Electric interventions are used to terminate arrhythmia. However, myocardial injury from the electrical intervention can follow unique pathways and it is unknown how this affects regional ventricular function. This study investigated the impact of transthoracic electrical shocks on systolic and diastolic myocardial deformation. Ten healthy anaesthetized female swine received five transthoracic shocks (5 × 200 J) and six controls underwent a cardiovascular magnetic resonance exam prior to and 5 h after the intervention. Serial transthoracic shocks led to a global reduction in both left  and right ventricular  peak circumferential strain as a marker of systolic function and to a decrease in LV early diastolic strain rate , assessed by feature tracking analysis. The extent of myocardial edema (ΔT1) was related to an aggravation of regional LV and RV diastolic dysfunction, whereas only RV systolic function was regionally associated with an increase in T1. In conclusion, serial transthoracic shocks in a healthy swine model attenuate biventricular systolic function, but it is the acute development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema. A key procedure to restore the heart’s normal rhythm in both immediate life-threatening arrhythmias and in elective situations are electrical interventions, defibrillation and cardioversion. Defibrillating shocks are used in emergency situations to terminate ventricular fibrillation or in the presence of unstable hemodynamics during ventricular tachycardia. Otherwise, cardioversion, applying R wave-triggered synchronized shocks, is the process of converting patients with atrial fibrillation back into sinus rhythm. External electrical cardioversion was first successfully performed in the 1950s2. Despite more than 70 years of using the technique, the effects of electrical interventions are still unclear. We previously showed using cardiovascular magnetic resonance (CMR) imaging that serial transthoracic shocks resulted in acute myocardial edema3. This was measured by increased myocardial T1, which was further confirmed histologically. Edema is often featured in acute myocardial injury, and can be identified with native myocardial T1 mapping5. However, myocardial injury follows unique pathways through the thorax in each individual and it is unknown how it impacts regional ventricular function. In swine, Aeillo et al. demonstrated that increased electrical burden, defined by the cumulative energy of unsuccessful shocks, was linked to reduced LV function and survival6. Common functional measures such as ejection fraction (EF) and volumes are limited in that they represent only global ventricular function and the effects of transthoracic shocks on regional myocardial function have yet not been systematically assessed.Atrial fibrillation is the most common sustained cardiac arrythmia worldwide, and is estimated to occur in approximately one-third of individuals7. Because strain can detect subtle abnormalities, even in the absence of global systolic impairment, it is thus interpreted as an earlier and more sensitive modality than conventional visual assessment. Multiple publications have reported that CMR-FT incrementally improves diagnostics and prognostication beyond the common ventricular function measures such as ejection fraction11. Strain has also been used for repetitive measures within the same subject to investigate temporal changes in function occurring over a short period of time15. In addition to assessing regional function, strain analysis is beneficial as multiple markers representing systolic and diastolic function can be derived simultaneously. This multiparametric approach of strain measurements is beneficial as it provides a comprehensive assessment of various components of myocardial function over the cardiac cycle17. CMR-FT has also been translated to experimental animal models18, and has been reported to be reproducible in swine hearts19, and related to myocardial injury21.CMR feature tracking (FT) is a post-processing technique that can quantify myocardial contraction and relaxation on a regional level Fig.  and can The purpose of this study was to investigate the impact of acute myocardial injury after serial transthoracic electrical shocks on regional systolic and diastolic myocardial deformation in a healthy animal model.3 prior to the start of the study. Seventeen female common landrace swine (32 ± 1 kg body weight), were premedicated with combination of 200 mg zolazepam, 200 mg tiletamine. 0.8 mg atropine and 2–4 mg/kg of intravenous propofol induced anaesthesia. Animals were then intubated and mechanically ventilated for the remainder of the experiment. A continuous propofol infusion (12–37 mg/kg/h) maintained anesthesia. For blood sampling, invasive blood pressure monitoring, as well fluid infusion, the femoral artery and vein were cannulated. At the end of the imaging experiment 40 mmol of intravenous KCL and 200 mg propofol was used for euthanasia.The study was performed in accordance with the ARRIVE guidelines and with the “Guide to the Care and Use of Experimental Animals” by the Canadian Council on Animal Care and approved by the animal care board of the Montreal Heart Institute, Montreal, Canada [#20125003]The animals were transferred to a clinical 3 Tesla MRI . Prior to any intervention all animals underwent a baseline imaging protocol involving native T1 maps acquired in three short axis views  and a short-axis cine stack of 7–10 slices crossing the ventricles. A 3(3)3(3)5-modified Look-Locker sequence was used for the T1 imaging . An ECG-gated balanced steady-state free precession sequence was used for the cine imaging .Six animals served as controls, while eleven underwent the electrical intervention. For this group one defibrillator pad was placed on the left postero-lateral chest wall in front of the scapula, and the second was placed on the right pectoral muscle close to the axilla. Five serial biphasic synchronized transthoracic shocks were applied using an automated external defibrillator . Five hours later, all subjects underwent cine and T1 imaging, similar to the baseline exam Fig. .Figure 2All datasets were recoded to blind the readers to the