afterload. Indeed, the ratio of elastances (Ees/Ea), referred to as RV-PA coupling, can be seen as the matching of the heart with its arterial circuit. Optimal Ees/Ea values related to optimal energy transfer from the RV to the arterial tree lie between 1.5 and 2.0. In PH, RV volume increases when Ees/Ea is <0.8, and RV-PA coupling is a main determinant of outcome [In the right-sided circulation, the resistive and pulsatile components of the hydraulic load opposed by the pulmonary circulation to RV ejection can be represented by a single factor: effective arterial elastance (Eme loops . This si outcome .a increase) results in a proportionate decrease in stroke volume [es, which may preserve stroke volume and keep the Ees/Ea ratio between 1.5 and 2.0 for some time  and microvasculature. In cardiomyocytes, protein synthesis pathways are activated by two distinct processes: (1) local stress sensing by integrins, stretch-activated ion channels and titin  and (2) ++ mobilization, activation of protein kinase C, MAP kinases, tyrosine kinases and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX), all of which regulate transcription factors associated with cardiac hypertrophy [1-adrenergic receptors induce cardiac hypertrophy through the activation of nuclear protein kinase A and subsequent phosphorylation of nuclear targets that further enhance gene transcription [++ availability or Ca++ responsiveness of the contractile system [In PAH, RAAS activation occurs both locally through increased wall stress and systemically through renal hypoperfusion , whereasertrophy . On the cription . In addie system . This me2 supply to larger cardiomyocytes and occurs through the effects of the vascular endothelium growth factor (VEGF) and angiopoietin-1 secreted by cardiomyocytes [In adaptive RV hypertrophy, little expansion of the ECM also occurs to enhance mechanical resistance to increased wall stress and to scaffold new vessels growing around hypertrophied cardiomyocytes, but fibrosis is minimal . New vesmyocytes .Although adaptive hypertrophy may preserve cardiac output and limit exercise intolerance in the early phase of most PH conditions, a chronic increase in RV afterload almost inevitably leads to RV failure . This evBMPR2 mutation carriers and scleroderma patients with PAH display reduced afterload-adjusted RV ejection fraction [Among the disease-specific factors, it is worth mentioning that fraction  and deprfraction , respectfraction . These mfraction .Factors generally associated with the transition from adaptive to maladaptive hypertrophy include deep metabolic perturbations and fibrosis, but also ischemia and excessive neurohormonal chronic overactivation, whose involvement is important regarding RV failure therapeutic options. 18F-FDG uptake on positron emission tomography imaging [2 demand, RV function may decline as a result of energy starvation. Interestingly, the therapeutic restoration of a better coupling between glycolysis and the mitochondrial oxidative pathway improved RV contractility in several animal models of PH [Whereas normal RVs derive the majority of their energy production from lipid oxidation, pressure-overloaded RVs evolving towards failure increasingly rely on glucose metabolism , as evid imaging . However imaging . As the ls of PH .The increasingly apparent fibrosis in failing RVs may be another important factor for systolic dysfunction . With th2 demand, but concurrent O2 supply may not fulfill O2 demand. First, all PH conditions lessen flow in the right coronary artery during systole by decreasing the pressure gradient between the aorta and the RV, and this may further worsen in cases of systemic hypotension [2 venous saturation on low cardiac output and the re-opening of the foramen ovale may also concur with ischemia. Besides reducing RV contractility, ischemia may also be a major contributing factor to fibrosis and apoptosis in failing RVs.In addition, ischemia seems to play a major role in the reduction in RV contractility with time. As discussed above, enhanced RV wall stress is paralleled by increased myocardial Ootension . Moreoveotension . Indeed,otension . In addi++ effusion from the sarcoplasmic reticulum after cell membrane depolarization and appears polynitrosylated by excessive oxidative stress in failing RVs [Finally, chronic SNS overstimulation leads to the downregulation of sarcolemmal β-adrenergic receptors, with loss of stimulation of the hypertrophic pathways, loss of inotropic stimulation, impaired RV relaxation and increased mortality in PAH . Consequling RVs .es/Ea threshold at which decoupling occurs is unknown, but values between 0.65 and 0.8 have been associated with a worse prognosis in clinical studies [If RV-PA coupling decreases, the RV may still dilate, attempting to preserve cardiac output through the Frank–Starling mechanism, also known as heterometric adaptation. Of note, the E studies ,57,58,59 studies . 