Few studies have examined the reference value of the left ventricular structure and function in preterm infants. This study was designed to establish a point-of-care echocardiographic reference range of left ventricular structure and function based on different gestational age, weight, and body surface area (BSA) for preterm infants within 7 days after birth.We retrospectively studied 489 patients with traditional echocardiographic data of left ventricular (LV) M-mode: LV end diastolic dimensions (LVED), LV end systolic dimension (LVES), end-diastolic interventricular septal thickness (IVSd), end diastolic LV posterior wall thickness (LVPWd), left atrial (LA) and aortic root (AO) diameters, and index of LA/AO, LV ejection fraction (LVEF), LV fractional shortening (LVFS), and pulsed wave Doppler: aortic valve flow rate (AV), peak mitral valve flow rate E(MV-E), peak mitral valve flow rate A(MV-A), and MV-E/A. The LV dimensions and the maximum blood flow velocities of the aortic valves and mitral valves according to gestational age, birth weight, and body surface area (BSA) are presented in percentiles tables. Percentile curves of aforesaid four cardiac measurements , MV-E, MV-E/A) using the R language Generalized Additive Models for Location, Scale and Shape (GAMLSS) method were developed according to different gestational ages and weights.Measurements of all cardiac dimensions and Doppler maximum velocities of AV, MV-E, and MV-E/A showed a correlation with gestational age, weight, and BSA. LVED, LAD, MV-E, and MV-E/A showed a trend of increasing values with gestational age and weight on the percentile curves.The percentile tables and graphs of these point-of-care echocardiographic data can provide reliable reference data for Chinese neonates. Normative values are recommended as a source of reference data for the identification of potentially abnormal echocardiography. Point-of-care echocardiography is an essential tool in critical care. Its role is emphasized in neonates, as other monitoring techniques may be unavailable . Point-oThis retrospective, observational, single-center study of the reports of point-of-care echocardiographic examinations was performed on a population of preterm Chinese infants in the first 7 days of life. Our study was conducted in the Department of Neonatal Intensive Care Unit, Peking University Third Hospital, from March 2017 to February 2020. The study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (2020114-02), exempted informed consent.2O [1 cmH2O = 0.098 kPa]), and/or inhaled oxygen concentration degree > 0.40.Inclusion criteria were: hemodynamically stable infants with at least one echocardiogram taken within 7 days after birth (including any patient with incomplete data). Exclusion criteria were: (1) Congenital heart disease and/or other congenital malformations; (2) hemodynamic significant patent ductus arteriosus (HSPDA); (3) sepsis; (4) persistent pulmonary hypertension; (5) renal failure; (6) necrotizing enterocolitis, gastrointestinal perforation or intestinal obstruction; (7) severe anemia or shock; (8) smaller or larger than gestational age; and (9) high-parameter invasive ventilation  and left artrial (LA) diameter/aortic root (AO) > 1.5; or the requirement of positive inotropic drugs, or mechanical ventilation; or if pulmonary edema was present, or gastrointestinal intolerance –19.Echocardiographic examinations were performed with a Mindray M7 scanner produced by Shenzhen Mindray Bio-Medical Electronics Co., (Probe: P12-4S Frequency 4–12 MHZ).Echocardiograms were performed by a neonatologist, and examinations were completed by a neonatologist proficient in echocardiography techniques. Instant measurements were reviewed by a cardiologist. Measurements were made over three cardiac cycles, and the mean values were obtained in the standard precordial positions using the published American Child Echocardiography Guide and Standards and American NICU echocardiography Practice Guide , 21. TheThe following clinical variables were noted: antenatal steroids, birth weight, gestational age, body length, fetal birth mode, cause of premature birth, Apgar score, maternal pregnancy complications, and vital data parameters including ventilation mode, mean airway pressure and inhaled oxygen concentration, heart rate, respiratory rate, systolic pressure, diastolic pressure, and mean pressure during measurement.+6 weeks, 32–33+6 weeks, and 34–36+6 weeks, and also divided into five groups according to birth weight(BW): <1000, 1000–1499, 1500–1999, 2000–2499 and ≥2500 g. Based on BSA, infants were equally divided into seven groups, ranging from 0.07 to 0.20 m2.According to the gestational age (GA), the preterm infants were divided into four groups: <28 weeks, 28–310.725 × weight(kg)0.425. Measurements of LVED, LVES, IVSd, LVPWd, LAD, AOD, AV, MV-E, and MV-E/A values were plotted against GA, BW, and BSA. Normality was then tested using the Kolmogorov–Smirnov test, and Spearman’s rank correlation was performed for each parameter. Descriptive statistics were presented as percentiles  for the GA, BW, and BSA subgroups. The R language Generalized Additive Models for Location, Scale and Shape (GAMLSS) package was used to draw scatter plots of each measurement in relation to GA and BW, and box-cox transformation and curved lines of centiles  show changes in the four important parameters  of GA and BW. A p-value less than 0.05 was considered significant.Data were analyzed using SPSS  version 24.0. BSA was determined using the DuBois and DuBois formula: BSA = 0.20247 × height(m)2 (range: 0.07–0.20 m2). The general characteristics of the infants are presented in Our study included 489 preterm infants with a mean GA of 32 weeks (range: 24–36.7), mean BW of 1,700 g , and mean BSA of 0.13 mp < 0.001). Echocardiographic parameters of LA/AO, LVEF, LVFS, and MV-A show no correlation with GA, BW, and BSA (p > 0.05).In We present reference ranges of the left cardiac dimensions, mitral and aortic valve maximum blood flow velocities for a complete population of preterm infants. The structure and function of the heart are considered to be related to race , 25. LopCardiac point of care ultrasound (POCUS) is increasingly being utilized in neonatal intensive care units for providing information in real time to aid clinical decision making. Cardiac POCUS refers to a basic, time-sensitive, and focused diagnostic echocardiographic assessment, including Hemodynamic assessment, HSPDA, and PPHN. In this study, cardiac ultrasonography was performed by neonatologists with formal cardiac ultrasound training. Reference values of LVED, LAD, LVEF, LVFS, MV E/A, and LA/AO, measured in preterm infants within 7 days are helpful for judging left ventricular volume load, left ventricular systolic and diastolic function, and HSPDA, during cardiac POCUS.The mean gestational age of the infants included in this study was 32 weeks. It is likely that extremely preterm infants under 32 weeks were more likely to develop systemic comorbidities such as HSPDA and PPHN within 7 days of birth, and were therefore excluded from the study.Studies have found that heart size is positively correlated with GA, body weight or BSA of the newborn. The timings in previous studies were within 0, 7, and 28 days of the newborn’s birth and within 36 weeks of the postmenstrual age of preterm babies , 27, 28 We found that the four indexes of echocardiography including LA/AO, LVEF, LVFS, and MV-A were not correlated with GA, BW, and BSA within 7 days of preterm infants. These four indexes are relatively independent and stable in the early postnatal period. LA/AO is currently the most commonly used method for predicting HSPDA. At present, many studies have suggested that HSPDA may occur when LA/AO ≥ 1.5 , 30. ThiThe LVED and LAD indices are important indicators that reflect left ventricular volume load. It can be seen that LVED and LAD display a gradual increasing trend with increase in GA and BW in the centile curves , 3. The +6 weeks found that MV-E and MV-E/A of the fetus increased with GA (The indices of MV-E and MV-E/A are important indicators of LV diastolic function. A study on the LV function of the fetus at 20–36 with GA . A meta- with GA . This st with GA , 3. In a with GA . This shThe reference range of the percentile tables of other cardiac diameters, wall thicknesses, and Doppler blood flow parameters are helpful in judging normal or abnormal hearts.We included a large sample of point-of-care echocardiographic data to establish the normal value of echocardiography of preterm infants from multiple angles. As a limitation, this was a retrospective, single-center study, and the time that each baby underwent echocardiography was not uniform. In this study, premature infants with stable circulatory conditions were selected as much as possible to reduce data deviation caused by time inconsistency. Finally, although 2D point-of-care echocardiography is important for cardiac structural and functional monitoring in preterm infants, we need to look at the overall clinical picture and also caveats about very limited data on three-dimensional functional assessments which are possible in older children and adults.Data from this large study in preterm infants provide reference values of LV structure and function based on different GA, BW, and BSA for preterm infants within 7 days of birth. This data could prove to be invaluable in helping neonatologists to judge normal or abnormal hearts in time and make rapid and correct clinical decisions for critically ill premature infants in the cardiopulmonary transition period. We recommending the involvement of more centers and an intra-group difference analysis in prospective studies.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 Peking University Third Hospital Medical Science Research Ethics Committee. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.D-FL: data collection, analysis, interpretation, literature search, and manuscript writing. X-MT and Y-FL: supervision, study design, and interpretation. HZ: data analysis and plotting. All authors contributed to the article and approved the submitted version.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.


