Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts.Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF.Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF. Heart failure (HF), a condition associated with high mortality and morbidity, constitutes a major and growing worldwide public health problem –4, resulNevertheless, left ventricular mechanical delays (LVMDs), assessed using ultrasound methods  are usefHowever, to this end, little is known about patterns of either normal or abnormal ventricular mechanical synchronization. This applies to both the right or left ventricle, whether to systolic or diastolic function, or to disparities between them, between different species of large mammals, or between healthy and diseased human hearts. Previous studies using M-mode, pulse-wave Doppler and tissue Doppler imaging have been confined to human studies of systolic as opposed to diastolic, and left ventricular asynchrony in HF patients –23. In pThe present study therefore extends these previous studies in the following respects for the first time. We examine diastolic in addition to systolic ventricular synchrony. We also provide simultaneous readouts from the right in addition to the left ventricle. Such measures are surveyed and compared in exemplars of large mammalian canine and nonhuman primate species, of potential value in future experimental studies, in addition to human hearts. Finally the analyses are extended to HF patients. We thus characterize and compare left and right ventricular, systolic and diastolic mechanical sequences in canine, primate, and normal and failing human hearts for the first time.We accordingly applied clinically accepted diagnostic electrocardiographic and echocardiographic methods to obtain and compare: (a) As systolic indicators: right and left ventricular pre-ejection periods (RVPEP and LVPEP) and (b) As diastolic indicators: mitral and tricuspid diastolic opening times (Q-MVE and Q-TVE). Corresponding values from these measurements were also compared between the right and left ventricles, between normal hearts in the species examined and in failing human hearts. This additionally provided incidences of the situations where there were relative right or left ventricular delays as well as the resulting interventricular, systolic or diastolic delays.We have demonstrated for the first time that (a) normal animal and human hearts show greater left than right delay times and therefore positive systolic (IVMDs) and diastolic IVMD delays (IVMDd). (b) In contrast, a greater proportion of individual HF patients show reversals in both these IVMDs and IVMDd trends.Our demonstration of such left/right mechanical differences and variations in patterns of both systolic and diastolic function between individual hearts thus have potential implications for clinical therapeutic techniques based on correcting mechanical activation times such as cardiac resynchronization therapy. Thus, the findings suggest that systolic and diastolic ventricular mechanical sequence assessment by echocardiography should be performed before and after CRT, in individual patients as a guide for the optimization of pacing indices. Furthermore, effectiveness of the therapeutic response may be optimized with the aid of determinations of ventricular mechanical sequence in individual patients and monitored by echocardiographic examinations.The experimental studies were performed on fifty-nine rhesus monkeys (age 15.5 ± 3.1 years) and fifteen beagle dogs (age 2 years). The animals were anesthetized  for echocardiography. All procedures were approved by the Animal Care and Use Committee of Peking University (2011-0010) and complied with the principles of laboratory animal care of the National Academy of Sciences/National Research Council of the People's Republic of China. The clinical studies were performed on 100 healthy subjects  and 39 patients with systolic heart failure . All human subjects provided clinical histories and underwent physical, electrocardiogram and transthoracic echocardiographic examination. This study was approved by the local Ethics Committee and the informed consents were obtained from all subjects.The inclusion criteria for normal subjects included: (1) normal electrocardiogram; (2) normal values in all echocardiographic measurements; left ventricular ejection fraction (LVEF) ≥ 55%, Peak velocity of mitral valve measured by Pulse wave Doppler / Peak velocity of mitral annulus measured by tissue Doppler in early diastolic of left ventricle (E/e') <15 for the septum and E/e' <13 for the lateral wall; (3) absence of any history of cardiovascular disease including hypertension, coronary, myocardial, diabetic and thyroid disease; (4) close to ideal echocardiographic image quality. The inclusion criteria for the HF patients were: (1) clinical diagnosis of heart failure with New York Heart Association (NYHA) Functional Classification grades II~IV; (2) LVEF derived using Bi-plane Simpson's rule ≤ 45%; (3) electrocardiographic sinus rhythm with QRS complex <120 ms in duration with no evidence of conduction abnormality; (4) no echocardiographic evidence for valvular disease; (5) no history of thoracotomy operations; (6) close to ideal echocardiographic image quality.PEP) was measured as the interval from the beginning of the QRS complex to the onset of aortic valve opening. The right ventricular pre-ejection period (RVPEP) was measured as the interval from the beginning of the QRS complex to the onset of pulmonary valve opening. Transmitral and transtricuspid inflow Doppler wave patterns were respectively recorded in apical five-chamber views. The diastolic opening time of the left and right ventricles was measured as the interval between the onset of the QRS complex and the beginning of the E wave for the mitral valve (Q-MVE) and for the tricuspid valve (Q-TVE) respectively. Four mechanical delay patterns are shown in PEP < LVPEP. Conversely, the existence of a right ventricular mechanical delay in systole (RVMDs) was identified when RVPEP > LVPEP . Standard two-dimensional echocardiography with Doppler examination was performed according to American Society of Echocardiography guidelines . All acq > LVPEP . Similar > LVPEP . The intt test for independent samples. When not normally distributed, continuous data was expressed as median  and compared between two groups by the non-parametric Mann-Whitney test. Categorical variables were expressed as percentages and compared between two groups by χ2 testing. Linear regression was performed to compare values of IVMDs, IVMDd and LVEF in the HF patients. Binary logistic regression analyses were performed to determine the influencing factors on the ventricular mechanical sequence. All tests were two-tailed and p-values were assessed with a significance level of 0.05. All statistical analyses were performed using SPSS version 21.0 .Continuous variables were expressed as mean ± SD and compared between two groups by E, Q-TVE) was greater than the systolic delay time , giving greater diastolic than systolic interventricular mechanical delays (IVMD). The human studies went on to demonstrate that HF patients showed greater RV and LV mechanical delays than normal subjects in systole and diastole. Furthermore, patients with HF showed significantly reduced or even negative IVMDd, suggesting a proportionally greater increase in RVMDd compared to normal subjects (subjects .p > 0.05)  .r = 0.06, p = 0.712), but a positive correlation between IVMDd and LVEF . The greater the negative value of IVMDd (RVMDd pattern), the lower the LVEF. Furthermore, HF showed differing occurrences in their patterns of particular systolic and diastolic characteristics. A greater proportion of HF patients showed associations between LVEF and RVMDs, than between LVEF and LVMDs . In contrast, HF patients showed less marked associations between LVEF and RVMDd than between LVEF and LVMDd .Linear regression was performed to compare IVMDs/IVMDd and LVEF in the patients with HF . This deWe performed comparative echocardiographic analyses of ventricular mechanical activation sequences bearing on the synchrony of left and right ventricular systole and diastole in experimental animals, normal human subjects and HF patients. We report a predominance of left ventricular mechanical delay in systole (LVMDs)  and highly consistent diastolic filling patterns (LVMDd)  on the basis of paired comparisons of LV and RV parameters in each subject, in normal canine, primate and human hearts. Previous reports , 22 had The present echocardiographic ventricular mechanical sequence findings have potential implications for therapeutic cardiac resynchronization therapy (CRT), with applicability to assessment and optimization of CRT. First, current bi-ventricular pacing in CRT typically sets the LV pacing time to be simultaneous with or slightly later than that of the RV. However, we here report differing ventricular mechanical sequences between individuals which could then confound the effectiveness of CRT. Furthermore, HF patients showed altered RV and LV mechanical sequences with potential implications for CRT optimization. Such differences in RV and LV systolic and diastolic sequences may require transthoracic echocardiographic determination for optimization and monitoring of CRT.Secondly, prolonged QRS duration is currently used to measure ventricular mechanical dyssynchrony as an indication for CRT in HF. However, electrical dyssynchrony may not exactly parallel mechanical dyssynchrony. Thus, Yu et al.  reportedThirdly, assessment of interventricular dyssynchrony may be critical for optimizing interventricular delays (V-V delays) in CRT. Their optimal timing improves ventricular filling capacity and stroke volume, reducing mitral regurgitation and reversing LV remodeling with subsequent reductions in short-term morbidity and mortality. Admittedly, there is evidence for intraventricular but not interventricular synchrony as an independent prognostic indicator in CRT patients. However, previous work had assessed IVMDs as a predictor without considering the interventricular mechanical sequence with V-V delays, setting LV timing simultaneously with or slightly earlier than RV. This contrasts with the LVMDs patterns we report here.The pressure difference between left and right ventricles may be one of the factors affecting the mechanical asynchrony between ventricles, but obtaining intraventricular pressure may need invasive examination. For healthy volunteers and some patients with hemodynamic instability, it is difficult to obtain such invasive intraventricular pressure measurement data.In addition, left ventricular systolic pressure and end diastolic pressure could also affect left and right ventricular synchrony. Finally, the consequent effects of parameters such as blood pressure and E/e 'may merit further research.By using Pulse-wave Doppler echocardiographic approaches, we have explored and characterized the cardiac mechanical sequence in LV and RV and their relationships in three large species. Significant variations in LV and RV systolic and diastolic mechanical sequences are demonstrated between healthy subjects and HF patients. Systolic and diastolic ventricular mechanical sequence assessment by echocardiography should be done before and after CRT, as a guide for the optimization of pacing indices. To gain a highly effective therapeutic response, ventricular mechanical sequence should be considered for individual patients and recorded in routine echocardiographic examination.The original data upon which this article is based is available from the corresponding author upon reasonable request.The studies involving human participants were reviewed and approved by the Peking University People's Hospital following approval by the local Ethics Committee. The patients/participants provided their written informed consent to participate in this study. All studies involving animal procedures were approved by the Animal Care and Use Committee of Peking University  and complied with the principles of laboratory animal care of the National Academy of Sciences/National Research Council of the People's Republic of China.TZ was responsible for overall study design. ML supervised the canine. XZ supervised the primate experiments. RZ, YZ, WZ, and YL performed the animal experiments. WJ, CY, DL, XQ, LK, and SL recruited and studied the healthy human subjects and heart failure patients. ZW performed data analysis and figure preparation. CH performed data statistical analysis and writing of this article. All authors contributed to the article and approved the submitted version.This study was funded by a National Key Research and Development (R&D) Program of China grant (2018YFA0801405), the Beijing Science and Technology Project (81670090) and the National Natural Science Funding of China .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