2) without increasing RAP (>8 mmHg) characterizes RV failure [The pathophysiologic consequences of RV dilatation are numerous. First, the eccentric remodeling of the RV is always accompanied by increased filling pressure due to the stiffening of fibrotic, hypertrophied, maladapted RVs, with a backward increase in RAP and systemic congestion . By defi failure . In the  failure . In PAH, failure . Renal c failure . Althoug failure .Functional tricuspid regurgitation (TR) may also occur as a consequence of both RV and RA remodeling, with tricuspid annular dilation, valve tenting and normal leaflets. Besides worsening congestion and RAP, TR also decreases cardiac output. In left heart disease, TR is actually a major determinant of stroke volume . By creaDuring heterometric adaptation, RV dilatation may still become significant enough to induce pericardial constraint. Competition for space is then triggered between both ventricles, a phenomenon called right–left ventricular interaction. As both cavities share the interventricular septum in addition to the pericardial space, LV transmural pressure may decrease during filling or even invert if RAP is high enough. This causes a mechanical septal leftward shift, leading to LV underfilling and low cardiac output . Indeed,2 demand and delivery, with a further decrease in RV contractility and cardiac output. Indeed, RV dilatation raises parietal tension and reduces wall thickness at the same time, which adversely affects wall stress and O2 demand. Simultaneously, the increased RV filling pressure reduces the gradient between aortic diastolic pressure and RV end-diastolic pressure, which may compromise diastolic flow in the right coronary artery and O2 delivery. In addition, the already reduced cardiac output and blood pressure may generally jeopardize coronary perfusion in both ventricles [Finally, ischemia can severely worsen during heterometric adaptation by enhancing the already existing mismatch between RV myocardial Ontricles .In ambulatory facilities, emergency departments or intensive care units, RV hemodynamics, size and systolic function are usually similarly evaluated by echocardiography at bedside . PH can 2 saturation. They are all critical prognostic factors in PAH and CTEPH [In addition to non-invasive imaging, right heart catheterization can be needed to assess important hemodynamic aspects addressing RV function like RAP, cardiac output, stroke volume and venous Ond CTEPH ,73, and nd CTEPH . Furthernd CTEPH . es of the considered single beat and the maximal theoretical Ees [a is then calculated by the ratio between end-systolic pressure and stroke volume, and coupling is finally obtained by the ESPVR/Ea ratio. The generation of pressure–volume loops is considered the gold standard method to assess RV-PA coupling. They are best created by the simultaneous high-resolution recording of both parameters with conductance catheters inserted in the right ventricle through the jugular or femoral vein . ESPVR cical Ees , with goical Ees . Ea is tes/Ea cut-off between 0.65 and 0.7 [es/Ea have been recently developed. Both methods were found useful to determine clinical worsening in populations with PAH and CTEPH with an E and 0.7 ,75, but es/Ea ratio can be simplified for pressure and expressed as a stroke volume/end-systolic volume ratio if the theoretical volume of the unloaded RV is assumed to be null [es/Ea assessed by the pressure–volume curve family model [Cardiac magnetic resonance imaging (MRI) is considered the gold standard non-invasive imaging modality for RV volume evaluation . It can  be null , which i be null . In spitly model  and to ply model .es/Ea have thus also been developed.Cardiac MRI remains, however, costly, not broadly available and quite cumbersome in regard to the long time needed to acquire all sequences (about 45 min). Echocardiographic surrogates of Ees/Ea [es/Ea  to be implemented in clinical practice [The ratio of the tricuspid annular plane systolic excursion (TAPSE) to the estimated systolic PAP (sPAP) is certainly the more investigated surrogate of Ees/Ea ,79. Desces/Ea , the asspractice . 