intervention, and one reader quantified T1 maps for both the LV and RV. T1 analysis of the LV was performed on the generated pixel-wise maps with placement epicardial and endocardial contours on 3 short axis slices, and data were reported for each of the 6 myocardial segments on the basal, mid and apical slices .A second reader blinded to the tissue characterization findings analyzed biventricular ejection fraction and deformation on the short-axis stack. For the FT strain measurements, the parameters of circumferential peak strain, time to peak strain and early diastolic strain rate were acquired for global measurements of the LV myocardium and RV free wall. To measure the regional response in LV FT strain measures, data were acquired per segment in the slices matching the T1 analysis. Mechanical dispersion was calculated as the standard deviation of the time to peak strain of all segments. For regional analysis of the RV, each acquired slice Fig.  was cons3.After euthanasia, 34 samples from the LV were available for histological analysis, with regional selection either randomly selected or guided by T1 analysis. The fraction of interstitial space was quantified from three representative areas of each sample using semi-quantitative planimetry slice . Blood samples were acquired at baseline and the 5 h timepoint and troponin I (TnI), porcine cardiac fatty acid binding protein (cFABP), creatine kinase (CK) and porcine cardiac creatine kinase-MB (CK-MB) were quantified as detailed previouslyt test. The regional changes in strain in comparison to the development of myocardial injury (ΔT1 mapping) over the course of 5 h were statistically assessed using a mixed effects model accounting for the electrical intervention and multiple measurements per individual17. Finally, receiver operator characteristics curves were calculated to assess the strain markers’ ability to discriminate myocardial injury defined by histology and incremental cut-offs of intracellular area indicating increasing levels of tissue injury. Statistical significance was defined with a two-sided p-value of < 0.05. GraphPad Prism version 9.0 , R software  were used for analysis.Initially, the difference in global CMR measures from baseline to the 5 h timepoint were compared for each group using a paired 3.Ten swine receiving 5 serial transthoracic shocks of 200 J and 6 control animals successfully completed the protocol with CMR images repeated 5 h after the intervention Fig. . Fluid mThe measurements of the global circumferential strain parameters at baseline and 5 h post-shock are depicted in Table −1 for every 100 ms increase in T1.As Figs. Thirty-four LV histology samples were assessed for interstitial area  and localized to the segments matching the feature tracking analysis. When using a low cut-off for increased interstitial space, only diastolic strain rate was associated with mild myocardial injury . Similar to the LV, RV diastolic function of an individual slice also worsened in the presence of increased RV T1, with a reduction of − 0.42 sT1 Table , Fig. 5.23. Yet, the electrical pathway from transthoracic shocks can vary across the heart and these global techniques cannot identify the unique distributions of myocardial injury that occur as a result. The development of feature tracking analysis to quantify regional strain allowed us to colocalize the myocardial dysfunction with acute changes in myocardial tissue injury providing a more sensitive assessment of acute myocardial caused by electrical interventions.In a heathy swine model, serial transthoracic shocks led to a global reduction in both right and left ventricular systolic function within 5 h of the intervention assessed by circumferential strain analysis with CMR feature tracking Fig. . This el25. In electroporation injury, the applied current forces ions through the cellular membranes, which disrupts the delicate balance of ions and molecules along the intracellular and extracellular side of the cell membrane, therefore causing an osmotic water influx into the cell and edema26. Many studies have focused on serological markers, such as troponins and creatinine kinases27. However, the evidence is not consistent and biomarkers cannot determine the exact location of the injury. A more direct approach has been assessed through histology, although a key limitation is histological findings require an invasive biopsy or post-mortem analysis. Imaging provides an ideal non-invasive approach for investigation into regional and current myocardial injury, and repetitive acquisitions can be easily acquired to allow for monitoring dynamic changes in cardiovascular features over time. Especially with CMR, a comprehensive approach can be undertaken to monitor both myocardial injury defined in this study by increases in myocardial T1 from quantitative T1 mapping sequences, and coinciding changes in biventricular function. Particularly, quantitative approaches such as strain analysis, provide a sensitive investigation into functional changes. As our results depict, both systolic and diastolic strain parameters worsened globally in the intervention group, despite the fact that neither RV nor LV ejection fraction changed. These findings are reflected by multiple publications from echocardiography and magnetic resonance imaging modalities where it was reported that strain provides earlier or incremental information on myocardial function, especially in preserved ejection fraction cohorts, when no change in ejection fraction is noted, or even as an early predictor for changes in ejection fraction33. Although our findings demonstrate global dysfunction, strain allows an even deeper quantitative analysis into the regional variations of functional change, consequently it can also be colocalized to regional tissue markers.The myocardial injury due to electrical shocks has been theorized to be a consequence of either local heating to high temperatures or as a result of breakdown of the cell membrane caused by electroporation35. Detwiller showed in an isolated swine heart model that the stress–strain relationship of papillary muscles shifted with progressive edema, indicating increased stiffness36. However other mechanisms for