There has been an increasing number of children with congenital heart disease that undergo primary or second systemic-pulmonary shunt, while there are few reports on the second systemic-pulmonary shunt. Therefore, this study summarizes the experience of second systemic-pulmonary shunt for congenital heart disease in our hospital.2 significantly increased. One patient died in hospital (1.54%) and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early complications occurred in 18 patients (27.7%). All the children were rechecked in our hospital every 3–6 months and the McGoon index significantly increased.Sixty-five children with congenital heart disease who underwent systemic-pulmonary shunt for the second time in our hospital were analyzed. At the early stage after the operation, cyanosis improved and SpOSystemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with pulmonary vascular dysplasia. With the steady improvement of the comprehensive strength in medicine, congenital heart disease continues to develop in a small, difficult, and in-depth direction while operative indications continue to expand and many forbidden zones have been constantly examined in terms of systemic-pulmonary shunt –7. The nFrom October 2010 to March 2019, 65 children with congenital heart disease who cannot be cured by one operation and thus underwent second systemic-pulmonary shunt at the Children’s Heart Center of Beijing Anzhen Hospital (597 patients completed the first systemic-pulmonary shunt in the same period) were enrolled in the present study. Among these patients, 42 patients were male and 23 patients were female. The age of these patients ranged from 4 months old to 18 years and 10 months old with an average age of 4 years and 8 months old, 25% interquartile was 12 months, median was 25 months, 75% interquartile was 6 years and 4 months. The body weight ranged within 4.5–58.2 kg with an average body weight of 15.3 kg, 25% interquartile was 9.3 kg, median was 12.9 kg, 75% interquartile was 17.5 kg. The patient’s diseases included the following: 39 patients (60%) had pulmonary atresia, in which 36 patients had a ventricular septal defect and three patients had an intact ventricular septum; 11 patients (16.9%) had tetralogy of Fallot; 9patients (13.8%) had a double outlet of the right ventricle and pulmonary artery stenosis; 3patients (4.6%) had complete transposition of the great arteries with pulmonary stenosis; and 3patients (4.6%) had single ventricle defect and pulmonary stenosis. A further 60patients (92.3%) had shunt stenosis or obstruction and 5patients (7.7%) had an excessive shunt.A total of 60 patients were assigned to this group. Five of them had acute obstruction within 24 h and the remaining patients were diagnosed during the follow-up sessions. Children with acute obstruction of the systemic-pulmonary shunt channel presented with lower oxygen saturation than those before the operation and increasing oxygen uptake concentration and improving ventilation did not significantly improve oxygen saturation. The murmur of the systemic-pulmonary shunt disappeared in clinical auscultation and was diagnosed by ultrasonography. Computed tomography (CT), three-dimensional cardiovascular reconstruction or angiography was not performed. All patients underwent an emergency reoperation. General anesthesia and tracheal intubation were given and the operation within the thoracic cavity was performed through the original incision. Under cardiopulmonary bypass (CPB) or off-pump, the original shunt channel was removed, and a new shunt channel was replanted at the original shunt site. The length and direction of the shunt channel were adjusted to avoid pulling and twisting the pulmonary artery and shunt channel.Fifty-five patients had chronic obstruction or stenosis and the children with cyanosis usually showed improvement in the early stage after the operation. In the later stage after the operation, the cyanosis was gradually aggravated and percutaneous oxygen saturation decreased. After the patient’s completed their exercise, their breathing significantly increased, activity endurance decreased, and pulmonary blood flow significantly decreased as shown on the chest X-ray films. All the patients underwent echocardiography again before the operation and 21 children underwent angiography and 35 children underwent CT three-dimensional cardiovascular reconstruction. The second operation was performed under CPB or off-pump . If the main pulmonary artery existed, the left and right pulmonary arteries were well developed and there was no obvious stenosis at the bifurcation, the pulmonary end of the second shunt channel was connected to the main pulmonary artery, the original shunt channel was removed or not removed, while the left and right proximal pulmonary artery stenosis were corrected accordingly. If the left and right pulmonary arteries were unevenly developed, the second shunt channel was usually anastomosed to the poorly developed pulmonary artery or the bilateral pulmonary arteries for the systemic-pulmonary shunt. If the first incision was a median size, the second operation could also include completing a lateral thoracotomy. Lateral thoracotomy is directed at the pulmonary artery on the dysplastic side, where the shunt channel is anastomosed between the ipsilateral pulmonary artery and the subclavian artery, which avoids entering the thoracic cavity through the original incision and free adherent tissue, reducing the possibility of massive hemorrhage. For the patients with large systemic and pulmonary collateral branches, which cannot be handled by median thoracotomy, lateral thoracotomy can often provide a beneficial counterpart to facilitate the construction of shunts while ligating large systemic and pulmonary collateral branches or fusing them into the intrinsic pulmonary artery. The larger diameter shunts are often replaced during reoperation.Five patients were assigned to this group. In all patients, the disease occurred early after the operation. Cardiac echocardiography showed that the shunt was unobstructed, while X-ray chest film showed increased pulmonary blood flow, increased pulse pressure difference, and decreased diastolic pressure (even less than 30 mmHg). The patients were unable to go off the ventilator or experienced difficulties off the ventilator. Recurrent pericardial effusion or (and) pleural effusion was observed. The thoracic cavity was accessed through the original incision. In all patients, instead of removing the original shunt channel, the Gortex vessels were clamped with clips to reduce the diameter of the lumen and increase the diastolic pressure, which was mostly more than 40 mmHg. In one patient, the vessels were clamped until the diameter of the lumen reached approximately 2/3 of the normal body weight required. After the operation, the child’s circulation was still difficult to maintain and the surgeons were required to open the patient’s chest again and the shunt channel was ligated.Routine 24-h continuous electrocardiograph (ECG) monitoring and invasive blood pressure monitoring was performed immediately after the operation in the intensive care unit. At 6 hours after the surgery, if there was no obvious bleeding, heparin was continuously infused with a rate of 2 mg/kg/24-h. Thereafter, the ventilator was removed, and aspirin was given orally at a dose of 3-5 mg/kg and the heparin was discontinued after 2 days. Due to the role of the systemic-pulmonary shunt, the pulmonary circulation blood flow increased, systemic circulation blood flow decreased, the coronary artery diastolic pressure decreased, and the relative insufficiency of cardiac blood supply led to heart failure. Through the support of ventilator therapy, cardiotonic drugs, and volume enhancement, the cardiopulmonary function was gradually adapted and recovered. Ventilation parameters were as follows: tidal volume = 8–12 mL/kg, inspiratory/expiratory = 1:1.5–2, positive end expiratory pressure = 3–5 mmHg. The below cardiotonic drugs were chosen according to patients’ conditions: dopamine 5–8 μg/kg/min, epinephrine 0.05–0.1 μg/kg/min, milrinone 0.5–1 μg/kg/min, or norepinephrine 0.05–0.1 μg/kg/min.2 in the arterial blood gas analysis at a normal high level and the oxygen saturation was 75–85%. Secondly, adequate blood volume was ensured to keep central venous pressure (CVP) at a normal high level. The volume status was measured by CVP. Finally, cardiotonic drugs were used to maintain diastolic blood pressure close to a normal level to ensure coronary blood supply, while strengthening myocardial contractility.Firstly, the respiratory parameters were adjusted to maintain the PCOP < 0.05 was considered statistically significant.Statistical analysis was conducted using statistical software SPSS19.0. Continuous data were analyzed by Shapiro-Wilktest to verify if they were normally distributed, and normally distributed measurement data were expressed as mean ± standard deviation (x ± SD) and compared using a t-test. 2) increased from 61.5 ± 10.2% before the operation to 81.7 ± 9.2% after the operation (P < 0.01). The result suggests that after shunt, oxygenation was improved significantly when compared with that before shunt. The duration of the ventilator-assisted ventilation in children was 8–256 h with an average duration of 46.2 ± 21.7 h. The duration of the children’s stay in the intensive care unit (ICU) was 1–140 days with an average duration of 11.8 ± 5.2 days. During hospitalization, one patient died of an excessive shunt, the fatality rate was 1.54%, and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early postoperative complications occurred in 18 patients (27.7%). Among these patients, severe low cardiac output syndrome occurred in 12 patients (66.6%), pulmonary infection occurred in 11 patients (61.1%), pleural effusion occurred in 7 patients (38.9%), pericardial effusion occurred in 6 patients (33.3%), 3 patients (16.7%) received thoracotomy again to stop bleeding, and cerebral infarction occurred in 2 patients (11.1%).In all children, the cyanosis symptoms were improved when compared with those before the operation, blood oxygen saturation (SpOP < 0.01). Children with well-developed pulmonary arteries who were close to the standard for radical treatment underwent cardiac three-dimensional CT or angiography to confirm whether they met the standard for radical treatment and the situations of body-lung collateral branches in order to decide whether or not opening the chest was required again for anatomical radical resection, waiting or the reoperation of the systemic-pulmonary shunts.All the children were rechecked in our hospital every 3–6 months in an outpatient follow-up period of 402 ± 330 days with a median of 450  days and pulmonary artery development and patency of shunt channel was confirmed by cardiac echocardiography. The McGoon index increased from 1.08 ± 0.26 before the operation to 1.55 ± 0.48 after the operation and the