P < 0.05). The left atrium filling index and ejection force were significantly increased in 28 patients with sinus reversion (P < 0.05). The decrease in left atrial diameter and the increase in left atrial ejection fraction were correlated with sinus conversion after surgery (P < 0.05). The modified operation is simple, the curative effect is definite, and the sinus reversion rate is high, which is beneficial to the restoration of left atrial structure, ejection function, and hemodynamic function.We aimed to study the long-term sinus reversion rate and recovery of left atrial function after modified surgical radiofrequency ablation for permanent atrial fibrillation caused by mitral valve disease. From March 2014 to May 2020, 35 patients who underwent modified surgical radiofrequency ablation during cardiac valve surgery in our hospital were selected as the study group, and 25 normal individuals without cardiac structural changes were selected as the control group. The time of modified surgical radiofrequency ablation and long-term sinus reversion rate were measured, and left atrial anteroposterior, superoinferior, left and right diameters, left atrial ejection fraction, left atrial filling index, and left atrial ejection force were measured before and 6 months after surgery. The mean ablation time was 23.2 min, and the long-term sinus reversion rate was 80.0%. The left atrium diameter decreased and the left atrium ejection fraction increased after the operation ( Atrial fibrillation is a common arrhythmia that is mostly secondary to valvular heart disease. Due to structural changes in the left atrium after valvular disease, atrial fibrillation often appears persistent. The main treatment for persistent atrial fibrillation is maze III surgery, with a success rate of 97%, but the operation is complex and traumatic . DevelopFrom March 2014 to May 2020, 35 patients with mitral valve disease combined with atrial fibrillation underwent mitral valve replacement or plasty and modified maze radiofrequency ablation in our hospital. There were 15 men and 20 women with an average age of 55 years . There were 9 cases of simple mitral valve disease, 18 cases of mitral valve combined with tricuspid valve disease, and 8 cases of mitral valve, aortic valve, and tricuspid valve combined disease. Twenty-five healthy individuals without cardiac structural lesions were selected as the control group. All patients were diagnosed by transthoracic echocardiography before surgery, and left ventricular ejection fraction (LVEF) and left atrial function were measured. The patients were treated with digoxigenin, furosemide, and amiodarone for 1-2 weeks. This study was approved by Zhongshan Hospital of Traditional Chinese Medicine. Written informed consent was obtained from the patient.Catheter drainage of the superior vena cava and inferior vena cava was used to establish cardiopulmonary bypass. The right superior and inferior pulmonary vein entrances were ablated under parallel circulation. After cardiac arrest, the left atrium was examined. If a thrombus was present, the thrombus was removed first. The left superior and inferior pulmonary vein entrances were ablated. The left atrial appendage was then excised. The left atrial appendage to the left superior pulmonary vein was ablated, and the left atrial appendage stump was sutured. If a thrombus was found in the left atrial appendage or if the patient was elderly (over 65 years old), ablation was performed at the root of the left atrial appendage and from the right superior pulmonary vein to the root of the left atrial appendage. The left atrial appendage was closed in the left atrium without removal of the left atrial appendage. Next, ablation of the right superior pulmonary vein to the left superior pulmonary vein was performed. The right superior pulmonary vein to the left inferior pulmonary vein was then ablated with ablation forceps around the lateral side of the right inferior pulmonary vein. In the same way, the right superior pulmonary vein to the mitral annulus was ablated. Subsequently, coronary sinus to isthmus ablation was performed. The right atrial incision was sutured as the eighth line. Each ablation line was ablated two to three times . Valve sρ × MVA × (VA) 2 × 10 − 3, where ρ is the viscosity coefficient 1.06/m3, MVA is the area of mitral valve orifice (cm2) measured using the pressure half-time method, VA is the A peak flow velocity of mitral valve orifice (cm/s), and the unit is kdynes [The patients were treated with vasoactive drugs to maintain hemodynamic stability and amiodarone to maintain sinus rhythm. An epicardial temporary pacemaker was set to 80 beats per minute to guarantee heart rate. The same drug treatment as before surgery was maintained until 3–6 months after surgery. Six months after the operation, the patients were followed up with electrocardiography and color Doppler ultrasonography. The LVEF, left atrial function including left atrial structure , mechanical function  was calculated), E peak, A peak, and their velocity time integral were measured by color Doppler ultrasound. Left atrial filling index (LAFI) was defined as LAFI = A peak time velocity integral/, and left atrial ejection force (AEF) was defined as AEF= 0.5 × P < 0.05.SPSS (version 16.0) was used to process the data. Statistical data were expressed as mean ± standard deviation. Statistical significance was set at All patients underwent radiofrequency ablation of atrial fibrillation. In mitral valve replacement, mechanical valve replacement was performed in 18 cases, bioprosthetic valve replacement in 12 cases, and mitral valvuloplasty in 7 cases. The average postoperative discharge time was 19 days. All patients were followed up for 6 months. The mitral valve membrane worked well, without stenosis or regurgitation. During the follow-up period, there were no instances of need to install a permanent pacemaker, stroke, or thrombosis complications. The average ablation time was 23.2 min. Of 35 cases, 28 cases converted to sinus rhythm 6 months after the operation, and the cardioversion rate was 80%.P < 0.005), and LAEF was increased (P < 0.005) (P=0.139), but the difference was shown in paired analysis (P=0.041). There were significant differences in left atrial structure and LAEF before and after the operation in paired analysis (P < 0.05).The results showed that the left atrial anteroposterior diameter and superoinferior diameter were decreased (< 0.005) ; there wP < 0.05)  .P < 0.05)  .In structural heart disease, mitral valve disease often causes atrial fibrillation, which may be caused by an increase in left atrial load and blood stasis resulting from mitral stenosis, and the impact of high-speed systolic blood flow from the left ventricle is caused by mitral regurgitation, both of which eventually lead to the enlargement of the left atrial structure and the formation of multiple reentry pathways in the left atrium. The treatment of atrial fibrillation has changed from the traditional “cut and sew” Cox maze III procedure to current radiofrequency ablation. Among them, bipolar radiofrequency ablation is effective with fewer side effects, and the ablation circuit is constantly improved. The maze radiofrequency ablation in this study followed the Cox maze III procedure; except that, while the right atrial longitudinal incision was “cut and sew” and the ablation route was simplified, the rest of the lines were radiofrequency ablation. Using this improved method, the right lower pulmonary vein incision can be omitted in the operation. Most patients had the left atrial appendage in the heart sutured, which reduced the risk of bleeding. The shortening of operation time plays an important role in myocardial protection and prevention of ischemia-reperfusion injury , and micWith the development of atrial fibrillation research, increasing attention has been paid to the role of left atrial function in cardiac function. Atrial fibrillation makes left atrial autonomic systolic function disappear, reducing the length of the left ventricular diastolic period, resulting in a change in cardiac stroke output, which affects the stability of hemodynamics, and leads to a decline in cardiac function. In the past, left atrial function was evaluated using echocardiography only in the structure. In recent years, the study of the left atrial function has changed from simple structure measurement to mechanical ejection function and hemodynamics. In this study, we measured the anterior and posterior diameters of the left atrium in the long axis view of the left heart, superior and inferior diameters, and left and right diameters of the left atrium in the four-chamber view. The LAEF was calculated from the changes in left atrial diastolic and systolic volume in the four-chamber view, the LAFI was calculated from the proportion of A peak area to evaluate the role of left atrial active contraction in the whole left ventricular diastolic period, and the left AEF was calculated from the maximum A peak velocity and mitral orifice area to infer the left atrial active systolic force. The above method is simple and can be used to evaluate left atrial function from multiple perspectives. However, there is no comprehensive index to evaluate left atrial function, and the LAEF is considered to be a more intuitive index.With respect to left atrial structure and function recovery, paired analysis showed that the left atrial structure and LAEF improved in the long term after the modified ablation. Recovery of the A peak is very important for the evaluation of left atrial hemodynamics. Compared with the patients without cardioversion, the left atrial structure and ejection function of the patients with cardioversion were better, and the left atrial filling index and left AEF were also significantly increased. Some studies have shown that the left atrial function of pure atrial fibrillation can return to normal after interventional radiofrequency ablation –11, but In general, modified surgical radiofrequency ablation is simple, the curative effect is definite, and the sinus reversion rate is high, which is beneficial to the restoration of left atrial structure, ejection function, and hemodynamic function. The modified operation is worth clinical promotion.


