Sodium–glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known glucose reduction power. The cardioprotective effects of gliflozins seem to be linked to the maintenance of cellular homeostasis and to an action on the main metabolic pathways. They improve the oxygen supply for cardiomyocytes with a considerable impact on both functional and morphological myocardial aspects. Moreover, multiple molecular actions of SGLT2i are being discovered, such as the reduction of both inflammation, oxidative stress and cellular apoptosis, all responsible for myocardial damage. Various studies showed controversial results concerning the role of SGLT2i in reverse cardiac remodeling and the lowering of natriuretic peptides, suggesting that their overall effect has yet to be fully understood. In addition to this, advanced imaging studies evaluating the effect on all four cardiac chambers are lacking. Further studies will be needed to better understand the real impact of their administration, their use in daily practice and how they can contribute to benefits in terms of reverse cardiac remodeling. Sodium–glucose cotransporter-2 inhibitors (SGLT2i), or gliflozins, are a class of drugs originally developed for patients with type 2 diabetes mellitus (T2DM) and now recommended for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), regardless of blood glucose value, by the latest European and American guidelines on HF ,2,3,4.Their mechanism of action is based on the capability to inhibit type 2 sodium-glucose cotransporter, the main isoform expressed in kidneys at the level of the S1 segment epithelial cells of the proximal tubule, which is responsible for the active reabsorption of approximately 90% of the glucose filtered by the renal glomerulus. Indeed, it has been shown that the drug is first filtered by the glomerulus and then inhibits the molecular target directly from the tubular lumen extracellularly . InteresThe diuretic effect has been one of the first to be explored, as congestion is a major cause of hospitalization both in HFrEF and HFpEF. Initially, it was thought to be primarily related to the inhibition of glucose reabsorption and, thus, to the osmotic action generated by glycosuria. Lately, several studies demonstrated the efficacy of these drugs regardless of the presence of T2DM in HF patients, and additional action mechanisms began to be brought to light, as SGLT2i drugs possess an important natriuretic effect, which is combined with the ability to increase glucose excretion. It contributes to the reduction of volemia without activating counterregulatory mechanisms, such as the sympathetic nervous system or the renin–angiotensin–aldosterone system (RAAS), which commonly lead to pathological cardiac remodeling . More spThe decongestive power of SGLT2i has been studied in acute settings ,11. SGLTHowever, all of these biological mechanisms linked to a diuretic effect are not enough to explain the many cardiovascular (CV) benefits of SGLT2i. Therefore, the off-target effects on myocardiocytes must also be considered .The main molecular effects of SGLT2i on cardiovascular circulation will be discussed in depth below and are summarized in 2+-ATPase 2a (SERCA2a) pump. The remaining calcium is thrown back out of the cell by the Na+/Ca2+ exchanger (NCX) and the plasma membrane Ca2+-ATPase (PMCA) pump, both expressed on the sarcolemma [Many clinical studies agree on the fact that most of the benefits of SGLT2i on myocardial activity are due to their ability to suppress the cardiac sodium–hydrogen exchanger isoform (NHE1), which has an important modulatory effect on intracellular sodium homeostasis and, subsequently, prevents cellular calcium overload . Indeed,rcolemma ,17. It hrcolemma .The direct effect of the overexpression of SGLT1 and NHE1 on myocardial sarcolemma is excessive sodium accumulation which, in turn, leads to a reduction in the activation of the NCX, with a further increase in intracellular calcium. This causes an increase in pathological mechanisms, mostly oxidative stress, which forces the cell itself to activate the molecular pathways of programmed death ,19,20. TA combination of these mechanisms could improve the clinical status of patients and reduce the risk of death or rehospitalization. Moreover, it can slow down, if not even reverse, the set of processes that lead to pathological cardiac remodeling by improving the supply of oxygen and cellular metabolic system .These drugs act not only on sodium and calcium but also on potassium, as recently suggested. In fact, a further association exists between SGLT2i and a reduced risk of hyperkalemia, a very frequent complication in HF patients that is closely related to comorbidities , as well as to HF therapy  inhibitors) . In patiIn addition, the intrinsic decongestant mechanism of SGLT2i has allowed for the reduction of the use and dose of loop diuretics in clinical practice, obtaining a great improvement in serum electrolyte homeostasis .The heart is clearly one of the most oxygen-consuming organs. Differently from the brain, where neurons are practically forced to use glucose as their only energy substrate to synthesize adenosine triphosphate (ATP) molecules, cardiac cells can adapt their energy source. This adaptation is based on the availability of the substrate, the degree of perfusion and the workload required ,27. At rp = 0.12) [In fact, a meta-analysis of randomized controlled trials showed that SGLT2i increases the risk of DKA significantly in patients with T1DM  in a dose-dependent way, with a 4.9-fold higher rate at high doses of SGLT2i (34 events per 1000 person-years) than at low doses (7 events per 1000 person-years) ,34. The  = 0.12) ,35.This feature makes gliflozins capable of stimulating those pathways that are normally activated by starvation, such as ketogenesis and gluconeogenesis, in addition to the reduction of hyperglycemia . AlthougHowever, glycosuria is related to an increased risk of urinary tract infection (UTI), one of the main reasons for the discontinuation of the treatment . The pre3; p < 0.001) and thickness , with significant improvement in type 1 diastolic dysfunction, while they did not find similarly significant improvements in LVEF [Cardiac microcirculation also plays a central role in the pathophysiology of HF, especially for HFpEF. Endothelial cells can undergo significant oxidative stress caused by inflammation. In their study, Uthman et al. hypothesized that inflammation activates the NHE1 transporter and, thus, alters the ionic homeostasis of the cell itself by increasing the inner concentration of sodium. This would potentially lead to the increased production of ROS. Starting from this hypothesis, they tested the effectiveness of empaglifozin in blocking this pathological pathway in vitro by inhibiting NHE1 . This ex in LVEF .A further protective mechanism against oxidative stress is represented by mitophagy, a selective autophagy that leads to the exclusive degradation of mitochondria damaged by ROS. In fact, both ischemia and reperfusion cause a series of damage to the microcirculation, including increased endothelial permeability and infiltration by neutrophil granulocytes. The combination of these alterations, known as endothelial dysfunction, leads to the increased expression of adhesion molecules for the recall of other inflammatory cells and to the production of molecules with vasoconstrictive action such as endothelin-1. It also causes a reduction in the expression of protective factors, such as cadherins, which are essential for maintaining adhesion between endothelial cells and pericytes, and nitric oxide synthase. In this regard, Cai and colleagues demonstrated, in a population of mice with ischemia/reperfusion injury, through Western blot analysis of mitophagy markers, that empaglifozin can safeguard cardiac microcirculation by minimizing oxidative damage to endothelial cells. Precisely, it is able to stimulate mitophagy by activating the AMPKα1 /ULK1 (Unc-51-like autophagy-activating kinase)/FUNDC1 (FUN14 domain-containing 1)/mitophagy pathway . FurtherClinically, several studies have confirmed the efficacy of SGLT2i in preventing hospitalization and CV death in both HFrEF and HFpEF patients, regardless of the presence or not of T2DM ,50,51,52p < 0.001) in NT-proBNP was already demonstrated at 1 year after canaglifozin administration and an even greater reduction at 6 years (p = 0.004), compared to the control group [p < 0.001) [p = 0.43), there were found a mean ≥5-point increase in KCCQ  and a ≥20% decrease in NT-proBNP  by 12 weeks [Thus, an attempt was made to find reliable cardiac biomarkers that could identify which patients would benefit the most from these drugs before treatment began. Patients with the highest amino-terminal pro-b-type natriuretic peptide (NT-proBNP) were supposed to have the highest CV risk reduction . Howeverol group . Januzzi< 0.001) . Finally< 0.001) . In the 12 weeks .p <  0.01) and the risk of rehospitalization or death at 60 days [Mostly, studies correlating SGLT2i therapy with improvement in bio-humoral assessment are conducted on patients with chronic HF. The EMPA-RESPONSE-AHF study aimed to test the use of empaglifozin against placebo in a population of 80 patients with acute HF. After 30 days of treatment, no significant differences were observed between the two groups in the visual analogue scale, dyspnea score, diuretic response, hospitalization time, or change in NT-proBNP, but they confirmed that SGLT2i are a safe and manageable class of drugs that can increase significantly diuresis compared to the placebo, especially during the first 4 days of hospitalization (difference 3449 (95% CI 578–6321) mL;  60 days .Pathological remodeling in HF is a complex process that involves structural and functional changes in the heart in response to various pathophysiological stimuli. It encompasses alterations in cardiac structure, including myocardial hypertrophy, fibrosis, and changes in chamber dimensions . SeveralConsidering SGLT2i’s well-known, significant results in reducing CV death and HF hospitalization , there iThe main effects of SGLT2i on cardiac reverse remodeling will be discussed more in depth below and are summarized in The effects of SGLT2i on LV volumes and mass have been widely explored over the last years through echocardiography and CMR assessment, with discordant results. A recent meta-analysis, including 32 different studies, pointed out a neutral effect of SGLT2i on LV end-diastolic volume (LVEDV) and a significant reduction of the LV end-systolic volume (LVESV) .LV volumes are a strong predictor of adverse CV outcomes in patients with myocardial infarction, and the potential effect of SGLT2i in reducing them is an interesting point to explore .Notably, a significant reduction of LVEDV and LVESV after 12 weeks of treatment emerged from a subanalysis of the EMPIRE HF trial . The samHowever, the DAPA-LVH trial did not show a significant change both in LVEDV and LVESV but rather a reduction of the LV mass (LVM) . MoreoveLV hypertrophy (LVH) significantly influences CV outcomes and overall mortality rates in the general population . In factLVEF represents the main parameter for the diagnosis of HF patients, tailoring therapeutic management and risk stratification. Its limitations to fully cover the complexity of the HF syndrome are well known, but it still remains the principal parameter in European and American guidelines to classify the different