edema-induced diastolic dysfunction have been proposed as well including, reduction of the myocardial oxygen supply through increased vascular resistance, abnormal extravascular pressure, and thicker myocardial walls37. Many of these mechanisms can impact contractility as well, with edema linked to both diastolic and systolic dysfunction38. Although we observed that systolic function worsened globally over the 5 h, we did not observe a direct regional correlation between systolic dysfunction and T1 in this study, and only with a significant interstitial area was systolic dysfunction locally associated with myocardial injury. As this analysis only investigated changes in edema and cardiac function over 5 h, this may indicate that diastolic dysfunction is impacted earlier than systolic function after the onset of myocardial edema in the LV. Interestingly, diastolic function being negatively affected prior to systolic function can also be seen in the well documented ischemic cascade39. The RV showed linear correlations with increased T1 and both peak circumferential strain and diastolic strain-rate, indicating that increased RV edema induced systolic and diastolic dysfunction during this timeframe. This could potentially be due to the fact the RV wall is thinner and may be more compromised by edema, or by the fact the RV could be more directly in the electrical pathway through the torso and in proximity to the defibrillator pad. Longer term studies would need to assess the temporal relationship between myocardial edema, and systolic and diastolic dysfunction. In a rabbit model it was shown that low-energy defibrillation shocks increase endothelin-1 levels both locally in the heart and in the blood serum, and the authors suggested this may lead to capillary blood flow abnormalities and potential post-intervention disease40.Segmental LV diastolic strain rate was colocalized to both imaging and histologic markers of edema. While native T1 is also linked to myocardial fibrosis, a rapid increase in T1 over a short period of a few hours can be attributed to increased local water content associated with swelling. Moreover, an increase in interstitial space on histology could be due to electroporation injury of the smooth muscle vascular endothelium or through a subsequent inflammatory response. A deceleration in regional LV diastolic strain rate was linearly associated with the increase in myocardial T1, while no linear connection was observed with LV peak strain, a marker of systolic function. Additionally, LV diastolic strain rate could discriminate even mild levels of interstitial edema shown by interstitial area in histological analysis, while peak strain could only detect a greater severity of interstitial area. The aggravation of diastolic dysfunction in accordance with increased myocardial edema likely attributed to stiffening of the heart. When myocardial edema accumulates, the rise of interstitial pressure increases myocardial stiffness reducing ventricular compliance41. As patients who undergo defibrillation or cardioversion are likely to have one or multiple of these underlying diseases impacting the RV42, it is thus important to not narrow findings on only the LV and expand assessments to the RV as well.While the majority of investigations focus on the left ventricle, we undertook a biventricular analysis. The pathway of electrical interventions crosses the heart and is very likely to involve the RV which can be observed in Fig. 17. Thus, the implications from our imaging findings can be translated to human investigations. It is important to consider that these imaging techniques can be prone to changes due to other factors occurring in a peri-operative environment including saturation levels, and heart rate44. Particularly the relative myocardial water content alters T1 relaxation times and this is relevant to fluid management. Luetkens et al. investigated the impact of hydration or dehydration state on T1- and T2-relaxation times45. Here, the hydration status led to a significant change of T1 and T2 relaxation times. Administered water also has an influence on functional parameters. Cardiac function is primarily dependent on systolic and diastolic function as well as loading conditions, to specify preload and afterload. Burns et al. demonstrated that LV peak systolic strain rate and peak systolic strain are sensitive to acute changes in fluid load in human subjects46. Moreover, it was demonstrated in swine that high afterload due to an increase in blood pressure can impact myocardial blood flow and strain47. Since the animals of this study received fluids during the extensive scanning, relative changes of myocardial water content is a possible confounder. Nevertheless, blood pressure, haemoglobin and hematocrit levels did not change between the two timepoints, and fluid administration was not different between groups.This was a translational study, which used an experimental healthy animal model to first demonstrate that electrical interventions lead to myocardial injury and that these acute changes in the heart can detected by non-invasive imaging techniques confirmed by histology. We applied the standard clinical mapping and strain sequences and analysis techniques that have been validated and implemented into clinical settings to investigate cardiovascular disease48. Dose-dependent relationships would be important to investigate in the future, in addition to other variables such as pad position50. In non-responders to electric cardioversion one could investigate if there is a potential benefit to determine the best vector for the electric current using imaging exams, however other factors, i.e. the electric resistance of the tissue between defibrillator pads, may play a more important role that the actual vector. This study investigates healthy swine who were in normal sinus rhythm prior to the intervention. This allowed us to isolate the impact of the transthoracic shocks without the confounding effect of underlying injury from an arrhythmia. As a result, we also observed that transthoracic shocks worsened synchronicity of segmental contraction, as shown by an increased mechanical dispersion. In contrast to our study, in a