The editors of the Journal of Mother and Child/Medycyna Wieku Rozwojowego invite you to read the fourth issue of our quarterly. The topics that are discussed in this issue encompass congenital malformations, including an excellent institutional review on over ten years’ experience with H-type tracheooesophageal fistula (H-TEF) and a case study on management with wrap disruption after Nissen fundoplication in a child with gastro-oesophageal reflux after congenital oesophageal atresia; perinatology comprising diagnostic challenges in a patient with neonatal cholestasis and growth restriction in twin pregnancies; and finally, an original paper presenting an association between single nucleotide polymorphisms (SNPs) and viral load (VL) in congenital cytomegalovirus infection.We start reading with an original article describing in detail 18 patients with a rare condition – congenital H-TEF – who were managed for over 10 years in the department of Paediatric Surgery at a tertiary institute . Tracheoesophageal fistula (TEF) without associated oesophagal atresia (EA), commonly called H-type or N-type or isolated fistula, is a rare congenital anomaly that accounts for 4–5% of all occurrences of congenital tracheoesophageal malformation. The malformation must be considered in the differential diagnosis when managing the patients with recurrent lower respiratory tract infection and in patients with ‘coughing and choking episodes. The repair of an H-type TEF is not a simple procedure and should not be taken lightly, since it is known to be associated with complications, i.e. damage to the recurrent laryngeal nerve.IL1B rs16944, IL12B rs3212227, IL28B SNPs rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) which were analysed in a study population of 233 newborns. They found IL12B rs3212227 to be associated with VL in cCMV, and symptomatic newborns had significantly higher viremia and viruria. Thus, we believe that SNPs’ role in the pathogenesis of cCMV is a clinically interesting subject and warrants further investigations.We will continue with another excellent original paper by Jedlińska-Pijanowska and colleagues, who try to define the role and significance of SNPs, which may determine VL in congenital CMV (cCMV) infection. The authors concentrated on eight polymorphisms in genes encoding cytokines or cytokine receptors . Foetal growth restriction is one of the most frequent prenatal pathologies, which complicates about 25–47% of twin pregnancies (vs. only 8% of singletons). A literature search was performed to present a comprehensive, critical and objective analysis of the current knowledge on growth restriction in twin pregnancies, including PubMed and SCOPUS, based on Medical Subject Headings (MeSH) terms.Professor Jaak Jaeken sensitises us that in a patient with a complex pathology, the possibility that he/she is affected by several genetic/metabolic diseases should also be considered. This is certainly not a common situation, but it is undoubtedly a diagnostic challenge. We encourage you to read the attention-warranting description of the patient, who was finally found to suffer from three rare diseases.The issue is closed with a mini-review on gastro-oesophageal reflux management after congenital oesophageal atresia . In about 86% of cases, EA is accompanied by a lower TEF. Although corrective surgery restoring oesophageal continuity is carried out in the first days of a child’s life, patients may be required to undergo life-long complications associated with a congenital anomaly that are possibly the consequences of surgical treatment. As stated by the authors, ‘In the case of relapses of reflux oesophagitis in patients after anti-reflux surgery, the possibility of distant complications such as dislocation or dissolution of the fundoplication cuff should be taken into consideration’; this is their take-home message.We hope that the presented papers will meet your expectations and encourage you to read the further issues of our Journal.


HRV was analyzed by spectral and Poincaré methods. Age-related z scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the superior vena cava’s entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG ( Since the first description of the Fontan procedure , the surHeart rate variability (HRV) measures the duration of consecutive RR intervals on an electrocardiogram (ECG) to assess beat-to-beat variation and is a well-established method of examining cardiac autonomic nervous activity. HRV increases with age during childhood; however, the increase is higher during infancy than late childhood .Reduced HRV is associated with an increased risk of cardiovascular events in adult populations without known cardiovascular disease . There iEarlier studies have shown reduced HRV in patients with Fontan circulation , 13. In Autonomic nervous ganglia density and distribution varies within the heart, with a moderately dense node located near the posterior surfaces of the superior vena cava (SVC) . During The study included patients with univentricular heart defects operated with Fontan surgery at the two centers for pediatric thoracic surgery in Sweden, the University Hospitals in Lund and Gothenburg.The Fontan operation was performed in two steps, in most cases, after a palliative neonatal procedure. Firstly, the BDG procedure was performed via a median sternotomy on a beating heart by cannulation of the SVC, the right atrium, and aorta. The SVC was detached at the entrance to the heart and the cardiac end oversewn. The SVC and right pulmonary artery were then connected with an end-to-side anastomosis.Secondly, TCPC was completed by creation of an intra-atrial tunnel or an extracardiac conduit. The intra-atrial tunnel surgery was performed via a median resternotomy, cardiopulmonary bypass and cardioplegic arrest (or induced ventricular fibrillation). A GORE-TEX® baffle was constructed to direct flow from inferior vena cava (IVC) to the superior end of an atriopulmonary anastomosis. The extracardiac conduit TCPC was performed via a median resternotomy. After atrial, bicaval and aortic cannulation, cardiopulmonary bypass was started. The IVC was transected and the cardiac end was oversewn. A GORE-TEX® tube graft was sutured to the IVC, and the other end connected to the right pulmonary artery. The procedure was performed on a “beating heart”.Ambulatory Holter-ECG recordings were performed in patients before BDG (pre-BDG), after BDG (post-BDG) and after TCPC (post-TCPC). Patients treated with beta-blockers or with a permanent pacemaker were excluded. Clinical records were reviewed for gender, anatomical diagnosis, surgical technique, age at time of each surgery, and complications such as protein losing enteropathy (PLE), heart transplantation or death. Records also provided information regarding saturation by pulse oximetry, medication, and echocardiographic findings at time points close to Holter-ECG assessment and procedures. Echocardiographic data included assessment of ventricular function and atrioventricular (AV) valve insufficiency. Semi-quantitatively assessed ventricular function was graded as “normal”, “mildly depressed”, “moderately depressed”, or “severely depressed” and the AV valve regurgitation was graded as “none”, “mild”, “moderate”, or “severe”.The healthy control group consisted of 38 children 24 female, (63%), and were recruited from the local population. All controls had normal baseline ECGs and echocardiographic scans. The median age was 20 (range 0–65) months.Heart rate variability analysis was carried out on five lead 24 h Holter-ECG traces collected during normal daily activity. One of the two channels (V2 or V5) was analyzed for arrhythmias before HRV analysis. Heartbeats were classified as: normal, supraventricular extra systolic, ventricular extra systolic, or beats of uncertain origin. All ECG data were reviewed and edited by one analyst who corrected undetected or misclassified heartbeats and excluded periods of noise or artifact.P) was determined for three spectral components: PVLF; very low-frequency region [0.003–0.04 Hz (Hz)]; PLF; low-frequency region (0.04–0.15 Hz); and PHF; high-frequency region (above 0.15 Hz). HF represents mainly parasympathetic activity, whereas LF represents the combined sympathetic and parasympathetic effect on cardiac autonomic nervous modulation. The LF/HF ratio was also calculated. Finally, total power (Ptot) was determined as the sum of the three spectral components. All spectral indices were calculated as average data over the complete recording period. Poincaré analysis is a geometric method in which each RR interval is plotted, on a scatter plot, as a function of the previous RR interval. HRV was quantified by the standard deviation (SD) in two perpendicular directions: SD2, the SD along the line of identity that represents the changes in mean RR; and SD1, the SD along the line that is perpendicular to the line of identity, representing the magnitude of the beat-to-beat variability in RR , 24 (27%) received a shunt , 16 (18%) had a pulmonary artery banding and 13 (15%) were operated on with Damus-Kaye-Stansel anastomosis and shunt. BDG surgery was performed at median age of 5.9 (1.5–54.3) months. At the end of the study 71 of 89 patients had a complete Fontan circulation: 68 (96%) had an extracardiac TCPC and 3 (3%) had a lateral tunnel TCPC. Median age at TCPC was 2.6 (1.5–9.6) years. During follow-up 2 (2%) patients had a permanent pacemaker implantation, 1 (1%) patient developed protein losing enteropathy and 10 (11%) had received a heart transplant or died.n = 11), pre- and post-BDG (n = 8), pre-BDG and post-TCPC (n = 7), post-BDG and post-TCPC (n = 13). Twenty-one, 15 ,and 14 patients performed only one Holter: pre-BDG, post-BDG, and post-TCPC, respectively. A total of 139 