types of HF, even if this can be criticized ,71,72.Several trials have explored the role of SGLT2i on left ventricle systolic function, with a particular focus on LVEF and global longitudinal strain (GLS). These studies did not provide definitive results, even if the impact of SGLT2i seems considerable ,73. For GLS is a relatively new parameter for HF patients, since it reflects the function of the heart’s longitudinal fibers. GLS emerged as a valuable parameter over the past few years because of its significant reliability and was included in the guidelines for what concerns the assessment of systolic function ,75.As for LVEF, GLS change has been one of the most important endpoints of studies on reverse cardiac remodeling. Ikonomidis et al. found a significant improvement in GLS after 12 months treatment with empaglifozin . SimilarHowever, the promising effects of gliflozins on reverse cardiac remodeling have not always been confirmed, particularly in improving LVEF and GLS. For instance, Rau et al.’s study showed that empaglifozin did not affect LV systolic function, as indicated by unchanged LVEF and GLS values . The samThus, the role of SGLT2i in increasing systolic function remains unclear, and further studies are needed in order to guarantee the best outcome for patients and a better understanding of the mechanisms behind their demonstrated benefits in HF.Left atrial volume (LAV) plays an essential role in HF, as an indicator of the prognosis and the progression of the disease. An enlarged left atrium is a sign of atrial remodeling, which can lead to atrial fibrillation (AF), further exacerbating HF. Monitoring and managing LAV is essential in the comprehensive care of HF patients, as it provides valuable information for risk stratification, treatment optimization, and prognosis. It is reasonable to explore, therefore, the impact of SGLT2i treatment on LAV reduction.The DAPACARD trial evaluated LAV after 6 weeks of treatment with dapaglifozin resulting in a significant reduction of LAV . The DAPBeyond the impact on LAV, other studies were meant to evaluate the effect of SGLT2i on AF onset. For instance, from Wang et al.’s meta-analysis, it emerged that the incidence of AF in patients treated with SGLT2i was significantly lower, deepening the current knowledge on the indirect antiarrhythmic effect of glyphozines .SGLT-2 has been shown to impact the patient’s prognosis regardless of LVEF ,87. In HHowever, considering all of the multiple characteristics of these drugs, SGLT2i appear to be molecules capable of acting on diastolic dysfunction from different points of view.The effects of SGLT2i on diastole have been studied for years. A study by Pabel et al. analyzed myocardial trabeculae isolated from advanced HF patients . EmpagliThe E/e ratio is significantly reduced after SGLT2i therapy ,96 from In a study by Marketou et al., dapagliflozin showed a significant improvement in LV diastolic dysfunction, evaluated using diastolic stress echocardiography, compared to the placebo with a significant reduction in E/e during exercise ,97.The same result was shown in the EMPA-REG OUTCOME study. It showed a rapid and progressive reduction in the E/e ratio without affecting other hemodynamic parameters, such as the cardiac index ,78,97.The STADIA-HFpEF and IDDIA trial also confirmed the beneficial effect of SGLT2i, both empaglifozin and dapaglifozin, on diastolic function ,85,97,98Also canaglifozin showed a significantly decrease in the E/e ratio after treatment, especially when the patients also experienced a gain in hemoglobin levels .On the contrary, in the Soga at el. study, even though there were no significative changes in the E/e ratio after 6 months of dapagliflozin therapy, the difference was bigger in patients with dyslipidemia .Given the complexity of diastolic function and also its interconnections with systolic function, Tanaka et al. demonstrated that the improvements in GLS and diastolic function after dapaglifozin administration were strictly connected .The encouraging results of the effects of dapaglifozin on hemodynamic changes during exercise are derived from the randomized trial of Kayano et. al, which showed an early and significant decrease in RVSP during exercise and E/e ratio after therapy with dapaglifozin, while not afflicting the cardiac index .However, the real effect of SGLT2i on diastolic dysfunction is of debate. For example, Prasad et al.’s meta-analysis concluded that there were no significant changes in diastolic or systolic function before and after dapaglifozin therapy against a substantial improvement in LV stroke volume . In a reThe efficacy of SGLT2i on improving the function and morphological remodeling of the left heart has been widely addressed in the literature. However, the same cannot be said of the right heart given the lack of studies in this regard.Several studies have shown the presence of RV systolic and diastolic dysfunction in T2DM patients with HFpEF. Hence, there is a growing interest in evaluating the possible impact of SGLT2i added to optimized therapy on the right heart, both on morphology and function.2, p < 0.001; 3DE RV end-systolic volume index: 25 ± 4 vs. 23 ± 4 vs. 22 ± 4 mL/m2, p < 0.001), with no significant difference in the three groups regarding the 3DE RV ejection fraction  [p < 0.001), RV ejection fraction , tricuspid annular plane systolic excursion (TAPSE) , s’ wave , and FAC  [For example, Tadic et al. demonstrated the presence of a higher deformation of the RV through a series of two- and three-dimensional echocardiographic screening in patients with T2DM and prediabetes compared to controls (3DE RV end-diastolic volume index: 69 ± 10 vs. 63 ± 8 vs. 58 ± 8 mL/m= 0.063) . A furth= 0.063) . Recentl= 0.029) .During the phases of the cardiac cycle, the ventricles apply forces on the blood generating directional changes, because of the cyclic alternation of contraction and relaxation, known as hemodynamic forces . These fGiven the counter-effect of forces themselves on the myocardium, many authors have, therefore, speculated that these hemodynamic forces are a result of increased wall tension and pathological remodeling .Hemodynamic forces can be analyzed by echocardiographic examination, both 2D and 3D, and this evaluation allows for highlighting very early abnormalities involving the deterioration of heart function .The quantification of the hemodynamic force of LV and RV has been verified in terms of reproducibility and accuracy, also with 4D flow CMR, allowing for the development of accurate software for their quantification .Although hemodynamic forces are beginning to find application in HF diagnosis and therapeutic success evaluation ,114, stuAdvanced echocardiography also allows for the reconstruction of the volume–pressure curves of the cardiac cycle. From this reconstruction, a series of “advanced parameters” can be calculated, including the myocardial work index (MWI), myocardial work efficiency (MWE) and myocardial wasted work (MWW) ,116. TheSGLT2i have recently become a key element in the therapeutic management of HFrEF patients and have shown equally promising results in HFpEF. In this review, in addition to the well-known glycosuric effect, we analyzed the role of gliflozins starting from microcellular effects, such as the ability to control intra and extracellular homeostasis and to optimize the main energy pathways of the myocardium, but also in reducing inflammation, oxidative stress and endothelial dysfunction.Given all these beneficial effects and others, it is not surprising that SGLT2i has shown a positive impact on reverse heart remodeling. In fact, they are associated with a significant reduction in the volumes of LV and LAV and a significant improvement in LVEF and diastolic dysfunction, posing as being responsible for a comprehensive cardiovascular remodeling, as reported in


IntroductionMultisystem inflammatory syndrome in children (MIS-C) is characterized by hyperinflammation, heart involvement, and multiorgan failure, which develop following coronavirus disease 2019. Ventricular arrhythmias have been identified during this syndrome. It is known that the risk of ventricular arrhythmia is associated with ventricular repolarization changes. The aim of this study was to investigate the corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio in MIS-C.MethodsThe study included 35 patients diagnosed with MIS-C and 35 subjects as the control group. The ventricular diameters, ejection fraction, valve insufficiency, and coronary artery were examined in both groups using echocardiography. Corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio were determined by 12-lead electrocardiogram.ResultsThe patient group had increased corrected QT interval (p<0.05), QT dispersion (p = 0.001), T-peak to T-end interval (p=0.001), and T-peak to T-end/corrected QT ratio (p = 0.001) compared to the control group. Moreover, there was a correlation between increased QT dispersion, T-peak to T-end, T-peak to T-end/corrected QT ratio, and decreased ejection fraction .ConclusionsOur study demonstrated increased QTc interval, QT dispersion, T-peak to T-end interval, T-peak to T-end/corrected QT ratio in MIS-C. This result may indicate an increased risk of ventricular arrhythmia for these patients. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although children usually have a mild form of the infection, some children later develop multisystem inflammatory syndrome (MIS), with symptoms similar to those of toxic shock syndrome or Kawasaki disease. It is thought to result from postinfectious dysregulation of the immune system . MIS in Electrocardiogram (ECG) abnormalities of varying degrees have been noted in MIS. ST-segmental changes, corrected QT (QTc) prolongation, and ventricular premature beats may also occur ,6. SerioAn enlarged QTc interval, QT dispersion, the interval between T-peak and T-end (Tp-e), and the ratio between T-peak and T-end/QTc (Tp-e/QTc) on the ECG are markers of susceptibility to ventricular arrhythmias and have been identified in previous studies -14. QT dStudy populationThe study was designed as a prospective observational study and included patients diagnosed with MIS-C between October 2020 and March 2021. Approval for the study was obtained from the local ethics committee, and informed consent was obtained from all participants . The diagnosis MIS-C was made according to the diagnostic criteria established by the Committee of the Centers for Disease Control and Prevention. The criteria included age < 18 years, the presence of fever, laboratory evidence of inflammation, and evidence of clinically severe disease requiring hospitalization involving multiple organs (more than two) , no alternative plausible diagnoses, positivity of current or recent infection with COVID-19 by RT-PCR, serology, or antigen testing, or exposure within four weeks before the onset of symptoms. The study included 35 MIS-C patients, who presented during the six months’ period, between 2 and 17 years of age, and 35 healthy, sex- and age-matched control subjects. The inclusion criteria for the patient group were as follows: children aged 2-17 years with a diagnosis MIS. Outpatients with myalgia or innocuous heart murmur without any history of disease were included as a control group. The exclusion criteria were as follows: obesity, smoking, hypertension, and congenital or acquired heart disease. Those whose echocardiographic and ECG measurements were