2, VE/VCO2 slope or LV ejection fraction in a mixed population of patients with heart failure and both preserved and reduced ejection fraction [es/Ea in these patients , a cut-off value <0.31 mm/mmHg identified Ees/Ea <0.805 with quite good predictive values  and independently predicted a worse outcome [The clinical relevance of the TAPSE/sPAP index was first investigated in patients with left heart disease. In the setting of heart failure with preserved ejection fraction, lower TAPSE/sPAP ratios were associated with worse hemodynamics, worse aerobic maximal capacity and higher NT-proBNP levels . Furtherfraction . Later, fraction . Althoug outcome . Interes outcome .es/Ea, but they have been so far less validated than TAPSE/sPAP [Of note, numerous other indices like RV fractional area change/mPAP, RV fractional area change/RV end-systolic area and RV longitudinal strain/sPAP were also suggested to represent EPSE/sPAP ,60,79. The management of pressure-overloaded RV failure relies on preload optimization, afterload reduction, maintenance of coronary perfusion and inotrope therapy . Acute mThere has been a quite recent change in paradigm regarding preload management in RV failure, emphasizing the importance of not overfilling the patient ,86. In aIn patients monitored invasively, there are no specific guidelines on the RAP to target, but values > 8–12 mmHg likely suggest a benefit from decongestion . Fluid rPreload and volume management are also important in chronic progressive RV failure occurring in ambulatory patients, and treatment mostly relies on oral diuretics that must be adjusted according to congestion clinical signs and renal function. As compared to furosemide, torasemide has a more predictable bioavailability and is usually the preferred loop diuretic. Combination therapy with thiazides is sometimes also necessary if resistance to loop diuretics develops . The management of RV afterload depends on the underlying cause of RV failure, and evidence-based guidelines are available for many scenarios, such as pulmonary embolism, PAH, CTEPH and left heart disease. On the other hand, management of RV afterload in the setting of critically ill patients in intensive care units may reflect expert opinions more closely.Patients with acute pulmonary embolism and hemodynamic instability (high-risk patients) should undergo immediate reperfusion therapy, in most cases via systemic thrombolysis, whereas still normotensive patients with signs of RV dysfunction on echocardiography or CT scan (intermediate–high risk) should be monitored for eventual worsening and anticoagulated . Occasionally, patients with PAH and CTEPH may be diagnosed with acute RV failure. Parenteral prostanoids should be promptly started and up-titrated in PAH in addition to oral endothelin receptor antagonists, phosphodiesterase type 5 inhibitors or soluble guanylate cyclase stimulators . Of note2 pressure, but with more intensity if hypercapnia, acidemia and low mixed venous saturation are also present [PH associated with chronic lung disease and/or hypoxia is usually mild to moderate and is rarely at the origin of RV failure , except  present ,103.2 saturation as well as on RV ejection fraction [Interventions aiming at relieving RV afterload should ideally correct blood gas and pH imbalance, but these goals may be at odds with the current ventilatory approach in ARDS patients, who benefit at the same time from low-volume ventilation and permissive hypercapnia . In addifraction ,106. Nevfraction .Finally, in patients presenting with RV failure in addition to LV failure, guidelines regarding acute heart failure therapy should be applied . Drugs aFighting RV ischemia is a mainstay of RV failure therapy. Vasopressors are often considered to restore blood pressure and improve blood flow in the right coronary artery. To that end, the ideal vasoactive agent should enhance systemic arterial pressure and at the same time decrease pulmonary vascular resistance, or at least keep it unchanged.1 receptors with higher affinity than to β1 and exerts a vasoconstricting effect at low doses with weak cardiac inotropy [1 receptors, and in patients with sepsis and RV failure, norepinephrine was associated with increased pulmonary vascular resistance and no change in RV ejection fraction despite improvement in RV myocardial O2 delivery [Norepinephrine binds to αinotropy . It is oinotropy ,86. In dinotropy . Howeverdelivery . Low-dose arginine vasopressin (0.01–0.03 U/min) may appear as the most appealing vasopressor in RV failure as it exerts simultaneous systemic vasoconstriction and pulmonary vasodilation  through V1 receptor stimulation , therebyImportantly, phenylephrine and dopamine are potent constrictors in both pulmonary and systemic circulations, and they are not considered for the treatment of acute RV failure ,86.2 delivery despite the optimalization of RV preload and afterload and after the initiation of vasopressors [Inotropic agents can be used in the management of unstable patients with RV failure when there is evidence of persistent inadequate Opressors . Of notepressors . 