difference was statistically significant , the disease gradually appeared during the follow-up sessions. In this study, after the first operation, although it’s not yet reached the standard of radical treatment, the children’s conditions developed well. Radical resection was performed in 10 out of 11 children (91%) during reoperation of systemic-pulmonary shunts (the replacement of the shunts of the same or larger diameter) and subsequent blockade of systemic-pulmonary collateral branches was completed. In 5 of these 10 children (50%), the pulmonary annulus developed sufficiently large and in the subsequent radical operation, the repair of the pulmonary valvular ring was not necessary, and the effect was good. In developed countries, the mainstream concept of treatment of tetralogy of Fallot is to seek an early operation and one-stop radical cure. The treatment experience of the investigators is that, for severe tetralogy of Fallot with younger and poorly developed pulmonary blood circulation, it is very difficult to treat it surgically and postoperatively even if it can be cured in one-stop. In this case, the hospitalization stay is long, the mortality rate is high, and the cost is large. The investigators tend to take a step-by-step approach, where the systemic-pulmonary shunt is first performed to promote pulmonary artery development and alleviate cyanosis and other symptoms so that the growth and development of children will not be greatly affected. Then, interventional methods such as systemic-pulmonary collateral branch occlusion, balloon dilation of the pulmonary valve, and second systemic-pulmonary shunt are performed to gain time and to gradually promote pulmonary artery development. In this method, the vast majority of children have been cured and there have been no deaths reported to date. This fully demonstrates the role of the systemic-pulmonary shunt in congenital heart disease with pulmonary blood deficiency. This also has an important impact on the improvement of reoperation skills but at present, the number of cases is small and needs further verification in the future.The risk of an excessive systemic-pulmonary shunt is far greater than that of the insufficient systemic-pulmonary shunt. In the present study, one child died. The child was 9 years old diagnosed with single atrium, single ventricle, and severe pulmonary artery stenosis with pulmonary artery dysplasia, and the child had mild atrioventricular regurgitation and cyanosis before the operation. Suitable shunt channels and shunt locations were chosen according to his age and weight. After the first systemic-pulmonary shunt operation, the cyanosis was improved significantly and the patient was extubated 5 days after the operation, but the heart function was poor, pericardial effusion and pleural effusion repeatedly occurred, and multiple surgical drainages were performed. However, these methods did not improve the patient’s poor heart functions. Finally, it was decided that the child should undergo the reoperation. During the operation, some systemic-pulmonary shunt channels were clamped to reduce the diameter of the channels. After the operation, the child’s cardiac function improved but the patient died of physical weakness and pulmonary infection. The child was hospitalized for more than 4 months. From this painful lesson, we realize that the harmfulness of an excessive shunt is far greater than that of insufficient shunt and that children with preoperative atrioventricular regurgitation need extra caution when undergoing the systemic-pulmonary shunt. Generally, shunt channels with diameters slightly smaller than the normal standard are selected to avoid excessive shunt. Gradual aggravation of atrioventricular regurgitation is an important indicator of excessive shunt. Re-operation should be done as soon as possible; otherwise, it is easy to miss the best treatment opportunity with serious consequences.2 in blood gas analysis was usually adjusted to 40-45 mmHg, the SpO2 was maintained at 80–85%, for children with cardiac dysfunction, the partial pressure of PCO2 in blood gas analysis was adjusted to 45-50 mmHg, and the SpO2 was maintained at 75–80% and can even be as low as 70–75% to keep lactate at a normal level to avoid the sudden increase of pulmonary blood flow that causes a serious impact on cardiopulmonary function while allowing a gradual adaptation in the body. It is important to note that, for children undergoing systemic-pulmonary shunt, careful attention should be paid to sputum suction and hand-controlled breathing and excessive ventilation should be avoided because high oxygen and low carbon dioxide can dramatically increase the lung blood volume, causing drastic and dangerous fluctuations in the circulation. The limitation of this study is that we did not collect the pro-thrombotic factors , which should be addressed in future studies.After the operation of the systemic-pulmonary shunt, maintaining cardiopulmonary function, preventing and treating low cardiac output syndrome, and gradually adapting cardiopulmonary function are the first and foremost tasks to be completed, which are related to the success or failure of the systemic-pulmonary shunt. The essence of the systemic-pulmonary shunt is to inject some blood of systemic circulation into the pulmonary circulation by high pressure through the shunt channels, which will inevitably lead to the corresponding increase of pulmonary circulation blood volume and left ventricular return blood volume. The result is a sudden increase in the left ventricular volume load, with relatively insufficient coronary artery blood supply caused by the decrease of systemic circulation diastolic blood pressure caused by the shunt and easily causes left heart failure. Although the improvement in oxygen supply is due to the increase in blood oxygen saturation, fine adjustments are still needed to avoid drastic changes in the circulation and only then the body can gradually adapt to the adjustments. First, blood volume needs to be replenished: especially in children undergoing off-pump systemic-pulmonary shunt as there is no process of adjusting blood volume by extracorporeal circulation. The volume should be replenished in time during and after the operation to accommodate the sudden increase in volume requirements. However, it is difficult to accurately estimate this volume requirement due to individual differences, with the central venous pressure reaching a normal high level as the standard. In terms of the rational use of cardiotonic drugs, a sudden increase in cardiac volume load will inevitably impact cardiac function, especially in children whose cardiac function is marginalized before the operation, thus, the rational use of cardiotonic drugs is very important. Vasoactive drugs such as dopamine, epinephrine, and norepinephrine are routinely used during and after the operation to help reduce further illness and mortality in children. In terms of the rational use of ventilators, the proper ratio of volumes of pulmonary circulation to systemic circulation can be adjusted by ventilator parameters. Overall, the circulation in children undergoing systemic-pulmonary shunt is mostly single ventricular physiology and the systemic-pulmonary shunt channel is an important channel for the blood flow adjustment between the two. When the diameter of the channel is constant, the resistance between the two circulations determines the size of the shunt. When the oxygen saturation is between 80 and 85%, the blood flow ratio of systemic circulation to pulmonary circulation is close to 1:1. When oxygen saturation is too high, it is likely to become excessive shunt and often not necessarily beneficial to the child. Initially, after systemic-pulmonary shunt, pulmonary artery pressure increases as a result of the massive blood flow to the pulmonary circulation. Evidently, effective filtration pressure of tissue fluid equates to  - . If other conditions remain unchanged, an increase in the capillary filtration pressure in the lung inevitably leads to an increase in tissue fluid production in the lung and the chance of pulmonary edema increases to affect oxygenation. This is the main reason why blood oxygen saturation increases and decreases immediately after a systemic-pulmonary shunt. In order to prevent sudden sharp changes in pulmonary blood flow, it is very important to set up reasonable ventilator parameters. In this study, the partial pressure of PCOIn summary, systemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with congenital heart disease, pulmonary blood deficiency, and pulmonary vascular dysplasia. With the continuous improvement of skills in the reoperation process, second systemic-pulmonary shunt is safe and feasible. While ensuring the patency of the shunt channel, early intensive monitoring and comprehensive treatment after the operation ensures successful surgery outcomes.


Systolic dysfunction of the left ventricle is frequently associated with isolated left ventricular non-compaction (iLVNC). Clinically, the ejection fraction (EF) is the primary index of cardiac function. However, changes of EF usually occur later in the disease course. Feature tracking (FT) and deformable registration algorithm (DRA) have become appealing techniques for myocardial strain assessment.n = 11) and EF < 50% group (n = 19). Receiver-operating-characteristic (ROC) analysis was performed to assess the diagnostic performance of the global strain values. Intraclass correlation coefficient (ICC) analysis was used to evaluate the intra- and inter-observer agreement.Thirty patients with iLVNC (36.7 ± 13.3 years old) and fifty healthy volunteers (42.3 ± 13.6 years old) underwent cardiovascular magnetic resonance (CMR) examination on a 1.5 T MR scanner. Strain values in the radial, circumferential, longitudinal directions were analyzed based on the short-axis and long-axis cine images using FT and DRA methods. The iLVNC patients were further divided based on the ejection fraction, into EF ≥ 50% group /% vs. controls: 37.4 ± 13.2 vs. 56.9 ± 16.4, P < 0.01]. ROC analysis of global strain values derived from DRA and FT demonstrated high area under curve . DRA showed excellent intra- and inter-observer agreement of global strain in both iLVNC patients (ICC: 0.995–0.999) and normal controls (ICC: 0.934–0.996). While for FT analysis, global radial strain of normal controls showed moderate intra-observer (ICC: 0.509) and poor inter-observer agreement (ICC: 0.394).Global radial strain (GRS) was statistically lower in EF ≥ 50% group compared with control group [GRS (DRA)/% vs. controls: 34.6 ± 7.0 vs. 37.6 ± 7.2, In patients with iLVNC, DRA can be used to quantitatively analyze the strain of left ventricle, with global radial strain being an earlier marker of LV systolic dysfunction. DRA has better reproducibility in evaluating both the global and segmental strain. Left ventricular non-compaction (LVNC) is an uncommon cardiomyopathy