insufficient to obtain data were excluded from the study.After a general physical and cardiac examination, bedside ECG and echocardiography were performed in the patients diagnosed with MIS-C. Sedation was not required in any patient to obtain data. In the patient group, measurements were performed before initiation of inotropic therapy, intravenous immunoglobulin, systemic glucocorticoid, or anakinra. QT interval was determined by ECG, and the longest value was recorded. The Bazett formula was used to calculate the QTc interval. The QT dispersion was determined from the difference between the longest QT interval and the shortest QT interval on a 12-lead ECG. The interval between the peak of the T wave and the end point of the T wave was measured on precordial leads. Data from the largest interval were used. On the basis of these measurements, the Tp-e/QTc ratio was calculated. Systolic and diastolic ventricular wall diameters and systolic and diastolic ventricular internal diameters were measured with the M-mode echocardiogram, and the ejection fraction was determined. In addition, valvular insufficiency and coronary arterial diameters were determined. Height, weight, and systolic and diastolic blood pressures were measured in all patients. Systolic and diastolic blood pressures were measured in the supine position with a mercury manometer on the right brachial artery after resting for at least 5 minutes before examination. Body mass index (BMI) was calculated by dividing body weight in kilograms by the square of height in meters.Echocardiographic examinationTwo-dimensional M-mode echocardiography recordings  were performed in all subjects. The 7-MHz transducer was used in children younger than 4 years. The 3-MHz transducer was used in children older than 4 years. During the study, a single-lead ECG was recorded continuously. Left ventricular systolic function was assessed with an M-mode echocardiogram in the parasternal long-axis view. Mitral insufficiency detected by color Doppler in the patients with MIS-C was performed on the basis of jet length measurement. It was defined as grade 1 if jet length was 1.5 cm or less, grade 2 if jet length was between 1.5 and 2.9 cm, grade 3 if jet length was between 3.0 and 4.4 cm, and grade 4 if jet length was more than 4.5 cm. Grade 1 was accepted as mild insufficiency, grade 2 as moderate insufficiency, and grades 3 and 4 as severe insufficiency .ECG evaluationTwelve-lead ECGs of the patients were recorded at rest and supine at a rate of 50 mm/s . All ECGs were scanned and transferred to a PC to reduce measurement errors and then magnified by 400% using Adobe Photoshop software. Patients with sinus rhythm were included in the study. The data from subjects whose T wave end point was not clearly identified on the ECG were not recorded. The QT interval was defined as the interval between the onset of the QRS complex and the end of the T wave Figure . MeasureStatistical analysisAll data from the patient and control groups were written into the Excel program. Then, the data in Excel were transferred to the SPSS program, and the statistical analysis was performed. The SPSS version 15.0 statistical program  was used for the statistical analysis. All values are expressed as median, mean plus or minus the standard deviation. The Pearson chi-square procedure was used for sex, and the Shapiro-Wilk test for normal distribution was performed for all other variables. The nonparametric Mann-Whitney U test was performed when variables did not conform to the normal distribution. Spearman correlation analysis was used for correlations. A p-value of less than 0.05 was considered statistically significant.In both groups, clinical characteristics were similar in terms of age, sex, and body mass index- standard deviation scores (BMI-SDS) Table . For echIn the patient group, the ejection fraction was less than 55% in 19 (54%) patients. An ejection fraction of less than 55% was considered impaired left ventricular systolic function. Coronary artery dilatation (Z-score between 2 and 2.5) was noted in four (11%) patients. However, there was no patient with coronary artery aneurysm. Eighteen (51%) of the patients had mitral insufficiency . In addition, minimal pericardial effusion was noted in five patients.Comparison of the patient group with the control group showed that the patient group had prolonged QTc interval (p < 0.05), QT dispersion (p=0.001), Tp-e interval (p=0.001), and Tp-e/QTc ratio (p=0.001) Table . CorrelaSevere ventricular tachycardia and ventricular fibrillation were detected in one of the patients included in the study.COVID-19 is a disease caused by SARS-CoV-2. Children with COVID -19 are often asymptomatic or have only mild symptoms. However, MIS-C may develop around six to eight weeks after infection with COVID-19. Symptoms of the disease are similar to those of toxic shock syndrome, Kawasaki disease, and hemophagocytic disease. Although the exact cause is unknown, it is thought to result from postinfectious dysregulation of the immune system . COVID-1Cardiac involvement is common and perhaps the most important and leading cause of mortality. Patients with MIS-C may develop myocarditis, left ventricular systolic dysfunction, and valvular insufficiency. Pericardial effusions and coronary artery dilatation are less common. Most patients have elevated troponin and NT-proBNP levels, which are markers of cardiac involvement . In addiThe QT interval includes the ventricular depolarization phase and the subsequent repolarization phase . HereditOne of the patients included in the study was found to have severe ventricular tachycardia and ventricular fibrillation. Previous studies have identified cases of ventricular tachycardia with significant hemodynamic effects in patients with MIS ,24. IncrHowever, the present study has several limitations. Small sample size, observational study, and low event rate are major limitations of the study. Also, serum levels of NT-proBNP were not measured and MIS-C patients were not monitored for possible ventricular arrhythmias with extended Holter monitoring.We demonstrated increased QTc interval, QT dispersion, Tp-e interval, and Tp-e/QTc ratio in MIS-C patients. In addition, a correlation was found between increased QT dispersion, Tp-e interval, and Tp-e/QTc ratio, and decreased ejection fraction. Left ventricular systolic dysfunction may be associated with an increased risk of ventricular arrhythmias. Susceptibility to ventricular arrhythmia is possible at MIS-C. More comprehensive studies are needed to determine this risk.


Several studies have shown that left ventricular (LV) dysfunction is increased in individuals with diabetes. However, there are scarce data about LV function in prediabetics. This study assessed the early changes in LV diastolic and systolic myocardial function in normotensive prediabetics using tissue Doppler echocardiography (TDE). We evaluated 94 patients with prediabetes  without known cardiovascular diseases and 70 healthy volunteers with similar demographic characteristics. Systolic and diastolic function of the left ventricle was evaluated with transthoracic echocardiography according to the latest consensus recommendations including TDE. The mean results of septal and lateral parts of the mitral annulus Pulsed wave TDE showed that myocardial systolic wave (Sm), myocardial early diastolic wave (Em) and Em to atrial peak velocity (Am) ratio were significantly lower whereas early diastolic peak flow velocity (E) to Em ratio, myocardial isovolumetric relaxation time (IVRTm), myocardial isovolumetric contraction time (IVCTm) and myocardial performance index (MPI) values were significantly higher in patients with prediabetes (preDM). In addition, mean left atrium (LA) diameter measured with M-mode echocardiography was significantly higher in prediabetics than controls. PreDM is associated with subclinical LV systolic and diastolic dysfunction as evaluated by TDE. Type 2 diabetes affects more than 8% of the United States population . The onsTherefore, in the present study, we aimed to investigate the possible impact of prediabetes on both LV systolic and diastolic function using conventional echocardiographic techniques including tissue Doppler echocardiography (TDE).The overall study population consisted of 164 subjects: 94 subjects with preDM  and 70 normoglycemic subjects with normal glucose tolerance. In each subject, fasting plasma glucose (FPG) and HbA1c levels were measured. The diagnosis of PreDM was ensured according to the FPG level and/or oral glucose tolerance test (OGTT) results confirmed by repeating the tests on another day and/or measuring the HbA1c level based on American Diabetes Association (ADA) guidelines  echocardiography, M-mode echocardiography, pulsed wave (PW) echocardiography and TDE. Diameter of the left atrium (LA), thickness of the interventricular septum (IVS), thickness of the posterior wall (PoW), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were obtained from the M-mode echocardiographic tracing under the guidance of 2D imaging. LV ejection fraction was calculated by the modified Simpson’s method. The pulsed Doppler sample volume was positioned at the mitral leaflet tips. Early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), E-wave deceleration time (DT), isovolumetric contraction time (IVCT), ejection time (ET) and isovolumetric relaxation time (IVRT) were measured by transmitral Doppler imaging. E/A ratio was calculated. Myocardial performance index (MPI) was calculated by summing of IVRT and IVCT and dividing by ET.Tissue Doppler echocardiography (TDE) was used to obtain LV myocardial velocities in the apical four-chamber view with a 5 mm sample volume on the medial and lateral corner of the mitral annulus and the mean results of these parameters were obtained. TDE program was set to the PW Doppler mode. Filters were set to minimize high-frequency signals, and Nyquist limit was adjusted to a velocity range of -15 to 20 cm/s. The following measurements were obtained in each region as: myocardial systolic (Sm) wave, myocardial early diastolic wave (Em) and atrial peak velocity (Am), Em/Am ratio, myocardial isovolumetric relaxation time (IVRTm), myocardial isovolumetric contraction time (IVCTm), myocardial ejection time (ETm) and IVCTm/ETm ratio. MPI was calculated by summing IVCTm and IVRTm and dividing by ETm value. In addition to these parameters, E/Em ratio, a reliable index of LV filling pressures was measured. All diastolic parameters were measured in three consecutive cardiac cycles and averaged.The analysis were performed using the SPSS 17.0 Software package program . Whether the distribution of continuous variables is normal or not was analyzed with the Shapiro–Wilk test. Data are expressed as mean ± SD for continuous variables, and as number of observations and percentage (%) for categorical variables. Significance of differences in terms of features obtained by measurements from control and patient groups were analyzed with Student’s t test or Mann-Whitney U-test. Pearson’s Chi-square test was used for comparison of categorical variables. A P-value less than 0.05 was considered statistically significant.vs 88.8 ± 6.4 mg/dL, respectively, p < 0.001) and HbA1c level  were significantly higher in preDM group compared to controls.The baseline characteristics of the study population were presented in vs 33.9 ± 4.4 mm, respectively, p = 0.010). However, when subgroup