recordings were analyzed. Patients were unavailable for Holter-ECG recordings for multiple reasons. In 18 cases, the final TCPC stage was not performed due to age (too young) (n = 7), operation not possible due to hemodynamic parameters or small size of the pulmonary arteries (n = 3), four had a heart transplantation, three died and one emigrated. During follow-up ten patients had a heart transplant or died (3 after TCPC).HRV was analyzed in pre-BDG Holter-ECGs in 47 patients , post-BDG in 47 patients , post-TCPC in 45 patients, aged 3.7 years, range 2.2–8.8 years. Repeated Holter recordings were available for 39 patients; at all stages (See Table Z score) indicating sinus node dysfunction  and in Poincaré analysis SD2 and SD1/SD2 ratio] were compared, a significantly lower HRV was revealed in patients before BDG compared to healthy controls  and in Poincaré analysis SD2, and SD1/SD2 ratio were decreased compared to before TCPC (post-BDG)  of the pre-BDG, 30% 14/47) of the post-BDG and 31% (14/45) of the post-TCPC recordings, patients showed marked sinus bradycardia . A subset analysis of patients with HLHS confirmed these results.A subgroup analysis by Wilcoxon test was carried out on data from patients with multiple Holter-ECG recordings. The same pattern of results was noted: increased RR interval and No significant differences in HRV were found between the 10 patients who received a heart transplant or died during follow-up compared the remaining patients in the study cohort.RR interval and HRV (SD2) occurred in children with univentricular heart defects after BDG. Further reduction in all HRV spectral indices one year after complete TCPC surgery, was also seen when compared to pre-TCPC HRV results.The main findings of this study were that a significant reduction in heart rate, increased Early diagnosis of arrhythmia is desirable in patients with Fontan circulation as arrhythmia is one of the main causes of postoperative morbidity , 19. KnoAlthough results showing reduction in HRV pre-BDG could be explained by pre-existing cardiac autonomic dysfunction in these patients , anotherRR intervals were significantly increased and, consequently, heart rate reduced. Interestingly, pre-BDG heart rate was within normal range  post TCPC surgery when compared with healthy controls [PHF and SD1 after the TCPC procedure compared to before the TCPC, indicating a reduced parasympathetic action of cardiac autonomic innervation. This is of special interest since the risk for arrhythmia is significantly increased when the autonomic innervation of the heart is sympathetically dominated [RR interval difference (RMSSD) and a lower PLF in the BDG group [In line with previous studies, we found that heart rate was lower  were operated with the extracardiac conduit variant of TCPC surgery. During this surgical procedure the IVC is transected, and the parasympathetic ganglia located close to the IVC–atrial junction, or at the medial and posterior surface of the IVC, may be affected , 25. We This study, to the best of our knowledge, is the largest longitudinal study of HRV during the stepwise progression to completion of Fontan circulation. Additionally, all but one Holter-ECG recordings were made without concurrent treatment with beta-blockers or other drugs known to interfere with HRV .A lack of data regarding HRV before neonatal surgery. This would have been of interest since most patients (96%) had neonatal cardiac surgery, which may affect HRV. Additionally, 24 h Holter-ECG recordings after each surgical step were not available for each patient.RR-interval) post BDG surgery and further significant reductions in HRV after completion of TCPC. These findings add to the current knowledge regarding autonomic regulation of cardiac rhythm and offer a possible explanation for postoperative arrhythmic events in patients with univentricular heart defects undergoing conversion to Fontan circulation.This study shows markedly reduced heart rate (increased


Segmentation was done on the four most central slices. The resulting T2 values were compared for all four measurements.Fifty-eight individuals  were prospectively examined at 3 T. This cohort study consisted of 19 patients, 20 rowers, and 19 volunteers. GRAPPATINI was conducted with the same parameters as a conventional 2D multi-echo spin-echo (MESE) sequence in 02:27 min instead of 13:18 min. Additional T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of the nucleus pulposus of normal discs differed significantly from those of bulging discs or herniated discs . For the posterior annular region, only T2-GRAPPATINI showed a significant difference (p = 0.011) between normal and herniated discs. There was a significant difference between T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of discs with and without an annular tear for the nucleus pulposus . The nucleus pulposus’ T2 at different degeneration states showed significant differences between all group comparisons of Pfirrmann grades for T2-GRAPPATINI (p = 0.000–0.018), T2-MESE (p = 0.000–0.015), T2-EVEN (p = 0.000–0.019), and T2-WO1ST (p = 0.000–0.015).T2 values as quantitative imaging biomarkers to detect disc pathologies such as degeneration, lumbar disc herniation, and annular tears while simultaneously shortening the acquisition time from 13:18 to 2:27 min.GRAPPATINI facilitates the use of T• T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1STof the nucleus pulposus of normal discs differed significantly from those of discs with bulging or herniation .• The investigated T2mapping techniques differed significantly in discs with and without annular tearing .• The nucleus pulposus’ T2showed significant differences between different stages of degeneration in all group comparisons for T2-GRAPPATINI(p = 0.000–0.018), T2-MESE(p = 0.000–0.015), T2-EVEN(p = 0.000–0.019), and T2-WO1ST(p = 0.000–0.015). Lower back pain (LBP) still ranks as the most common cause for years lived with disability (YLD) and disability-adjusted life years (DALY) according to the Global Burden of Disease Studies of 2016 [The intervertebral disc (IVD) is mainly composed of an inherent architecture of dense collagen fibers, the annulus fibrosus, surrounding the nucleus pulposus with its high concentration of glycosaminoglycans (GAG) that facilitate its water-storing capabilities .Degenerative disc disease, caused by an irreversible decay of the IVD structural integrity, leads to an inadequate biomechanical response to pressure or load . This puVisceral pain aggravates with distension and is highly responsive to inflammatory stimuli. It is difficult to localize, while the pain is often described as profound, pressing, and blunt.To assess the intervertebral disc, non-invasive MRI established itself as the method of choice .Using conventional magnetic resonance imaging (MRI), intervertebral disc degeneration is typically scored using the Pfirrmann classification .However, this presumably simple task is only semi-quantitative, depends on weighted contrast images, is evaluator-dependent, and comes with pitfalls such as magnetization transfer effects, which can cause a lower signal intensity in the nucleus pulposus, resulting in a lower signal intensity and therefore a lower Pfirrmann classification.2 mapping provide objective results, which have already shown excellent discriminability when it comes to disc degeneration [Quantitative magnetic resonance imaging (qMRI) methods such as Tneration .2 mapping is widely available and well-suited for the evaluation of the disc’s biochemical state, correlating with histology, water content, and degeneration is one of the most often used quantitative methods in research regarding low back pain [As Tack pain .2 mapping can depict changes in very early stages of disc degeneration that remain invisible to conventional morphological imaging sequences [Also, Tequences .2 mapping of the IVD can therefore be considered an important biomarker in clinical applications [Tications , 11.2 mapping is usually performed using a two-dimensional multi-echo spin-echo (2D-MESE) sequence which samples multiple contrasts at successive, equally spaced echo times (TE) [2 maps are reconstructed by performing a mono-exponential voxel-wise fit on the measured signal decay. However, the clinical feasibility of the MESE sequence is limited due to long acquisition times and specific absorption rate (SAR) limitations. These limitations become especially restrictive at a higher in-plane resolution  [Conventional Tmes (TE) . The res× 1 mm2) .2 values compared to a typical MESE sequence in MRI of the brain, knee, prostate, and liver [To overcome these obstacles, GRAPPATINI combines “model-based accelerated relaxometry by iterative non-linear inversion” (MARTINI) and “generalized autocalibrating partial parallel acquisition” (GRAPPA) . GRAPPATnd liver .2 maps reconstructed from a conventional MESE sequence dataset, (b) to discriminate between different degeneration states, reflected by Pfirrmann classifications, (c) to differentiate discs with and without herniation, and (d) to distinguish between discs with and without annular tear.The aim of this study was (a) to investigate whether GRAPPATINI can be used in direct comparison with TUpon approval by the institutional review board, 60 individuals were prospectively enrolled in this prospective cohort study. Initially, 20 patients, 20 healthy volunteers, and 20 professional rowers were registered between January 2017 and November 2018. The rowers were included in the study to assess early degenerative changes. One patient aborted the measurement due to pain in prolonged supine position and one healthy volunteer was excluded due to motion artifacts in all sequences. In total, 58 MRIs were evaluated  from 19 patients , 19 volunteers , and 20 rowers . No measurement