clinical scenario, the patients receiving this intervention will have existing arrhythmia. Future clinical studies will need to investigate how electrical interventions impact myocardial tissue features and function in an already diseased heart and the net impact of cardioversion comparing the benefit of restoring sinus rhythm in comparison to the induced myocardial injury. While the alternatives are limited to avoiding this intervention, a better understanding of the regional myocardial tissue abnormalities and dysfunction potentially induced by electrical procedures and the variation in the onset of dysfunction between individuals may improve the understanding of myocardial recovery post-cardioversion. Additionally, investigation of the myocardial injury arising from the electrical pathway in patients with unsuccessful cardioversions could facilitate more effective pad placement. This study focused on the acute effects of acute injury within a 5 h timeframe after electric transthoracic shocks and its impact on regional function, however, we do not know how long the dysfunction endures or if these result in a permanent injury. Further studies in clinical populations are required to establish if transthoracic shocks result in permanent effects on the myocardium.There are further considerations prior to translating these findings to a clinical setting. A cumulative energy of 1000 J was applied from 5 shocks. This is higher than applied in a typical cardioversion in a clinical setting but is still within a realistic treatment range. For example in a study of 101 patients undergoing elective external cardioversion, Lobo et al. reported the median shocks and cumulative dose delivered was 1 shock at 161 J, yet up to 6 shocks with a cumulative dose of 1668 J was provided in one instanceWhile serial transthoracic shocks in a healthy swine model led to a global attenuation in biventricular peak strain, the acute development of regional diastolic dysfunction was associated with the onset of colocalized myocardial injury. Future studies are warranted to assess these effects of electrical interventions in clinical settings.


To elucidate the value of texture analysis (TA) in detecting and differentiating myocardial tissue alterations on T2-weighted CMR (cardiovascular magnetic resonance imaging) in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM).In this retrospective study, 100 CA  females) and 217 HCM  females) patients who underwent CMR scans were included. Regions of interest for TA were delineated by two radiologists independently on T2-weighted imaging (T2WI). Stepwise dimension reduction and texture feature selection based on reproducibility, machine learning algorithms, and correlation analyses were performed to select features. Both the CA and HCM groups were randomly divided into a training dataset and a testing dataset (7:3). After the TA model was established in the training set, the diagnostic performance of the model was validated in the testing set and further validated in a subgroup of patients with similar hypertrophy.p = 0.898). All seven texture features showed significant differences between CA and HCM .The 7 independent texture features provided, in combination, a diagnostic accuracy of 86.0%  in the training dataset and 79.2%  in the testing dataset. The differential diagnostic accuracy in the similar hypertrophy subgroup was 82.2% . The significance of the difference between the AUCs of the TA model and late gadolinium enhancement (LGE) was verified by Delong’s test (Our study demonstrated that texture analysis based on T2-weighted images could feasibly differentiate CA from HCM, even in patients with similar hypertrophy. The selected final texture features could achieve a comparable diagnostic capacity to the quantification of LGE.Trial registration Since this study is a retrospective observational study and no intervention had been involved, trial registration is waived.The online version contains supplementary material available at 10.1186/s12872-022-02671-0. Cardiac amyloidosis (CA) is a progressive and infiltrative cardiomyopathy that frequently leads to heart failure and cardiac death . At presWith the development of “Radiomics”, mining the existing basic imaging data and obtaining useful novel parameters from the radiological images with the use of computer algorithms has become an area of research interest. Texture analysis (TA) quantifies the texture of an image based on spatial distributions of pixel signal intensity and relationships of values between neighboring pixels . TA has The T2-weighted imaging (T2WI) is widely used to identify pathological lesions in many organs, such as the brain, liver and muscles. Abnormal T2 signal intensity is correlated with edema, cellular proliferation, and vessel densities , 8. In tIn this preliminary study, we sought to use texture analysis to find novel and useful parameters from the routinely acquired T2WI images, which could discriminate the myocardial tissue of CA from hypertrophic cardiomyopathy (HCM), a subtype of left ventricular hypertrophy (LVH) of different etiology.We retrospectively included 317 subjects  who underwent CMR scans between January 2016 and June 2020. For patients with CA, most of them were initially diagnosed with systemic disease (such as plasma cell dyscrasia or multiple myeloma) or amyloidosis in other extra-cardiac organs . They were referred to CMR to see if the heart was involved. CA was diagnosed on the basis of positive myocardial biopsy or extracardiac biopsy in conjunction with a mean LV wall thickness  ≥ 12 mm on CMR [For patients with HCM, they were referred to CMR because of abnormal electrocardiography or left ventricular hypertrophy by echocardiography, as CMR could provide more accurate measurement of morphological alterations and evaluate the extent of myocardial fibrosis. The diagnosis of HCM was based on the presence of unexplained LV wall thickness ≥ 15 mm or ≥ 13 mm with a family history of HCM or apical hypertrophy in the absence of other conditions capable of producing a similar degree of hypertrophy [The exclusion criteria for all subjects were valvular heart disease (greater than mild stenosis or greater than moderate