characterized by excessively prominent trabeculations and deep inter-trabecular recesses. The thickened wall of left ventricle (LV) consists of a thin compacted epicardial layer and a thick non-compacted endocardial layer. This disease is likely to result from an arrest of normal embryogenesis, mainly involving the endocardium and myocardium . It may Cardiac magnetic resonance (CMR) imaging is considered as the standard of reference to clinically assess volumes and global systolic function of left ventricle . LV systIn the present study, we aimed to 1) investigate the role of strain assessment in detection of early dysfunction of left ventricle in patients with iLVNC, 2) assess the accuracy of global strain to distinguish iLVNC from healthy people, and 3) compare the reproducibility of global and segmental strains derived from DRA and FT in healthy volunteers and iLVNC patients.The diagnosis of LVNC was based on the presence of established CMR and clinical criteria: 1) a thin, compacted (C) epicardial layer and a thick, non-compacted (NC) endocardial layer with prominent trabeculations and deep intertrabecular recesses; 2) NC/C ratio measured at end-diastole > 2.3 in at least one LV segment . ExclusiAll subjects underwent a standard CMR examination with a 1.5 T scanner . A stack of short-axis views and three long-axis  views were acquired. The whole LV was imaged from the base to the apex with the following parameters: repetition time (TR)/echo time (TE) of 2.9/1.2 ms, slice thickness of 6 mm, matrix of 186 × 256 pixels, and flip angle of 80°.A dedicated workstation employing commercial software  was used to analyze LV volume and function. Cardiac volumetric and functional parameters were quantified based on manual delineation of the endocardial and epicardial borders using a stack of continuous short-axis cine images. The trabeculae and papillary muscles were included in the left ventricular cavity. The end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) were measured and indexed to the patient’s body surface area (BSA).Cine bSSFP-based peak systolic strains were analyzed using a prototype DRA software  and FT software . For FT analysis, we delineated the endocardial and epicardial contours manually at end-systole and adjusted them at end-diastole. For DRA analysis, the contours were drawn manually at end-diastole; then the consecutive contours on the other phases were tracked automatically through the cardiac cycle Fig. . DetaileSPSS  and MedCalc  software was used to perform the statistical analyses. The Anderson–Darling test was used to check the normality. Continuous data were expressed as the mean ± standard deviation. Means of two continuous normally distributed variables were compared by independent samples Student’s t-test. Other comparisons were performed using the Mann–Whitney U test. Pairwise comparisons between groups were performed using one-way ANOVA  or Kruskal–Wallis test with Bonferroni correction .Receiver-operator-characteristic (ROC) analyses of global strains determined by DRA and FT were performed to assess the diagnostic capability of strain parameters in distinguishing iLVNC from healthy volunteers. The comparisons of areas under the curve (AUC) were performed using Delong test . CorrelaFor strain analysis, reproducibility was tested by using the intraclass correlation coefficient (ICC) on 15 healthy volunteers and 15 iLVNC patients. Inter-observer variability was analyzed on the same image set by two independent investigators . Intra-observer variability was analyzed on the same image set by one investigator (J.L.) with two readings 2 weeks apart. Based on the 95% confidence interval of the ICC estimate, values less than 0.50, between 0.50 and 0.75, between 0.75 and 0.90, and greater than 0.90 were indicative of poor, moderate, good, and excellent reliability, respectively [All demographic and cardiac MRI characteristics are shown in Table P < 0.001 for all).Correlations between left ventricular ejection fraction (LVEF) and global strain values derived from DRA and FT in iLVNC patients are shown in Fig. As shown in Table P > 0.05).The results of ROC analyses using global strains to distinguish iLVNC patients from normal controls are shown in Table Intra- and inter-observer agreements of global myocardial strain for DRA and FT are shown in Table As shown in Table Our study found that global radial strain derived from DRA and FT was reduced in iLVNC patients with normal EF. Global strain values had high diagnostic capability to distinguish iLVNC from healthy volunteers. Compared with FT, DRA showed better intra- and inter-observer agreement for global and segmental strains in both normal controls and iLVNC patients.In our study, global strains derived from both DRA and FT had good correlation with the LVEF. Compared to EF which acts as a global functional parameter, strain reveals the microscopic view of myocardial function. Murphy and colleagues have stated that there is a long preclinical phase of disease during which patients have no symptoms or are pauci-symptomatic . A previIn our study, all three global strains by the DRA and FT had high AUC values (0.743 and higher) in distinguishing iLVNC from healthy volunteers. However, there was no statistically significance difference of the AUC values between the two methods in any orientation. As mentioned, arrest of the compaction process is prone to occur in the apical endocardium of the ventricle . HoweverR2 = 0.75; P < 0.0001) and GCS , and DRA demonstrated consistently lower coefficient of variation (CV) than tagged CMR [When evaluating the robustness of a strain-analysis method, reproducibility is an important factor. In our study, the reproducibility analysis was performed in both iLVNC patients and volunteers. We found that the intra- and inter-observer agreements of global and segmental strains were better for DRA than FT in both normal controls and iLVNC patients, especially for radial strain analysis. This is probably because that DRA is a novel method to analyze cardiac strain on a pixel-by-pixel basis. Furthermore, DRA can automatically segment the left ventricle on CMR cine images. It helps obtain the deformation from any frame to any other frame in the cardiac cycle by recovering a set of both forward and backward deformation fields. Different segmentation contours can be formed on each phase in the cardiac cycle, and then propagated to other phases , 22. Thegged CMR .P < 0.001) [A study using speckle tracking echocardiography indicated that apical circumferential strain may be a potential diagnostic tool for children with noncompaction cardiomyopathy  . Since DMeanwhile, we found that reproducibility of FT-based GRS performed in iLVNC patients was better than that in normal controls, while FT-based GCS and GLS both showed a good reproducibility in controls and iLVNC patients. The radial strain estimate heavily depends on how well the myocardial border is detected, and large variations were observed in radial strain . As for This study has some limitations that should be acknowledged. Patients with iLVNC were retrospectively enrolled, the limitations of which are well known. Additionally, our study was a single-center study and the sample size was relatively small. We also didn’t consider the possible combination of iLVNC with myocardial fibrosis.In conclusion, DRA can be used to quantitatively analyze the strain of left ventricle in patients with iLVNC, and GRS is an earlier marker than LVEF of LV systolic dysfunction. Global strains can distinguish patients with iLVNC from healthy subjects with high diagnostic accuracy. Compared with FT, DRA has an excellent reproducibility in evaluating both global and segmental strain values in iLVNC patients and healthy population. Therefore, DRA can be a reliable tool to clinically assess global and segmental myocardial function of iLVNC patients.


Identifying coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) is challenging. Adenosine stress native T1 mapping with cardiovascular magnetic resonance (CMR) may accurately detect obstructive CAD and microvascular dysfunction in the general population. This study assessed the feasibility and reliability of adenosine stress native T1 mapping in patients on haemodialysis.The feasibility of undertaking rest and adenosine stress native T1 mapping using the single-shot Modified Look-Locker inversion recovery (MOLLI) sequence was assessed in 58 patients on maintenance haemodialysis using 3 T CMR. Ten patients underwent repeat stress CMR within 2 weeks for assessment of test-retest reliability of native T1, stress T1 and delta T1 (ΔT1). Interrater and intrarater agreement were assessed in 10 patients. Exploratory analyses were undertaken to assess associations between clinical variables and native T1 values in 51 patients on haemodialysis.p = 0.019; β = − 0.297, p = 0.013; β = − 0.455; p < 0.001, respectively).Mean age of participants was 55 ± 15 years, 46 (79%) were male, and median dialysis vintage was 21  months. All patients completed the scan without complications. Mean native T1 rest, stress and ΔT1 were 1261 ± 57 ms, 1297 ± 50 ms and 2.9 ± 2.5%, respectively. Interrater and intrarater agreement of rest T1, stress T1 and ΔT1 were excellent, with intraclass correlation coefficients (ICC) > 0.9 for all. Test-retest reliability of rest and stress native T1 were excellent or good . Test-retest reliability of ΔT1 was moderate to poor . On multivariate analysis, CAD, diabetes mellitus and resting native T1 time were independent determinants of ΔT1 (β = − 0.275, Rest and adenosine stress native T1 mapping is feasible and well-tolerated amongst patients with ESRD on haemodialysis. Although rater agreement of the technique is excellent, test-retest reliability of ΔT1 is moderate to poor. Prospective studies should evaluate the relationship between this technique and established methods of CAD assessment and association with outcomes. Patients with chronic kidney disease and end stage renal disease (ESRD) experience excess mortality from cardiovascular disease .. DeveloNative T1 mapping is a non-contrast parametric mapping technique on CMR that allows quantitative tissue characterisation on a pixel-by-pixel basis . T1 relaIn this study we assessed the feasibility of non-contrast rest and stress T1 mapping in patients with ESRD on haemodialysis. We aimed to assess the ΔT1, its reliability with test-retest measurements, interrater and intrarater agreement in patients on haemodialysis and we conducted an exploratory analysis to investigate associations between clinical variables and ΔT1.Patients with ESRD on haemodialysis were recruited as part of the CYCLE-HD study (ISRCTN11299707). The study was approved by the NHS Research Ethics Committee East Midlands . All patients provided written informed consent to participate in the study. Adult patients undergoing in-centre maintenance haemodialysis for at least 3 months were eligible for inclusion in the study, provided