analysis were performed, LA diameter was not significantly higher in IFG+IGT group compared to controls . Pulse-wave echocardiographic measurements of the subjects were demonstrated in The conventional echocardiographic results of the subjects were presented in The mean results of the lateral and septal wall Pulse-wave tissue Doppler echocardiographic results of the subjects were presented in In this study, we have found that patients with preDM have both impaired LV systolic and diastolic function. Because of the fact that we excluded patients with HT, CAD and other chronic systemic illnesses, LV dysfunction observed in patient group probably depends directly on impaired glucose metabolism seen in preDM. Hyperglycemia has been demonstrated to cause the formation of advanced glycosylation end products (AGE) and it enhances progressive loss of cardiomyocytes and increases fibrosis resulting from oxidative stress and inflammation. In diabetic heart, ventricular hypertrophy, metabolic abnormalities, extracellular matrix remodelling, fibrosis, vascular changes, insulin resistance, oxidative stress and apoptosis are the most important changes that may affect the myocardial function. Therefore, it has been assumed that prediabetic patients may have decreased LV function due to prolonged exposure to high glucose levels ,9. A recSeveral studies have showed that, LV diastolic dysfunction represent the earliest pre-clinical manifestation of myocardial involvement in diabetes, preceding systolic dysfunction ,13. MoreWe used TDE in addition to conventional echocardiographic techniques to evaluate LV function. TDE is used in varying cardiac conditions with validation as a marker of LV systolic dysfunction ,16 and dTo evaluate myocardial systolic function, we have utilized the Sm and MPI parameters of TDE. Sm velocity mesures longitudinal LV contraction and is surrogate of LV systolic function. It demonstrated good correlation with LV ejection fraction. Em velocity is a measure of LV relaxation in early diastole and is relatively load independent . The ratIn the present study, the significant decrease in LV Em and Em/Am ratio and increased E/Em ratio among prediabetic subjects compared to controls may imply subclinical phase of LV diastolic dysfunction. Furthermore, the significant increase in MPI and decreased Sm velocity may imply subclinical LV systolic dysfunction. Our results were consistent with the results of a recent study performed by Ceyhan and cols. . Using tThere are some limitations of our study. First, the coronary artery disease was ruled out based on the history, physical examination, electrocardiography and echocardiography. The more precise imaging modalities like myocardial perfusion scintigraphy, conventional angiography or computed tomography angiography were not performed. Therefore, there may be subjects with CAD in our study population. Second, the relatively small number of patients included in this study prevents the generalization of these results to all prediabetic patients and made difficult to perform subgroup analysis. Third, tissue Doppler echocardiography measurements are angle dependent and therefore the values obtained through this method may be influenced by that limitation. To overcome this, our values were evaluated by 2 investigator. Third, although LA volume is a more precise indicator of chronic diastolic dysfunction, we have utilized LA diameter. Fourth, global longitudinal strain (GLS) measured by 2-dimensional longitudinal speckle-tracking echocardiography may be a more sensitive measure of left ventricular function than conventional LV ejection fraction (EF), and more useful than MPI.In conclusion, our data demonstrated that there is both systolic and diastolic left ventricular dysfunction in prediabetic patients. TDE is especially important in detecting the early subclinical LV systolic and diastolic dysfunction at this group of patients and its subgroups. For that reason, utilization of TDE during conventional echocardiographic measurements of prediabetic patients may have prognostic significance. These early abnormalities observed in LV function may explain the increased morbidity and mortality seen in patients with preDM. However, the clinical significance of our findings remains to be determined with larger scale studies.


Despite the cardiotoxic effect of anthracycline on the left ventricle (LV) was totally identified. The assessment of the anthracycline effect on the right ventricle(RV) by conventional echocardiography was a challenge due to its complex geometry. We aimed to evaluate the impact of anthracycline on the RV volume and function using 3 dimensional –echocardiography (3DE) and 2 dimensional -speckle tracking echocardiography (2D-STE) in patients with breast cancer.This prospective study was conducted on 66 female patients with breast cancer receiving anthracycline chemotherapy, in addition to full echocardiography, 2D-STE and 3DE evaluation of RV function and volume were done at baseline, after 4th cycle of chemotherapy, six and nine months after the end of chemotherapy.Cardiotoxicity from anthracycline occurred in 18 patients whose LV ejection fraction became significantly reduced after 9 months of therapy according to that, the patients were divided into the non-cardiotoxic group (n:48) and the cardiotoxic group (n:18). At cardiotoxic group, 3D RV end-systolic volume, and 3D RV end-diastolic volume increased significantly at 6 months and continued till 9 months after the therapy end compared to baseline values  and .LV global longitudinal strain (GLS) showed a significant reduction early after 6 months of therapy, 2D GLS and free wall longitudinal strain (FWLS) of RV were significantly decreased at 6 months and continued till 9 months after therapy  and  respectively. The variation of RV FWLS was a predictor of cardiotoxicity, the relative drop of RV FWLS > 19.3% had 83% sensitivity and 71% specificity, (AUC = 0.82) to identify patients who developed cardiotoxicity.3DE is a promising modality in recognizing the early changes in RV volumes and minute alteration in RV function and 2D-STE is a reliable predictor of RV systolic dysfunction which identify the subclinical affliction. Breast cancer is shown to be the most common malignancy and plays a major role in death related to cancer worldwide amongst adult females in Global Cancer Statistics (GLOBOCA N) 2020 .Anthracycline is considered the first-line drug according to the guidelines for the treatment of cancer breast and the category-recommended drug for neoadjuvant chemotherapy. It has a cardinal role in the postoperative adjuvant chemotherapy of breast cancer, with a powerful positive impact on breast cancer prognosis and survival. .Though, anthracycline has toxic side effects such as myelosuppression and cardiotoxicity, especially cardiotoxicity with considerable clinical symptoms, this restricts its clinical use and influences the treatment course and the survival prognosis of patients with cancer . The EurWhile most studies have shown that early administration of angiotensin-converting enzyme inhibitors and beta blockers can result in LVEF regaining and a reduction in adverse cardiac events , 6, earlTo the best of our knowledge, limited data are accessible regarding its effect on right ventricular (RV) function and regarding the parameters which could reflect subclinical RV dysfunction. Several studies addressed the importance of RV function as a strong predictor of prognosis in patients with LV systolic dysfunction , 9 and mThe RV is characterized by its complex geometry and function; therefore, conventional two-dimensional echocardiography (2DE) has its limitations. Cardiac magnetic resonance (CMR) imaging is the gold standard in the evaluation of RV function and volumes; although it is costly, time-consuming, and inapplicable to every patient. , 12Three-dimensional echocardiography (3DE) is a new well-established modality that overcomes the 2D limitations and provides a precise assessment of RV volumes and functions in comparison to CMR. , 14Novel echocardiographic techniques, such as speckle tracking echocardiography (STE) for assessment of LV myocardial deformation, and global longitudinal strain (GLS) have been proven to identify subclinical LV cardiotoxicity . SimilarOur study was designed for the early detection of RV dysfunction using 3DE and myocardial longitudinal strain analysis in breast cancer patients receiving anthracycline chemotherapy.This prospective study was conducted on 73 female patients diagnosed with breast cancer who presented to the Clinical Oncology Department at Tanta University Hospital, from March 2020 to January 2022.This study was conducted in the clinical oncology and cardiology departments at Tanta University Hospital. Privacy of all patients’ data was guaranteed, and every patient had a file with a private code number that included all investigations and kept the private data of every patient. Consent was obtained from all patients after a full clarification of the benefits and risks of treatment. Seven patients were lost during follow-up visits and hence excluded; 66 patients completed the whole study.Female patients with breast cancer who had confirmed pathological biopsy, negative metastatic workup, Her2neu score negative, and adequate hematological, renal, and hepatic profiles.Any patients with one of the following criteria were excluded from the study: non-sinus rhythm, history of ischemic heart disease or prior coronary intervention, any degree of LV systolic dysfunction at baseline study, significant valvular heart disease or prosthetic heart disease, poor echocardiographic window, chronic kidney disease, and diabetes mellitus. In addition, patients with any concomitant other chemotherapeutic agents, radiation therapy, or double malignancies, patients with severe malabsorption syndrome, and those with a performance status of more than 2 according to the WHO/ECOG (Eastern Cooperative Oncology Group) scores were all excluded from the study.All patients were subjected to proper staging through a complete history, full clinical examination, and resting standard 12-lead surface electrocardiogram, in addition to a revision of all patients’ files. Surgical excision with axillary lymph node dissection. Biomarkers on tissue biopsy were done including the estrogen receptor (ER), the progesterone receptor (PR), proliferation marker Ki-67, and the human epidermal growth factor receptor-2 (HER2).All the patients received chemotherapy in the form of 4 cycles  repeated every 21 days. Followed by Paclitaxel 80 mg/m2 IV infusion weekly for 12 weeks.Imaging screening was accomplished in all patients, including bilateral mamo-ultrasonography or bilateral breast ultrasonography (US), chest X-ray, computed tomography (CT) chest, pelvic abdominal US and/or triphasic CT abdomen and pelvis with contrast, and a bone scan (if indicated). If quarry metastatic lesions were suspected, 18 F-fluorodeoxyglucose positron emission myography would be performed.The echocardiographic acquisition was performed using General Electric Vingmed Ultrasound Vivid E 9 system equipped with M3S transducer of 2–5 MHz for 2D and 4 V-D transducer of 1.5–4.0 MHz for 3D acquisition, and the images were sent to Echo Pack 2.02 for offline analysis. The echocardiographic examinations were done in the following 4 stages: before starting chemotherapy, after the 4th cycle of chemotherapy, and then at six and nine months after