of the remaining 58 analyzed individuals had to be excluded due to artifacts or other measurement-specific reasons.Inclusion criteria were 16 to 90 years of age, more than two exercises longer than 1 h per week (rowers only), more than 18 months of training (rowers only), or persistent low back pain (patients only). Exclusion criteria were previous spine surgery, a scoliosis with a Cobb angle of more than 15°, a present oncological diagnosis, a systemic disease affecting bone or cartilage, and claustrophobia.2 mapping techniques as the results should be comparable in healthy, degenerated, or herniated discs or discs with annular tears as the resulting T2 values can be quite different depending on the discs state.The study population was chosen specifically to compare young individuals with different degrees of spinal load during everyday life to assess early degenerative changes alongside comparably healthy discs in order to cover a wide spectrum of intervertebral disc states. This rationale seemed adequate to assess the broad applicability of different Tfit, Siemens Healthcare) with a gradient strength of 80 mT/m, using a 32-channel spine matrix coil in supine position. Individuals received a standard leg support with a maximum height of 15 cm placed under their knees during the measurement. The protocol consisted of the following morphological sequences: sagittal T1-weighted TSE, sagittal T2-weighted TSE, sagittal T2-weighted STIR, and a coronal and axial T2-weighted TSE sequence with three sections per intervertebral disc. After the morphological sequences, T2 mapping was performed with a MESE sequence and the GRAPPATINI prototype directly afterwards.MR examinations were performed at a field strength of 3 T  was used in the T2 mapping sequences to recover the magnetization in every voxel prior to every echo train [A repetition time (TR) of 3500 ms  without the first echo (WO1ST) and using only even echoes (EVEN).Therefore, the echoes acquired with the MESE sequence were used to calculate two additional T2 map reconstruction. The reference MESE sequence used only a conventional two-fold GRAPPA acceleration. GRAPPATINI T2 maps were automatically reconstructed as previously reported [GRAPPATINI was set to an undersampling factor of 5 and two-fold GRAPPA, effectively resulting in ten-fold undersampled k-space data relative to a fully sampled acquisition for the Treported .2 mapping sequences are listed in Table The sequence parameters for all morphological and TMorphological images were assessed strictly adhering to the Lumbar Disc Nomenclature 2.0 of Fardon et al . Additio2-weighted TSE sequence using the four most central slices by a radiology resident with 5 years of experience in musculoskeletal imaging using ITK-Snap [2 maps after successful automatic co-registration.The resulting images were manually segmented on the sagittal TITK-Snap . First, ITK-Snap , the segAll statistical analyses were performed by a biomedical statistician using IBM SPSS for Windows version 25 (IBM). Given metric and normal distributed data are described using mean ± standard deviation (SD). In case of skewed metric data, median  was used. Correlations were assessed using Spearman’s correlation coefficient. Univariate ANOVA with post hoc tests depending on homogeneity of variances choosing either GT2 after Hochberg (no difference in variance) or Games-Howell (different variance) were used to compare groups . ROC analyses were used to test for discriminability regarding disc herniation, bulging, and annular tear.p value of ≤ 0.05 was considered to indicate statistically significant results. In order to avoid an increasing error of the second type, no multiplicity corrections were performed [A erformed .2-GRAPPATINI  showed a very strong Spearman correlation coefficient  when compared with T2-MESE  as well as with T2-EVEN  and T2-WO1ST . Overall, T2-MESE showed significantly higher T2 values in the nucleus pulposus than T2-GRAPPATINI, T2-WO1ST, and T2-EVEN .Overall, the nucleus pulposus Tp < 0.001; r = 0.446 to 0.465) of T2-GRAPPATINI , T2-MESE , T2-EVEN , and T2-WO1ST .The posterior annulus fibrosus assessment showed a fair Spearman correlation . However, T2-MESE showed insignificantly lower T2 compared to T2-GRAPPATINI (p = 0.074).Overall, T2 values with 95% confidence intervals, see Table For an overview of all the different assessments and the resulting average median TOf all evaluated 290 intervertebral discs, 46 were labeled as bulging discs in 29 individuals and 40 showed lumbar disc herniation in 25 individuals.2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of the nucleus pulposus of normal discs differed significantly from those of bulging discs or herniated discs (p < 0.001). There was no significant difference between bulging discs or herniated discs for T2-GRAPPATINI (p = 0.682), T2-MESE (p = 0.072), T2-EVEN (p = 0.076), or T2-WO1ST (p = 0.075).T2-GRAPPATINI showed a significant difference (p = 0.011) between normal and herniated discs. All other group comparisons of T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST showed non-significant results (p = 0.086 to 0.999). An example of a patient with herniation in segment L5/S1 is given in Fig. 2 map overlays.For the posterior annular region, only T2, the area under the curve (AUC) was 0.895 (0.851–0.939) for T2-GRAPPATINI, 0.888 (0.844–0.931) for T2-MESE, 0.888 (0.844–0.931) for T2-EVEN, and 0.890 (0.847–0.933) for T2-WO1ST.Calculating a receiver operating characteristic (ROC) assessing healthy discs with neither herniation nor bulging present using the NP T2-GRAPPATINI, 0.774 (0.700–0.849) for T2-MESE, 0.775 (0.700–0.849) for T2-EVEN, and 0.776 (0.702–0.850) for T2-WO1ST.Calculating an ROC for bulging discs, the AUC was 0.810 (0.742–0.878) for T2, the area under the curve (AUC) was 0.845 (0.787–0.904) for T2GRAPPATINI, 0.872 (0.829–0.916) for median T2MESE, 0.872 (0.829–0.915) for median T2EVEN, and 0.874 (0.831–0.917) for median T2WO1ST.Calculating a receiver operating characteristic (ROC) assessing disc herniation using the NP TOf all 290 intervertebral discs assessed, 32 showed a high-intensity zone in 22 individuals in the posterior annular region, indicating annular tearing.2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of discs with and without HIZ for both the nucleus pulposus and the posterior annular region .There was a significant difference between T2-GRAPPATINI assessment (p = 0.052).There was one exception with the posterior annular region closely missing the level of significance in the T2, the AUC was 0.919 (0.886–0.953) for T2-GRAPPATINI, 0.913 (0.873–0.953) for T2-MESE, 0.911 (0.871–0.950) for T2-EVEN, and 0.915 (0.876–0.954) for T2-WO1ST. An example patient with a combination of lumbar disc herniation and annular tear of the L5/S1 segment alongside a HIZ in the L4/L5 segment is given in Fig. 2 map overlays.Calculating an ROC for HIZ for the nucleus pulposus TOf all 290 discs, the Pfirrmann grades were distributed as follows: I, 151 IVDs; II, 55 IVDs; III, 35 IVDs; IV, 48 IVDs; and V, 1.2-GRAPPATINI , T2-MESE (0.000 to 0.015), T2-EVEN (0.000 to 0.019), and T2-WO1ST (0.000 to 0.015).For the NP, there was a significant difference between all group comparisons of Pfirrmann grades for T2GRAPPATINI , T2-MESE (0.000 to 0.979), T2-EVEN (0.002 to 0.995), and T2WO1ST (0.005 to 1.000).The annular region showed less discriminability between Pfirrmann grades for T2 mapping from 13:18 to 2:27 min while maintaining the known advantages of quantitatively reflecting the most common disc pathologies.Our data show that GRAPPATINI is capable of significantly shortening the acquisition time needed for accurate T2-GRAPPATINI of the nucleus pulposus showed an AUC comparable to the other methods when assessing discs with neither bulging nor herniation present. The same was true when assessing discs for bulging. Additionally, T2-GRAPPATINI showed the only significant difference in the posterior annular region for healthy discs compared to discs with herniation present. Furthermore, T2-GRAPPATINI showed an AUC equally high as the other methods for HIZ present in the annulus fibrosus.T2 mapping may be employed to assess the ultrastructural composition of intervertebral discs, namely highly hydrated glycosaminoglycans (GAG) in the nucleus pulposus and dense collagen fibers in the area of the annulus fibrosus [Over a decade ago, it has already been demonstrated by Perry et al and Watanabe et al that Tfibrosus , 21.With ongoing degeneration, the IVD GAG content decreases, leading to a falling swelling pressure and an increased risk for annular tears and disc herniation , 22.2 mapping can do that with similar or better discriminability when it comes to disc degeneration [Since allegedly simple tasks, such as the semiquantitative Pfirrmann classification  for degeneration , 23.2 mapping correlated with the water and proteoglycan content of the nucleus pulposus in a histological specimen study of calf and human discs [In line with this statement, Schultz et al reported that the biomechanical properties of the intervertebral discs are better correlated with the collagen fiber structure integrity than with the Pfirrmann classification . Also, Man discs .2 values in patients with chronic lower back pain compared to healthy controls [Ogon et al even showed significant differences in the posterior annular region with lower Tcontrols .2 mapping of hardly any cartilaginous tissue has found its way into clinical routine mainly due to the clinically unfeasible measurement times.However, even after multiple promising studies, T2 values between the different grades of disc degeneration. However, GRAPPATINI was acquired in just 02:28 min with preserved spatial resolution. Furthermore, no sequence-specific artifacts were observed that would