The characteristics are still unclear due to lack of systematic research on patients with myocardial infarction non-obstructive coronary arteries (MINOCA) in China. This study aimed to explore the clinical and imaging features of MINOCA patients.The patients who were diagnosed as suspected MI were studied. Cardiac magnetic resonance (CMR) was performed after coronary angiography or coronary computed tomographic angiography examination within one week. Myocardial infarction (MI) was determined by late gadolinium enhancement CMR.The patients with MI were divided into MINOCA and MICAD group according to whether the degree of coronary stenosis was greater than 50%. Cardiac function and imaging characteristics between the two groups were analyzed.P < 0.05). Besides, MINOCA patients had smaller area of MI, less score of transmural extent, fewer involved segments. Furthermore, the transmural extent of MI in MINOCA patients was mainly grade I, that is, most of them were subendocardial MI, which was significantly negatively correlated with the amount of first-pass perfusion.21 patients with MINOCA and 30 patients with myocardial infarction with obstructive coronary artery disease (MICAD) were analyzed. MINOCA patients were younger, and the electrocardiogram was commonly featured by non-ST-elevation. The parameters of left ventricular function were significantly different between the two groups including left ventricular ejection fraction, stroke volume, cardiac output, myocardial mass, and peak ejection rate (The clinical characteristics combined with imaging features of CMR may be effective to evaluate the cardiac function in order to make clinical decision for MINOCA patients in China. Acute myocardial infarction (AMI) is a common critical disease with high morbidity and mortality, and almost 6% patients with AMI have MINOCA . As we kEuropean Society of Cardiology (ESC) proposes the concept of MINOCA, and points out that the loss of myocardial viability determined by imaging is an important basis for the diagnosis of MINOCA . RecentlThe aim of this study was to explore the clinical and imaging features of patients with MINOCA. Our study demonstrated that most of patients with MINOCA had non-ST segment elevation and better myocardial viability than patients with MICAD. In addition, segments with MI were mainly located in anterior wall, anteroseptal wall, and inferoseptal wall, which were dominated by the LAD coronary artery. Furthermore, transmural extent of MI in MINOCA patients was mainly grade I, that is, most of them were subendocardial MI, which was significantly negatively correlated with the amount of first-pass perfusion.2; (5) had contraindications using CMR or lack of rationality according to the judgement by researchers.A total of 21 patients with MINOCA were screened out of patients who were diagnosed as suspected AMI but without significant coronary artery obstruction on CAG or coronary computed tomographic angiography (CTA) from January 2013 to February 2018 in the our hospital  CCTA or CAG was completed during the study period, and CMR was completed within one week. (2) Stenosis is greater than 50% in any one of the coronary arteries. (3) LGE-CMR showed the presence of MI, and the infarcted segment was located in the blood supply area with coronary stenosis greater than 50%. The reason for selecting 30 patients was to match the number of patients in the MINOCA group as much as possible. MINOCA group finally included 21 patients, and MICAD selected the top 30 patients who met the criteria during the same period. All patients underwent CMR examination and determination of myocardial infarct segments were using late gadolinium-enhanced (LGE)-CMR. The MICAD group included acute ST-segment elevation myocardial infarction (STEMI)  and non 2.Hypertension was defined as office systolic blood pressure values ≥ 140 mmHg and/or diastolic blood pressure values ≥ 90 mmHg in the absence of antihypertensive medication or current antihypertensive treatment. Diabetes mellitus was defined as having a clear history of diabetes or diabetes treatment. Diagnosis of dyslipidemia is based on “Chinese guidelines on prevention and treatment of dyslipidemia in adults (2016 revised edition)” . In brieThe study was approved by the Institutional Ethics Committee of our hospital and allowed exemption from informed consent. All procedures were performed in accordance with the World Medical Association’s Declaration of Helsinki.2), smoking history, examination results of 12-lead electrocardiogram and myocardial injury marker were collected.Clinical characteristics including patient’s gender, age, admission symptoms, statistics of risk factors including hypertension, diabetes, dyslipidemia, obesity  including the following steps. Images were captured by balanced turbo field echo (B-TFE) sequence  in the orientations of 2-chamber-long axis, 4-chamber and short-axis views covering the entirety of the left ventricular from base to apex. During repeated breath-holds in expiration, cine imaging was performed using cine sequence .Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was administered intravenously by power injection with a dosage of 0.08 mmol/kg body weight and a flow rate of 5 ml/s. Following 8–15 min delay, the images were obtained approximately using breath-hold phase-sensitive inversion recovery prepared turbo field echo (PSIR-TFE-BH) sequence. Parameters of the sequence contained long axis slice thickness was 5 mm, short-axis slice thickness was 8 mm, layer spacing was 0 mm, TR was 5.4 ms, TE was 1.0 ms, field of view was 380 × 280 mm, matrix was 220 × 192, flip angle was 25° and TI was 280–380 ms.All images were interpreted by the consensus of two experienced observers who were blinded to electrocardiographic (ECG), laboratory, and angiographic results. CMR was performed after coronary angiography (CAG) or coronary computed tomographic angiography (CCTA) examination within one week. This study focused on patients in the acute phase within 1 month. On the images obtained by CMR, the division of left ventricular segmentation and the corresponding blood supply is based on the American Heart Association 17-segment model . Transmu2 test and expressed as rate or percentage. The quantitative data were presented expressed as means ± standard deviation (SD). The differences between various groups were analyzed by a one-way ANOVA followed by the LSD-t test, and the data of the two groups was assessed using the Student’s t test. Kendall correlation analysis was used to assess statistical correlation between myocardial perfusion and transmural extent. P < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS version 17.0 . The categorical data were analyzed using χP > 0.05).21 patients with MINOCA and 30 patients with MICAD were included in our study. Baseline characteristics of the patients were listed in Table P < 0.05). The electrocardiogram was commonly featured by non-ST segment elevation in MINOCA patients, while ST segment elevation in MICAD patients. The cTnT level in the MINOCA group was significantly lower than that in the MICAD group (P < 0.05). In addition, the rates of dyslipidemia and hyperhomocysteine in the MINOCA group were lower than MICAD group (P < 0.05).However, patients of MINOCA group were younger than that of MICAD group, and the numbers of smokers in the MINOCA group were fewer than that in the MICAD group (P < 0.05). In terms of left ventricular function parameters, left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), myocardial mass (MM), and peak ejection rate (PER) in the MINOCA group were significantly higher than those in the MICAD group (P < 0.05). However, the peak filling rate (PFR) in the MINOCA group was notably lower than that in the MICAD group (P < 0.05). Additionally, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and cardiac output index (CI) were not significantly different between the two groups (P > 0.05).The results of CMR were shown in Table P < 0.05). However, there was no obvious difference in the sites of MI (P > 0.05).As shown in Table Furthermore, a total of 357 myocardial segments in 21 MINOCA patients were analyzed and found that 84 segments caused MI. The distribution of segments of MI showed 3 segments in the apex, 16 segments in the apical cap, 34 segments in the mid-cavity, and 31 segments in the base  was shown in Table P = 0.025).Furthermore, we analyzed the first-pass perfusion curves of 336 myocardial segments (apex segments not included) in patients with MINOCA and the results showed that the number of segments with abnormal myocardial were more than those of MI, indicating the range of abnormal myocardial perfusion was greater than that of MI Table . The resOur study investigated the clinical and imaging features of CMR presenting with patients with MINOCA. The major findings were (1) MINOCA patients were younger, and the electrocardiogram was commonly featured by non-ST-elevation; (2) Patients with MINOCA had smaller area of MI and score of transmural extent, fewer number of involved segments, and better heart function; (3) Segments of MI were mainly located in anterior wall, anteroseptal wall, and inferoseptal wall, which were mostly dominated by the LAD coronary artery, indicating the myocardium dominated by LAD coronary artery had a high probability of infarction; (4) the transmural extent of MI in MINOCA patients was mainly grade I, that is, most of them were subendocardial MI. These findings of this study may provide valuable information for clinical decision making and identify the cause of MINOCA.Previous studies have confirmed that age, gender, dyslipidemia, hypertension, smoking, diabetes and impaired glucose tolerance, obesity, and family history are risk factors for coronary heart disease –15. WithCine CMR imaging is widely used to evaluate myocardial structure and function in clinical study including heart structure, and movements of valve and ventricular wall . After sPrevious studies have confirmed that the quality of left ventricular myocardium has important value in risk stratification and prognosis assessment of coronary heart disease . MoreovePrevious study has indicated that the area of MI, involved segments, and score of transmural extent are the key factors for ventricular remodeling . AdditioWe acknowledged that our study has several limitations. First, sample size is limited, and more patients should be included in future research. Second, the data was from only one medical center, more center studies are needed. In addition, another limitation of our study etiology of MINOCA patients is not explored using intravascular ultrasound (IVUS) due to the high cost of IVUS examination.Patients with MINOCA were younger, and had fewer smoking history, lower cTnT level and rates of dyslipidemia and hyperhomocysteine. Additionally, the electrocardiogram of patients with MINOCA was commonly featured by non-ST-elevation. Furthermore, the clinical characteristics combined with imaging features may be effective to evaluate the cardiac function in order to make clinical decision for MINOCA patients in China.