1 and β2 receptors, decreased PA resistance and increased RV contractility and RV-PA coupling [1 receptor downregulation occurring in chronic RV pressure overload, these observations could not be repeated in chronic RV failure. In experiments performed on rat models with persistent PH induced by various methods, dobutamine-recruitable RV contractile reserve and cAMP concentrations in RV cardiomyocytes were actually severely reduced as compared to controls [2 receptor stimulation [1 and β2 stimulation may still be harmful as they worsen myocardial O2 demand and ischemia and trigger arrythmias and hypotension. In anesthetized dogs with acute PA constriction, dobutamine (5–10 μg/kg/min), an agonist of βcoupling . Howevercontrols . On the mulation ) and incmulation . Similarmulation , but themulation . In addi++ release from the sarcoplasmic reticulum and finally enhances inotropy without β-receptor stimulation [Phosphodiesterase-3 (PDE3) inhibitors like milrinone may appear as a more attractive alternative. Milrinone works by inhibiting the intracellular breakdown of cyclic adenosine monophosphate (cAMP), which promotes Camulation ,122,123.mulation  that is mulation . By combmulation ,127. Howmulation , PDE3 inmulation . ++ sensitizers”, levosimendan may also be an interesting alternative to dobutamine. Unlike β-adrenoreceptor agonists and PDE3 inhibitors, myofilament Ca++ sensitizers do not increase cAMP and Ca++ cytosolic concentrations, but they enhance cardiac Troponin C (TnC) sensitivity to Ca++ [++-associated cardiac TnC and stabilizes the cation–protein link, which triggers more cross-bridging between actin and myosin and generates more force. With this drug, cardiomyocytes need less O2 to increase their contractility than with β-adrenoreceptor agonists and PDE3 inhibitors because there is no cytosolic Ca++ excess to be actively pumped back into the sarcoplasmic reticulum during diastole, which is a real advantage. Belonging to the family of “myofilament Ca to Ca++ . During + channels in arterial and venous smooth muscle cells, inducing membrane hyperpolarization and cell relaxation, including in the lung vessels. In various animal models of acute and chronic RV failure and PH, levosimendan was thus consistently shown to restore RV-PA coupling by simultaneously improving RV contractility and reducing RV afterload [Besides targeting the heart, levosimendan opens ATP-sensitive Kfterload ,134,135.fterload . Although clinical data regarding levosimendan accumulate in the fields of septic shock, post-cardiopulmonary bypass low output syndrome and advanced heart failure, there is currently no high-quality randomized controlled trial available for PH-associated RHF. However, numerous small studies reported promising results. In the context of PH associated with left heart disease, levosimendan was consistently associated with reductions in PAP and pulmonary vascular resistance and with the improvement in echocardiographic indices of RV function ,138,139.Regarding safety, levosimendan was mostly studied in the setting of acute and chronic advanced heart failure. In the landmark SURVIVE and REVIVE trials, systolic and diastolic blood pressure declined significantly more with levosimendan than with comparators (dobutamine or a placebo), which was partly due to a no longer recommended high-dose bolus preceding the 24 h infusions ,142. Hyp2 demand on medical therapy and only as a bridge to recovery or transplantation. Indeed, there is currently no validated option for long-term MCS and destination therapy in RV failure [Mechanical circulatory support (MCS) can be considered if cardiac output remains insufficient to match body O failure ,146,147.2-desaturated blood to an oxygenator, and an arterial canula is inserted in the ascending or descending aorta to restitute oxygenated blood to all organs. The benefits of ECMO are numerous: quick installation in emergent situations, rapid correction of hypoxemia and capacity to address both isolated RV failure and bi-ventricular failure