impede assessment of an intervertebral disc. This facilitates T2 mapping of the entire lumbar spine in 02:28 min as opposed to 13:18 min using a conventional MESE sequence with the same sequence parameters.Our data confirm the aforementioned literature with significant differences of T2 values significantly differ between herniated and non-herniated discs [2 values of the nucleus pulposus could be used as a predictive biomarker for new lumbar disc herniation at follow-up [Lumbar disc herniation is commonly found in the general population and frequently asymptomatic. However, the presence of lumbar disc herniation is an important finding in symptomatic patients as it significantly worsens prognosis . Hoppe eed discs . In a 5-ollow-up .2 differences in normal discs compared to herniated discs with a similar performance for the investigated T2 mapping techniques as measured by the AUCs of calculated ROCs. However, T2-GRAPPATINI was the only assessment showing significant differences in the posterior annular region of herniated compared to normal discs.Our data are coherent with the literature with significant TAnother important finding in general morphological imaging of the lumbar IVDs is the high-intensity zones of the posterior annulus fibrosus .They are caused by torn fibro-cartilage lamellae of the annulus fibrosus containing trapped nucleus pulposus tissue. This promotes the ingrowth of vascularized granulation tissue into the disc. Simultaneously, sinuvertebral nerve endings begin to sprout into the disc which attribute to the visceral pain qualities of chronic low back pain .2 values in the nucleus pulposus and the posterior annular region compared to discs without HIZs with T2-GRAPPATINI of the nucleus pulposus showing an AUC comparable to the other T2 mapping methods when testing for discriminability.In this study, discs with HIZ showed significantly different T2 mapping [This is concordant with the findings of other studies that reported measurable differences in discs with and without HIZ using T mapping .2 mapping sequences like GRAPPATINI.However, groups like Sharma et al have stated that annular tears precede and accelerate—or actually cause—disc degeneration rather than mainly occurring in already degenerated discs . Our dat2-MESE of the nucleus pulposus when compared to T2-GRAPPATINI, T2-EVEN, and T2-WO1ST. This overestimation is mainly caused by stimulated echoes which instigate an increased signal proportion along the echo train. This results in an overestimated T2 relaxation time and unstable fitting procedure. The fitting can, however, be substantially improved by calculating the T2 maps without the first or with only even echoes, as reflected in T2-WO1ST and T2-EVEN. This approach to mitigate bias caused by stimulated echoes has already been used in other studies [2.Another noteworthy finding in the presented data is the significantly higher T studies , 16, how2 mapping has been a challenging field for many years already due to imperfect slice profiles, field inhomogeneities, and flip angle offsets [Additionally, robust T offsets .2 relaxation time measurements, like radial T2 mapping sequences, the three-dimensional triple-echo steady-state sequence, or, in a much broader perspective, magnetic resonance fingerprinting (MRF) [2 mapping of the lumbar intervertebral disc to this date. This can be attributed mostly to the heterogeneity in the field of view, significant pulsation artifacts from the aorta, and the challenging distance combined with the narrow potential for parallel imaging using spine coils [There are other attempts to shorten the acquisition time needed for Tng (MRF) –33. Howene coils .Also, MRF remains a promising, but investigational approach with ongoing dispute considering the generation of used dictionaries, image reconstructions requiring unusual computational resources, and the currently restricted in-plane resolution in clinically feasible acquisition times.This study has some limitations to be addressed.max = 144 ms) for an undersampling factor of 5, which may cause the fitting of a noise plateau in the calculated T2 decay for voxels with shorter relaxation times. However, this can be relativized by the annular T2 values which still show significant differences for the assessed pathologies at relatively short T2 times which were not superimposed by a noise component.First, GRAPPATINI requires a long echo train since it uses the information along the echoes to recover non-sampled k-space lines. Consequently, the final protocol had to include 16 echoes  with the potential to use the resulting T2 maps as an imaging biomarker for disc degeneration, annular tear, and herniation. At the same time, T2-GRAPPATINI showed an equal or better performance when directly compared to T2-MESE, T2-EVEN, and T2-WO1ST.In conclusion, the presented study shows that “generalized autocalibrating partially parallel acquisition and model-based accelerated relaxometry by iterative non-linear inversion,” in short GRAPPATINI, facilitates robust T


TVR may not always be the best option in the setting of functional regurgitation. However, when repair is indicated, concurrent subvalvular procedures could support the use of TVR. As we learn more about combining these procedures, their efficacy will increase and potentially offer more hope for patients in RVF.282.See Article page ,There is an unmet need to halt the sequelae of right ventricular failure (RVF) and reduce tricuspid valve (TV) deterioration. Left-sided heart failure and pulmonary hypertension result in RVF, triggering in a vicious cycle that leads to increased morbidity and mortality. Due to pulmonary hypertension, volume overload, and/or ischemic wall motion abnormalities in RVF,Couetil and colleagues,Similar to the case of left ventricular papillary muscle approximation during mitral valve repair,


Background andObjectives: Current guidelines on cardiac rehabilitation (CR) suggest moderate-intensity physical activity after acute coronary syndrome (ACS). Recent report have shown that high-intensity interval training (HIIT) could be more effective than moderate-intensity continuous training (MCT) in improving cardiac performance. Our aim was to analyze the effects of HIIT protocol after ACS on advanced echocardiographic parameters of myocardial function. Materials and Methods: In total, 75 patients with recent ACS, with or without ST segment elevation, were enrolled and compared with a control group of 50 age- and sex-comparable healthy subjects. Patients were randomized to perform a MCT training or HIIT-based rehabilitation program. A complete echocardiographic evaluation, including left ventricular (LV) and left atrial (LA) global longitudinal strain (GLS) and myocardial work (MW) through speckle-tracking analysis, was performed for all patients, before and after cardiac rehabilitation training. A cardiopulmonary exercise testing (CPET) was also performed at the end of the rehabilitation program. Results: Patients who followed the HIIT rehabilitation program showed improved LV diastolic function compared to the MCT group . Similarly, LV systolic function showed significant improvement in the group of patients performing HIIT . In addition, LA strain was improved. MW efficiency was also increased in the HIIT group , and was closely related to peak effort measurements expressed in peak VO2 by CPET. Conclusions: In patients with recent ACS, the HIIT rehabilitation program determined reverse cardiac remodeling, with the improvement of diastolic and systolic function, assessed by standard echocardiography. In addition, cardiac deformation index as GLS, LA strain and MW efficiency improved significantly after HIIT, and were associated with functional capacity during effort. Cardiac rehabilitation (CR) is a complex intervention offered to patients usually after myocardial infarction, cardiac surgery or with chronic heart failure . It inclOn the other hand, high-intensity interval training (HIIT) would seem to be more effective than moderate-intensity continuous training (MCT) in improving cardiac performance and function . HIIT geRecently, a new echocardiographic index for the evaluation of LV deformation and function was introduced, namely myocardial work (MW). MW considers cardiac afterload in the strain analysis through the relation with non-invasive LV pressure . This teTherefore, the purpose of this study was to compare the effects of two different cardiac rehabilitation protocols, HIIT vs. MCT, on cardiac remodelling and deformation indices in patients with recent ACS.Our prospective study was based on CONSORT guidelines as a randomized controlled trial. Eighty patients with ACS, with or without ST segment elevation and undergoing complete percutaneous coronary revascularization, were enrolled within 30 days of discharge from the Intensive Coronary Care Unit of Umberto I° Hospital , between September 2020 and September 2021 (NCT04511181). Exclusion criteria were the following: ischemic or hemodynamic instability, severe valvular diseases, major arrhythmias not well controlled, symptomatic peripheral arterial disease, any contraindication to physical activity , inability to exercise, poor acoustic window. According to these criteria, 5 patients were excluded .Since the study protocol was designed for parallel groups , a contrAll patients of the study were enrolled from the population of Nocera Inferiore , with comparable social, economic, cultural and environmental settings.The study was approved by the Institution’s ethics committee (protocol number 121-2021), and each participant provided informed consent.All subjects enrolled underwent a comprehensive clinical and laboratory evaluation. Electrocardiogram (ECG), standard colour Doppler echocardiography, LV 2D speckle-tracking derived GLS and MW