they were able to undertake exercise and undergo CMR scanning. Inclusion and exclusion criteria are as previously described .0, minimum T1 120ms, inversion-time increment 80 ms. The MOLLI sequence was chosen due to local expertise [CMR imaging was performed on a 3 T CMR platform  with an 18-channel phased-array anterior coil. To ensure consistency of fluid status, all patients underwent CMR assessment on a non-dialysis day, not after the two-day break, between 18 and 24 h of the last haemodialysis session. The same standardised CMR protocol was used for all study participants as previously described , in linexpertise . All parxpertise . Stress 42  was used for both left ventricular (LV) and native T1 analyses. LV quantification was performed by a single reader (MGB) as previously described [All scans were anonymised and analysed offline by blinded observers. The software package CMRescribed . A separescribed . Brieflyescribed , 23–25:Image quality was graded as excellent, moderate or non-analysable.An additional, descriptive analysis comparing regional wall motion (RWM) scores to ΔT1 scores was completed. The mid-ventricular, short-axis LV cine image corresponding to the mid-ventricular native T1 maps for each subject were scored for RWM abnormalities. Each segment was scored 1 , 2 (hypokinetic), 3 (akinetic) or 4 (dyskinetic) (AA). Segments were then compared to corresponding ΔT1 segment for analysis.Ten patients underwent an identical CMR scan within 2 weeks of the baseline scan as part of a reliability sub-study. Test-retest reliability was assessed by a single, blinded observer (FP). Interrater agreement was assessed by analysis of the same 10 scans by two independent, blinded readers . Intrarater agreement was assessed by re-analysis of 10 scans by a single blinded reader (FP), 1 month apart.This sample size of 10 was supported by a power calculation previously done to detect a 2.5% difference in native T1 between test-retest scans with 90% power .Exploratory analyses were undertaken to establish potential associations between ΔT1 and clinical indicators of CAD, including age, sex, heart rate (HR), blood pressure (BP), smoking status, previous history of CAD, diabetes mellitus, previous renal transplant, hypertension and dyslipidaemia. All CMR images used for the exploratory analysis were acquired as part of the baseline assessment, with patient demographic details, comorbidities, medications, haematological and biochemical data were recorded prospectively. Total time on renal replacement therapy (RRT), time with a functioning kidney transplant and haemodialysis vintage were prospectively collected and calculated from electronic hospital records. The presence of CAD was defined as any of: reported diagnosis of CAD on baseline assessment; fixed or reversible ischaemia on myocardial perfusion scan; significant stenosis on invasive coronary angiography; infarcted myocardium on CMR; previous coronary revascularisation (coronary artery bypass graft or percutaneous coronary intervention). Individuals who had a non-analysable stress scan were excluded from this analysis.t-tests data and Mann-Whitney U tests for normally and non-normally distributed data, respectively. Differences between nominal variables were assessed using Chi-squared and Fisher’s exact tests. Correlations between variables were assessed with Pearson’s and Spearman’s rank analysis for normally and non-normally distributed data, respectively. Multivariable linear regression analyses were conducted to assess independent determinants of ΔT1. Variables inputted into regression models were limited to avoid overfitting. Statistical significance level was defined as a two-tailed p-value < 0.05. The exploratory analysis comparing RWM to regional ΔT1 are presented as descriptive statistics due to the imbalance in numbers between groups.Statistical analyses were performed using SPSS  and GraphPad Prism . Categorical data are reported as frequency (%) of observation. Normality was assessed using histograms and Shapiro-Wilk tests for continuous data. Normally distributed data are expressed as mean ± standard deviation (SD). Non-normally distributed data are expressed as median . Test-retest reliability, interrater and intrarater agreement were assessed using coefficients of variability (CoV), intraclass correlation coefficients (ICC) and Bland-Altman analyses . Reliabin = 93) or moderate (n = 29) for the remaining 122 resting T1 maps. Seven of 58 (12%) stress T1 maps were not analysable. Image quality for the remaining 51 stress T1 maps was either excellent (n = 32) or moderate (n = 18). All patients with analysable stress T1 maps also had analysable matched resting T1 maps. Of the 58 participants who underwent stress testing, six required an increase in adenosine dose. Only one participant had an inadequate haemodynamic response despite maximal dose of adenosine. All patients tolerated and successfully completed the scan with no complications necessitating termination of the scan. After the administration of adenosine, there was a significant increase in HR  and a significant drop in systolic BP . 86% of the patients experienced mild symptoms  or during stress .The baseline scans of 58 of the 130 participants of the CYCLE-HD study agreed to have both rest and adenosine stress native T1 mapping. Baseline characteristics are shown in Table rate n = 9 for then = 18; stress, n = 11) or moderate . The interrater and intrarater agreement of all parameters were excellent (ICC > 0.9). Test-retest reliability was good-excellent for rest and stress native T1, while it was moderate-poor for ΔT1 . For test-retest scans, all T1 images were analysable. Image quality was either excellent . ΔT1 decreased with increasing age and increasing haemoglobin A1c (HbA1c)  or diabetes   . ΔT1 was not significantly different in patients with or without hypertension or dyslipidaemia. ΔT1 was not significantly associated with HR and BP. ΔT1 was inversely related to resting native T1  but it was not significantly correlated with stress native T1.For the 51 participants with analysable stress T1 maps, an exploratory analysis was conducted to establish associations between ΔT1 and clinical characteristics. ΔT1 was not significantly different between males and females (1c) Fig. . ΔT1 wasOn multivariate analysis, CAD, diabetes and resting native T1 remained independent determinants of ΔT1, after adjustment for age and proportion of total RRT time with a functioning graft Table .Table 5For the 51 participants with analysable stress T1 maps 306 segments were analysed on corresponding mid-ventricular LV cine images. 279 segments were scored ‘1’, 19 segments were scored ‘2’ and 8 segments were scored ‘3’. All but one of the segments scored ‘3’ corresponded to an area on T1 maps identified as infarct which was too thin to contour. Mean ΔT1 in segments scored ‘1’ was 3.01% (3.5), mean ΔT1 in segments scored ‘2’ was 1.6% (3.4) and the only segment scored ‘3’ with an analysable T1 maps had a ΔT1 of 1.5%.This is the first study to assess the feasibility of stress T1 mapping in patients on haemodialysis. We have shown that adenosine stress T1 mapping is a safe, feasible and well-tolerated technique for the potential assessment of myocardial ischaemia in a cohort of 58 patients with ESRD on haemodialysis and that there were no adverse events associated with its use. We have shown native T1 mapping at rest and during stress to be a highly reproducible technique and have described the reliability and agreement of ΔT1 for the first time in this population, which was moderate. ΔT1 was independently associated with CAD, diabetes and resting native T1.Our group has previously demonstrated the excellent reliability of rest native T1 mapping in patients with ESRD, independent of fluid status . In our We have shown the mean ΔT1 for this population is 2.9 ± 2.5%, substantially below the ΔT1 previously reported in healthy population (6.3 ± 1.1%)  and equiWe acknowledge that we have analysed ΔT1 of the whole mid-ventricular short axis slice, as opposed to individual coronary territories meaning that the ΔT1 might average across normal and non-normal segments, possibly leading to a higher degree of variation. We also found that increased resting myocardial native T1 was an independent determinant of a blunted ΔT1 amongst patients with ESRD. Two possible explanations may account for this finding. Firstly, a higher resting native T1 might signify increased levels of myocardial fibrosis or other pathological processes related to excess water, such as oedema or inflammation . PerivasWith regards to concerns of the influence of body water content on native T1 measurement, our group have previously demonstrated that myocardial native T1 was unaffected by changes in fluid status . FurtherThe cross-sectional design of this feasibility study precludes from any causal relationship to be inferred from the findings we present and does not allow the assessment of clinical endpoints including cardiac events and mortality. Our study was conducted at 3 T using the classic MOLLI sequence, therefore our findings in terms of reliability are not necessarily generalisable to a 1.5 T platform, other MOLLI variants or saturation-recovery single-shot acquisition sequences. Despite not finding a significant correlation between HR and T1 values, we recognise that the HR dependency of the MOLLI sequence may have led to underestimation of stress T1 values and, consequently ΔT1, although maximum HR was rarely elevated above 100 bpm. While this study offers important information with regards to the feasibility, reliability and clinical determinants of ΔT1 in patients with ESRD, the lack of basal and apical slices meant that we could not build the complete American Heart Association 16-segment model for analysis of individual coronary territories and global myocardium. We were unable to provide a direct comparison of stress T1 mapping findings against invasive coronary angiography or non-invasive investigations for CAD, as there was no simultaneous screening for CAD, meaning that we cannot be sure we captured all patients with CAD. This also meant that CAD was assessed as a binary variable, without taking into account extent or severity of disease. Additionally, although obviously infarcted segments of myocardium were excluded from analysis, we acknowledge small areas of replacement fibrosis might not have been detected and, therefore, excluded. As high levels of replacement fibrosis would account for a blunted ΔT1, this is another reason why direct comparison with established investigations for CAD is required.Rest-vasodilator stress native T1 mapping is feasible in ESRD although test-retest reliability is moderate. These data support the development of an adequately powered prospective study to evaluate the diagnostic accuracy of stress T1 mapping in an ESRD population through direct comparison to invasive coronary angiography and non-invasive measures of CAD.