The study of laboratory biomarkers that reflect the development of adverse cardiovascular events in the postinfarction period is of current relevance. The aim of the present study was evaluation of oncostatin M (OSM) concentration changes in the early and late stages of myocardial infarction and evaluation of the possibility of its use in prediction of adverse left ventricular (LV) remodeling in patients with myocardial infarction with ST-elevated segment (STEMI).The study involved 31 patients with STEMI admitted in the first 24 hours after the onset of MI and 30 patients with chronic coronary artery disease as a control group. Echocardiographic study was performed on day 3 and in 6 months after STEMI. The serum levels of biomarkers were evaluated on the day of hospital admission and 6 months after MI using multiplex immunoassay.OSM level increased during the first 24 h after the onset of the disease, with the following decrease in 6 months. OSM concentration at admission had correlated with echocardiography parameters and Nt-proBNP, troponin I, CK-MB levels. Our study has demonstrated association of the increased levels of OSM at the early stages of STEMI with development of the adverse LV remodeling in 6 months after the event.Elevation of OSM levels in the first 24 h after STEMI is associated with the development of the adverse LV remodeling in the long-term post-infarction period. Myocardial infarction (MI) remains the leading cause of mortality and morbidity all over the world. Patients who suffered MI with ST-elevated segment (STEMI) have an increased risk of sudden death and recurrent events in the future, mainly due to the subsequently developing heart failure (HF) both with the preserved and reduced ejection fraction Even though modern therapeutic approaches allowed to significantly improve management of STEMI patients, the post-infarction HF still represents a challenge in the modern medicine Neutrophils and monocytes/macrophages are recruited to the injured myocardium, performing phagocytosis of the necrotic tissue meanwhile releasing mediators of inflammation, such as leukotrienes, thromboxane, prostacyclin, which may increase tissue damage even further Cytokines of IL-6 family are known to play an important role in initiation, sustainment and resolution of the local and systemic inflammation In summary, currently there are no consistent results indicating the role and prognostic value of OSM in left ventricular post-infarct remodeling and its relationships to the widely used biomarkers of heart injury and stress. And the existing data were mainly acquired in animals and have not yet been properly translated into clinics.Thus, the aim of the present study was evaluation of OSM concentration changes in the early and late stages of myocardial infarction and evaluation of the possibility of its use in prediction of adverse left ventricular remodeling in the late post-infarct stage in patients with acute anterior STEMI.In total 31 patients with primary anterior STEMI (58.5±8.5 y.o.), admitted to the intensive care unit during the first 24 hours after the onset of myocardial infarction, have been recruited to the study. Patients with poor visualization of the heart, acute LV dysfunction (Killip class III-IV), sinus bradycardia, permanent atrial fibrillation, valvular heart disease, HF decompensation (NYHA class III-IV), severe concomitant pathology, refusal to participate and patients older than 75 y.o. were excluded from the study. The control group is recruited from patients with chronic coronary artery disease (CAD) (n=30). The protocol of the study was approved by the local ethic committee (protocol #116 from 30.01.2014), and it was developed in compliance with the Medical Association Declaration of Helsinki »Ethical principles for medical research involving human subjects«. All patients signed an informed consent forms prior to participation in the study.Echocardiography was performed in all patients on day 3 and in 6 months after STEMI. Quantification was performed according to the recommendations of the American and European Associations of Echocardiography. End diastolic and systolic volumes (ESV), and left ventricular ejection fraction (LV EF) were determined using Simpson's method. To assess post infarction myocardial remodeling, the dynamics of ESV was evaluated on day 3 of hospital admission and in 6 months after MI. The widely excepted approach to acknowledge the presence of the adverse left ventricular remodeling is an observed increase of left ventricular end-diastolic (and/or end-systolic) ventricular volume (LVEDV and/or LVESV) by at least 20% since the first post-myocardial measurement Venous blood was drawn into sterile vacutainers at admission to the clinics and in 6 months after STEMI. Obtained blood samples have been stored at the room temperature for 30 min and were centrifuged at 3000 rpm for 15 min. The serum samples have been collected and stored at –40 °C until the measurements were performed.The levels of OSM, troponin I, N-terminal fragment of brain natriuretic peptide (Nt-proBNP) and creatine phosphokinase cardiac specific isoenzyme MB (CK-MB) were evaluated in serum using multiplex immunoassay with the FLEXMAP 3D System  and the Human Cardiovascular Disease Panel 1 . The study was conducted using the Core Facility »Medical genomics«, Tomsk NRMC.The analysis of the obtained data was performed using the STATISTICA 10.0 and SPSS 10.0 software. The type of the distribution of the data was evaluated by Kolmogorov-Smirnov test. Results were presented as mean ± standard deviation (x̅ ± SD) in the case of normal distribution and as the median value and the interquartile range ) in the case of non-normal distribution. Wilcoxon test was used to estimate the significance of differences in the values of the dependent parameters. The Mann-Whitney U-test was used to estimate the significance of differences between independent groups. The Spearman's rank correlation coefficient was calculated to assess the relationship between the parameters. A value of p<0.05 was considered statistically significant in all statistical evaluations. Linear regression model was created to evaluate input of OSM in the development of the left ventricle adverse remodeling. The prognostic value was determined using the ROC analysis. The area below the ROC curve was calculated, and the sensitivity and specificity were calculated to evaluate the characteristic curves.Clinical characteristics of STEMI and chronic CAD patients were comparable .The serum levels of all studied biomarkers in STEMI patients at admission were increased compared to patients with chronic CAD .Only OSM remained elevated in STEMI patients in 6 months of observation compared to chronic CAD patients .We have revealed the significant decrease of the OSM concentration in the long-term post-infarct period (6 months of observation) compared to the elevated values at admission . Other bThe results of correlation analysis demonstrated strong direct relations between OSM and widely acknowledged biomarkers of myocardial injury, stress and necrosis: troponin I, Nt-proBNP and CK-MB . We haveDuring analysis of interactions between concentrations of biomarkers and long-term echocardiographic data we revealed negative correlations between OSM concentration at admission and EF LV in 6 months of observation after STEMI A. ConcenThe total group of patients was divided into 2 groups: group 1 – patients without LV remodeling (∆ESV<20%); group 2 – patients with adverse LV remodeling (∆ESV 20%). Medical history and clinical characteristics of patients depending on the presence of the adverse LV remodeling are represented in .The comparative analysis demonstrated that patients in group 2 had significantly elevated values of ∆EDV and ∆ESV in 6 months, ESV LF at day 3 and LV EF in 6 months compared to patients in group 1 .We have also revealed significant differences in the level of OSM at admission in groups 1 and 2 . ConcentEven though Troponin I and CK-MB have been shown to reflect the infarct size and hence predict the development of adverse remodeling We have created the model of the paired logistic regression with binary dependent variable to evaluate input of OSM in the development of the adverseLV remodeling. The dependent variable had taken the value «1» if a patient should have been assigned to the group 1, and value »2« if a patient should have been assigned to the group 2. The model employed OSM as a predictor. Logistic regression demonstrated that elevated concentration of OSM at admission was associated with adverse LV remodeling in 6 months . The logistic regression model had the level of the statistical significance p=0.002, the Chi-square = 13.965. The parameters of the logistic regression are represented in The ROC analysis showed that the OSM measured at admission to the hospital is a promising informative indicator for predicting an increase in LVESV in 6 months after MI.The area below the ROC curve was 0.867 (p<0.05), which made it possible to classify it as »of high quality« . The optOur study has demonstrated association of the increased levels of OSM at the early stages of STEMI with development of the adverse LV remodeling in 6 months after the event. OSM concentration in patients with STEMI at admission had also correlated with the echocardiography parameters in 6 months and widely accepted biomarkers of heart failure and myocardial necrosis at admission .OSM is known to have multiple biological functions, including regulation of hematopoiesis, proliferation, inflammation, differentiation of mesenchyme stem cells, apoptosis and various tissues' regeneration Increase of the circulating levels of OSM in subjects with coronary artery disease, heart failure, pulmonary arterial hypertension, atrial fibrillation has been demonstrated in a number of experimental and clinical studies Thus, OSM secreted by macrophages in atherosclerotic plaques may favor progression of atherosclerosis and dysfunction of the vascular endothelium On the other hand a number of studies demonstrated a cardio protective role of OSM The prior AMI is known to initiate processes of the structural reorganization in myocardium, leading to the development of post-infarct remodeling. Chronic subclinical inflammation, accompanied by the prolonged release of inflammatory cytokines, has a great impact on this process. The data on the involvement of OSM in heart remodeling in patients after AMI remain controversial and scarce.In the recent work of Han et al. Kubin et al. In our study we revealed that patients with acute primary STEMI are characterized by the significant elevation of OSM during the first 24 hours after the event, which is associated with unfavorable outcome in the long-term period. Identified positive associations between the level of OSM and widely studied biomarkers of heart injury and myocardial stress, which are currently used in the protocols for patients' follow-after STEMI, is a new finding which allows to regard OSM as a promising laboratory cardio-marker. Even though Bolognese et al. The comparatively small number of the recruited patients may be regarded as the major limitation of our study. However, all the patients included in our study, underwent rigorous screening to correspond to the strict inclusion and exclusion criteria, including admission time-frame, existing comorbidities, HF severity, etc. This makes us to believe that the obtained results may also be applicable to a larger cohort of STEMI patients. This does not exclude the necessity of a larger scale studies to be performed to verify the prognostic significance of the OSM early stage elevation in post-infarct heart remodeling.Thus, patients, who endured primary STEMI, demonstrate elevated concentrations of OSM in peripheral blood during the first 24 h after the event with its subsequent decrease in 6 months. Direct interconnections between OSM and troponin I, Nt-porBNP and CK-MB are detected. The level of OSM during the first 24 h correlates with left ventricular EF, as well as with the value of the LV ESV increase in 6 months after AMI. We have demonstrated that elevated levels of the biochemical marker OSM is associated with the development of the adverse left ventricular remodeling in the long-term post-infarction period and may be used to increase the efficiency of the laboratory diagnostics in patients, who experienced the primary STEMI.All the authors declare that they have no conflict of interest in this work.CAD, coronary artery disease;
CK-MB,creatine phosphokinase cardiac specific isoenzyme MB;
ESV,end systolic volumes;
LV, left ventricular;
Nt-proBNP, N-terminal fragment of brain natriuretic peptide;
OSM, oncostatin M;
STEMI, myocardial infarctionwith ST-elevated segment.