if necessary. Whereas devices that increase trans-pulmonary flow  can be considered in pure RV pump failure , they are not contemplated in cases of pulmonary vascular disease because PA pressure may excessively increase and induce vascular lesions and lung hemorrhage [In cases of significant pulmonary vascular disease, veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is usually the only possible MCS option ,146,147.morrhage ,146,147.Typical VA-ECMO complications include thrombus formation around canulae, arterial embolism, limb hypoperfusion and local infections that occur increasingly with support duration. In a recent multicentric retrospective evaluation of the outcome of patients treated with VA-ECMO in Germany (43.4% implanted in the context of cardiopulmonary resuscitation), the overall complication rate was 18.4% for bleeding, 0.9% for stroke, 6.6% for abdominal ischemia and 7.6% for limb ischemia .In recent years, clinicians and scientists have regained interest in RV pathophysiology, and a great deal of effort has been placed on understanding its function in health and disease. Invasive methods were developed to accurately assess its function and adaptation, but the non-invasive evaluation of its coupling to the pulmonary circulation at bedside remains challenging. In addition, therapeutic options aimed at the preservation or improvement in its function principally target pulmonary vessels and not the myocardium. Nevertheless, promising results were also obtained with modulators of metabolism and reactive oxygen species production, as well as with microRNA and long non-coding RNA in animal models of RV failure . In addi


Cancer therapy‐related cardiovascular toxicity (CTR‐CVT) is a major contributor to poor prognosis in breast cancer (BC) patients undergoing chemotherapy. Left ventricular global longitudinal strain (LV GLS) has predictive value for CTR‐CVT, while few researchers take into account late‐onset CTR‐CVT. This study sought to provide a guide for the prediction of late‐onset CTR‐CVT in primary BC over the 2 years follow‐up via strain and contrast‐enhanced echocardiography.Anthracycline and anthracycline + targeted medication groups were created from 111 patients with stage I–III primary BC who were prospectively included. The left ventricular diastolic function, LV global long‐axis strain (GLS); left ventricular ejection fraction by contrast‐enhanced echocardiography (c‐LVEF), and electrocardiograms were collected at baseline, 3, 6, 12, and 24 months after the start of cancer treatment. The high‐sensitivity troponin‐T and NT‐pro BNP at baseline and 3 months after chemotherapy were measured.p < 0.001), and the cut‐off is 20.32%.(1) LV GLS decreased in BC patients over time. (2) After 12 months' follow‐up, the LV GLS in the anthracycline+ targeted group was lower than in the anthracycline group. After 24 months' follow‐up, the GLS and c‐LVEF in the anthracycline + targeted group declined while the E/e’ increased. (3) Decreased LVEF (56%) and arrhythmia (38%) are the common causes of CTR‐CVT. Lower LVEF was a major factor in late‐onset CTR‐CVT. (4) Combination of LV GLS and c‐LVEF at 3 months were used as predictors for CTR‐CVT and exhibited a higher AUC than either one alone . LV GLS at 3 months can predict the late‐onset CTR‐CVT  patients is largely due to chemotherapy‐induced cardiotoxicity (CTIC). Few researchers take into account late‐onset CTR‐CVT. With a 2‐year follow‐up, the results of this study were used to build a more accurate and trustworthy strategy for managing CTIC risk variables. Regarding of the late‐onset CTR‐CVT, LV‐GLS at 3 months had a prediction value. LVEF was suggested by several guidelinesLeft ventricular global longitudinal strain (LV GLS) has predictive value for CTR‐CVT and HF and can detect early subclinical myocardial impairment related to cancer treatment,The objectives of this prospective cohort study were to evaluate the changes in the LV function of primary BC patients via GLS and contrast‐enhanced echocardiography, sought to provide a guide for the prediction of late‐onset CTR‐CVT (≥1 year) in primary BC over the 2 years follow‐up via strain and contrast‐enhanced echocardiography.22.1http://www.chictr.org.cn). Consecutive patients with stage I‐III primary breast invasive ductal carcinoma receiving anthracycline chemotherapy or followed by sequential targeted therapy between May 2019 and December 2019 were enrolled. The patients were diagnosed with BC by Version 3. 