analysis were also performed at rest. They were randomized by a computerised random number generator to follow the MCT (40 patients) or HIIT-based (35 patients) rehabilitation program, lasting 8 weeks for a total of 16 rehabilitation sessions .2 peak or ≥85% heart rate reserve (HRR) or ≥90% heart rate (HR) peak) interspersed with lower level exercise, whereas MCT is a form of exercise performed with continuous intensity  (1). After the rehabilitation treatment cycle, all patients were re-subjected to the same clinical, ECG and echocardiographic evaluation, and to a cardiopulmonary exercise testing (CPET). Both the patients and the echocardiographic examiners were blinded to the rehabilitation program.According to recent guidelines, HIIT consists of short periods of intense exercise .2 for men and >95 g/m2 for women. Left atrial volume index (LAVI) was calculated with area-length formula. In addition, LV diastolic function was assessed (E and A peak velocities (m/s), E/A ratio, E-wave deceleration time (ms), isovolumic relaxation time (IVRT), the early diastolic septal and lateral velocities e’and the average E/e’ ratio). Peak tricuspid regurgitant velocity (TRV), systolic trans-tricuspid gradient and pulmonary artery systolic pressure (PASP) were calculated. B-lines were assessed by lung ultrasound with the 4-site scan, from mid-axillary to mid-clavicular lines on the third intercostal space, and each site was scored from 0 = A-lines to 10 = white lung.LV systolic function indices were assessed, including LV ejection fraction (LVEF) with the biplane Simpson method, and the stroke volume from the LV outflow tract (LVOT) diameter and LVOT time-velocity integral. LV mass and LV mass index were calculated. LV hypertrophy was defined for a LVMI > 115 g/mLV Strain. LV GLS was assessed by the 2D STE technique with the software EchoPAC Version 202 . Adequate loops from the apical forth, second, and third chamber, were analysed, manually tracing the endocardial borders in the end-systolic frame of each cardiac cycle and identifying the timing of the aortic valve closure. If tracking was accurate, then the software generated a region of interest (ROI) of the entire myocardial thickness, and calculated the segmental (6 segments) and GLS for each loop. The bull’s eye summarizes the regional and GLS obtained for each cardiac segment.LA strain. An ROI was traced on the endocardial border of the LA (in systole) in the apical four-chamber view. Then, an epicardial border was automatically generated. The final ROI included the entire LA myocardial wall. LA longitudinal strain myocardial thickening was indicated by a peak positive value, color-coded as red; LA myocardial thinning was characterized by a peak negative value, color-coded as blue. LA strain peak represents an index of LA passive deformation and was calculated in the middle segment of LA lateral wall.MW was estimated with a specific software. Non-invasive arterial pressure was measured (average of three measurements) before the echocardiography and introduced in the software. The software created a LV pressure-strain loop, and the area within the loop was used as index of MW for each cardiac segment and global. Constructive work , wasted work  and myocardial work efficiency (MWE = CW/(CW + WW) were also assessed. A bull’s eye with the segmental and global MW, CW, WW and MWE values was provided .2(L/min)). Peak VO2 was indexed for body weight .Subjects underwent a cardiopulmonary exercise test after the rehabilitation protocols using an upright cycle ergometer . Respiratory gas analysis was performed with Quark PTF Ergo Cosmed  with assessment of oxygen uptake  and by Bland–Altman analysis.Continuous variables were reported as median  or means ± standard deviation (SD). To analyse differences within and between groups, paired and unpaired Linear regression analysis and Pearson’s partial correlation test were performed to assess relations between echocardiographic and clinical data. The multivariate analysis, with an interactive stepwise model, was performed to identify the independent predictors of exercise capacity.SPSS Statistics for Windows, Chicago, IL, USA).Statistical analyses were performed by SPSS for Windows release 21.0  systolic function, assessed by traditional echocardiographic indices such as TAPSE and S’ wave rate, was impaired in ACS patients. Of note, a certain degree of pulmonary congestion was observed in the ischemic patients’ group, as evidenced by the finding of B- lines on chest ultrasound.At the echocardiographic evaluation after CR protocols, ischemic patients showed a statistically significant improvement in LA deformation and in both LV systolic and diastolic function compared to baseline, without changes in dimensional parameters but associated with a significant reduction in lung congestion. Conversely, RV systolic functional parameters did not change significantly after the rehabilitation programs .p < 0.01), and with a significant WW reduction  in the HIIT group , LV E/e’  and to the number of B-lines during effort  at multivariate analysis.LV MWE at rest was closely associated to peak VOIntra-observer variability: COV: LV MWE: 5.33 ; Bland–Altman analysis: LV MWE . Inter-observer variability: COV: LV MWE: 7.26 (ICC 0.76); Bland–Altman analysis: LV MWE .2, LV diastolic function and pulmonary congestion.The main findings of our study are as followers: (i) In patients with recent ACS, HIIT rehabilitation protocol showed a significant improvement of both diastolic and systolic function compared to MCT protocol. (ii) Functional improvement in patients undergoing HIIT protocol was mainly detected by LA strain, GLS and MWE increase and WW reduction. (iii) LV MWE at rest was strongly associated with measurements at peak effort by CPET, expressed in peak VOCR has a primary role in secondary prevention of cardiovascular conditions, involving lifestyle behaviour changes, psychological support and exercise training . Interna2 at ventilatory threshold, LV size, cardiac contractility and endothelial function compared to MCT [Previous studies have clearly shown several benefits in patients receiving CR. In particular, HIIT protocol lasting more than 6 weeks appears to be more effective than MCT in improving cardio-respiratory performance in ACS patients, although prognostic information about this type of training cannot be provided . In partd to MCT ,4,9.Whereas data on cardiorespiratory fitness improvement related to HIIT are well established, the effects of this protocol on cardiac deformation in patients with recent ACS are still little known.Several studies have demonstrated the accuracy of GLS in detecting the LV risk area, its correlation with scar extension by cardiac magnetic resonance ,11 and iIn addition, in ischemic patients undergoing a CR program, STE seems to provide a better quantification of LV reverse remodelling after myocardial infarction (MI), as traditional echocardiographic indexes, such as LVEF, are less sensitive for the study of subclinical contractility changes . In a poOur study confirmed, in a larger population of patients undergoing CR after ACS, a significant improvement of both LA and LV systolic function after 8 weeks of training, detected by an increase of LV GLS and of LA strain. This improvement in myocardial longitudinal function was even more consistent in patients following HIIT compared to MCT.Furthermore, we provided more insight in an analysis of myocardial recovery post-CR, investigating, for the first time, the effects of two different rehabilitation programs on myocardial performance measured by LA strain and non-invasive MW indices.MW is an innovative echocardiographic tool for the evaluation of LV deformation through the simultaneous analysis of myocardial strain and non-invasive LV pressure. Its reliability in detecting early, subclinical myocardial damage has been demonstrated in several clinical settings, also showing, at times, its superiority over GLS and other traditional indices of systolic function . In non-In our study population, including both STEMI and NSTEMI patients, we demonstrated that MW, in particular WW and MWE, are sensible markers of myocardial systolic function, being more impaired than controls early after ACS and significantly improving after CR. We further characterized the extent of functional recovery comparing MW indices in two different CR protocols, demonstrating higher improvement after HIIT protocol compared with MCT. In addition, given its independent association with peak effort capacity, diastolic function and signs of pulmonary congestions, both LA strain and MWE seem to be reliable tools for the study of cardiac function in patients with CAD undergoing to CR training. Thus, a complete strain study could have a key role in helping clinicians with the management of patients with CAD undergoing CR.The sample size is too small to give definitive conclusions concerning the myocardial deformation and work in ischemic patients. Furthermore, the group of ischemic patients is heterogenous, with different types of ACS, as well as numbers and characteristics of coronary lesions. The results of our study are applicable only in CAD patients capable of exercising.CR training after ACS allows for the improvement several echocardiographic parameters, resulting in a greater functional performance of the patients and higher quality of life, regardless of the type of exercise performed. In our population of ischemic patients, HIIT showed a greater anti-remodelling effectiveness than the MCT protocols, improving not only the standard echocardiographic parameters but also the deformation index, such as LA strain, LV GLS and MWE, a LV load-independent parameter that might represent a better expression of the contractile efficiency of the LV myocardium.