Cardiac MRI measurements have diagnostic and prognostic value in theevaluation of cardiopulmonary disease. Artificial intelligenceapproaches to automate cardiac MRI segmentation are emerging but requireclinical testing.To develop and evaluate a deep learning tool for quantitative evaluationof cardiac MRI functional studies and assess its use for prognosis inpatients suspected of having pulmonary hypertension.A retrospective multicenter and multivendor data set was used to developa deep learning–based cardiac MRI contouring model using a cohortof patients suspected of having cardiopulmonary disease from multiplepathologic causes. Correlation with same-day right heart catheterization(RHC) and scan-rescan repeatability was assessed in prospectivelyrecruited participants. Prognostic impact was assessed using Coxproportional hazard regression analysis of 3487 patients from the ASPIRE registry, including a subset of 920patients with pulmonary arterial hypertension. The generalizability ofthe automatic assessment was evaluated in 40 multivendor studies from 32centers.r = 0.72 vs 0.68;P = .03). Interstudy repeatability of cardiac MRImeasurements was high for all automatic measurements  and similarlyrepeatable to manual measurements . Automated right ventricle and leftventricle cardiac MRI measurements were associated with mortality inpatients suspected of having pulmonary hypertension.The training data set included 539 patients . Automatic cardiac MRI measurements were bettercorrelated with RHC parameters than were manual measurements, includingleft ventricular stroke volume (An automatic cardiac MRI measurement approach was developed and tested ina large cohort of patients, including a broad spectrum of rightventricular and left ventricular conditions, with internal and externaltesting. Fully automatic cardiac MRI assessment correlated strongly withinvasive hemodynamics, had prognostic value, were highly repeatable, andshowed excellent generalizability.Clinical trial registration no. NCT03841344Published under a CC BY 4.0 license.Online supplemental material is available for thisarticle.Ambale-Venkatesh and Lima in this issue.See also the editorial by An earlier incorrect version appeared online. This article wascorrected on June 27, 2022.  Artificial intelligence cardiac MRI measurements were validated and used toassess future patient mortality.■ A retrospective training data set of 539 patients with left andright heart disease was used to train an artificial intelligence (AI)model for cardiac MRI measurements.r = 0.74 vs 0.68; P = .03;n = 178).■ Same-day cardiac MRI and right heart catheterizationdemonstrated strong correlation that was higher with AI measurementsthan with manual measurements for left ventricular stroke volume.■ AI-measured right ventricular end-systolic volume, ejectionfraction, and mass all predicted mortality in patients with pulmonaryarterial hypertension  is a challenge because of thevariation in the shape, thickness, and complex anatomy, particularly at the base andoutflow tract ,3. AdditThe aim of our study was to develop and comprehensively evaluate an automated deeplearning quantitative analysis of LV and RV cardiac MRI measurements. We also soughtto assess the hypothesis that an AI cardiac MRI biventricular analysis correlateswith invasive hemodynamics, predicts mortality in pulmonary hypertension, and isrepeatable and generalizable.AppendixE1 [online]).Our study involved a retrospective training data set and a testing data set. The traThe Budapest data set included 192 patients with 211 MRI studies randomly chosenin patients referred for investigation of suspected or confirmed LV disease.Overall, the data set included 180 MRI studies with LV disease and 32 normal MRIstudies. The Budapest studies were performed with a Philips MRI system and wasused to train the initial LV and RV segmentation model. For the Sheffield dataset, consecutive patients suspected of having pulmonary hypertension whounderwent cardiac MRI were identified from the Assessing the Severity ofPulmonary Hypertension In a Pulmonary Hypertension Referral Centre (known asASPIRE) registry between 2007 and 2021 . Patientn = 46); a prospective same-day rightheart catheterization (RHC) cohort (n = 179); an external testcohort (n = 40) from 32 centers across England, Wales, andScotland; and MRI studies not included in the training from the ASPIRE registryused for the assessment of mortality prediction (n = 3782).For the clinical testing, four data sets were included: a prospective same-dayrepeatability cohort . Ethical approval for the study was granted by thelocal ethics committee and institutional review board . All prospectivelyrecruited participants gave written informed consent. All data were strictlyanonymized before analysis. We followed the Checklist for ArtificialIntelligence in Medical Imaging (known as CLAIM) for reporting AI studies . Multisection short-axis cine imageswere obtained by using a standard cardiac-gated balanced steady-state freeprecession sequence of 8-mm section thickness and 20 phases per cardiac cycle, 6-mm section thickness and 25 phases per cardiaccycle , and 8-mm section thickness and 25 phases percycle . The parameters (repetition time msec/echotime msec) were 3.7/1.6 , 38.92/1.13 , and 2.72/1.36 . Two-dimensionalphase-contrast sequences were acquired perpendicular to the long axis of theaortic lumen by using through-plane velocity encoding. All phase-contrastsequences were performed with GE MRI systems with the following imagingparameters: 5.6/2.7; section thickness, 10 mm; 20 phases; and velocityencoding, 150 cm per second in the section direction.Image analysis.—Manual segmentations ofbiventricular epicardial and endocardial contours on short-axis stack images forthe training and testing data sets were performed by seven observers . All manual contourswere reviewed by one author . Trabeculations were included in the blood pool, and the outflowtract was included for both the RV and LV. In the ASPIRE cohort, trabeculationswere excluded from the blood pool (performed by D.C.). Manual segmentation forthe Dice accuracy analysis was performed independently (by K.K. and A.J.S.), andfor the external cohort testing (by S.A. and A.J.S). The scan-rescansegmentations were performed by a senior cardiac MRI radiographer with 3 yearsof experience who was not involved in the model training. All manual contouringwas performed blinded to the clinical data and RHC results. Software was usedfor manual contouring . A visual quality review for all segmentation was performed together bytwo authors (S.A. and A.J.S.) to identify the failure rate of the finalsegmentation model. Failed segmentations were those that resulted in visuallyunacceptable contours and would lead to incorrect measurement. Contours withminimal errors that were deemed to not effect cardiac MRI measurements werelabeled suboptimal segmentations.https://github.com/dmolony3/ResUNet) with16 convolutional layers, including residual learning units, and was implementedby using Python  and TensorFlow(version 1.12) (AppendixE2 (online).The convolutional neural network used for the experiments had a UNET-likearchitecture (similar in implementation to on 1.12) . Input iContinuous variables are presented as proportions, means ± SDs, or medianswith interquartile ranges for data with asymmetric distributions. Variablestandardization was performed to allow comparison of the different continuousvariables on the same scale by subtracting the mean for each variable anddividing it by its SD. Cardiac MRI volumetric measurements were indexed for bodysurface area. Measurements were corrected for age and sex by calculating thepercentage predicted values per published reference data ,10.ttest was calculated to compare the differences in scan-rescan measurementsbetween AI and manual assessment. Spearman correlation coefficient was used tocompare the LV stroke volume to the stroke volume derived from RHC and theaortic forward flow volume at the LV outflow tract measured by phase-contrastimaging. RHC stroke volume was derived by dividing cardiac output by heart rate.RV ejection fraction and ventricular mass index was correlated to RHC pulmonaryvascular resistance and mean pulmonary artery pressure. Ventricular mass indexwas calculated as the RV end-diastolic mass–to–LV end-diastolicmass ratio (RV mass–to–LV mass ratio). The z testusing the method by Steiger (The interstudy repeatability was assessed with interclass correlation coefficient(ICC) and Bland-Altman analysis to compare the scan-rescan variation in theautomated and manual cardiac MRI measurements. The paired  Steiger  wasperfr greater than 0.8 was considered to be closely related.All patients were followed up until the all-cause mortality or administrativecensoring date . No patient was lost to follow-up. The interstudyrepeatability was assessed with ICC and Bland-Altman analysis to compare thescan-rescan variation in the automated and manual cardiac MRI measurements. Thepaired t test was calculated to compare the differences in thescan-rescan measurements between AI and manual assessment. The agreement betweenthe AI and manual cardiac MRI measurements in the external test data set wasanalyzed with ICC and Bland-Altman plots. The accuracy of the AI contoursrelative to the manual contours was estimated by calculating the Dice similaritycoefficient in 30 studies from an internal test data set randomly chosen fromthe cohort and in the 40 studies from the external test data set. The Dice scoremeasured the ratio of overlap and distance between the manual and automaticallysegmented areas; a higher value indicated better accuracy of the contouringmodel relative to the manual segmentation. Statistical analyses were performedby using the Pingouin (version 0.5)  and Lifeion 0.5)  Pythonlion 0.5) . A P valThe total study sample included 4289 patients and 5630 cardiac MRI studies, afterexcluding 244 patients because of either incomplete or unretrievable imaging. The medAn example of the AI segmentation of the short-axis stack throughout the cardiaccycle is shown in r = 0.74 vs0.68, respectively; P = .03) , although variability isevident between the methods of stroke volume calculation, which may in part bedue to technical factors and intracardiac shunts in some patients  than the manual measurements.The mean for cardiac MRI-estimated LV stroke volume were 78 mL ± 24 (SD)and 79 mL ± 26 for AI and manual assessments, respectively. TheRHC-derived LV stroke volume was 66 mL ± 23 and the phase-contrast meanaortic forward flow volume was 68 mL ± 21. The correlation between RHCand cardiac MRI LV stroke volume was highP = .03) , Table 3patients . The AI-patients and meanFig4E), with no evidence of a differencebetween AI and manual readings. Pulmonary vascular resistance and mean pulmonaryartery pressure correlated similarly with AI and manual RV ejection fraction.There were good correlations between RV ejection fraction and mean pulmonaryartery pressure  and pulmTableE1, FigE1 [online]).The correlation between AI-based cardiac MRI measurements and RHC was confirmedin 2051 patients in the ASPIRE cohort (n = 920) (TableE2 (online).Automatic cardiac MRI measurements were assessed in 3487 patients from the ASPIREregistry. The study population included patients with multiple pathologicdisease, predominantly pulmonary arterial hypertension , leftheart disease , lung diseases , chronicthromboembolic pulmonary hypertension , and without pulmonaryhypertension . During the mean follow-up period (3.8 years)1604 of 3487 (46%) patients died. Other than RV stroke volume, all cardiac MRIparameters predicted mortality . RV paran = 920) . RV ejecn = 920) . The unit test P =.73 for RV ejection fraction and .8 for LV ejection fraction)(TableE3 [online]).The interstudy repeatability of cardiac MRI measurements was high for both AI andmanual measurements. The automatic LV and RV volumetric and mass measurementsICC were 0.92 and 0.99, respectively. The ICC for LV and RV ejection fractionwas 0.80 and 0.90, respectively . The difFigureE2 (online).Bland-Altman plots showed strong agreement between manual and automaticmeasurements, with small mean absolute differences ranging between 0 mL and 4 mLin the scan-rescan measurements .ExampleTableE4 [online]). The ICC was 0.93 for LVejection fraction and 0.94 for RV ejection fraction, and the ICCs for LV and RVmass were 0.95 and 0.92, respectively. Bland-Altman plots showed small absolutemean differences  external data set. Theinterobserver ICC ranged between 0.94 and 0.99 for LV and RV volumes(TableE5 [online]). The Dice values in theinternal data set s ranged between 93% and 96% for the LV and 93%–95% inthe RV. The Dice values were slightly lower in the external cohort and rangedfrom 89% to 95% in the LV and 88% to 92% in the RV.Dice analysis showed excellent agreement in the AI and manual LV and RV epi- andendocardial end-systolic and end-diastolic contours in both the internal andexternal test cohorts , pulmonary vascular resistance , and mean pulmonary artery pressure.Additionally, we showed excellent scan-rescan repeatability of artificialintelligence (AI) measurements for assessing LV and right ventricular (RV)measurements, including the more challenging RV mass . At a population level, we evaluated theprognostic value of AI-based cardiac MRI measurements and showed its ability topredict mortality in a cohort with multiple pathologic diseases, and furtherevaluated RV parameters in a subgroup of patients with pulmonary arterialhypertension. Finally, we have shown excellent generalizability of AI contours in anexternal cohort.Our study developed and comprehensively analyzed the performance of a fully automatedbiventricular cardiac MRI assessment in a large cohort of patients. We demonstratedthat fully automated left ventricular (LV) stroke volume and ventricular mass indexassessment had a correlation that was stronger than manual assessment with invasivehemodynamics parameters such as LV stroke volume . Therefore, we believe thatestablishing normal ranges of AI segmentation is important. Additionally, despitesimilar repeatability between the automatic and manual segmentation, consistentdifferences were noted in the manual segmentation of the scan-rescan cohort, such asexcluding portions of the right ventricular outflow tract. Whereas this consistencymaintained excellent repeatability, the manual segmentation was less accurate. Thescan-rescan segmentation was performed by a cardiac MRI practitioner not involved inthe AI model training, highlighting the existence of subjective differences in theinterpretation of the base of the heart even within the same institution.Furthermore, the AI segmentation fails in some patients, showing the need forfurther training. Failed AI segmentation will be continuously identified andincorporated in future training rounds to improve the accuracy of the model.Our study had limitations. First, the validation, including comparison with heartcatheterization and prediction of mortality, was performed in a single center withtwo MRI systems and limited cohort description. Second, direct comparison between AIand manual measurements in the large ASPIRE cohort for RHC correlation and mortalityprediction could not be performed because of differences in handling trabeculations.Third, the segmentation algorithm cannot be made publicly available because the deeplearning code would require extensive documentation and compatibility scripts toenable the application by external parties. However, we encourage readers to contactthe corresponding author for research access to the Mass software and the AIsegmentation tool.In conclusion, we described a human-in-the-loop artificial intelligence (AI) approachto develop a biventricular cardiac MRI assessment tool. We provided a comprehensiveevaluation of AI-based cardiac MRI measurements in a large cohort of patients with awide spectrum of right and left ventricular pathologic abnormalities and normalvariants. Fully automatic cardiac MRI assessment correlates with invasivehemodynamics and has prognostic value. Training to target apex errors and moreextreme pathologic abnormalities could advance the AI method further. Futureresearch that uses cardiac MRI as a clinical end point can benefit from the highrepeatability and generalizability of AI measurements.