2018, National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines.This study is a single‐center prospective cohort study from a registered study with the identifier ChiCTR1900022108 , tumor node metastasis (TNM) stage and endocrine therapy, and thoracic radiation. Holter was carried out if the electrocardiogram (ECG) revealed any new arrhythmias. At baseline (T0), follow‐up at 3 months T1), 6 months (T2), 12 months (T3), and 24 months (T4) post‐chemotherapy, TTE and ECG were conducted. At T0 and T1, the myocardial injury biomarkers including NT pro‐BNP, troponin‐T, and creatine kinase isoenzyme (CK‐MB) were collected. Follow‐up terminated by January 31, 2022. Figure , 6 month2.3The ultrasound system (Philip Epiq7C and Philip CVx) with a 1–5 MHz phased‐array transducer (M5S) was used. Standard echocardiography, including two‐dimensional (2D), M‐mode, and Doppler echocardiography, was performed according to the guidelines of the American Society of Echocardiography.Apical four‐, two‐, and three‐chamber images of at least five cardiac cycles were captured and used to calculate the LV GLS. The strain analytical software  automatically detects, segments, and monitors LV myocardium after selecting the region of interest for examination, with strain curves being computed simultaneously. To provide a good portrayal of ventricular motion, every track was examined. Poorly tracked segments were manually corrected until a higher tracking quality was attained. When more than two portions of a video could not be tracked satisfactorily, the video was deemed to have “failed”.2.4All patients received an intravenous injection of Sono vue (Bracco SpA). Apical four‐, three‐, and two‐chamber images of at least five cardiac cycles were digitally recorded and archived for analysis. LVEF (designated as c‐LVEF) was estimated from the contrast recordings in the Philips system using the biplane Simpson's rule Figure . Bland–A2.5CTR‐CVT includes cancer treatment‐related cardiac dysfunction (CTRCD), which is defined by the European Society of Cardiology guidelines as having an LVEF<50% or a decrease of >10% post‐chemotherapy, or a new GLS decrease of 15% relative to baseline, immune checkpoint inhibitor‐induced myocarditis, cancer treatment‐related vascular toxicity, cancer treatment‐related arterial hypertension, and cancer treatment‐related arrhythmia.2.6t‐test, and one‐way analysis of variance (ANOVA) were used, respectively. The non‐normal distribution was tested using the Wilcoxon signed‐rank test. Binary variables were compared using Fisher's exact test and the Chi‐square test. To evaluate the risk factors of CTR‐CVT in more detail, multivariable logistic regression models were applied. The multivariate regression analysis model included contained univariate regression analysis of positive factors. After accounting for echocardiographic indices, a receiver operating characteristic (ROC) curve analysis was carried out. Bland–Altman plots were used to display the difference in intra‐observer and inter‐observer of c‐LVEF and GLS, along with the average bias and 95% limits of agreement. p < 0.05 were taken into consideration. IBM SPSS for Windows, version 19.0 (IBM Corp) was used for all analyses.For normally distributed data, continuous variables were displayed as mean standard deviation (SD) or median (25th percentile and 75th percentile) for non‐normally distributed data. Frequencies were used to present categorical variables. For comparing two and three independent groups of normally distributed data, the 33.1n = 5), reluctance to contrast (n = 4), and renewed treatment regimen due to distant metastasis (n = 5). Finally, this study enrolled a total of 111 patients and 77 controls. At 3 months (T1), 105 patients (94.6%) were on follow‐up, 35 patients (31.5%) at 6 months (T2), 89 patients (80.2%) at 12 months (T3), and 88 patients (79.3%) at 24 months (T4).Fourteen patients were removed, as in Figure Age, body mass index (BMI), chronic diseases like hypertension, and diabetes, tumor node metastasis (TNM) stage, and other treatment indicators for BC did not significantly alter between baseline and follow‐up Table .3.2p < 0.05). When compared to LV GLS at 3 months (T1) follow‐up, LV GLS at 1 year (T3) and 2 years (T4) decreased. E/e’ increased at 3 months (T1), 1 year (T3), and 2 years (T4) compared to baseline (T0). Additionally, when compared to baseline (T0) and 3 months (T1), serum myocardial injury biomarkers, such as CK‐MB, increased at 6 months (T2) (p < 0.05) , but the c‐LVEF showed no difference (Table p < 0.05) in the anthracycline + targeted group