regurgitation), significant coronary artery disease, and other confirmed systemic diseases. Images of poor quality were excluded. Hypertensive patients with concentric hypertrophy were also excluded.CMR imaging was performed in accordance to a standard protocol, as previously published by our group . All CMR42; Circle Cardiovascular Imaging, Inc., Calgary, Canada). The extent of LGE was quantified by using the full width half maximum technique [Conventional CMR parameters including LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV ejection fraction (LVEF), LV mass, maximum LV wall thickness (MWT) and LGE extent were calculated using commercially available software  was calculated to assess the intra- and interobserver reproducibility of the selected features. Features with ICCs < 0.75 were excluded, ICCs ranging from 0.75 to 1 considered “excellent” . The BorAfter the radiomics signature was established, the diagnostic efficiency and accuracy of the model was validated in patients with similar hypertrophy matched by LV mass index as well as age, sex and maximum wall thickness (MWT).Statistical analysis during the construction of the radiomics signature was performed in R   with RStThe clinical and CMR characteristics of the 317 included patients  are presented in Table p < 0.001 for both).The patients with CA were older and had higher NYHA functional classes than the HCM patients. The HCM group had a higher body mass index. Moreover, more hypertensive patients were found in the HCM group than in the CA group. The NT-proBNP and troponin T levels were markedly higher in the CA group than in the HCM group , while the EDV index was higher in the HCM group . The LV mass index was comparable between the two groups , whereas the MWT was higher in the HCM group than in the CA group . CA patients displayed a remarkably higher LGE extent than HCM patients .The ESV index was higher in the CA group than in the HCM group  LHL; GLRLM-Short Run Emphasis (SRE) LHL; GLRLM-LRE LLH; and GLDM-Small Dependence High Gray Level Emphasis (SDHGLE) HLH) and three original features ; GLCM-Correlation). All seven texture features showed significant differences between CA and HCM Table . Correlap = 0.898).The 7 selected texture features provided, in combination, a diagnostic accuracy of 86.0%  in the training dataset and 79.2%  in the testing dataset Fig. . The sigThe ICCs of the 837 radiomics features ranged from 0 to 0.983. Among them, 614 features had an ICC < 0.75 and were excluded from further analyses. The reproducibility of the final selected 7 features was considered excellent (ICCs ranging from 0.757 to 0.949)  the light-chain amyloidosis (AL). Even though there is little difference in signal features between the AL and the other subtype of amyloidosis, our study result is limited to the AL amyloidosis and needs to be confirmed in other subtypes of CA. Third, considering the histological alterations within a disease process are unlikely to be the same throughout the heart, the ROI used in this study can only reflect the regional characteristics of the myocardium. In addition, the sub-analysis of patients with similar hypertrophy was limited by the small sample size. Further well-designed prospective studies are necessary to determine the utility of these TA parameters for a more general application.In Additional file 1: Additional information about the feature selection process.


Since its first description in 1971, the Fontan procedure and its modifications have led to a substantial improvement in the survival rates of patients with a variety of types of complex Congenital Heart Disease (CHD) characterised by the presence of a single, dominant ventricle. However, despite the significant improvement of the prognosis over the years, Fontan patients are still exposed to several cardiovascular and systemic complications. It is, therefore, important to fully understand the pitfalls hidden behind a Fontan anatomy and the potential predictors of ventricular failure. Cardiovascular imaging plays a key role in this context, allowing for the early identification of complications with important prognostic implications. Echocardiography remains the first-line imaging modality for serial evaluation of Fontan patients. However, there is a growing role of cardiovascular magnetic resonance and cardiac computed tomography from pre-operative assessment to longitudinal follow-up. The aim of this paper will be to provide a comprehensive overview of the role, strengths, and weaknesses of each imaging modality in the assessment of congenital cardiac conditions palliated with the Fontan procedure. Children as well as adults with a single ventricle (SV) after Fontan palliation are exposed to numerous complications over the course of their lifetimes, such as failure of the SV performance ,2. The mRecognizing predictors of ventricular failure is an unmet need of current clinical research, in order to identify patients at a higher risk who need closer monitoring, along with potential percutaneous or surgical interventions to prevent or relieve ventricular failure ,2,3,4.“A big ventricle is a bad ventricle” is what, as cardiologists, we have learned for decades. On the contrary, when referring to Fontan patients, it is known that there is a short route between an underfilled ventricle and one with a volume overload, because the SV is acutely sensitive to a preload reduction, which would obligate the patient into a low-output state ,2,3,4,5.Single ventricles may be, indeed, relatively dilated in order to perform, on the Starling Curve, at increased contractility, considering that an SV with a Fontan circulation is required to work as two ventricles. However, just as for normal hearts, there is a break point of dilatation that may become damaging ,2,3,4,5.Many underling reasons may explain what usually happens besides an intrinsic myocardial failure, such as the atrio-ventricular and semilunar valve regurgitation, the chronotropic insufficiency, and the systemic to pulmonary collateral burden ,2,3,4,5.In these circumstances, the (single) ventricular work and output are increased as well. Accordingly, hepatic fibrosis, which is a common complication, may cause an additional