Background & aims Intracardiac shunts are abnormal channels of blood circulation within the heart that develop either as an additional blood flow pathway or as a replacement for the normal channels of blood circulation. They are the commonest types of congenital heart defects. Various methods are available in the present times to identify, localize or quantify left-to-right intracardiac shunts. Methods may vary in sensitivity, indicators, or types of equipment available. One such method used in almost all cardiac centers for a long time has been oximetry run to detect step-up differences in oxygen saturation values. In the oximetry run the main approach to detect and estimate the left-to-right (L-->R) shunts requires the oxygen concentration expressed as a proportion of saturation to be evaluated in blood samples which are obtained from the right atrium (RA) and pulmonary artery (PA), respectively. A left-to-right shunt can be considered if there is a significant increase (step-up) in blood saturation. A significant step-up is defined as a substantial rise in blood oxygen content or saturation that is higher than normal values.Methods 2) & RASO2 before and after surgery was significant. As a result, the difference in O2 saturation helped detect the residual ventricular septal defect (VSD) after the surgery.Using a prospective observational design, this article investigates the application of the step-up method in detecting intracardiac shunts. The study was conducted between 2021 and 2022 on 35 pediatric cardiac patients  diagnosed with post-tricuspid shunts. The pulmonary artery and right atrium were sampled before and after cardiopulmonary bypass surgery and analyzed using a blood gas test. As a result, nearly 91% of the patients had a saturation below 8%. However, the difference between PA oxygen saturation  echocardiography.ConclusionA combination of physical findings, chest radiography, electrocardiogram (ECG), and echocardiography is routinely done for all these patients undergoing pediatric cardiac surgery. Echocardiography can detect the occurrence of shunt but does not calculate the shunt ratio. Transesophageal or epicardial echocardiography is the standard of care but has its limitations like perception difference between the operating surgeon and the person performing echocardiography.In this study, we have added an oximetry analysis of blood-gas samples before and after surgery and compared it to 2D echocardiography to test the validation of oximetry in isolation and comparison to 2D echocardiography. A large number of people are affected by cardiovascular diseases including diseases of the heart and circulatory system; therefore, introducing effective diagnostic and monitoring methods is crucial for the well-being of these patients. In the normal body, blood flows in a unidirectional manner from the left to the right heart through the vascular bed of the circulation system. However, under pathological conditions, oxygen-rich blood takes a shorter path from the left to the right heart i.e., left-to-right shunts (L--->R shunt), without passing through the vascular bed. That could happen in many pathological cases such as atrial septal defects (ASD), ventricular septal defects (VSD), or patent ductus arteriosus (PDA). Congestive heart failure results from congenital causes as described above, or acquired causes such as myocardial infarction . About 0.8% to 1.2% of births globally are associated with some type of birth defect. Shunts are divided into two types: cyanotic and non-cyanotic. The presence of a shunt can also affect left and/or right heart pressure [One such method that has long been used in almost all cardiac centers is the oximeter to detect differences in oxygen saturation. Oximetry has been used for more than five decades now to diagnose intracardiac and great-vessel shunts. In the oximetry run, the basic way to detect and estimate the L--->R shunt requires measuring the oxygen level or saturation of blood samples taken from the right atrium (RA) and pulmonary artery (PA), respectively. An L-->R shunt can occur following a substantial increase in oxygen content or if blood saturation is detected in any of the heart's chambers. It is often used to identify VSDs that persist after surgical repair in the operating room .A significant step-up is defined as a rise in blood oxygen concentration or saturation beyond the normal values. If oxygen content in the PA is unexpectedly high i.e., a saturation >80%, then there is a likelihood of L--->R intracardiac shunt. This can help determine if the post-tricuspid shunt has not been treated properly and perhaps indicate a re-do surgery. If an increase in oxygen content in the blood sample from the distal side is detected at higher levels compared to the proximal chamber, then an L--->R shunt is assumed to have occurred. Due to differences in blood flow and rapidly changing physiological functions of blood and oxygen levels in the heart, increased oxygen levels may not reflect the true effect of residual VSD. In rare cases, L-->R and right-to-left (R-->L) shunt shunts could appear simultaneously in the same patients.The effect of fluctuations in hemoglobin level can also be used to evaluate the step-up in saturation by comparing changes in the proportion of oxygen saturation and oxygen concentration. It was also observed that different values of percent saturations were known to help rather than changes in oxygen concentration for visualizing the cardiac shunt. For instance, VSD is diagnosed with a step-up of 5% between the right ventricle (RV) and PA.Heparinized arterial blood gas (ABG) analysis is done by the addition of fluid. This statistically decreases the partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), bicarbonate (HCO3), and base excess, while pH remains unchanged.Echocardiography can also be used to detect the occurrence of a shunt but it cannot calculate the shunt ratio. This could be the critical factor that influences the treatment option. Contrast echocardiography studies have higher sensitivity and are very useful in diagnosing small to large L-->R shunts. Tomography or “thin section” imaging can be provided by two-dimensional (2D) echocardiography .Transesophageal or epicardial echocardiography is preferred for care. However, it has its limitations. For quantitative and qualitative assessment of cardiac anatomy and features, transthoracic echocardiography (TTE) is an extensively available, reproducible, non-invasive imaging modality . TransthThe transesophageal echocardiogram (TEE) can be used to non-invasively compare stress gradients between heart chambers or between heart chambers and blood vessels. This allows the estimation of the intra-cavity pressure. It is expensive to purchase and additionally, there may be a perception difference between the operating surgeon and the person performing the echocardiography .Rarely, deoxygenated blood can flow in the opposite direction of the L-->R shunt, taking the path from the right to the left heart. Eisenmenger's syndrome is one of these rare cases that can develop if mild or large VSD is not treated on time ,7.Detection of intracardiac shuntThe shunt can be diagnosed using invasive and noninvasive methods, including MRI in addition to Doppler echocardiography, and many others. Presently, many clinicians suspect the occurrence of shunts based on physical examination or electrocardiogram (ECG) along with the diagnosis on echocardiography followed by quantification via right-heart catheterization.Shunts in the heart can be diagnosed using various methods, and subsequently localized and quantified through cardiac catheterization. Indicator dilution is a historical method limited to the research area and is not currently applicable in the practical field. This method involves the intravenous administration of agents like indocyanine blue, or its direct injection into the right heart. Later, the dye curve measurements generated from the continuous monitoring of the dye in the systemic circulation system provide a reasonable assessment of the shunt. However, the procedure is time-consuming and requires special instruments that are no longer available in catheterization laboratories. Another way to evaluate the shunt is contrast-enhanced angiography, which can be used to detect and diagnose VSD. In this method, the contrast agent is injected into the high-pressure chamber of the suspected shunt (such as the left ventricle)Because of its simplicity, reproducibility, and availability in modern labs, measurement of oxygen saturation at various locations of oximetry or analysis of the venous system and right heart, is a frequently used invasive procedure.Aims and objectives This study aimed to: · Detect and quantify residual intracardiac post-tricuspid shunt in pediatric patients undergoing cardiac surgery. Additionally, we aimed to compare the RA and PA saturation in pediatric patients who underwent cardiac surgery. This was done using samples of heparinized arterial blood gas pre and post-bypass (that were collected intraoperatively), and cardiopulmonary bypass (CPB) indices. · Analyze the usefulness of step-up measurement in detecting residual VSD post-operatively.· Enhance literature on step-up analysis and its usefulness in present times.