the end of chemotherapy.Full 2D, M-mode, and Doppler echocardiographic examinations were done using the standard precordial views . Estimation of left ventricular volumes and function (EF%) by Simpson’s biplane method in 2D mode A 2D evaluation of RV function, including Tricuspid annular plane systolic excursion (TAPSE), was obtained via the M-mode method in the apical 4-chamber view and tissue Doppler parameters, especially peak tricuspid systolic velocity. FAC was calculated by tracing the RV endocardial contours at systole and diastole and applying the formula: 100 (RV end-diastolic area– . RV end-systolic area / RV end-diastolic area). Pulmonary artery systolic pressure (PSAP) was estimated using the continuous wave Doppler of the tricuspid regurgitation jet.The LV global strain (LVGLS) was assessed by GE AFI LV software from LV apical views  without foreshortening. At each view, two points were placed at the base and one at the apex. Then the software automatically tracked the LV contour. The measurements were approved after ensuring optimal tracking of the whole LV contour. LVGLS was automatically calculated as the averages of regional values from the 17 myocardial segments.2D-STE - RV strain was measured offline using GE AFI RV software from RV-focused apical views, ensuring the capture of the whole RV without foreshortening using the RV automated function imaging software. After defining the region of interest (ROI) that involves the complete right ventricular myocardium and interventricular septum. Three points were placed at the basal RV free wall, the base of the septal wall, and the RV apex. Subsequently, the ROI automatically tracked the RV free wall and septal wall and divided them into . RV GLS was calculated from the average of all six segment values, and RV free wall longitudinal strain (RV FWLS) was obtained from the average of the three RV free wall segments.At the end of the 2D examination, RV 3D full-volume acquisition was attained from the RV-focused apical 4-chamber view using 4 or 6 consecutive beats to achieve adequate temporal resolution (26–40 volumes/s) during breath holding after adjusting gain, contrast, depth, and sector size, certifying complete RV visualization without stitching artifacts. The 4D Auto RVQ software was used for offline analyses. with the alignment of the RV vertical axis and its horizontal planes. Afterward, place six landmark points . Finally, the RV model was established with the possibility of editing if needed. 3D RV end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume, and EF were calculated by the software.Data were analysed using Statistical Program for Social Science (SPSS) version 20.0 The mean standard deviation (SD) was used to express quantitative data.Qualitative data were expressed as frequency and percentage. The following tests were done:Independent-sample t-test of significance was used when comparing two means.A one-way analysis of variance (ANOVA) when comparing more than two means.Chi-square (X2) test of significance was used to compare proportions between two qualitative parameters.Pearson’s correlation coefficient (r) test was used for correlating data.ROC-curve: Receiver Operating Characteristic curve analysis.Regression analysis to influence one or more independent variables on a dependent variable.This prospective study included 66 female patients diagnosed with cancer breast, who received their treatment in Clinical Oncology Department at Tanta University Hospital, and their cardiac assessment was done in the Cardiology department at Tanta University Hospital.In our study, all the patients were her2neu - and received chemotherapy .The study was conducted on 66 patients, taking into consideration the cut–off value for cardiotoxicity definition , and the patients were sub grouped into the cardiotoxic group (n = 18) and the non-cardiotoxic group (n = 48).The study was conducted on 66 patients, taking into consideration the cut–off value for cardiotoxicity definition , and the patients were sub grouped into the cardiotoxic group (n = 18) and the non-cardiotoxic group (n = 48). As regard the patient characteristics in the Table  during follow-up, 6 patients were diagnosed with cardiac dysfunction at 6 months after the end of therapy, and 12 patients developed cardiotoxicity after 9 months, LVEF was significantly reduced in the group after 9 months compared to baseline .The changes in the standard echocardiographic parameters at the beginning of chemotherapy and subsequent follow-up were demonstrated in Tables ,3. AmongTAPSE wasn’t significantly decreased (p = 0.776 and 0.069 at 6 and 9ms); it only became slightly significant in 3 patients. FAC became significantly reduced at 9 months after the end of chemotherapy (p = 0.001). Tricuspid annular S` showed no significant differences during follow-up (p = 0.08), and no significant changes were observed in SPAP (p = 0.08), Table .In comparison with the baseline of the cardiotoxic group, there was a significant increase in both RVEDV and RVESV starting at 6 months (p = 0.021 and 0.005) and continuing after 9 months from the end of chemotherapy (both p = 0.001). However, the significant deterioration of RVEF was recognized at 9 months with a p-value of 0.001, mainly in 10 patients, Table , Table  compared to baseline values. RV GLS showed a significant reduction at follow-up after 6 and 9 months compared to the baseline, Table .Δ LVGLS decreased by 25% to predict subclinical cardiotoxicity in our study, which was higher than the reported percentage (a reduction of 15% was enough to predict cardiotoxicity). The ROC curve analysis of the changes in RV FWLS established that a relative drop in RV FWLS > 19.3% after 6 months had an 83% sensitivity and a 71% specificity (AUC = 0.82) to identify patients who developed cardiotoxicity, fig (c).Furthermore, there was a significant association between the cumulative dose of anthracycline and the changes in RV FWLS .Univariate regression analyses for the predictors of subclinical chemotherapy-induced cardiotoxicity (CTRCD) were done, showing the significance between the percentage variation for the following parameters  and the cumulative dose of anthracycline, Table . Also, aAnthracyclines are considered the most predominant cardiotoxic drug that generates reactive oxygen species and negatively affects cardiac tissues, leading to HF . In factIn this study, the effects of anthracyclines on LV function were assessed in 66 women with breast cancer.18 patients who developed cardiotoxicity had a significant deterioration in LVGLS early before the reduction in LVEF, Clinical, and subclinical anthracycline-related LV dysfunction had been well-researched in breast cancer patients. , 24However, RV dysfunction was not considered in the diagnosis of cardiotoxicity. The anthracycline-related toxic effects on the RV have become the focus of intense interest ,as the prognostic significance of RV dysfunction on the outcome of patients with HF has been established. , 26 The In the current study, the conventional RV echocardiographic parameters showed a slight reduction in FAC measurement that appeared late during the follow-up by 6 months, and this reduction increased to become significant at the end of 9 months after the chemotherapy. On the other hand, TAPSE did not show a significant reduction at the end of chemotherapy or through follow-up period. Similar studies reported a significant reduction in RV FAC during the period of chemotherapy and follow-up, even though the reduction was within the normal range. , 28 OtheThe RVESV and RVEDV in the cardiotoxic group in our study statistically increased after the end of chemotherapy by 6 months and continued by 9 months. However, the increase in ESV was more significant than in EDV at 6 months from the end of chemotherapy (P = 0.005 vs. P = 0.021 respectively). RVEF decreased alongside with LVEF, and they started during the follow-up and reduced significantly after 9 months, 10 patients  had a significant RV dysfunction (RVEF < 45%). The reduction in RVEF wasn’t accompanied by an increase in PASP (afterload), and this could be supported by the direct toxic effect of anthracycline on RV as well as LV. Similarly, Rui et al.  studied Moreover, Wang et al.  reportedOur study reported in the cardiotoxic group, RV dysfunction was detected in 10 patients (55%) by RVEF, concomitantly with the reduction in LVEF, and detected in 16 patients (88%) by RV FWLS early after 6 months of therapy. Both RV FWLS and RVGLS significantly decreased after 6 months and continued to decrease after 9 months (p = 0.001) compared to baseline values. RV dysfunction evaluated by conventional parameters TAPSE and S` showed no significant changes.In the same line with Vahabi et al.  who studThe study of Xu et al.  who asse2, and 18% at 700 mg/m2. Consequently, it was suggested that the maximum lifetime cumulative dose of anthracycline should not exceed 550 mg/m2 [2 [2. Similarly, Planek et al. [2 and found a significant deterioration in RV FAC, RV FWLS, and RV GLS. In fact, one study has exhibited 1.6 folds of getting HF at a dose of 300 mg/m2 [Initially, anthracycline-associated cardiotoxicity was linked to some factors, including high cumulative doses and patients with a history of cardiovascular diseases. It was revealed that a dose of > 400 mg/m2 was associated with the highest risk of cardiac injury, with an early incidence of HF of approximately 3%, 7% at a dose of 550 mg/m50 mg/m2 . Then, img/m2 [2 . Based omg/m2 [2 , the fork et al.  reportedThere is no consensus in the literature regarding the RV GLS value that can predict cardiotoxicity; an essential argument in RV strain analysis is whether GLS or FWLS should be assessed. The ROC curve analysis for the changes in RVFWLS proved that the relative drop of RV FWLS > 19.3% had a sensitivity of 83% and a specificity of 71% (AUC = 0.82) to identify patients who developed cardiotoxicity, and RV FWLS had a higher predictive value than GLS for the identification of cardiotoxicity. Keramida et al.  observedCherata et al.  who asseAnother study reported that the optimal cut-off value of 17.5% of 3D RV FWLS percent changes showed high prognostic accuracy for subclinical cardiac dysfunction, with an AUC of 0.74, a sensitivity of 80.5%, and a specificity of 65.8% .Our study found that longitudinal strain analysis can find subclinical RV dysfunction early even when the standard 2D indices of RV function are not changed. FWLS is more accurate than RV GLS in the evaluation of RV systolic function since the intraventricular septum is a constituent part of the LV.Longitudinal strain analysis by 2D STE allows the recognition of subclinical RV dysfunction when conventional indices of RV function are unaffected. 3DE is a simple and low-cost technique that is not inferior to CMR for the assessment of RV volumes and function. RV FWLS could predict subsequent cardiotoxicity in breast cancer patients receiving anthracycline chemotherapy. These new echocardiographic parameters could add a further prognostic assessment for cancer patients, especially those who are at high risk of CTRCD.Small sample size, short follow-up period, and in our institute, there is no routine follow-up for patients by echocardiography after their therapy has been completed, therefore the recovery of LV dysfunction is difficult to be estimated, and that recovery would be influenced in patients with reduced RV FWLS, so further studies are needed.