compared to the anthracycline group.After a year of follow‐up, GLS in the anthracycline + targeted group decreased in comparison to the anthracycline group , 13 arrhythmias, and 1 with newly developed hypertension. Twelve patients had late‐onset CTR‐CVT, including nine with decreased LVEF, two with arrhythmia, and one with newly developed hypertension. Figure 3.4p = 0.034). Furthermore, we found that left thoracic radiotherapy can affect the early‐onset CTR‐CVT (p = 0.009). Out of a total of 22 patients with early‐onset CTR‐CVT, 12 patients had received left chest radiotherapy.Plots illustrating the cumulative incidence of CTR‐CVT for the three groups—without CTR‐CVT, with CTR‐CVT, and with late‐onset CTR‐CVT—were made Table . No diffUnivariate logistic regression analysis was used to examine potential risk variables for CTR‐CVT. The multivariate regression analysis model took the data with discrepancies into account Table . The modp < 0.001) and c‐LVEF  at 3 months predicted CTR‐CVT according to ROC curve analysis . GLS at three‐month predicted late‐onset CTR‐CVT . In addition, the cutoffs for the GLS at 3 months for predicting CTR‐CVT and late‐onset CTR‐CVT were 20.96% and 20.32%, respectively. The c‐LVEF cutoff for the treatment's anticipated CTR‐CVT at 3 months was 54%. When combination of LV GLS and c‐LVEF were used as predictors, the ROC curve in Figure. GLS , and the cut‐off is 20.32%.Our major findings can be summarized as follows Figure : (i) In The 2‐year follow‐up of this study showed that the incidence of CTR‐CVT including early‐onset and late‐onset was 30.6% in primary BC patients, which was commensurate with the incidence of cardiotoxicity events (3%–35%) described in earlier studies.In the 3‐month follow‐up, the E/e’ increased concurrently, implying diastolic dysfunction. Additionally, 3‐months E/e’ predicted BC patients' late‐onset CTR‐CVT. Unfortunately, because of the limited sample size, we did not get a positive result by ROC. Anthracyclines can affect diastolic function.We assessed serum cardiac markers including myoglobin, troponin T, and CK‐MB at baseline, 3 months, and 6 months after anthracycline‐based therapy. Previous research has shown that CK‐MB levels also increase during chemotherapy but with a different time course. In the anthracycline + targeted group, CK‐MB levels peaked at 3 months and then stabilized at 6 months and 1 year, while in HER2−patients, CK‐MB levels behaved similarly to the other biomarkers, with a slight increase at 3 months, a peak at 6 months, and a stabilization at 1 year after treatment.2.The cumulative dose of doxorubicin was not significantly linked with cardiotoxic events in our investigation, which is consistent with Slamon et al.'s findings [12], despite earlier studies reporting that anthracycline‐induced myocardial injury was dose‐dependent.There are several limitations of our study. The early stages of the COVID‐19 outbreak in 2020 (January to June) had an impact on follow‐up rates. As a result, only a small number of BC patients returned to the hospital for follow‐up at T2, which is a major limitation of this study. A larger sample size would have allowed us to draw more conclusive results, which could present a statistical limit in multivariate analysis and ROC curve.5As time went on, the systolic and diastolic dysfunction of BC patients get worsened. Reduced LVEF was the predominant manifestation of both CTR‐CVT and late‐onset CTR‐CVT, which was then followed by an arrhythmia. The combination of LV GLS and c‐LVEF is better in the prediction of CTR‐CVT. Only the LV GLS at 3 months can predict the late‐onset CTR‐CVT.Zhiyue Liu: Data curation ; writing – original draft . Mei Liu: Data curation ; project administration . Xiaorong Zhong: Project administration . Yupei Qin: Data curation . Ting Liang: Data curation . Ting Luo: Project administration . Xi Yan: Project administration . Zhuoqin Tang: Software . Xi Wang: Resources . Shichu Liang: Resources ; software . Qian Li: Data curation ; software ; visualization . Xiaomiao Ruan: Formal analysis ; investigation . Wenfeng He: Data curation . He Huang: Supervision (lead); Writing – review & editing .HH is funded by Key Research and Development Programs of the Science and Technology Department of Sichuan Province. (Grant no. 2019YFS0414).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.This study was approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University , and all patients provided informed consent.