· Compare the usefulness of step-up over intraoperative echocardiography to detect significant residual VSD. Especially in pediatric heart centers that do not have full-time pediatric cardiologists to analyze 2D echocardiography, and who can instead, rely on this calorimetric testing for an assessment of residual VSD Figure . A basic mixed venous blood flowchart with normal pressures and O2 saturation physiology is shown in Figures Study populationThis prospective observational investigation included pediatric patients (sample size n=35) who underwent CPB surgery at Bhanubhai and Madhuben Patel Cardiac Centre, Karamsad, Gujarat, India Table .The research proposal was discussed and approval was obtained from the Institutional Ethics Committee of H.M. Patel Centre for Medical Care and Education, Bhaikaka University . This study was conducted between June 2021 to June 2022.Inclusion criteriaThe study included patients with congenital heart disease and grown-up congenital heart disease as well as those with post-tricuspid shunts.Exclusion criteriaPatients with pre-tricuspid shunts, single ventricle physiology, arch anomalies, and those that had a re-do surgery and require an emergency CPB, were not included in the study. Anesthesia protocolAll patients included in the study had a standardized anesthetic technique according to the protocol of our cardiac anesthetic department. Anesthesia was induced with fentanyl (1 to 2 µg/kg), ketamine (0.5 to 1 mg/kg), midazolam (0.02 to 0.03 mg/kg), vecuronium (0.08 to 0.1 mg/kg), and glycopyrrolate (2 to 4 µg/kg) and maintained with sevoflurane and top up doses of fentanyl, midazolam, and vecuronium. The standard monitoring included central venous pressure, invasive arterial pressure, and femoral arterial monitoring in addition to transoesophageal echocardiography.MethodCardiopulmonary bypass was initiated after heparinization to achieve a target-activated clotting time of greater than 480 seconds with intermittent intravenous heparin administration during the surgery. Non-pulsatile CPB was performed using a membrane oxygenator, namely the Terumo Capiox Baby FX 05 , Terumo Capiox Baby RX 05, and Dideco Lilliput D 902 , with an arterial filter (Baby Sherlock) and a roller pump. The oxygenator to be used is determined by the metabolic needs of the subjects which are usually related to age, body size, and body composition.The blood samples to localize a step-up within the heart are received using an oximetry run. This study is technically performed on diagnostic oximetry runs, oxygen measurements, and blood flow calculations. The ABG test uses blood obtained from an artery where both the oxygen and carbon dioxide concentrations in addition to acid-base (pH) levels can be measured. This measures the pressure of oxygen dissolved in the blood and how well oxygen can move from the airspace of the lungs into the blood. This test requires a 2ml sample of blood from any of the following locations: the mid-portion, high point, or low or close to the tricuspid valve in the RQ; left and/or right PA; main PA.Time of SamplingThe first sample of RA and PA was obtained just before the initiation of the bypass Figure . The secPre and post-bypass RA and PA samples were taken from the above-mentioned locations. The blood sample was then analyzed through a transportable device or at an on-site laboratory. The sample was analyzed within 10 minutes of the procedure to ensure an accurate test result by using a standard ABG analyzer  which is set to give a reading at a corrected temperature of 37oC. After the sampling, the RA saturation and PA saturation were noted down, and the pre and post differences were carried out. This test provided a precise measurement of oxygen in the body.The findings from a blood gas test can help diagnose different diseases and also monitor response to treatment. The primary outcome variable of the present study was to find out the difference between the RA saturation and PA saturation pre and post-bypass in pediatric cardiac surgery done intraoperatively on CPB. The secondary outcome variable was the CPB time, aortic cross-clamp time (ACC), ventilator hours, and hospital stay. The O2 saturation step-up in this study is classified as follows: 8% to 10%=low, 11% to 15%=moderate, and 16% and above=high.A total of 35 patients completed this study. Out of which, 24 were male and 11 were female (Table The preoperative minimum difference between RASO2 and PASO2 observed was 2 and the maximum was 62 while the post-bypass saturation minimum difference between RASO2 and PASO2 was -15% and the maximum was 28%. The preoperative mean (SD) difference between RASO2 and PASO2 was 18.65 (13.8) after surgery it was found to be 1.8 (7.3), which was statistically significant . The median of the difference between RASO2 and PASO2 before surgery was 17  and after surgery, the median was 1  with p-value <0.001 (using Wilcoxon signed-rank test), which was also statistically significant.The number of VSD closures was 15. The mean (standard deviation (SD)) aortic cross-clamp (ACC) time was 47.5 (10.7) minutes, and the CPB time was 75.5 (14) minutes. These patients had a mean (SD) ventilator hours of 27.5 (46.9), an ICU stay of 4.46 (2.1) days, and a hospital stay of 8 (2) days. Patients with ICR were 7 with a mean (SD) CPB time of 185.1 (14) minutes, ACC time of 135.8 (17) minutes, ventilator hours of 113.8 (78), and a hospital stay of 11.7 (4.2) days  had a small residual VSD but had a significant step-up. It appears significant but as the total number is small (eight patients), a large study will be better to look for statistical significance. On the other hand, no significant step-up almost ruled out large residual VSD.Statistical analysis All patient data were entered into Microsoft Excel. Data analysis was carried out using Stata version 14.2 . Continuous and categorical variables were reported using mean (SD), median , and frequency (%). To compare the results, we used the Student's t-test (continuous variable) and Wilcoxon Mann-Whitney test . A p-value of <0.05 was considered the cut-off value for the statistically significant test.The ideal management for patients with VSDs would be a single-stage repair with complete VSD closure and avoiding complications such as heart block, arrhythmias, and ventricular dysfunction. The efficacy of the surgery is dependent on early operative risk, septal function after surgery, and the rhythm status. However, the morbidity and mortality related to VSD treatment remain higher than in other types of cardiac surgery. There were no early or late mortality and morbidity in the patients. Of the 35 patients with an intracardiac L-->R shunting, the PA saturation was higher than RA preoperatively. The saturation difference between RA and PA postoperatively suggests the mixing of blood from LV to RV shows that still a small to large VSD is present.In our study, the RA blood samples were drawn from the mid-lateral portion of the RA, which is crucial because its saturation is minimally affected by inferior vena cava or coronary sinus blood. On the other hand, blood samples from PA were drawn from the pulmonary trunk. Also, in our study, one patient with a large VSD had a step-up of >15%, and another patient with a small residual VSD had a significant step-up of >15%. In the remaining 32 patients, no significant step-up was observed. As this study did compare data of oximetry with 2D echocardiography, the errors in missing out on correctable residual lesions diminished vis-a-vis performing the oximetry as a standalone study. In the first two patients who had residual VSD and step-up of >15%, no surgical re-intervention was done.Left-to-right shunt leads to a rise in the oxygen level in the RV. However, even in normal and healthy people, it was quickly recognized that there was a discrepancy in the measured oxygen levels in the right heart. This variation was thought to occur from incomplete mixing of venous flow, assessment errors, and changes in the physiological status of the patients . SeveralThe RA receives input from three sources: the superior vena cava, the inferior vena cava, and the coronary sinus. However, the variation in the oxygen saturation is resulted from incomplete venous mixing, making RA a poor choice to truly estimate oxygen saturation. Therefore, the dependence on the results of only one or two samples to estimate oxygen increase is highly susceptible to error ,9. On thTwo-dimensional echocardiography allows visualization of intra-cardiac communication with L-->R shunts. It provides excellent visualization of the inter-ventricular septum as well as color flow mapping which allows the detection of large L-->R shunts in VSD patients. This approach is highly sensitive in locating VSDs; either congenital or acquired ,12. HoweIn Doppler color flow imaging, the size of the flow is relative to the shunt size. Trans-thoracic or TEE can detect small colorful jets generated by L-->R shunt in VSD cases, even if the oximetry results are negative . EchocarIt is necessary to highlight the limitations of the model in order to build a valid mathematical model for the system. First, the model excluded any physiological fluctuations in oxygen saturation due to the incomplete mixing of venous blood in the vena cava and RV, particularly in the RA. To isolate the oximeter error in consideration in the detection of the shunt, we excluded the cause of this well-known venous saturation variation, which has been widely studied by others. Second, when we calculated the possibility of successfully detecting a shunt, the diagnosis was made completely without oximetry, but we believe that saturation levels are the only information available . AlternaSimilarly, the crucial role of oximeter error is related to the stability of systemic circulation. Both the shunt according to Fick cardiac output measurements and oximeter diagnostics are known to be steady-state methods. Therefore, the manual recommends taking a blood sample as soon as possible for “running the oximeter” ,18. HoweTherefore, oximeter errors play an important role in shunt diagnosis when routine precautions are considered towards lowering changes in systemic perfusion. In conclusion, this study has shown the use of oximetry run to detect the residual shunt is a useful and safer technique and can help in detecting the size of the shunt and oxygen saturation in RA and PA Table .LimitationsThis study is limited due to the nature of the sampling methods, either whilst procuring from the non-designated locations in the cardiac chambers and/or not adjusting ventilator settings to achieve a FiO2 of 50% at the time of second sampling post-surgery. Step-ups in oxygen content may be preferable to increases in saturation, since an increase in content by a given amount is an unambiguous measure of a given size of the shunt, while increases in saturation differ not only due to the occurrence of the shunt but also with the concentration of total hemoglobin. Until extra records are to be had concerning the correctness of the gadgets that determine each oxygen level material and saturation, the diagnosis of the presence of shunts needs to be based on the premise of step-ups in saturation as opposed to oxygen content material. Taking the average values of two or more blood samples obtained from each site and utilizing an oximeter having an error of 1% substantially increases the possibility of arriving at an accurate diagnosis. With the currently available devices, oximetry could possibly detect saturation step-ups as little as 3.6% (17% shunt) and it is safe to use and cheaper. Oxygen saturation data compared to oxygen content data is preferred to detect the occurrence of a shunt. Oximetry testing is handy in the setting of a primary VSD closure wherein significant step-ups post VSD closure point to an additional shunt not manifested in the preoperative echocardiography, provided the primary repair of VSD is satisfactory. This is the unlimiting factor of this test.This study gains significance as facilities for echocardiography in the postoperative period is not routinely available at centers conducting pediatric heart surgeries due to varied reasons. In our institution, we had a double-check method of echocardiography as well as oximetry.