volume overload in an already compromised ventricle, potentially accentuating cardiac fibrosis and ventricular failure along with a poor outcome .Assessing the ventricular end-diastolic volume may be complicated in Fontan patients, as the heterogeneity of the anatomy cannot be compared in a unique cohort  or left ventricle (LV) morphology, D-looped or L-looped).For these reasons, cardiovascular magnetic resonance (CMR) is the gold standard for assessing ventricular volumes and performance according to the most valuable recommendations .Most recently, speckle-tracking echocardiography (STE) has been confirmed as being a reliable technique, allowing for the evaluation of ventricular deformation without any geometric assumption or the impact of acute preload changes . AlthougBorrelli et al.  recentlyMeyer et al.  brought The scope of this review is to summarise and propose a surveillance imaging testing toolkit for the follow-up care for patients with a Fontan circulation. Gaps in knowledge along with areas for future focus of investigation are emphasised, with the aim of building the best follow-up protocol in order to create a normal life for these unique individuals.Transthoracic echocardiography (TTE) remains the cornerstone technique of cardiac diagnostic imaging in patients with congenital heart disease. Considering the large accessibility, reproducibility, and ease of use of the method, it has been widely adopted even in patients with single-ventricle physiology . HoweverWhen a patient with complex univentricular cardiopathy presents with an unclear surgical history and anatomical details, a comprehensive evaluation is needed to define the anatomical and haemodynamic characteristics of the single-ventricular circulation. It is necessary to use a methodical process for the segmental analysis in order to provide a reliable morphological assessment .The segmental analysis involves the evaluation of anatomical and embryological blocks, which are the main components of the mammalian heart, in a step-by-step approach. The veins and atria represent the first segment, followed by the ventricles and major arteries. The cardiac position, function, and connection of all segments should then be described. First, the location of the heart is defined, along with the anatomical pattern of the abdominal and thoracic organs.Situs solitus is the usual arrangement of the body’s organs, where the liver, cecum, and appendix are right-sided, and the spleen, pancreas, stomach, and sigmoid colon are left-sided. The left mainstem bronchus is longer and more horizontal and runs inferior to the left pulmonary artery, and the left lung consists of two lobes. The right mainstem bronchus is shorter and runs posterior to the right pulmonary artery, and the right lung has three lobes. In situs viscerum inversus, the orientation of the body organs is reversed, mirroring that of situs solitus. The third arrangement, situs ambiguous (left and right isomerism), is characterised by the abnormal symmetricity of the body organs. Since the echocardiographic evaluation of the atria situs can be difficult, the abdominal and thoracic situs are generally used to guide the definition of the atrial situs. However, it should be noted that there is no 100% correlation between the thoracic or abdominal characteristics of the visceral situs and the atrial situs. The echocardiographic short-axis subcostal view is commonly used to define the visceral situs. In situs solitus, the aorta is pictured as a pulsatile vessel anterior; to the left of the spine, the inferior vena cava (IVC) is pictured as a collapsible vessel further anterior; and, to the right of the spine, the liver is rightward, while the spleen is leftward. This visceral arrangement is generally associated with atrial situs solitus. In situs inversus, the aorta is visualised to the right of the spine, while the IVC is to the left. Accordingly, the right atrium and left atrium are in a mirror position.Cardiac position refers to the heart localisation relatively to the midline. The terms levoposition and dextroposition denote the majority of heart mass to the left or to the right of the midline, respectively. When the heart is mesopositioned, it is located around the midline.Cardiac orientation refers, instead, to the orientation of the base-to-apex axis. Normally, the base-to-apex axis points to the left, defining the cardiac levocardia. In dextrocardia and in mesocardiac, the base-to-apex axis points to the right and downward, respectively.The next step is defining the atrio–ventricular connection and ventricular looping. Ventricular looping is the term used to describe how the heart tube loops during embryological development. When the looping is to the right (D-looping), the right ventricle is anterior and to the right of the left ventricle. When the looping is to the left (L-looping), the morphological right ventricle is to the left of the morphological left ventricle. Then, it should be defined if a biventricular or single-ventricle connection is present. While in a biventricular connection two atrio-ventricular valves are present with two possible connections of the atria to the ventricles (concordant or discordant), a univentricular connection is more challenging.The term SV refers to various forms of complex congenital heart defects in which there is one single-ventricle chamber or a large dominant ventricle with a rudimentary ventricle.In the presence of a single functional ventricle, a double inlet (where two atria empty into a single ventricle) or a single inlet (where a single atrium empties into a single ventricle) can be present.A ventricle morphology evaluation can also be tricky in univentricular hearts. In this case, the type of rudimentary ventricle can give some clues. If the rudimentary ventricle is positioned posteriorly to the main ventricle, the single-ventricle morphology is of the right type. On the contrary, if the rudimentary ventricle is positioned anteriorly to the main ventricle, the single-ventricle morphology is of the left type.Finally, the ventricular–arterial connection is determined. A concordant, discordant, or double-outlet connection can be present. In a concordant connection, the