Systolic anterior motion (SAM) can be caused by multifactorial mechanisms, including structural, morphological and functional factors. We report an unusual case of a 76-year-old woman presenting with SAM associated with constrictive pericarditis. Echocardiography showed no septal hypertrophy but SAM and left ventricular outflow tract obstruction and moderate mitral regurgitation. The restoration of diastolic function after complete pericardiectomy successfully eliminated it. A 74-year-old woman, with end-stage renal failure caused by IgA nephropathy, underwent haemodialysis for 2 years. A 74-year-old woman, with end-stage renal failure caused by IgA nephropathy, underwent haemodialysis for 2 years. She was referred to our hospital because her systolic blood pressure was below 80 mmHg during haemodialysis and exertional dyspnoea. Transthoracic echocardiography (TTE) revealed a narrowed left ventricle with 36-mm diastolic dimension. The ejection fraction of the left ventricle was 82%. A thickened pericardium of 20 mm was seen around the heart maximal behind the mitral annulus, as a finding of constrictive pericarditis Fig. . The antThrough a median sternotomy, the pericardium was incised and dissected. The thickened pericardium consisted of a capsule of fibrous tissue (like an old haematoma). Pericardial tissues were fully resected around the ventricles without cardiopulmonary bypass (Video 2).The patient was extubated on postoperative day 1. From days 1 to 4, continuous renal replacement therapy was administered, and on day 5, the treatment transitioned to haemodialysis. On day 7, TTE showed a considerable alleviation of SAM, with a peak pressure gradient of 7 mmHg. Additionally, the previously present mitral regurgitation had completely resolved. The systolic blood pressure during haemodialysis rose above 110 mmHg, and subsequently, the associated exertional dyspnoea improved, and the patient was discharged on day 15.On the 6-month follow-up TTE, the left ventricular diastolic dimension was normalized to 43 mm, and SAM completely disappeared, with a peak pressure gradient of 3.2 mmHg (Video 3). right ventricular outflow tract diameter was 16.8 mm; the diameter at the base of RV at four-chamber view was 37.9 mm. All values improved postoperation. On computed tomography, the size of the short- and long-axis diameter of the heart was dilated (Fig. Constrictive pericarditis represents cardiac function impairment by restricting the ventricular filling during the diastolic phase because of the thickened and calcified pericardium. The thick and calcified pericardium causes small ventricles or narrowing and tubular deformation of the right or left ventricle .et al. [It rarely causes valvular dysfunction, whereas pericardiectomy could occasionally cause alteration of ventricular morphology and affect atrioventricular valve function. Tabucanon et al.  reportedSAM is defined as the displacement of the mitral valve into the left ventricular outflow tract during systolic ejection, typically concomitant with septal hypertrophy. However, SAM could occur even without septal hypertrophy. Morphology factors contributing to SAM include long anterior or posterior leaflets, bulging septum, small left ventricle and anterior deviation of the papillary muscle . MoreoveOur patient had some potential contributing factors for SAM, other than septal hypertrophy. The anterior mitral leaflet was relatively long, and the patient had a small, tubular ventricular cavity and hyperdynamic state. Moreover, since the left ventricular cavity is smaller not only in the short axis but also in the long axis, elongation of the mitral valve leaflet is accentuated. Furthermore, the thickened pericardium exerted external pressure on the mitral valve, pushing it forward from the posterior wall side, and consequently LVOTO. The mechanism of SAM appeared to be of the length of the anterior mitral leaflet, shortening in the short and long axes and thickening of the posterior wall due to constrictive pericarditis. Pericardiectomy increased the distance between the papillary muscle and mitral annulus in the long axis and the left ventricular dimension in the short axis. Ultimately, the factors leading to SAM were successfully addressed without requiring any intracardiac manoeuvres.Constrictive pericarditis should be recognized as an unusual cause of SAM. Complete pericardiectomy resulted in the long- and short-axis dilation of the left ventricular cavity and eliminated SAM, mitral regurgitation and LVOTO.Consent of the patient was obtained for this study.Conflict of interest: none declared.