To assess quantitative water T2 relaxometry for the early detection of neuromuscular diseases (NMDs) in comparison to standard qualitative MR imaging in a clinical setting.This retrospective study included 83 patients with suspected NMD who underwent multiparametric MRI at 3 T with a subsequent muscle biopsy between 2015 and 2019. Qualitative T1-weighted and T2-TIRM images were graded by two neuroradiologists to be either pathological or normal. Mean and median water T2 relaxation times (water T2) were obtained from manually drawn volumes of interests in biopsied muscle from multi-echo sequence. Histopathologic pattern of corresponding muscle biopsies was used as a reference.In 34 patients, the T1-weighted images showed clear pathological alternations indicating late-stage fatty infiltration in NMDs. In the remaining 49 patients without late-stage changes, T2-TIRM grading achieved a sensitivity of 56.4%, and mean and median water T2 a sensitivity of 87.2% and 97.4% to detect early-stage NMDs. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.682, 0.715, and 0.803 for T2-TIRM, mean water T2, and median water T2, respectively. Median water T2 ranged between 36 and 42 ms depending on histopathologic pattern.Quantitative water T2 relaxometry had a significantly higher sensitivity in detecting muscle abnormalities than subjective grading of T2-TIRM, prior to late-stage fatty infiltration signal alternations in T1-weighted images. Normal-appearing T2-TIRM does not rule out early-stage NMDs. Our findings suggest considering water T2 relaxometry complementary to T2-TIRM for early detection of NMDs in clinical diagnostic routine.Quantitative water T2 relaxometry is more sensitive than subjective assessment of fat-suppressed T2-weighted images for the early detection of neuromuscular diseases, prior to late-stage fatty infiltration signal alternations in T1-weighted images.• Normal-appearing muscles in fat-suppressed T2-weighted images do not rule out early-stage neuromuscular diseases.• Quantitative water T2 relaxometry should be considered complementary to subjectively rated fat-suppressed T2-weighted images in clinical practice.•  Magnetic resonance imaging (MRI) is widely used clinically to diagnose and monitor neuromuscular diseases (NMDs). Late-stage disease manifestation of NMDs such as fatty infiltration can be identified in T1-weighted images by hyperintense signal alterations. Similarly, elevated T2 signals in muscle, an unspecific surrogate marker of the strength of underlying pathophysiological processes, but also of early pathological tissue alterations . HoweverQuantitative MRI provides objective and sensitive measures of nuclear MR tissue microstructure. Quantitative MR parameters such as the percentage of fatty infiltration of muscle (fat fraction) and the muscle water T2 relaxation time (water T2) are well-established MR parameters in NMDs –7. The pThe early detection of disease might be beneficial for clinical care of patients with NMDs. By early detection, a potential treatment could be initiated before irreversible muscle damage has occurred. Additionally, the diagnostic yield of muscle biopsy could be increased by targeting more suitable muscles for histopathological analysis. Diagnostically, an imaging-based early detection of NMDs might either be possible by using fat-suppressed T2-weighted sequences, or by quantitative water T2 relaxometry , 6, 8, 9We conducted a retrospective study to determine the value of quantitative water T2 relaxometry for the early detection of NMDs. We hypothesized that more early-stage NMDs could be identified by quantitative water T2 relaxometry compared to standard, qualitatively assessed, fat-suppressed T2-weighted sequences.n = 83 patients  referred to our tertiary center for neuromuscular diseases between January 2015 and May 2019 due to suspected NMD  who underwent both multiparametric muscle MRI and subsequent muscle biopsy. All patients had previously given oral and written informed consent and the study was approved by the local ethics committee.Our study compromised a cohort of fit  using 12-channel body coils and spine coils. Images of calves and thighs were acquired using the following protocol: axial T1-weighted sequences, axial T2-weighted sequences with turbo inversion recovery magnitude for fat saturation (T2-TIRM), and quantitative water T2 relaxometry derived from axial multi-slice multi-echo (MSME) sequences. T1-weighted sequences were acquired using a repetition time (TR) of 270 ms, echo time (TE) of 11 ms, field of view (FoV) read of 400 mm, FoV phase of 50%, base resolution of 384, and slice thickness of 5 mm. T2-TIRM sequences were acquired using a TR of 2020 ms, TE of 44 ms, flip angle (FA) of 140°, inversion time (TI) of 200 ms, FoV read of 400 mm, FoV phase of 50%, base resolution of 384, and slice thickness of 5 mm. Water T2 relaxometry was derived from MSME sequences with a TR of 3000 ms, 17 echoes with TEs of 9.5 ms, 19.5 ms, …, 161.5 ms, FA of 180°, FoV read of 448 mm, FoV phase of 50%, base resolution of 320, parallel imaging mode GRAPPA with factor 2, slice thickness of 5 mm, and 9 slices. The choice of the MSME sequence parameters corresponds to what is typically used in clinical neuromuscular MRI [All MR examinations were performed on a 3 T Siemens MAGNETOM Skyraneurogenic myopathic inflammatory unspecific normal All patients underwent a biopsy of skeletal muscle tissue originating from one muscle selected based on abnormalities on standard T1-weighted image, T2-TIRM image, and water T2 relaxometry map. Our clinical protocol defines that the chosen muscle should show mild abnormalities in T1-weighted and T2-TIRM images. Only if no abnormalities are present in weighted images, the water T2 relaxometry map is consulted to select a muscle with elevated water T2 values for the biopsy. Histopathological analysis of the muscle biopsies was performed according to standard protocols . The bioThe image analysis involved a subjective grading of the standard qualitative MR images, and a calculation of the mean and median of the water T2 values obtained from T2 relaxometry map. In T1-weighted and T2-TIRM images, muscles were graded to be either pathological  or normal by two radiologists. Both raters have over 5 years of experience in musculoskeletal and neuromuscular diagnostics and were blinded to the clinical data and each other’s result. In case of disagreement, the two raters consulted to reach a consensus. For water T2 relaxometry, the exponential decay of the signal was fitted voxel-wise from the MSME images using a bi-component extended phase graph (EPG)–derived signal model  to obtaip < 0.05. We used R version 4.1.2 (R Core Team) to conduct all statistical analyses.To test the hypothesis that more early-stage NMDs can be identified with quantitative water T2 relaxometry compared to T2-TIRM, patients with a pathological grading of the T1-weighted image were excluded from the statistical analysis as visible alternations in T1-weighted images indicate late-stage fatty infiltration in NMDs. In patients with normal grading of the T1-weighted images, the diagnostic performance of the subjective T2-TIRM grading and the quantitative mean and median water T2 values of the VOIs with the histopathology as a reference was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated for further comparison between the different gradings. To determine if there is a difference of water T2 values between the histopathologic patterns, we used the non-parametric Kruskal-Wallis and Wilcoxon rank-sum tests . All statistics were conducted with the level of significance at n = 40), biceps femoris long head (n = 26), adductor magnus (n = 2), adductor longus (n = 1), semimembranosus (n = 6), gracilis (n = 1), tibialis anterior (n = 3), and gastrocnemius (n = 4). In our cohort of 83 patients, 34 patients showed clear late-stage fatty infiltration based on subjective grading of the T1-weighted images, which were excluded in subsequent statistical analysis. T1-weighted images, T2-TIRM images, and water T2 relaxometry maps of a patient with normal histology and MR imaging and a patient with late-stage fatty infiltration are shown in Fig. n = 15), inflammatory (n = 6), myopathic (n = 14), unspecific (n = 4), and normal (n = 10). Exemplary T1-weighted images, T2-TIRM images, and water T2 relaxometry maps of two patients without late-stage changes are shown in Fig. Histopathology confirmed 70 patients to have pathological muscles in our cohort of 83 patients. In 13 patients, no pathological alterations were found. Muscle biopsies were taken from vastus lateralis  for T2-TIRM, 0.715 (95% CI: 0.560–0.871) for mean water T2, and 0.803 (95% CI: 0.674–0.931) for median water T2, as shown in Fig. p = 0.102). For the median water T2 values, there is a significant difference between the histopathologic patterns (p = 0.008). The Wilcoxon rank-sum test with Bonferroni adjustment for multiple comparisons determined that myopathic (p = 0.042) and unspecific (p = 0.043) patterns differ statistically from normal patterns but neurogenic (p = 0.110) and inflammatory (p = 0.066) patterns do not differ statistically from normal patterns. The mean and standard deviation of the mean and median water T2 were 36.7 ± 2.7 ms and 38.3 ± 2.5 ms for neurogenic, 39.2 ± 2.5 ms and 42.3 ± 3.8 ms for inflammatory, 37.5 ± 3.7 ms and 39.8 ± 3.1 ms for myopathic, 36.5 ± 0.9 ms and 40.3 ± 1.3 ms for unspecific, and 35.3 ± 1.5 ms and 36.5 ± 1.8 ms for normal pattern. The differences in mean and median water T2 are associated with an asymmetric distribution of water T2 in the VOIs of the muscles resulting in a more robust median water T2 measure. Normal patterns were found to have high water T2 mostly due to confounding vascular pathologies of the lower limbs in six patients .Water T2 values of the histopathological pattern are shown as box-and-whisker plots in Fig. We determined the value of quantitative water T2 relaxometry for the early detection of NMDs compared to subjective grading of T2-TIRM images with histopathology as a reference. The median water T2 had a significantly higher sensitivity in detecting early-stage muscle abnormalities than the subjective grading of T2-TIRM images, prior to visible signal alternations in T1-weighted images. Therefore, normal-appearing muscles in T2-TIRM images do not rule out disease manifestation in muscles . For definitive clinical recommendation of water T2 relaxometry, a larger sample size is clearly required. The retrospective setting also does not allow to draw any conclusions on specific NMDs beyond assessing water T2 in different histopathological categories Fig. . These fIn conclusion, we showed an increased sensitivity of quantitative water T2 relaxometry over subjective grading of standard T2-TIRM images for the early detection of NMDs, prior to late-stage fatty infiltration. Therefore, normal-appearing muscle in T2-TIRM images does not rule out disease manifestation in NMDs. Our findings suggest considering quantitative water T2 relaxometry complementary to subjective grading of T2-TIRM images for early detection of NMDs in clinical diagnostic routine.