Reduced LPA/BSA (mm/m2) and larger diameter of neo-ascending aorta pre-BDCPC were associated with an increased likelihood of PA-stent implantation post-BDCPC . Stent re-dilatation was performed in 36/40 (89%) after 1 (0.8–1.5) year. Pulmonary artery diameters pre-BDCPC were lower in the PA-stent group: McGoon (p < 0.001), Nakata (p < 0.001). Indexed pulmonary artery diameters increased equally in both groups but remained lower pre-TCPC in the PA-stent group: McGoon (p < 0.001), Nakata (p = 0.009), and Lower Lobe Index (p = 0.003). LPA and RPA grew symmetrically in both groups. Single RV, larger neo-ascending aorta, and small LPA pre- BDCPC are independent risk factors for PA-stent implantation post-BDCPC. Pulmonary artery diameters after PA-stent implantation and stent re-dilatation showed significant growth together with the contralateral side, but the PA-system remained symmetrically smaller in the stent group.After bidirectional cavopulmonary connection (BDCPC) central pulmonary arteries (PAs) of single ventricle (SV) patients can be affected by stenosis or even closure. Aim of this study is to compare SV patients with and without PA-stent implantation post-BDCPC regarding risk factors for stent implantation and outcome. Single center, retrospective (2006–2021) study of 136 SV consecutive patients with and without PA-stent implantation post-BDCPC. Patient characteristics, risk factors for PA-stent implantation and PA growth were assessed comparing angiographic data pre-BDCPC and pre-TCPC. A total of 40/136 (29%) patients underwent PA-stent implantation at median (IQR) 14 (1.1–39.0) days post-BDCPC. 37/40 (92.5%) underwent LPA-stenting. Multiple regression analysis showed single LV patients to receive less likely PA-stents than single RV patients (OR 0.41;  Pulmonary artery growth, a sufficient cross-sectional area, and low resistance of the pulmonary vascular system strongly influence long-term outcome of patients with single ventricle (SV) physiologies undergoing Fontan completion –4.obstruction, which is due to external compression by the reconstructed aorta (anteriorly) or left main bronchus (posteriorly)  had a higher incidence of PA-stent implantation. Patients with no intervention at stage I (p = 0.05) or central pulmonary banding (p = 0.04) at stage I had a lower incidence of PA-stent implantation. All other patients’ characteristics and parameters are shown in Table Comparison between group 1 and group 2 showed, that patients with a single RV (2(4) = 26.398, p < 0.0001. The model explained 35.0% (Nagelkerke R2) of the variance necessity for PA-stent implantation. Single RV patients were more likely to need a PA-stent than single left ventricle patients . Since majority of the single RV patients are HLHS, the increased incidence of LPA stent in these patients can be attributed to a natural “overcorrection” of the neo-aorta often undertaken during surgery. Smaller diameter of LPA (mm/m2) and larger diameter of the (neo-)ascending aorta pre-BDCPC were associated with an increased likelihood of PA-stent implantation after BDCPC . Age at BDPCP did not add significantly to the model .A logistic regression was performed to ascertain the effects of the PA-dimension pre-BDCPC, diameter of the (neo-)ascending aorta pre-BDCPC, and ventricular anatomy on the likelihood of needing a PA-stent implantation after BDCPC. The logistic regression model was statistically significant, χBased on the results of this logistic regression, we built a prediction model to estimate the predicted probability of LPA-stent implantation after BDCPC.The equation of the model is (as described in the methods):We tested the specificity and sensibility of the predicted probability on a ROC-curve (AUC = 0.78) and according to our ROC-curve the threshold with the highest sensitivity and specificity was 0.45 Fig. . This thp = 0.007). Overall, pulmonary artery diameters pre-BDCPC were lower in the PA-stent group, specifically Nakata (p < 0.001), RPA mm/m2 (p = 0.01), and LPA mm/m2 (p = 0.001). Lower Lobe Index was tendentially lower, however not reaching statistical significance (p = 0.08). From the assessment pre-BDCPC and pre-TCPC absolute pulmonary arteries diameters increased in both groups but indexed pulmonary artery diameters decreased in both groups. The individual relative growth (%) was not different within the groups for all parameters. At cardiac catheterization pre-TCPC age was similar between the groups. Nakata (p = 0.009), RPA mm/m2 (p = 0.01), and LPA mm/m2 (p = 0.01), and Lower Lobe Index (p = 0.003) remained lower pre-TCPC in the PA-stent group. RPA:LPA ratio and LLL:RLL ratio remained symmetric at both assessments between and within the groups.At cardiac catheterization pre-BDCP the PA-stent group was younger  ascending aorta pre-BDCPC, and cardiac anatomy consistent with HLHS-complex. These predictors align with the intraprocedural findings, according to which a compression from the (neo-) ascending aorta presumably is the main cause of LPA stenosis, whereas two of three patients that underwent RPA-stenting had a right aortic arch.Pulsatile compression from a larger (neo-) ascending aorta is an important anatomic feature for potential postoperative LPA compression , 11, 12.The surgical approach with a comprehensive stage I and II had been associated with higher incidence of PA-interventions , 9, but SV patients, depending on their cardiac anatomy, might have small pulmonary arteries directly after birth –4. DurinSince the growth of the PAs depends on blood flow , improveIt is well reported in literature, that early postoperative cardiac catheterization after surgery for congenital heart disease is feasible and safe, even when acting on freshly formed sutures or hemodynamic instable patients , 14–17. The selection of a particular stent is mainly depended on the size of the reference vessels , 30, theSince stents implantation was performed in growing vessels, repetitive stent re-dilatations were performed to accommodate the vessel diameter for somatic growth. Stent re-dilatation was always feasible .When performing stent implantation stents that can be dilatated to reach the adult diameter of the pulmonary arteries (ca. 15 mm) should be preferred . Until nA model for prediction of the necessity for an LPA-stent implantation after BDCPC would be an appealing tool for the clinician and could potentially lead to a change in the clinical management of these patients. In fact, our prediction model might estimate the probability of the necessity for PA-stent implantation and could be used to (a) perform a close follow-up or (b) plan an exit-angiography directly after BDCPC in patients at risk for pulmonary artery complications or, in high-risk patients, (c) perform a hybrid procedure for LPA stenting during BDCPC surgery.In summary, a stent implantation , when clinically indicated, ensures symmetrical pulmonary flow and growth of the hilar and intrapulmonary vessels. However, side branch PA stents require multiple catheter interventions to match the child’s growth.Our study is a retrospective study with its inherent limitations. A group comparison with patients that had a stenosis in the PA-system but did not receive a PA-stent is impossible from an ethical perspective. The growth of the pulmonary arteries is influenced by many other factors, such as the blood flow distribution to the left and right PA, that we did not assess. The direct clinical impact of the PA-implantation is hard to define and therefore not assessed in this analysis. The aim of our study focused on the time frame between BDCPC and TCPC rather than long-term outcome. Further surgical factors such as placement of the pulmonary artery confluence to the left or right of the midline , 34 coulPA-stent implantation early after BDCPC is feasible and safe. Single RV, larger (neo-) ascending aorta, and smaller LPA prior to BDCPC are independent risk factors for PA-stent implantation early post-BDCPC. Our results suggest a pre-BDCPC risk-stratification for PA-stent implantation is theoretically feasible and at least an exit-angiography should be discussed in risk cases. PA diameters after PA-stent implantation and stent dilatation show symmetric but limited growth together with the contralateral side, similar to the no-PA-stent group. Therefore, PA-stents do not negatively influence peripheral PAs growth and should not be withheld, if clinically indicated.