aorta arises from the left ventricle, while the pulmonary artery arises from the right ventricle. In a discordant connection, on the contrary, the aorta arises from the right ventricle, while the pulmonary artery arises from the right ventricle. If one artery arises completely from the right ventricle, and the other arises more than 50% from the same right ventricle, a double-committed connection is present.However, in a Fontan circulation, both the main arteries serve as the systemic outflow of the single ventricle .As ventricular function in the palliated univentricular heart declines, there is a significant potential for negative clinical outcomes. Considering the lack of a subpulmonary ventricular pump, there is a limited possibility to increase the cardiac output by raising the preload of a failing single ventricle. As a consequence, a failing single ventricle of a Fontan circulation results in a low cardiac output status, which is particularly vulnerable.The dominant ventricle in Fontan patients may be morphologically left, as in tricuspid atresia or a double-inlet left ventricle, or morphologically right, as in hypoplastic left heart syndrome. Moreover, two relatively well-formed ventricles can be present, as in patients with a large ventricle defect where a double-ventricle correction strategy cannot be pursued.When a morphological left ventricle is present, from the apical four-chamber view, ejection fraction by biplane Simpson’s method is the technique of choice to estimate ventricle function.More challenging can be the analysis of a morphological right ventricle. From the apical four-chamber view the fractional area change can be evaluated using the formula: [(end-diastolic area − end-systolic area)/end-diastolic area] × 100.Information on ventricular performance can also be obtained via Doppler-derived systolic rates of ventricular pressure change (dP/dT). It is worth noting, there are no precise reference limits for these functional parameters in single ventricles, so perhaps added value may be gained from follow-up longitudinal reevaluations . In adult Fontan patients, Bunting et al. demonstrated that a 3D echocardiography ejection fraction correlated strongly with the one evaluated by CMR and can be used for serial functional assessments .The AV valve S/D ratio allows the assessment of ventricular function without anatomical assumption and represents an independent predictor of mortality in adult patients with a Fontan circulation .Recently, STE has been demonstrated to be a reliable technique to evaluate single-ventricle performance without any geometric assumption or influence of acute preload ,16. A drIn a study by Rösner et al., a typical dyssynchrony pattern by STE was found in several patients with a Fontan circulation. This pattern was characterised by an early shortening of the dyssynchronous segments (‘flash’), followed by systolic stretching; while, on the contrary, segments with a conduction delay showed early stretching, followed by delayed contraction. Among the different functional parameters, the presence of electromechanical dyssynchrony was the strongest predictor for mortality and heart transplantation . Diastolic dysfunction is common in patients with a Fontan circulation, even in the presence of normal systolic function. The significant prolongation (>28 ms) of the pulmonary venous atrial reversal flow, relative to atrial forward flow duration into the ventricle, suggests that the single ventricle’s filling pressure is elevated. Reductions in the deceleration time of the atrio-ventricular valve inflow have been also associated with diastolic dysfunction .Yamazaki et al. demonstrated that Fontan patients performed less well at exercise stress echocardiography when compared to healthy subjects; this was largely due to an impaired contractile reserve, chronotropic incompetence, lower ventricle filling capacity, minimal preload variability, and less afterload reduction . The study of fluid dynamics ,24 can pVentricle function assessment by echocardiography is shown in High atrial pressure hampers transpulmonary flow, especially in the absence of a subpulmonary ventricle pump, as in a Fontan circulation. Accordingly, as in the case of atrioventricular (AV) valve stenosis or regurgitation, the increase in atrial pressure may be poorly tolerated by Fontan patients. Routine assessment of the AV valve comprises the morphologic evaluation of thickness and mobility of the leaflets, together with a semi-quantitative doppler estimation of AV valve regurgitation . Any diastolic transvalve gradient should also compromise Fontan physiology and be accurately evaluated.Coarctation of the aorta (as in a hypoplastic left heart with a neo-aortic arch), subaortic stenosis (as in a double-inlet left ventricle with a restrictive bulboventricular foramen), and pulmonary arteries distortion are the most frequent issues after the Fontan procedure. Ventricular outflow obstruction can increase end-diastolic pressure and compromise cardiac output in Fontan patients. It is, therefore, necessary during echocardiographic examination to carefully evaluate the semilunar valve, measure the annular and subaortic dimensions, and look for thickness, prolapse, or mobility restrictions. It is also recommended to determine semilunar valve stenosis and regurgitation by using standard Doppler methods. Moreover, the aortic arch must be thoroughly scanned for anatomic narrowing throughout its length . ResiduaThe lack of a subpulmonary ventricular pump results in non-pulsatile flow in the pulmonary vascular bed and Fontan pathway. As a result, the fluid dynamics of the stenoses will be more like a venous obstruction, and the Doppler flow gradient is frequently low. Therefore, the size of the Fontan connection and of the pulmonary arteries should be carefully examined. Any reduction and enlargement downstream should be taken into consideration and studied by both a continuous and a pulsed wave Doppler . A reducSometimes, at the time of Fontan pathway creation, fenestrations are purposefully kept in place to increase cardiac output. The flow across these fenestrations should be recorded, and the mean pressure gradient should be estimated