Moreover, in PPCM, the LV global longitudinal strain (p = 0.03), global circumferential strain rate (p = 0.04), and global longitudinal strain rate (p < 0.01) were less impaired than in DCM. Both PPCM and DCM patients with LGE had more dilated ventricles and more impaired LV and left atrial function than in PPCM and DCM patients without LGE. Conclusions: Subtle differences appear on CMR between PPCM and DCM. Most importantly, the RA is larger and more impaired, and LV global longitudinal strain is less reduced in PPCM than in DCM. Furthermore, similarly to DCM, PPCM patients with LGE have more dilated and impaired ventricles than patients without LGE.Background: Peripartum (PPCM) and dilated (DCM) cardiomyopathies are distinct forms of cardiac disease that share certain aspects in clinical presentation. Aim: We hypothesized that different cardiac structural changes underlie PPCM and DCM, and we aimed to investigate them with cardiovascular magnetic resonance (CMR). Methods: We included 21 PPCM patients (30.5 ± 5.9 years) and 30 female DCM patients (41.5 ± 16.8 years) matched for left ventricular ejection fraction. Biventricular and biatrial volumetric and functional parameters were assessed along with ventricular and atrial strain indices based on feature-tracking techniques. The presence of late gadolinium enhancement (LGE) was also assessed. Results: In PPCM, the left ventricular (LV) stroke volume index was lower ( TTN, MYH7, and SCN5A genes . Th. Th13]. SSFP images were used to calculate left (LV) and right ventricular (RV) volumes and ejection fractions (EF) with the use of dedicated software , as previously described . Left atCMR-FT analysis was carried out by using CVi42 . LV and RV end-diastolic endocardial and LV epicardial contours were drawn automatically. RV epicardial contours were manually traced at the end-diastole. All contours were propagated, with manual readjustments performed as required. The global longitudinal strain and global longitudinal strain rate parameters were obtained from the 4-chamber view for the RV  and from the 2-chamber and 4-chamber views for the LV . Circumferential and radial strains and strain rates parameters for both the RV  and the LV  were determined in the short-axis view in the basal and mid-sections of the ventricles. Due to the known tendency for artifacts and lower muscle thickness in periapical slices, these images were not included in the FT analysis. The basal slice in the short-axis view was defined as the first slice below the atrioventricular level showing a circumferential myocardial enclosing. The midventricular slice was localized at the level of both papillary muscles. The values of the circumferential and radial strains and strain rates obtained in each slice of RV and LV were averaged.The atrial strain and strain rates were also analyzed . LA endot-test or the Wilcoxon–Mann–Whitney U test for continuous variables, and chi-square or Fisher’s exact tests were used for categorical variables where appropriate. Intraobserver and interobserver variability were evaluated by using the Bland–Altman test and expressed as the mean difference ± SD, intraclass correlation coefficients (ICCs) with a 95% confidence interval (CI), and the coefficient of variation (CoV). A two-sided p value of less than 0.05 was considered to indicate statistical significance. Statistical analyses were performed with MedCalc 12.1.4.0 software .All continuous variables were expressed as the mean ± standard deviation (SD) or as the median and interquartile range and were tested for normal distribution with the use of the Kolmogorov–Smirnov test. Comparisons between groups were performed using the Student’s p = ns). Expectedly, DCM patients were older than PPCM patients . PPCM patients more often presented with severe symptoms of heart failure as assessed by NYHA classification  and had higher resting heart rates  as they less frequently received β-blocker therapy in comparison to DCM patients Overall, we included 21 patients with PPCM and 30 female patients with a diagnosis of DCM, matched for ejection fraction  in another four patients with PPCM.2 vs. 44.5 ± 10.5 mL/m2, p = 0.04). Similarly, there were no differences in left atrial volumetric and functional parameters. However, in patients with PPCM, right atrial minimal and pre-systolic volumes were higher than in women with DCM . Moreover, the total RA EF was lower in PPCM in comparison to DCM . There were no differences with regards to the frequency and the extent of LGE between PPCM patients and women with DCM  presented with mid-wall fibrosis of the interventricular septum and/or the inferior insertion point. Only one PPCM patient was found to have subendocardial LGE on CMR. Similarly, mid-wall fibrosis was detected in 10 (55%) female DCM patients. In the remaining eight (45%) DCM patients, LGE of both mid-wall and subendocardial distribution was observed.p = 0.03) and GLS rates  in comparison with female patients with DCM. Furthermore, PPCM patients had less impaired left ventricular GCS rates . However, there were no differences in the right ventricular and biatrial mechanical indices between the groups  and LV mass index (p < 0.01) in comparison to DCM patients without fibrosis.Expectedly, both PPCM and DCM patients with LGE had more dilated left ventricles and more impaired LV function in comparison with PPCM and DCM patients without LGE . Additiop = 0.01; DCM: p = 0.01), RV end-systolic volume index , and more impaired RV EF . Additionally, female DCM patients with LGE also had higher RV end-diastolic volume (p = 0.04) and RV end-diastolic volume index (p = 0.02) when compared to DCM women without LGE.Regarding the RV, PPCM and DCM patients with LGE had higher RV end-systolic volume  and more impaired total (p < 0.01) and passive (p < 0.01) LA EF than PPCM patients without LGE. Female patients with DCM presenting with LGE had lower total LA EF (p = 0.02) than compared to women without LGE. While there were no differences in RA volumetric and functional indices in the PPCM group, DCM patients with LGE had smaller right atria (p < 0.01) and lower total (p = 0.01) and passive (p = 0.01) RA EF in comparison with DCM patients without LGE. Furthermore, PPCM patients with LGE on CMR had larger LA  and DCM groups . In PPCM group the mean value of LV GLS rate was higher in patients without LGE than in LGE positive patients but the difference did not meet statistical significance (p = 0.053). The analysis of all left ventricular strain and strain rate parameters showed that they were more impaired in patients with LGE than in patients without LGE in both PPCM , RV GRS , and GRS rate  in comparison to PPCM and DCM patients without LGE. Additionally, female DCM patients with LGE had more impaired GCS rate in comparison with DCM patients without LGE .With regards to RV mechanics, PPCM and DCM patients with LGE had more impaired RV GCS  and DCM  patients without LGE than in PPCM and DCM patients with LGE. There were no differences in the right atrial mechanical indices in PPCM patients with and without LGE. While in DCM patients with fibrosis, the RA GLS total (p = 0.01), RA GLS passive (p < 0.01), and RA SRS (p = 0.02) were more impaired than in the group of DCM patients without LGE (Similarly, some of the LA mechanical indices were better preserved in PPCM (LA GLS total: hout LGE .The indices of reproducibility for atrial and ventricular strain and strain rate parameters were satisfactory—intraobserver and interobserver ICCs ranged between 0.50 and 0.99 for all components of myocardial performance .Patients with PPCM have lower LV stroke volume index and higher RA volume with lower RA total ejection fraction in comparison to women with DCM.In patients with PPCM, some indices of LV mechanics such as LV GLS and LV GLS rate, as well as LV GRS rate, are less impaired than in DCM women.Both PPCM and DCM female patients with LGE have more dilated and impaired left and right ventricles in comparison to patients without LGE on CMR imaging.Almost all LV and RV mechanical indices are more impaired in patients with LGE in comparison to patients without LGE in both PPCM and DCM groups.Our main findings can be summarized as follows:The role of CMR in the diagnosis and follow up process in patients with DCM and PPCM is well established. Firstly, an accurate assessment of RV size and function can be challenging by using other techniques, such as echocardiography, because of its complex and variable shape. Reduced RV ejection fraction on CMR is an independent predictor of all-cause mortality and adverse heart failure outcomes in DCM and PPCM ,16. In dCMR also allows accurate quantification of left and right atrial volumes by using the biplane area-length method  and is sFinally, given its accuracy in the assessment of cardiac muscle function, CMR is the method of choice for the follow up of patients with DCM after pharmacologic and surgical interventions  and shouData on the role of LGE in PPCM are limited . ImportaCMR-derived feature tracking strain analysis represents another promising tool for improving PPCM patients’ risk stratification. There is evidence which suggests that FT parameters can predict survival in DCM and improve risk stratification beyond clinical parameters, biomarkers, LVEF, and LGE . SimilarIn PPCM patients, LV GLS and LV GLS rates, as well as the LV GRS rate, were found to be less impaired than in women with DCM. This fact may be associated with shorter disease duration in the PPCM group despite the matched ejection fraction.While there are data that echo-derived LVGLS was the most accurate method for detecting LV fibrosis as assessed by histopathologic examination in patients undergoing heart transplantation , this isThe limitations of our study are related to its design. It is a single center retrospective study with a relatively small number of patients with PPCM. It must also be noted that CMR mapping techniques were not applied to our cohort, whereas they are now considered important in the diagnosis of PPCM. Our results may suggest the use of biventricular strain parameters for predicting fibrosis severity in PPCM . HoweverIn conclusion, some subtle differences in CMR imaging are present between PPCM patients and women with DCM. Most importantly, the right atrium is larger and more impaired in PPCM in comparison to DCM, and the left ventricular global longitudinal strain is less reduced in PPCM than in DCM. Furthermore, similarly to DCM, PPCM patients with LGE on CMR have more dilated and impaired left and right ventricles than compared to patients without LGE. The results of this study provide new insights into the cardiac phenotype of PPCM in comparison to DCM and may thereby provide valuable information to complement the clinical findings needed in establishing a diagnosis of PPCM. This study also shows that CMR can be a useful and robust tool to help differentiate between PPCM and DCM if the clinical picture is ambiguous.