The influence and mechanism of porous structure on the deformation failure of cement sheaths under hydraulic pressure is still unclear. To solve this problem, a net slurry cement sheath and a liquid silicon cement sheath were prepared by using a cement material and a liquid silicon suspension. The distributions of the pore radius and spatial location were analyzed using computed tomography scanning and statistics to obtain their probability density distribution functions. Based on the distribution functions, the single-layer and double-layer porous reconstruction models of the net slurry cement sheath and liquid silicon cement sheath were constructed using a FLAC 3D program. A series of numerical simulations were conducted to study the deformation failure of the cement sheaths under in situ stress and hydraulic pressure. The effects of the porous and double-layer structures on the breakdown pressure, plastic failure zone, radial deformation, and stress distribution of the cement sheaths were analyzed. As a result, the mechanisms for the influence of the porous and double-layer structures on the failure mode, failure path, and interaction between the cement sheath and metal casing were revealed. The results of this research provide a theoretical basis for an in-depth understanding of the failure mechanisms of porous cement sheaths. The safety of metal casings in fractured wells is crucial for implementing hydraulic fracturing technology in the field8. To ensure the safety and stability of a metal casing, cement mud should be injected between the metal casing and the wellbore to form a cement sheath. The cement sheath can effectively prevent corrosion, deformation, and failure of the metal casing12. Failure of the cement sheath can cause annular pressure and oil and gas interflow in the strata, resulting in a poor stimulation effect for oil and gas recovery. Moreover, it can cause deformation of the metal casing and fracturing well collapse, which can result in hydraulic fracturing process failure and very large economic losses16. Studies have found that the cement type, stratum conditions, fracturing methods, and temperature environment significantly affect the safety of cement sheaths26. Therefore, ensuring the integrity and safety of cement sheaths is crucial for the safe exploitation of unconventional oil and gas resources.Hydraulic fracturing is a common stimulation method for exploiting unconventional oil and gas resources, such as coalbed methane, shale gas, and shale oil, in low-permeability fields29. In the 1990s, a double-layer concentric casing simulation device was established to study the influence of stress on the tightness of a cement sheath under different temperatures and pressures30. The results showed that radial cracks in the cement sheath caused by the casing pressure considerably influenced cement ring failure. Furthermore, a mathematical model of the coupling of temperature and stress on a cement sheath under nonuniform in situ stress conditions was established. The effects of changes in casing temperature and pressure on stress magnitude and distribution in a cement sheath under nonuniform in situ stress were studied31. Subsequently, the Mohr‒Coulomb failure criterion was used to evaluate the integrity of a cement sheath based on cement mechanical properties, casing pressure, and initial temperature32. To explore the failure mechanism of cement sheaths and establish preventive measures, a set of integrity test devices for cement sheaths was developed, and experimental research on cement sheath integrity was conducted under concentric and eccentric conditions. Available research indicates that reducing the elastic modulus of a cement sheath can decrease stress and prevent its failure33. Some scholars added rock asphalt particles modified by plasma technology into cement sheaths and tested their mechanical parameters. They found that rock asphalt particles could effectively strengthen a viscoelastic cement sheath and increase the frictional force between cracks, thereby improving the impact resistance and plasticity of the cement sheath34.As early as the 1970s, researchers found that stress effects could affect the integrity of cement sheaths38. At present, research on cement sheath failure mainly focuses on the material characteristics of cement sheaths, crack geometry, and damage behavior47. Few studies have been conducted on the distributions of porous structures in cement sheaths and their influence on the stress distribution and deformation of cement sheaths, especially their failure modes and failure paths. The mechanisms by which porous structure influences the deformation failure of cement sheaths are ill understood. Therefore, it is necessary to explore the effects of porous structure on the stress distributions, deformation characteristics, failure modes, and failure paths of cement sheaths and revealing their deformation and failure mechanisms. This can effectively prevent damage of cement sheaths and improve their integrity to reduce the very large economic loss caused by cement sheath failure in oil and gas exploitation.In summary, these studies have played a positive role in deepening the understanding of the deformation and failure mechanisms of cement sheaths and improving their integrity and stability. However, cement is a heterogeneous material with numerous micropores that can considerably influence the deformation and failure of cement sheaths under conditions of in situ stress and hydraulic fracturingTo solve the abovementioned problems, two types of cement sheaths with different porosities were prepared: a net slurry cement sheath and a liquid silicon cement sheath. The distribution characteristics of the micropores of the two types of cement sheaths were analyzed using CT scanning experiments. A FLAC 3D program was developed in this laboratory and applied to construct porous models of the net slurry cement sheath and liquid silicon cement sheath to simulate their deformation and failure process under the combined action of in situ stress and hydraulic pressure. The reconstruction of porous models of cement sheaths is shown in Fig. ϕ25 mm × 50 mm. The materials included cement, quartz sand, water reducer, water, and liquid silicon suspension. The ratios of materials were based on the engineering ratios on site, as shown in Table In this study, two types of cylindrical cores of cements with different porosities were fabricated: net slurry cement cores and liquid silicon cement cores. The sizes of the cylindrical cores were Uniaxial compression tests, Brazilian splitting tests, and triaxial compression tests were performed to obtain the mechanical parameters of the net slurry and liquid silicon cement cores. The experimental results for the mechanical properties of cement sheaths were used as the material properties of the numerical models to ensure the accuracy of the results from the numerical simulations. The loading rate for the uniaxial compression test was 0.5 mm/min. Three groups of experiments were conducted for each cement type. The experimental results were averaged to obtain the uniaxial compressive strength, elastic modulus, and Poisson ratio. The loading rate in the Brazilian splitting experiment was 0.1 mm/min. Three groups of experiments were also conducted for each type of cement, and the experimental results were averaged to obtain the tensile strength. Triaxial compression tests were performed using a triaxial servo testing machine with confining pressures of 5, 15, and 25 MPa to test the cohesion force and internal friction angle. The experimental results are listed in Table To analyze the distributions of the porous structures of the net slurry and liquid silicon cement sheaths, CT scanning experiments were performed by using an industrial CT scanning system. Consequently, CT scanning images of their porous structure were obtained. A total of 1950 CT images of each type of cement core were obtained using volume scanning with a scanning interval of 25.6 µm. The CT images were preprocessed to improve quality. First, a Gaussian filter and the median filter algorithm were used to process the noise points and ring artifacts of the CT images. Second, a threshold segmentation method was used to binarize the CT images. The binarized CT images of the porous structures are shown in Fig. Using the program developed in this laboratory, the porosities of all binarized CT images of the net slurry cement sheath and liquid silicon cement sheath were calculated, and the average value was obtained. The average value represents the porosity of the cement sheath. The calculated results show that the porosity of the net slurry cement sheath was 1.25%, and that of the liquid silicon cement sheath was 0.86%.In this study, the distributions of the spatial locations of the pores of the clean slurry cement sheath and liquid silicon cement sheath were analyzed, and the distribution curves were obtained. The specific analysis process was as follows: Ten CT images were selected as representative layers from 1950 CT images of each type of cement sheath, numbered 140, 335, 525, 715, 905, 1095, 1285, 1475, 1665, and 1855. The CT images of all representative layers were evenly divided into 20 equal parts along the circumferential direction, and the number and probability density of pores in each part of each representative layer were calculated using a program developed in this laboratory. The probability density curves of the pores of every representative layer along the circumferential distribution were obtained, as shown in Fig. For both the net slurry and liquid silicon cement sheaths, the probability density of the pore distribution along the circumferential direction of all representative layers was concentrated in the range of 4–8%, which was approximately constant. This indicates that the spatial locations of the pores were approximately uniformly distributed along the circumferential direction.Analyzing the binarized CT images of the porous structure showed that the radial distribution of the pores the net slurry cement sheath was 35.65–356.48 μm and that of the liquid silicon cement sheath was 33.3–333.02 μm. According to the upper and lower limits of the distribution range of each cement sheath type, the distribution range of the pore radius was divided into 10 equal parts. The number and probability density of pores in each part were calculated using a program developed in this laboratory. Figure 2, while that in the liquid silica cement sheath was approximately 99.91 μm, and its area was 3.1 × 104 μm2, approximately 15% smaller than that of the net slurry cement sheath. The liquid silicon cement sheath had a smaller pore radius than the net slurry cement sheath. This indicated that adding an appropriate amount of liquid silicon suspension in the mixture of material could effectively reduce the pore size and porosity of the cement sheath and increase its compactness. The probability density distribution functions of the pore radii of the two types of cement sheaths could be expressed as shown in Eq. (Figure L0, r0, A, and B are the statistical parameters and The pore radius probability density distribution function:The pores were treated as spheres in the reconstructed model. Let the volume be According to the probability density distribution function of the pore radius, the number entclass1pt{minima in Eqs. :2\documeA hexahedral mesh was used as the porous reconstruction model. According to Eq. , the numAccording to the aforementioned analysis, the spatial locations of the pores satisfied a uniform distribution, and the probability densities of the pore radii satisfied a Gaussian distribution. According to the probability densities of different pore radii, the number of each level of pores in the constructed model was calculated. Using the Monte Carlo method and the program developed in this laboratory, three sets of uniformly distributed random numbers were generated in turn as the coordinates of the pores. Subsequently, data integration was performed to obtain the coordinates of all pores for the target model. The pores in the reconstruction model were determined by combining the mesh number of pores and their spatial coordinates.According to the field data, the geometric dimensions of the cement sheath and metal casing with a depth of 1200 m are listed in Table The pore size was very small compared to the cement sheath size, with a difference of five orders of magnitude. To accurately reproduce the micropores in the reconstruction model, the mesh of the reconstruction model was finely divided. As a result, the number of meshes and the computational scale increased sharply. This complicated numerical calculations or even made them impossible. To solve this problem, the geometric dimensions of the cement sheath and metal casing were reduced by 10 times in equal proportion in this study. The detailed geometric parameters are given in Fig. According to the abovementioned geometric parameters of the cement sheath and pore formation method, a porous model of the cement sheath was constructed using a FLAC 3D program developed in this laboratory. To analyze the interaction between the cement sheath and metal casing and their deformation and failure behaviors during the fracturing process, porous reconstruction models of a single-layer cement sheath and double-layer cement sheath were established.Figure According to stress conditions, the cement sheath and metal casing generally do not exhibit axial deformation failure or bending instability. Therefore, vertical displacement constraints were imposed on the upper and lower surfaces of the cement sheath reconstruction model to limit its vertical deformation. An in situ stress of 28 MPa was applied to the surrounding surface of the reconstruction model. Hydraulic pressure was applied to the inner wall of the reconstruction model, which was gradually increased from 0 until the cement sheath failed.The Mohr–Coulomb criterion Eq.  was usedAn isotropic elastic constitutive model was used to characterize the material properties of the metal casing. The volume modulus and shear modulus were set to 167 GPa and 76.9 GPa, respectively.The isotropic elastic constitutive equation is as follows Eq. :6\documeFigure To analyze the evolution of the plastic failure zones of the cement sheath during fracturing, 25%, 50%, and 100% of the peak hydraulic pressure were selected as loading ratios. The plastic failure characteristics of these three loading ratios were