We aimed to evaluate the relationship between quantitative plaque metrics derived from coronary CT angiography (CTA) and segmental myocardial ischemia using dynamic perfusion CT (DPCT).In a prospective single-center study, patients with > 30% stenosis on rest CTA underwent regadenoson stress DPCT. 480 myocardium segments of 30 patients were analyzed. Quantitative plaque assessment included total plaque volume (PV), area stenosis, and remodeling index (RI). High-risk plaque (HRP) was defined as low-attenuation plaque burden > 4% or RI > 1.1. Absolute myocardial blood flow (MBF) and relative MBF  were quantified. Linear and logistic mixed models correcting for intra-patient clustering and clinical factors were used to evaluate the association between total PV, area stenosis, HRP and MBF or myocardial ischemia (MBF < 101 ml/100 g/min).p = 0.001). Area stenosis and HRP features were not linked to MBF or MBFi . Increase in PV led to reduced MBF and MBFi after adjusting for risk factors including hypertension, diabetes, and statin use . Similarly, using multivariate logistic regression total PV was associated with ischemia  after adjustments for clinical risk factors, area stenosis and HRP.Median MBF and MBFi were 111 ml/100 g/min and 0.94, respectively. The number of ischemic segments were 164/480 (34.2%). Total PV of all feeding vessels of a given myocardial territory differed significantly between ischemic and non-ischemic myocardial segments (Total PV was independently associated with myocardial ischemia based on MBF, while area stenosis and HRP were not. Currently luminal stenosis is the most dominant factor in the management of coronary artery disease (CAD) . QuantitCT angiography (CTA) is a uniquely suited imaging modality that can simultaneously evaluate plaque morphology and ischemia . Also, CFormer observational studies evaluated the link between coronary plaque burden and global myocardial ischemia using qualitative/visual assessment by either static CT perfusion (CTP) , stress Our aim was to elucidate the association between quantitative atherosclerotic plaque metrics derived from coronary CTA and segmental myocardial ischemia based on myocardial blood flow (MBF) as detected by DPCT imaging.n = 1). Patients were enrolled in the analysis if found eligible based on inclusion and exclusion criteria. Flow chart of the study is shown in Patients with stable chest pain and > 30% coronary stenosis detected on rest CTA were screened for our prospective, single-center study. Inclusion criteria were at least 30% stenosis in one of the main coronary arteries and excellent image quality for the quantitative analysis of the whole coronary tree. Exclusion criteria were prior myocardial infarction or revascularization, heart transplantation, contraindication to regadenoson or low image quality for quantitative assessment of coronary lesions. Regadenoson stress DPCT was performed at a separate appointment after written informed consent was obtained from all patients. Subjects with low image quality for the assessment of myocardial ischemia were excluded  and was performed in accordance with the Helsinki declaration.Demographic data and comorbidities were collected by reviewing patients’ medical records. Hypertension was determined as systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg based on office measurements or the use of antihypertensive therapy. Diagnosis of hyperlipidemia was based on total cholesterol level > 200 mg/dL or the administration of lipid-lowering medication. Diabetes mellitus was defined as elevated plasma glucose levels  or the use of antidiabetic medication or insulin therapy.Per os beta blocker was administered 1 h prior examination if the heart rate (HR) was above 65 beats/min. All patients received 0.8 mg of sublingual nitroglycerine before CTA scanning if systolic blood pressure was > 100 mmHg, and in case of HR > 60 beats per minute intravenous beta blocker was additionally administered. Image acquisition was performed at diastole  or at systole  in case of HR > 70 beats per minute despite premedication. The following scan parameters were applied: 270 ms gantry rotation time, 128 × 0.625 mm collimation, tube voltage 100–120 kVp, and tube current 200–300 mAs based on patient’s body mass index (BMI). A four-phasic contrast injection protocol was used with 85–95 ml contrast agent at a flow rate of 4.5–5.5 ml/s. Axial images were reconstructed with 0.6 mm slice thickness using iterative reconstruction .Prospectively triggered CTA scan of the heart was performed according to the guidelines of the Society of Cardiovascular Computed Tomography (SCCT) with a 256-slice multidetector row CT  . Per os ®, GE Healthcare) (Stress DPCT scan was performed after rest CTA at a separate appointment with the same scanner. Hyperemia was induced using single dose of 400 μg intravenous regadenoson (Rapiscanlthcare) . Stress lthcare) . PatientCoronary artery segments were defined using an 18-segment model as recommended by the SCCT guidelines . CTA imaDPCT images were analyzed using a dedicated software . Elastic registration and temporal filtering were applied for motion artifact reduction. Time-attenuation curves (TAC) created in the left ventricular outflow tract were used as arterial input function for perfusion analysis. Short-axis views were created for the assessment of the left ventricular myocardial tissue. MBF was computed applying a hybrid deconvolution method . The assCoronary lesions were assigned to the corresponding myocardial segment based on the modified method after Cerci et al. for the CORE320  trial . Former After the adjudication was performed by B.S.,—with 8 years of experience in cardiac imaging—volumes for total, NCP and CP of all relevant supplying coronary segments were summed for each myocardial segment. LAP burden was also calculated from the summed LAP and vessel volume. If LAP burden exceeded 4% of all plaque supplying a given segment, or the highest RI of the corresponding lesions was > 1.1, we marked as HRP. Summed plaque volumes (PVs), the highest degree of lumen area stenosis and HRP (LAP burden > 4% or a RI > 1.1) of the supplying coronary segments were analyzed for the corresponding myocardial segment.t-test was used to compare parameters describing coronary plaque burden between ischemic and non-ischemic segments. Pearson correlation was used to define the association between total, NCP and CP volumes. Linear and logistic mixed models correcting for intra-patient clustering and clinical factors were used to assess the association between total PV, maximal area stenosis, quantitative HRP features and absolute MBF, MBFi or myocardial ischemia using 101 ml/100 g/min as cut-off value for MBF. Models were adjusted for predefined clinical risk factors of CAD and possible modifiers of ischemia including hypertension, diabetes mellitus and statin therapy.Continuous variables are presented as mean and standard deviation, whereas categorical parameters are presented as frequency with percentages. Independent P < 0.05 was defined as statistically significant.Intraclass correlation coefficient (ICC) of MBF was calculated for 160 segments of 10 randomly selected patients between two readers with 3 or more years of experience in cardiac CT imaging (BV and SB). ICC values greater than 0.80 were considered good, values above 0.90 were considered to have excellent reproducibility. Also, reproducibility of quantitative plaque assessment was evaluated between two independent readers based on 10 plaques of randomly selected patients. All statistical analyses were performed using SPSS (version 24.0) and R software (version 3.6.1). 2) are summarized in The baseline characteristics of the 30 analyzed patients  vs. 31.6 (12.4–73.8) mm3; CP volume: 15.9 (0.1–78.2) vs. 17.3 (2.2–46.1) mm3. p = 0.072). HRP was present in 21.3% in ischemic and 19.0% in non-ischemic territories (p = 0.539).Total PV, NCP volume, and CP volume differed significantly between ischemic and non-ischemic myocardial segments, 120.5 ± 119.5 mmectively . Median Number of ischemic segments were 164/480 (34.2%). Median MBF was 111 ml/100 g/min, while median MBFi was 0.94.r = 0.73, p < 0.001) and CP volume , we therefore included total PV in the multivariate prediction models to avoid multicollinearity.Total PV strongly correlated with NCP volume .On multivariate analysis, total PV increase led to reduced absolute and relative MBF values even after adjusting for clinical risk factors, lumen area stenosis and HRP features: per 10 mmp = 0.033 (per 10 mm3). However, on multivariate analysis HRP feature and lumen area stenosis were not linked to ischemia (both p > 0.05).On univariate logistic regression total PV and lumen area stenosis were significant predictors of myocardial ischemia based on MBF < 101 ml/100 g/min . After aWe used a novel approach to define the contribution of coronary PV to limited flow (ischemia) of all feeding coronary segments considering only coronary lesions prior to a given myocardial territory. We established that total PV influenced myocardial perfusion on a segmental level, independent from stenosis severity, HRP and risk factors. Moreover, maximal luminal area stenosis and the presence of HRP were not linked to myocardial ischemia based on MBF. Reproducibility was excellent for the evaluation of MBF or total PV.2O PET-MPI and coronary CTA and found that plaque length and volume were inversely associated with MBF in a sub-study of the PACIFIC trial . This observation seems valid across different stages of stenosis severity and thus detailed plaque quantification could effectively guide secondary prevention therapy in a large spectrum of contemporary chest pain patients. Integrating plaque burden in the clinical CTA reports and thus in personalized patient management should be in the focus rather than luminal narrowing per se.Conflicting results regarding the relationship of plaques and ischemia may originate from the different capabilities of the modality utilized in the trials. CT has several advantages as compared with other techniques such as better spatial resolution, robust plaque assessment and reproducible quantitative measures of perfusion. CT imaging can define the hemodynamic significance of CAD by defining either lesion-specific ischemia using CT derived fractional flow reserve (FFR) or global ischemia on DPCT imaging. Radiation dose however still limits its use—especially using dynamic CT protocols—for a large subset of patients. Growing body of evidence suggests that anatomical information derived from CTA outperforms traditional ischemia testing for defining lesion-specific ischemia as obtained from invasive FFR. The CREDENCE trial demonstrated a strong association between atherosclerotic PVs, lumen size and invasive FFR . Our stuWe acknowledge the limitations of our study. First, the sample size is limited after excluding patients with non-diagnostic image quality for quantitative plaque analysis or patients without intermediate stenosis. Excellent image quality is a prerequisite for quantitative plaque analysis. This could result in selection bias for our analysis. Quantitative plaque analysis is time-consuming and currently only a research tool, not used in routine clinical practice. However, experts of the field underline its role in risk prediction and tools are being developed for automated quantification in the near future. Also, our study is underpowered for the assessment of gender differences in CAD and corresponding ischemia or for outcome analysis.Total coronary PV was independently associated with myocardial ischemia based on MBF derived from DPCT imaging, while area stenosis and HRP were not. Incorporating these quantitative plaque characteristics in a comprehensive coronary CTA evaluation could improve the prediction of ischemic CAD, independently of lesion severity.The data that support the findings of this study are available from the corresponding author, upon reasonable request.The studies involving human participants were reviewed and approved by National Institute of Pharmacy and Nutrition—OGYÉI/719/2017. The patients/participants provided their written informed consent to participate in this study.BS, MK, PM-H, and BM contributed to conception and design of the study. BV, SB, and BS performed the measurements. BV, SB, MB, MV-N, FS, ÁJ, and BS contributed to patient enrollment. BV, SB, and MB organized the database. BS and MK performed the statistical analysis. BV and BS wrote the first draft of the manuscript. MK, MV-N, FS, SB, and MB wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.