Coronary atherosclerosis and periodontal disease, due to their prevalence, are a serious epidemiological problem. Pathophysiological evidence points to their possible common inflammatory etiopathological background. The aim of the study was to analyze the relationship between the presence and severity of periodontitis, systemic inflammation and selected parameters of myocardial injury and heart function in patients with acute myocardial infarction.The study group consisted of 71 patients 54.22 (7.05)-year-old hospitalized due to acute myocardial infarction. The patients underwent a coronary angiographic examination and echocardiography. The following laboratory parameters were determined: blood morphology, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen, troponin I, creatine kinase myocardial band (CK-MB), brain natriuretic peptide (BNP), lipidogram, glucose, creatinine, glomerular filtration rate (GFR), thyroid stymulating hormone (TSH), glycated hemoglobin (HbA1c). Dental assessment of the patients was performed and the following indicators were included: the number of teeth preserved, approximal plaque index (API), bleeding on probing (BoP), pocket depth (PD), the number of bleeding periodontal pockets ≥ 4 mm in depth (NoPD ≥ 4 mm), the percentage of bleeding periodontal pockets ≥ 4 mm in depth (%PD ≥ 4 mm), clinical attachment loss (CAL). The control consisted of 40 patients 52 (± 8.43)-year-old without a history of coronary heart disease. These patients were subjected to a periodontal examination using the above parameters and classification methods. The following statistical tests were implemented: Shapiro–Wilk test, Levene's test, Mann Whitney's U analysis, Univariate Analysis of Variance (ANOVA); the post-hoc analysis was performed with the use of Tukey's honest significant difference test (HSD), Kruskal–Wallis's non-parametric test, Spearman's rank correlation, logistic regression analysis, linear regression analysis and ROC analysis.p-0.006). All indices regarding the pocket depth correlated significantly with the number of leukocytes: PD , NoPD ≥ 4 mm , %PD ≥ 4 mm . PD  and NoPD ≥ 4 mm  were also associated significantly with the level of hsCRP. The BoP is correlated closely with the levels of BNP . The multifactorial analysis showed that significant predictors of myocardial infarction are API and BoP. The analysis showed that API and BoP are important predictors of troponin levels. Linear regression analysis showed that only CAL is a significant predictor of BNP.The BoP (bleeding on probing) significantly correlated with fibrynogen (R-0.36; Patients with acute myocardial infarction have worse periodontal status compared to people without coronary heart disease. Greater severity of periodontitis, plaque accumulation and bleeding on probing are associated with acute myocardial infarction. Periodontitis is a risk factor for myocardial infarction and also affects the degree of post-infarction left ventricular damage, which means that there is an inflammatory link between these two diseases. Due to their prevalence, cardiovascular diseases are considered as social diseases; they are also among the most common causes of death worldwide . Periodo2, and tumour necrosis factor-α  men and 15 [21%] women) hospitalized due to myocardial infarction. The average age in the study group was 54 (from 36 to 65 years of age). The clinical characteristics of the study group are shown in Table Annotation: American Academy of Periodontology (AAP): Stage I—incipient periodontitis, Stage II—moderate periodontitis, Stage III—periodontitis with potential for additional tooth loss, Stage IV—advanced periodontitis with extensive tooth loss and potential loss of dentition.p < 0.05), while advanced periodontits were more prevalent in study group   Fig. .Fig. 3CoAn analysis of the relationship between periodontological indices and inflammatory biomarkers showed that most of the evaluated indices were significantly associated with hsCRP and leukocytes levels. The BoP was statistically significantly associated with the level of fibrinogen in the study group. All indices regarding the pocket depth  correlated significantly with the number of leukocytes. PD and NoPD ≥ 4 mm were also associated significantly with the level of hsCRP. There was also a statistically significant relationship between CAL and hsCRP levels in the study group. However, the number of teeth preserved was associated with ESR Table .Table 2Analysis of the relationship of periodontological indices with biochemical markers of heart injury and function showed few significant correlations. It has been shown that the BoP is correlated closely with the levels of BNP in both the study group. The other analyzed periodontological parameters did not correlate with parameters of myocardial injury and function Table .Table 3SA multifactorial analysis was performed in order to determine whether the analyzed periodontological indices are independently related to the myocardial infarction occurrence and markers of heart injury and function.In order to determine the model explaining the probability of occurrence of myocardial infarction, logistic regression analysis was performed using the backward elimination method, taking into account the likelihood ratio, where the explained variable was the occurrence of myocardial infarction, and predictors: number of teeth, API, BoP, PD, CAL. The Hosmer Lemeshow test turned out to be irrelevant, which indicates a good fit of the model to the data. Important predictors of myocardial infarction are API and BoP Table . With anThe ROC analysis was used to show the performance of the proposed model of prediction of myocardial infarction. The ROC analysis was applied to assess the quality of the classification of the occurrence or the lack of occurrence of a myocardial infarction based on the following three variables: API, BoP and PD. Figure Based on ROC curves for the group with and without myocardial infarction we concluded that API and BoP have the diagnostic value, while PD proved to be insufficient to present satisfactory prognostic value. In the case of both variables, that is API and BoP, the AUC value indicated very good classification, while for the PD, the classification didn’t differ from random.The evaluation of the classifier was performed in reference to the Gini coefficient and the Kolmogorov–Smirnov test. The curve was generated on the basis of the variables. For the API the sensibility was 67.2% and the correct prediction of 86.6% cases that is the indication of myocardial infarction patients was possible due to the BoP value.p = 0.001 for API and p = 0.006 for BoP) indicated a slightly lower statistical significance both the API and BoP, the predictors were important from the perspective of myocardial infarction. With an increase in API by 1%, the probability of the occurrence of a heart attack increases by 7% (OR = 1.07), while with a 1% increase in BoP, the probability of the occurrence of a heart attack decreases by 5% (OR = 0.95).All metabolic syndrome related markers are of an increased level in the study group. Considering that, the association of periodontal parameters and the acute myocardial infarction may be linked with the metabolic syndrome, therefore an additional analysis adjusted for the metabolic syndrome related markers was performed Table . This anTo check which of the parameters of periodontitis affect TnI levels, a linear regression analysis was carried out by means of backward elimination. In the model, predictors were introduced: number of teeth, API, BoP, PD, NoPD ≥ 4 mm, CAL. The analysis showed that API and BoP are important predictors of TnI levels. With 1% increase in API, TnI levels decrease by 0.3 units, while with 1% increase in BoP, TnI levels increase by 0.26 units Table .Table 7LThe next step focused on establishing a model explaining the BNP level. For this purpose, linear regression analysis using backward elimination was used. Model includes the number of teeth, API, BoP, PD, NoPD ≥ 4 mm, CAL as predictors. Linear regression analysis by backward elimination showed that only CAL is a significant predictor Table . As the p > 0.210) and none of the analyzed coefficients were significant left ventricle ejection fraction predictors (p > 0.05).For the left ventricle ejection fraction prediction, none of the analyzed models were statistically significant  mm/h, the levels of hsCRP 8.34 (± 18.72) mg/L, and fibrinogen 4.62 (± 1.09) g/L. In the conducted analysis, a correlation was revealed between the values of periodontal parameters attesting to the presence and the severity of a periodontal disease and the blood level of inflammation parameters. Moreover, there was an inverse correlation between the number of teeth and ESR . This may be due to the fact that periodontal inflammation is the main reason for teeth loss.The main assumption of the thesis that periodontitis affects the initiation and progression of atherosclerosis is the fact that the periodontal disease cause subtle systemic inflammation. The present study has revealed elevated levels of inflammation markers in the study group. Leukocytes count was 10.82 (± 3.87) 10p = 0.01), NoPD ≥ 4 mm ; moreover, there was a positive correlation with the clinical attachment loss CAL . Different results were obtained by Górski et al., who did not demonstrate any correlation between CRP levels and periodontal markers [p < 0.001); what is more, they proved positive correlations between hsCRP levels and fibrinogen and the measured periodontal parameters .An increased level of systemic inflammatory response markers, such as leukocytes count, and the levels of hsCRP and fibrinogen, is significant in the pathogenesis of cardiovascular diseases. Determining the levels of these markers may be important in assessing the risk of an acute coronary syndrome. In the experimental models, the influence of CRP on the onset of endothelial dysfunction, increasing expression of adhesion molecules, and on the recruitment of monocytes into the vessel wall was demonstrated. Moreover, CRP contributes to the production of foam cells, formation of reactive oxygen species and to the proliferation and migration of smooth muscle cells . The sys markers . However markers , demonstp = 0.006). Fibrinogen is a protein synthesized by hepatocytes and fibroblasts in response to inflammation. The level of fibrinogen in the blood correlates with the severity of atherosclerotic lesions, the risk of an acute coronary syndrome, and mortality among patients with myocardial infarction. Fibrinogen participates in the thrombotic process; it is also pro-inflammatory, as it increases the expression of adhesion molecules and stimulates production of inflammatory mediators by endothelial cells [p = 0.0587), as well as between the number of lost teeth and the level of fibrinogen (p = 0.0003). Seringec et al. [Another extremely important result of the present study is the relationship between periodontal disease and fibrinogen. Namely, a positive correlation between the values of the BoP marker, indicating active inflammation of periodontium, with the level of fibrinogen , NoPD ≥ 4 mm , as well as %PD ≥ 4 mm . Numerous epidemiological studies showed positive correlation between leukocytes count and the risk of coronary artery disease. In a prospective NHAHES I epidemiological study, a group of people with the leukocytes count < 6600 cells/mm3 was compared with a group with the leukocytes count > 8100 cells/mm3; it was found that increased leukocytes count is linked to an increased risk of coronary artery disease among white males  and white females  aged 45–74, taking into account other cardiovascular risk factors [3 was connected to the total RR of 1.4 [The present study has demonstrated correlation between the leukocytes count and the parameters indicating the severity of the periodontal disease, such as PD . Linear regression analysis using backward elimination