analyzed. Figures For the single-layer cement sheath, Fig. With an increase in hydraulic pressure, the plastic failure zones gradually extended to the outer wall of the cement sheath. This indicated that the failure path of the single-layer cement sheath was from the inner wall to the outer wall. When the hydraulic pressure reached its maximum, the plastic failure zones covered most parts of the cement sheath, and the cement sheath failed completely. The plastic failure zones of the net slurry cement sheath were mainly caused by shear failure, whereas those of the liquid silicon cement sheath were induced by shear failure and tensile failure. The porous structure significantly affected the failure mode of the cement sheath. These pores were likely to cause shear failure in the cement sheath. Cement sheaths with low porosity underwent tensile and shear failures, whereas cement sheaths with high porosity mainly underwent shear failure.For the double-layer cement sheath, the interaction between the cement sheath and metal casing resulted in a significant change in the failure mode compared with the single-layer cement sheath Fig. . At the To analyze the deformation behaviors of the cement sheaths during fracturing, radial plane displacement images of the cross sections of the cement sheath with the three loading ratios were obtained. Figures According to Fig. The deformation characteristics of the double-layer cement sheath differed considerably from those of the single-layer cement sheath. Because the casing was stiffer than the cement sheath, the minimum radial displacement occurred at the metal casing at the initial stage of loading, and the maximum appeared in the inner and outer layers of the cement sheath. The magnitude of the displacement of the inner layer of the cement sheath did not differ from that of its outer layer. With a gradual increase in hydraulic pressure, the radial displacement of the inner layer of the cement sheath increased rapidly, whereas that of its outer layer increased slowly. When the hydraulic pressure reached its maximum, the radial displacement was maximum in the inner layer of the cement sheath, and the radial displacement gradually decreased along the radial direction of the cement sheath outward. Compared with the single-layer cement sheath, the distribution of the radial displacement of the double-layer cement sheath was more symmetrical and showed an annular distribution. The double-layer structure weakened the effect of pores on the deformation of the cement sheath. The maximum radial displacements of the net slurry and liquid silicon cement sheaths were 202 μm and 425 μm, respectively. The maximum value of the radial displacement of the liquid silicon cement sheath was larger than that of the net slurry cement sheath, which was consistent with the conclusion about the single-layer cement sheath. However, the maximum radial displacement of the double-layer cement sheath was considerably larger than that of the single-layer cement sheath, indicating that the double-layer structure also effectively improved the deformation ability of the cement sheath.The influences of pores and the single-double layer structure of the sheath on the stress distribution and the internal failure mechanism of the cement sheath were analyzed. To this end, the major principal stress evolution of the cross sections of the cement sheathes were analyzed during fracturing. Figures At the early stage of loading, the major principal stress of the single-layer cement sheath was completely in a state of compressive stress. Because the pore sizes in the liquid silicon cement sheath were smaller than those in the net slurry cement sheath, its stress concentration was more obvious, and the magnitude of the compressive stress value was greater. As the hydraulic pressure was increased, the major principal stress of the cement sheath gradually increased. When the hydraulic pressure reached its peak load, the stress distribution in the cement sheath changed significantly. Both compressive and tensile stresses appeared in the cement sheath. The compressive stress zones were significantly larger than the tensile stress zones in the net slurry cement sheath, whereas there was a slight difference between them in the liquid silicon cement sheath. In other words, the net slurry cement sheath was still dominated by compressive stress, whereas the liquid silicon cement sheath was dominated by both compressive and tensile stresses. Therefore, the net slurry cement sheath mainly underwent compressive-shear failure, whereas the liquid silicon cement sheath underwent shear and tensile failures. This indicated that the porous structure had a significant influence on the failure mode of the cement sheath from a stress perspective.48. The results are shown in Fig. The influence of pores on the stress distribution of the single-layer cement sheath was analyzed further. To this end, the stress results for the porous cement sheath were compared with those for a nonporous cement sheath obtained by other researchersIn contrast, the major principal stress of the cross section of the nonporous cement sheath was in a state of complete tensile stress. The magnitude of the stress of the inner wall was greater than that of the outer wall of the cement sheath. This indicated that the failure mode of the nonporous cement sheath was mainly tensile failure, and the failure path was from the inside to the outside. However, the porous structure significantly changed the stress state of the single-layer cement sheath, which transformed from only tensile stress to both tensile and shear stresses. Accordingly, the failure mode of the porous cement sheath changed from tensile failure to a combination of tensile and shear failures. The larger the porosity was, the larger the proportion of shear failure. This indicated that the pores were tended to cause shear failure of the cement sheath. Notably, the porous structure did not change the failure path of the cement sheath. Regardless of the porosity, the failure path of the porous cement sheath was from the inside to the outside.The major principal stress distributions differed significantly for the double-layer and the single-layer cement sheaths. Compressive and tensile stresses appeared in the cement sheath during the early stage of loading. Tensile stress mainly occurred in the metal casing, and compressive stress appeared in the cement sheath. The magnitude of the compressive stress was greater for the inner layer than the outer layer of the cement sheath. This indicated that the double-layer cement sheath failed first at the inner layer of the cement sheath. This conclusion was consistent with that obtained from the analysis of the plastic failure zone. With an increase in hydraulic pressure, the compressive stress of the inner layer of the cement sheath gradually reached the maximum value, whereas the compressive stress value was always less for the outer layer than the inner layer. When the hydraulic pressure reached the maximum, the major principal stresses of both the net slurry and liquid silicon cement sheaths completely entered the compressive stress state. The major principal stress of the metal casing remained in a state of tensile stress. Compared with the single-layer cement sheath, the stress state of the double-layer net slurry cement sheath changed slightly, and the major principal stress was still compressive stress. However, the stress state of the double-layer liquid silicon cement sheath was very different, from a state of both tensile stress and compressive stress to a state of only compressive stress. The double-layer structure strengthened the influences of the porous structure on the stress distribution and failure mode of the cement sheath, which led to a single shear failure in the cement sheath with low porosity.The spatial locations of the pores in the net slurry cement sheath and liquid silicon cement sheath approximately satisfied uniform distributions along the circumferential direction, and the pore radii followed Gaussian distributions. The pore size and porosity of the liquid silicon cement sheath were smaller than those of the net slurry cement sheath. Adding liquid silicon suspension to a mixture of materials effectively reduced the pore size and porosity of the cement sheath and increased its compactness.The smaller the porosity of the cement sheath was, the higher the breakdown pressure. The breakdown pressure was significantly higher for the double-layer cement sheath than the single-layer cement sheath. The double-layer structure and liquid silicon suspension can effectively improve the fracture resistance and prevent damage to the cement sheath.The failure path of the cement sheath occurred from the inner wall and pore periphery to the outer wall, and the porous structure slightly influenced this failure path. However, the porous structure significantly influenced the failure mode of the cement sheath. The liquid silicon cement sheath with little porosity underwent tensile and shear failures, whereas the net slurry cement sheath with much porosity underwent mainly shear failure. Under the same hydraulic pressure, the more porous cement sheath was more likely to undergo plastic failure. However, the double-layer cement sheath effectively prevented failure of the metal casing. Moreover, the double-layer structure enhanced the effect of pores in the plastic failure zone of the less porous cement sheath, and the shear plastic failure zone became larger.The porous structure significantly affected the radial deformation of the cement sheath. When the cement sheath was less porous, it underwent larger radial displacement. Owing to the influence of pores, the distribution of radial displacement of the single-layer cement sheath was asymmetrical, and the radial displacement of the outer wall was less than that of the inner wall. The double-layer structure weakened the effect of pores on the deformation of the cement sheath such that the radial displacement of the double-layer cement sheath has a certain symmetry and showed a circular distribution. The radial displacement was significantly larger for the double-layer cement sheath than the single-layer cement sheath. Both the liquid silicon suspension and double-layer structure effectively improved the deformation ability of the cement sheath.In this study, porous reconstruction models of single- and double-layer cement sheaths were established. Based on the reconstruction models, the deformation failures of the cement sheaths were studied under in situ stress and hydraulic pressure. The effects of pores and single-double layer structure on the deformation failure of the cement sheaths were analyzed in terms of breakdown pressures, plastic zones, deformations, and stress distributions. The results revealed the failure mechanisms of the porous cement sheath. The main conclusions were as follows:The results of this study provide a basis for an in-depth understanding of the effects and mechanisms of the influence of porosity on the breakdown pressures, deformations, stress distributions, and failure modes of cement sheaths. Previous engineering practice has shown that shear damage is the main cause of cement sheath failure during exploitation of unconventional energy sources. The results showed that the use of the double-layer structure of the cement sheath and the reduction in cement sheath porosity effectively prevented shear damage of the cement sheath. The study provides a theoretical basis and concept for the prevention of shear damage of cement rings in engineering applications in terms of both the structural and porosity of cement sheaths. Notably, this study considers a cement sheath with one material ratio as the research object, and it will be necessary to verify whether the conclusions are applicable to cement sheaths with other material ratios. However, the reconstruction method of the porous model of the cement sheath presented in this paper provides an effective approach to study the failure mechanisms of cement sheaths with other material ratios.


Dear readers,2 As such, better knowledge of the rate of RV pacing may facilitate the adoption of physiologic pacing over RV pacing.Interest in physiologic pacing, including left bundle area pacing, has grown over the past few years due to the lack of responsiveness to biventricular pacing in many patients and the deleterious effect of chronic right ventricular (RV) pacing. However, current literature estimates of the burden of RV pacing in patients undergoing pacemaker implantation vary widely.The Journal of Innovations in Cardiac Rhythm Management contains an important article titled “Exploring the Temporal Patterns of Right Ventricular Pacing Burden,” in which Chattopadhyay et al.3 report the findings of a retrospective study analyzing the burden of RV pacing in 1263 patients who underwent pacing for bradycardia during a 5-year period. The study contains several important findings, including that the overall burden of RV was higher than previously reported and remained stable over time. Also, patients with sinus node dysfunction continued to have a low burden of RV pacing when the initial P–R interval was <250 ms, but this was not true in cases where the interval was >250 ms, wherein the burden of RV pacing exceeds 70%.This issue of 4 Meanwhile, there are no data concerning the role of advanced pacing strategies, such as physiologic pacing, in patients with bradycardia and preserved LV function. The described study by Chattopadhyay et al. reporting that all patient groups, except those with sinus node dysfunction and short P–R intervals, can be expected to have a high burden of RV pacing makes a strong case for considering physiologic pacing in most patients, even when the LV function is preserved. At a minimum, the study findings highlight an urgent need for the completion of randomized studies comparing physiologic and RV pacing in patients with normal LV function. This study and others may accelerate the development of technologies to facilitate and improve physiologic pacing.Biventricular pacing is superior to conventional RV pacing in patients with atrioventricular block and left ventricular (LV) dysfunction.Sincerely,md, fhrs, faccMoussa Mansour, Editor in ChiefThe Journal of Innovations in Cardiac Rhythm ManagementMMansour@InnovationsInCRM.comDirector, Atrial Fibrillation ProgramJeremy Ruskin and Dan Starks Endowed Chair in CardiologyMassachusetts General HospitalBoston, MA 02114