showed that a significant predictor of BNP is only CAL. As the CAL increases by one unit, the BNP value increases by 31.33 units. For the left ventricle ejection fraction prediction, none of the analyzed models were statistically significant  and none of the analyzed variables were a significant predictor of left ventricle ejection fraction (p > 0.05). BNP is recognized as a prognostic marker in patients with acute coronary syndromes. It is believed that BNP inhibits the growth of cardiomyocytes and fibroblasts, impairs collagen synthesis in relation not only to the myocardium but also to periodontal tissues [Bearing in mind the main purpose of the research, the correlation between periodontical markers and myocardial injury and heart failure indicators was also important observation. Univariate analysis has demonstrated a significant relationship between BoP and the level of BNP in the study group  [An interesting observation is the relationship between the severity of periodontitis and TnI levels. Linear regression analysis showed that significant predictors of the level of TnI are API and BoP. With 1% increase in API, TnI levels decrease by 0.3 units, while with 1% BoP increase, TnI levels increase by 0.26 units. The present research is consistent with the results obtained by Marfil-Alvarez et al., who found a significant correlation between BoP and TnI level  . Moreove< 0.025) . Indeed,< 0.025) .p = 0.001 and p > 0.001; for BoP respectively: p = 0.006 and p = 0.001). With an increase in API by 1%, the probability of having a heart attack increases by 7% (OR = 1.07), while with a 1% increase in BoP, the probability of having a heart attack decreases by 5% (OR = 0.95).An equally important and original result of the study is the significant association of periodontitis with risk of myocardial infarction. The logistic regression analysis showed that API and BoP are significant predictors of myocardial infarction. With the increase in API by 1%, the probability of myocardial infarction increases by 8% (OR = 1.08), while with a 1% increase in BoP, the probability of myocardial infarction decrease by 7% (OR = 0.93). The current findings are consistent with the results of the PAROKRANK study of 805 people . A relatTo sum up, it should be noted that although the metabolic syndrome related disorders undoubtedly affect the relationship between periodontitis and the risk of myocardial infarction, periodontitis still has an independent influence on the occurrence of a heart attack.On the basis of the conducted analyses, it may be concluded that periodontitis is a condition which may affect the risk of the development of ischaemic heart disease as well as its complications in the form course of myocardial infarction, as it causes a mild systemic inflammatory response. Undoubtedly, social awareness of the possible clinical implication of periodontitis is insufficient. Considering the prevalence of the ischaemic heart disease, high mortality resulting from cardiovascular diseases, and the ubiquity of periodontitis in the Polish society, the periodontal health of the patients with ischemic heart disease should be taken into account and appropriate preventive and curative measures ought to be introduced. Moreover, patients with periodontitis should have their cardiovascular risk assessed. Focusing on any possible correlation between periodontal inflammation and the occurrence of ischaemic heart disease is of utmost importance due to the fact that this may be a modifiable risk factor. The importance of chronic periodontitis should be taken into account in both primary and secondary prevention of cardiovascular disease , 47. WhaThe obvious and permanent limitation of studies with extensive research methodology is a relatively small number of patients. For two reasons, the undoubted indubitable limitation is also used pharmacotherapy for two reasons. Firstly, the use of statins, which is a known anti-inflammatory agent, may modify the severity of the systemic inflammation. However, patients with acute myocardial infarction have not yet used statins in most cases, and blood samples were taken before the drug was started. In turn, antiplatelet drugs may by their nature increase bleeding, including those associated with stomalotological assessment. The more that periodontal examination was performed 24 h after the onset of myocardial infarction and thus anti-platelet activity was fully developed. For ethical reasons, however, this restriction cannot be eliminated because it is not possible to delay the treatment of myocardial infarction for periodontal assessment. It should be emphasized, however, that both in the case of statins and antiplatelet drugs the limitation resulting from their use loses some strength due to the fact that almost all patients had the same treatment. It proves the pharmacological uniformity of the examined group, which increases the reliability of the results. Another limitation is also possible coexistence of other inflammatory processes in patients from the study group. To this end, special care was taken to exclude from the study patients who, at the time of inclusion in the physical examination or in additional examinations, had additional, beyond the periodontium, detectable foci of inflammation.One of the most important factors allowing the collection of accurate results is probing reproducibility. The factors affecting the repeatability of the assessment may be as follows: measurements taken by different dentists, variable pressure during the examination, the use of different types of periodontal probes. Study looked at intra-examiner and inter-examiner reproducibility for threshold probing depths of greater than 1 mm and found an accuracy rate of 91.3% . ProbingThe cardiovascular risk factors considered in the study were the commonly recognized risk factors for periodontal diseases. The common risk factors for both diseases include: smoking, diabetes, male gender, age, obesity, dyslipidemia and increased CRP and fibrinogen levels. The multitude of common risk factors makes it difficult to adjust into the multifactorial analysis, which should be considered a study limitation.In order to avoid possible bias on the part of people conducting individual examinations , the examinations were performed independently of each other, and the investigators did not have access to the test results obtained by others. Moreover, in order to standardize the dental examination, it was performed by one person. It may also be considered a limitation of the examination since the dental assessed by another independent investigator.An undoubted advantage of the study is the extensive dental methodology using many periodontological indices. Both the detailed assessment of the periodontal status and the multitude of periodontal indices applied in the study can guarantee an increased reliability of statistical analysis of the obtained results. These studies can increase the interest in the prevention and treatment of periodontal disease in order to improve both the periodontal status and the prevention of cardiovascular diseases in the population.Patients with acute myocardial infarction have worse periodontal status compared to people without coronary heart disease.Higher severity of periodontal disease, poorer oral hygiene and increased activity of the periodontitis lead to greater manifestation of systemic inflammation in patients with acute myocardial infarction.Periodontitis is a risk factor for myocardial infarction and also affects the degree of post- infarction left ventricular damage, which means that there is an inflammatory link between these two pathogenetically inflammatory diseases.


Noninvasive cardiac imaging is crucial for the characterization of patients who are candidates for cardiac ablations, for both procedure planning and long-term management. Multimodality cardiac imaging can provide not only anatomical parameters but even more importantly functional information that may allow a better risk stratification of cardiac patients. Moreover, fusion of anatomical and functional data derived from noninvasive cardiac imaging with the results of endocavitary mapping may possibly allow a better identification of the ablation substrate and also avoid peri-procedural complications. As a result, imaging-guided electrophysiological procedures are associated with an improved outcome than traditional ablation procedures, with a consistently lower recurrence rate. In the last decades, the role of noninvasive cardiac imaging has been greatly expanding, with all the available imaging modalities having now a relevant role in the characterization and risk stratification of patients with a wide range of cardiac pathologies. In this general context, the use of information obtained through noninvasive cardiac imaging has been steadily increasing also in the field of interventional cardiology, where an imaging-guided in-depth characterization of patients has become a mandatory step before any invasive procedure. Specifically, in the field of electrophysiology (EP), noninvasive cardiac imaging may be used to individuate the substrates of cardiac arrhythmias, selecting patients who will likely benefit from an ablation procedure –5. On thConsidering the limited efficacy of pharmacologic therapies for the treatment of ventricular arrhythmias (VAs), cardiac ablation strategies have improved rapidly, becoming the reference techniques for the treatment of malignant VAs .Similarly, noninvasive cardiac imaging has been also evolving, playing now a relevant role in the characterization of patients with VAs. For example, in patients with nonischemic cardiomyopathy (NICM), multimodality imaging can help in identifying the arrhythmogenic substrate and in characterizing the specific anatomical–functional components of the ventricular tachycardia (VT) circuits , 3, 6–9.However, given the consistent etiological heterogeneity of the underlying myocardial disease , the long-term success rate of cardiac ablation tends to be quite variable –12.Patients with NICM are usually classified using their specific functional and structural phenotypic or genotypic findings .Recently, Vaseghi et al. published a multicenter study on a population with all types of NICM submitted to VT ablation procedures. In the appraisal, a 69% 1-year success rate of catheter ablation was revealed, with better outcomes of patients with dilated cardiomyopathy, myocarditis, and arrhythmogenic right ventricular cardiomyopathy (ARVC) and a rather dismal prognosis of patients with hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and valvular heart disease . The resThe different NICM etiologies exhibit different substrates of arrhythmogenicity, an aspect that is closely related to the efficacy of the ablation procedure. In particular, cardiac magnetic resonance (CMR) can be able to classify patients with ischemic cardiomyopathy (ICM) or NICM according to the presence of specific patterns of scar –19.The pathophysiology of cardiac arrhythmogenicity in patients with ICM and a previous myocardial infarction (MI) is classically represented by an unexcitable necrotic area surrounded by a border zone of jeopardized myocardium with heterogeneous conduction that can predispose to the development of VAs .Accordingly, considering the presence of a macroscopic arrhythmic substrate, it is not difficult to understand how ventricular ablation can be considered the treatment of choice in patients with VA in the setting of ICM, in addition or not to implantable cardioverter defibrillators (ICDs) .Traditionally, VA ablation strategies were related to the identification of the re-entrant circuit, targeting its critical isthmus through activation map, using electro-anatomic mapping (EAM). In this case, despite a still sub-optimal success rate, catheter ablation significantly reduces disease-related hospitalizations and arrhythmic events when compared with conventional treatment . HoweverThe advent of contact mapping technologies involving multielectrode acquisition has represented a turning point for VA mapping, allowing a rapid delineation of the mechanisms of the arrhythmic circuit with higher resolution . Recentl2 in the late gadolinium enhancement (LGE) CMR images and a mean myocardial wall thickness on CCT ≤ 3.59 mm predicted the presence of the arrhythmogenic substrate as identified by EAM, showing the importance multimodality cardiac imaging for the characterization of scar-related VAs  . Accordiated VAs .An alternative strategy is based on the technique of the ablation of the substrate that used the abnormal substrate evaluated during sinus or paced rhythm for targeting the areas with slow conduction , 27. In One of the most promising substrate-based ablations is the ablation of local abnormal ventricular activities (LAVAs) , whose eNoninvasive imaging can be used routinely to identify different types of substrates, and it could be particularly helpful to define the location and extent of the VT substrate, in order to guide the pre-procedural planning.Even if the ECG is not considered by many as an “imaging” technique, it is always mandatory for the characterization of VAs and before every ablation procedure. A 12-lead ECG obtained during sinus rhythm is needed for the initial evaluation of the presence of underlying heart disease and is frequently able to identify the location of a myocardial scar  as well as the possible origin of related VAs. In the presence of focal VAs that occur in the absence of structural heart disease (SHD), the ECG may indicate with a reasonable accuracy the site of origin of the arrhythmia. On the other hand, in the presence of VAs occurring in the setting of myocardial scarring , the ECG abnormalities indicate the exit site from the reentrant circuit, which may not represent the best ablation target , a mixture of fibrotic and viable tissue, called gray zone . The graClassical studies have demonstrated the presence of pathologic myocardial fibrosis also in non-infarcted regions of patients with ICM, playing a possible role in arrhythmogenicity .Interstitial fibrosis may be quantified with T1 mapping technique, associating with adverse prognosis . HoweverIn the presence of right VAs, the use of LGE for assessment of arrhythmogenic site is limited by several factors. First of all, the right ventricle has a thinner wall than the LV, allowing the case for partial volume effect to occur , 52. MorIn NICM patients waiting for VT ablation procedures, SI maps derived from LGE-CMR may be helpful to guide the procedure –53, becaFinally, LGE imaging may be crucial for the risk stratification of patients with NICM, allowing to identify those who would likely benefit from ICD implantation. In this respect, despite the results of the “Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure” (DANISH) study, showing a neutral impact on all-cause mortality of prophylactic ICD implantation in patients with symptomatic systolic heart failure (HF) not caused by coronary artery disease (CAD) , conclusThe presence of cardiac implantable electronic devices (CIEDs) has been generally considered a contraindication for CMR. However, several studies demonstrated that CMR could be performed safely in patients with CIEDs, if all the appropriate precautions are taken –64. It hBesides its known abilities in delineating coronary anatomy, CCT imaging may also allow an accurate identification of myocardial scar burden by delayed enhancement technique, which may individuate accurately the regions of low bipolar voltages on EAM . The intThe main advantage of CCT over CMR is the higher spatial resolution, which could reach the submillimeter range. Among the tissue characteristics that may indicate the presence of myocardial scar at CCT, a reduced wall thickness (<5 mm) , presencFinally, CCT allows the detection and quantitation of the epicardial fat thickness that is important in the pre-procedural ablation planning, because it can cover epicardial VT target sites , 73.Moreover, the CT evaluation of epicardial fat can facilitate the correct interpretation of epicardial voltage maps, distinguishing epicardial fat from necrotic/scar area and increasing the efficacy of the epicardial energy applications. Finally, epicardial voltage readings may be used to identify the regions surrounded by fat, separating sites with and without overlying epicardial fat .Nuclear cardiac imaging has always represented the gold standard for the evaluation of myocardial perfusion, offering for a combined evaluation of myocardial blood flow regulation and tissue viability. However, the output of traditional perfusion nuclear imaging analysis is not sufficient to allow the precise identification of a VA focus, and, hence, perfusion imaging alone has a limited practical application in this setting , 75.123I-metaiodobenzylguanidine (123I-MIBG) is generally used to this purpose  transporter (NET), and is similarly stored into vesicles as NE   and conv purpose . 123I-MIes as NE –79. Iodiough NET , 78. Whiervation .Moreover, SPECT imaging may allow the combined evaluation of perfusion and innervation, in a regional as well as global way, enabling the localization and quantitative estimation of those jeopardized viable myocardial regions showing an impaired sympathetic innervation despite a still preserved perfusion  –83.In this respect, it has been repeatedly demonstrated that the location of areas showing an “innervation/perfusion mismatch” may co-localize with the sites of origin of the VA, representing possible ablation targets , 85 Fig. In partAccordingly, particularly in the setting of patients with ICM and VA, it is reasonable to foresee a wider application of combined innervation/perfusion nuclear imaging for the planning of complex ablation procedures and for the follow-up of patients.18F-fluorodeoxyglucose (FDG) has been proposed as an innovative noninvasive test for the noninvasive depiction of focal myocardial inflammation, which may represent a possible trigger of ventricular arrhythmogenicity. In this respect, PET imaging with FDG has been traditionally considered the reference standard for the noninvasive diagnosis of cardiac involvement of sarcoidosis , a preprocedural transesophageal echocardiogram should be performed to rule out the presence of left atrial (LA) thrombus and to minimize the risk of thromboembolic events, particularly when a transthoracic cardioversion is foreseeable .AF is characterized by ineffective and uncoordinated atrial electrical activation and contraction. Despite being generally considered as a rather benign pathology, AF is associated with an increased risk of cardiovascular events such as stroke, heart failure, and death .The physiopathology of AF is multifactorial and differs according to the type of disease . As a general rule, the presence of a triggering mechanism as well as a substrate is believed to be necessary for the arrhythmia to become persistent . It has Once the arrhythmia has developed, AF results in electric and structural atrial remodeling leading to progressive fibrosis, ultimately leading to the development of multiple reentry circuits that sustain the arrhythmia . InteresConsidering the complexity of the pathology, pre-procedural imaging may be helpful in patients with AF who are candidates for ablation procedures. Specifically, imaging allows to reconstruct the anatomy of the target cardiac structures anatomy and to anticipate future technical difficulties and risks of the procedure , possiblTransthoracic echocardiography (TTE) is still the workhorse of noninvasive cardiac imaging, allowing to easily obtain key information on atrial structure and function. Accordingly, TTE is generally performed to evaluate LA size, a parameter that is used frequently to decide whether a patient will most likely benefit or not from an ablation procedure , being cIn addition to that, 3D echocardiography may allow a finer evaluation of LA structure and function, entailing a complete assessment of the most relevant descriptors of chamber physiology, such as reservoir, suction, and pump functions . On the CMR allows a multiparametric evaluation of atrial structure and function, with many MRI-derived parameters being correlated with postablation AF recurrence. Besides being able to quantify atrial volume in absolute terms, MRI allows the quantization of LA emptying function, as well as atrial strain and strain-rate whose abnormality may predict AF recurrenceAbove all, MRI has been proposed as a valuable technique for the evaluation of atrial fibrosis, which has been recently classified into four stages: stage I (<10% fibrosis), stage II (10–20% fibrosis), stage III (20–30% fibrosis), and stage IV (>30% fibrosis) . In thisInterestingly, while the evaluation of LA fibrosis with LGE-CMR has generally remained controversial because of the limited reproducibility of the available methods, Benito EM et al. have been recently successful in standardizing the methodology for its evaluation, providing a reproducible tool for the identification of dense atrial fibrosis . DespiteThe elevated spatial and temporal resolutions of cardiac MRI are instrumental for the in-depth characterization of LA function, allowing the estimation in measuring chamber relaxation, which has been repeatedly associated with AF development , 115. InCCT has an invaluable spatial resolution that makes it ideal for the pre-procedural cardiac anatomical assessment. CCT measurement of atrial volume correlates well with CMR . MoreoveCCT images are generally fused with EAM, allowing the match between anatomy and electrical signals and improving procedural efficacy . If comp123I-MIBG scintigraphy allows the noninvasive evaluation of myocardial sympathetic tone. After the first episode of paroxysmal AF, a reduced late H/M may predict the development of permanent AF at follow-up , the spatial resolution of traditional SPECT cameras may be inadequate to this purpose. The novel cardiac cameras equipped with cadmium–zinc–telluride (CZT) detectors offer a significantly increased resolution than standard Anger cameras, appearing more suited for the localization of GPs. Recently, Stirrup et al. defined a high-resolution CZT SPECT/CT protocol to identify GPs with good accuracy and reproducibility  in the epicardial fat pads that overlie the atria . Four ofcibility   trial, ~50% of the patients randomized to catheter ablation relapsed during 48.5 months' follow-up , a figurSimilarly, according to recent appraisals, the recurrence rate of VT ablation procedures is far from being excellent, with a still significant proportion of patients with SHDs relapsing at short-term follow-up. In particular, 50% of patients with sarcoidosis and 43% of those with valvular cardiomyopathy submitted to VT ablation recur after 1 year . On the In this context, multimodality cardiac imaging may play a pivotal role in pre-procedural patients' characterization and risk stratification, possibly allowing the selection of only those patients who would more likely benefit from an invasive approach . For exaCross-sectional imaging can be used to integrate information and to plan different kinds of electrophysiological procedures, thanks to the evaluation of anatomy, functional abnormalities, and the substrate. Furthermore, noninvasive imaging can optimize the procedure by fusion with the mapping system.Finally, image-guided electrophysiological procedures were found to have better short- and long-term outcomes than were conventional procedures.AG, SE, and RL wrote the manuscript and prepared the figures. All authors contributed to the article and approved the submitted version.SE declares the following: consultant for Biosense Webster, Stereotaxis Inc, and Spectrum Dynamics; and grants from Catheter Precision, Spectrum Dynamics, and Baylis Medical. The remaining 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.


Numerous congenital or secondary diseases, including, heart disease, respiratory disease, sepsis and many others, can lead to neonatal death. B-type natriuretic peptide (BNP) is a peptide hormone secreted by ventricular cells following an increase in ventricular wall tension. BNP functions to promote vasodilation, diuresis, and sodium release to regulate blood pressure. BNP is a sensitive index reflecting ventricular function, which may aid the diagnosis and monitoring of various neonatal diseases. In neonates, there is currently no consensus on a reference BNP level, as the plasma BNP concentration of healthy newborns varies with age, peaks in the first week after birth, and then gradually decreased to a stable level. In disease states, the correlation between the plasma BNP concentration and the results of echocardiography is good, which is of great significance in the screening, monitoring, and prognosis evaluation of neonatal cardiovascular diseases, including congenital heart disease, patent ductus arteriosus, etcetera. It also facilitates the judgment of the efficacy of treatment and perioperative management. Moreover, the monitoring of plasma BNP concentration provides guidance for the diagnosis, evaluation, and treatment selection of certain neonatal respiratory diseases and neonatal sepsis. This review summarizes the normal BNP values and discusses the application value of BNP in relation to physiological and pathological aspects in neonates. B-type natriuretic peptide, or B-type natriuretic peptide (BNP), is a member of the natriuretic peptide family in addition to cardiac natriuretic peptide (ANP). BNP is mainly secreted by ventricular myocytes, which respond to the ventricular load, and is widely distributed in the brain, spinal cord, and heart and lung, with the highest content observed in the heart. At present, studies on the pathophysiological significance and clinical diagnostic value of BNP in adults are relatively mature, and BNP can be used as a reliable biomarker for the diagnosis of structural and functional abnormalities of the cardiovascular system. Its application involves the diagnosis, severity evaluation, therapeutic effect evaluation, and prognosis evaluation of various diseases of the cardiovascular system. In recent years, the study of BNP in children has increased; however, due to the particularities of the age of neonates from intrauterine fetal hemodynamics to the neonatal period, the arterial ductus closes, pulmonary artery pressure decreases, and the systemic circulation pressure increases, leading to dynamic changes in early postnatal BNP. In addition, preterm and term infants have different disease spectrums, which are influenced by both developmental factors and diseases. The physiological and pathological significance of BNP is also different between preterm and term infants. This article reviews the normal range of BNP in neonates and the application of BNP in neonatal diseases.Mammalian cardiac myocytes are composed of a group of phenotypically heterogeneous cells, representing various functions of different subtypes of cardiac myocytes, including electrical pulse generation, electrical pulse conduction, ventricular contraction, atrial contraction, and secretion. The cardiac myocyte contraction-secretion biphenotype is the basis for regulating the secretion of two natriuretic peptide hormones, ANP, and BNP.BNP is an expression product of the NPPB gene , which iAll three types of natriuretic peptides (NP) have a common 17-amino acid ring structure that protects the cardiovascular system from volume overload. The storage of BNP is the smallest in atrial granules, where it is synthesized and secreted explosively. The wall stress caused by volume expansion or pressure overload initiates the synthesis of pre-proBNP in ventricular myocytes. BNP also circulates as a hormone in various tissues in the body, promoting vasodilation, and diuresis . In addiThe plasma BNP level of healthy full-term infants increases immediately after birth. The concentration is relatively high in the first week and then decreases significantly. Subsequently, the BNP level slowly decreases further and gradually reaches a stable level 1 month after birth. The mechanism of the sharp increase in BNP level after birth is not clear, and it is likely to be caused by many factors. The change in the perinatal circulation and the redistribution of blood from the placenta to the lungs increase ventricular volume and pressure load, which stimulates the synthesis of BNP in the left and right atrium and ventricle and secretes it into the circulation after birth . HoweverSo far, many groups have reported the reference range of plasma BNP at different times after birth . Neves eThe BNP level of newborn is related to the growth and development of fetus . MannariAs there is currently no unified standard for neonatal BNP levels, when explaining the neonatal BNP level, a comprehensive consideration and evaluation should be carried out according to the characteristics of the individual and environment.The International Society for Heart and Lung Transplantation defines childhood heart failure as a clinical and pathophysiological syndrome caused by ventricular insufficiency and volume or pressure overload, alone, or in combination . The mosMany studies have shown that children with CHD characterized by left ventricular volume overload have higher BNP concentrations, with similar results observed , 26, 27 Pressure overload, also known as afterload overload, is an increase in the resistance load that the heart bears during contraction; it includes left ventricular pressure overload and right ventricular pressure overload. For neonates, left ventricular pressure overload is mainly caused by obstructive CHD on the left side of left ventricular pressure, including aortic stenosis, coarctation of aorta, and Shone complex. Pressure overload near the stenosis (left ventricle) leads to increased systolic wall tension and hypertrophy, decreased ventricular compliance, and increased left ventricular end-diastolic and left atrial pressure, resulting in cardiac insufficiency . Cowley Cardiomyopathy The change in BNP can predict the cardiac dysfunction caused by various etiologies. Hayakawa et al. (P < 0.01) and the normal heart function group (P < 0.05), the plasma BNP level of patients treated with Adriamycin was significantly increased. Notably, BNP levels were significantly associated with systolic function, not diastolic function. It has also been demonstrated that plasma BNP level may be a marker of doxorubicin-induced cardiac toxicity in children. As a quantitative biomarker of heart failure, BNP is closely related to the stimulation of ventricular myocytes by transmural pressure. Therefore, the classification of cardiomyopathy according to morphology may be of more significance to the study of BNP.a et al.  found thBNP plays a diagnostic role in some types of cardiomyopathy but not in others. Restrictive cardiomyopathy (RCM) is characterized by increased ventricular wall stiffness, decreased diastolic function, and limited filling. In the early stage, the atrium is significantly dilated, and the systolic function of the left ventricle is significantly decreased with the progression of disease. BNP levels have been shown to be significantly higher in neonates with RCM. BNP can also be used to distinguish RCM from constrictive pericarditis as BNP is higher in patients with RCM than in those with constrictive pericarditis. Although there may be some overlap, a clearer distinction can be made by also considering the tissue Doppler phenomenon . HypertrHowever, BNP has prognostic value in some types of cardiomyopathy. Dilated cardiomyopathy (DCM) is characterized by the enlargement of the left or both ventricles with systolic dysfunction and often leads to ventricular arrhythmias, heart failure, and death. The study of Noori et al.  demonstrSeverity of Neonatal Asphyxia Based on the Degree of Myocardial Injury After Hypoxia. Neonatal asphyxia is a common emergency after birth and is an important factor of neonatal disability and death. Early diagnosis of neonatal asphyxia is important to take the correct measures to improve the survival rate and reduce the incidence of complications  and disease severity. In older children, postoperative biomarker levels are typically higher than preoperative levels, with levels peaking 12–24 h after surgery and remaining higher than preoperative levels at discharge. However, Cantinotti et al.  suggesteBNP plays a role in preoperative and intraoperative evaluation of patients with heart failure and cardiac interventional surgery. Pichette et al.  includedr = 0.51–0.65, all P < 0.001). Several studies have shown that the higher the level of BNP in pediatric cardiac surgery patients before surgery, the worse the prognosis, the longer the time of intubation, and the longer the ICU stay. In a linear regression analysis of 336 pediatric cardiac surgery patients, Cantinotti et al. (P < 0.001). In multivariate logic analysis, an independent correlation between preoperative BNP and intubation time was shown in 89 newborns (P = 0.039). Kim et al. (P = 0.005). The study by Nahum et al. (P = 0.05)  . The resBNP level may be related to postoperative development in newborns. In the study by Butts et al. , multivaIn general, BNP has a certain predictive value in the operation of neonatal heart-related diseases, but how to eliminate confounding factors to achieve the application effect of clinical practice remains to be explored. The predictive effect of BNP on prognosis in non-cardiac surgery is supported by some studies in adults, but such data are lacking in neonates.Neonatal sepsis can be serious, from subclinical infection to focal or systemic disease, with complications including pulmonary hypertension, heart failure, and other cardiovascular system symptoms, resulting in septic shock and even death of the newborn . BNP hasCirculatory dysfunction in children with septic shock is associated with mortality and is an independent risk factor for death in children with septic shock , 56. WilIn full-term infants, the ductus arteriosus usually contracts after birth and functionally closes within 72 h. However, in premature infants, the closure is delayed, which may lead to PDA. Some children will present a series of clinical symptoms and complications, some of which may even be life-threatening, known as symptomatic PDA (sPDA). Significant hemodynamics is often used to distinguish between meaningful and insignificant patent ductus arteriosus. Therefore, early diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) is of great significance . In receAt present, there is no standard best cutoff value for the diagnosis of hsPDA or sPDA using BNP level, but some studies have shown that the predictive diagnosis of PDA based on blood plasma BNP levels in newborns within 7 days after birth has value . Tauber PDA is a relatively common disease in CHD. At present, many studies have shown that there is a significant correlation between the BNP level of children and the size of PDA , 73, 74.The plasma BNP level of PDA neonates is significant for treatment decision-making. Non-steroidal anti-inflammatory drugs and other drugs are used to close PDA to prevent such complications. Indomethacin and ibuprofen are considered the standard drugs for the treatment of PDA . Hsu et CHD has a very high mortality rate worldwide, and its prevalence is gradually increasing . MoreoveSome studies have shown that BNP plays a role in the diagnosis of CHD in children and adults and can help identify critical heart disease in children in acute care settings , 87. ForIt has been shown that BNP levels are significantly increased in neonates with cardiovascular disease . The ageThere is also a certain relationship between the severity of neonatal CHD and the level of plasma BNP. Das et al.  showed tPlasma BNP can also be combined with other detection indicators to predict neonatal CHD. Sahin-Uysal et al.  attemptePH is a pathophysiological state of elevated pulmonary artery pressure in the resting state (right heart catheter ≥ 25 mmHg at sea level), which can be accompanied by different degrees of right heart dysfunction . Due to For infants without congenital heart disease, BNP is a simple and non-interference measurement index to evaluate PPHN. The study of Fu and Zhang  found thBNP can be used in the diagnosis of PPHN. Previous studies have found that plasma BNP in infants with PPHN is significantly higher, as shown in BNP can be used to evaluate the severity of PPHN and to judge the prognosis and therapeutic effect. Reynolds et al.  found a Continuous measurement of the plasma BNP level is helpful to evaluate the clinical progress of PPHN and give corresponding management. Vijlbrief et al.  found thBPD is a respiratory disease that mainly affects premature infants and low birth weight infants and is related to prenatal lung injury or postpartum mechanical ventilation. Due to damage of the lung structure and function, patients with BPD are more prone to respiratory tract infection, chronic lung disease, and chronic pulmonary heart disease in the whole life process . The incThe plasma BNP level can be used in the diagnosis, assessment, and prognosis evaluation of patients with BPD. Kalra et al.  found thCDH is a pediatric clinical emergency involving the respiratory and circulatory symptoms, respiratory failure caused by pulmonary hypoplasia and pulmonary hypertension is the main cause of death .Partridge et al.  found thBNP can also be used to judge the prognosis of infants with CDH, as an assistant index of echocardiography. Steurer et al.  found thIRDS is related to the deficiency of pulmonary surfactant and incomplete development of lung structure and has a higher incidence rate in preterm infants. Patients usually present with progressive dyspnea, intractable hypoxemia, and respiratory distress rapidly after birth. Severe cases can involve respiratory failure and multiple organ dysfunction and may eventually lead to death , 110.For infants with respiratory distress, BNP is an important index to distinguish whether the symptoms come from respiratory or circulatory system. As mentioned above, infants with respiratory failure caused by circulatory diseases may be accompanied by a significant increase in plasma BNP, which does not occur in infants with only respiratory diseases. And as Koulouri et al.  suggesteThe BNP concentration can also be used to evaluate the clinical prognosis of patents with IRDS. Reel et al.  found thHX contributed to writing part of the review content and checking and summarizing the content. YH contributed to writing part of the review content and the layout and planning of the article. QC contributed to consulting, collecting and sorting out the early materials, and is responsible for writing part of the review. XH contributed to the concept of research, constructive discussion, and overall arrangement. 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.