by continuous wave Doppler echocardiography. In the absence of stenoses, the pressure in the Fontan channel is equivalent to the pulmonary arterial pressure, while the pressure in the functional left atrium will be equivalent to the pulmonary venous pressure in the absence of pulmonary vein stenosis. As a result, the mean pressure gradient across a fenestration will reflect the transpulmonary gradient. A haemodynamically stable Fontan circulation is associated with a transpulmonary gradient of 5 to 8 mmHg.Venovenous collaterals can develop gradually after Fontan surgery and be responsible for significant desaturation . SometimIn patients with poor acoustic windows, transoesophageal echocardiography (TEE) can provide a more accurate visualisation. In Fontan patients, TEE can be used to evaluate thrombus, AV valve function, ventricular function, and residual Fontan fenestration . In ordeCMR is an advanced cardiac imaging technique that allows for study of the morphology, haemodynamics, and tissue characterisation of the heart without the use of ionising radiations ,28. ImagCMR can overcome echocardiography’s limitations of suboptimal acoustic windows, operator-dependent measurements, and non-classical cardiac anatomy ,28,29. IOn the other hand, CMR has a long acquisition time that can lead to reduced patient compliance in breath-holding. It has a high cost and limited availability and requires high expertise in the performance and interpretation of the images. Arrhythmias and metallic devices can generate artefacts, but nowadays there are techniques to overcome these limitations. Implantable pacemakers or defibrillators could be a contraindication for CMR, and in these patients these should only be considered in specialised centres ,33,34. Given the advantages of this diagnostic method, CMR is performed routinely in Fontan patients. In most centres, patients undergo yearly echocardiographic studies and a CMR every five years starting from the age of 8, unless an urgent assessment is necessary ,35. The CMR protocol generally includes the following sequences: dark- and bright-blood single-shot images, balanced steady-state free precession (bSSFP) cine images, flows, a 3D whole heart, and an angiography. Gadolinium agent is administered when needed .CMR studies usually start with dark-blood or bright-blood single-shot imaging in the axial, coronal, and sagittal planes of all of the thorax ,38,39 ThbSSFP cine images give information on anatomy and function; these are usually breath-hold acquisitions, preferably at end-expiration, but young children may better tolerate the acquisition at end-inspiration. In the non-compliant cases, the bSSFP cine images could be acquired during free breathing, with some decrease in spatial resolution. A transaxial cine bSSFP stack, which consists of transaxial slices covering all the vertical length of the heart in the thorax, gives general information regarding heart function and intracardiac anatomy.bSSFP cine sequences are also performed in long- and short-axis views: a long-axis view of the inflow and outflow of the dominant ventricle, including the atrioventricular valves; an aortic arch should be acquired in case of previous coarctation and/or repair; outflow tracts; a stack of contiguous slices that covers the dominant and non-dominant ventricles from the base to the apex, which will be used to calculate the volumes and ejection fractions; a modified four-chambers view with a horizontal long axis including the dominant ventricle and the eventual rudimentary together with the atrioventricular valves and atria; a modified two-chambers view in a vertical long-axis that includes the dominant ventricle with its respective atrium, Fontan conduit, pulmonary arteries, superior, and inferior vena cava. The presence of an atrial septal defect (ASD) or a ventricular septal defect (VSD) needs to be assessed carefully in order to exclude restrictions at such levels.Angiography sequences are realised through gadolinium-based contrast agents. The sequence is acquired when the contrast agent arrives in the vessel of interest. In this way, it is possible to study the Fontan pathway, the great vessels, and the venovenous, arterial venous malformation, and aortopulmonary collaterals. In addition, it helps to clarify the flow direction, potentially discovering stenosis and blockages of the blood pathways. Twist is another angiography protocol based on multiple and continuous acquisitions of the arterial, mixed, venous-phase images during the passage of a contrast agent through the vascular anatomy.Moreover, 3D whole-heart SSFP allows a comprehensive and detailed evaluation of intracardiac and extra-cardiac morphology; it permits the visualisation of the arterial and venous systems together with their collaterals and the measurements of their vessels’ size. In adolescents and adults, it is acquired during mid-diastole when the heart is still, but, in children, due to the high heart rate, it may be necessary to plan it at the end-systolic phase of the cycle Flow across a vascular structure can be assessed through phase-contrast imaging (PCI), which can quantify velocities and blood flow volumes. Two-dimensional (2D) PCI remains the clinical standard for flow quantification, and 2D PCI are conventionally acquired in the following planes: aorta at the sinutubular junction, superior vena cava, inferior vena cava, Fontan tunnel (pre- and post-fenestration), right and left pulmonary arteries, and right and left pulmonary veins. It can also be used to assess flow velocity across VSD, Damus–Kaye–Stansel anastomosis, and the aortic coarctation site in order to study the presences of stenosis, which can be deleterious in the context of a Fontan circulation.A new type of sequence that is gradually affirming itself in CMR scans is 4D flow. This might require longer acquisition times, but with a single free-breathing sequence, reproducible data on the three-directional velocities inside all the cardiac structures is obtained. In addition, 3D velocity encoding allows for the determination of the global and local blood flow characteristics. There are also promising data that correlate flow viscosity with liver fibrosis/oedema ,40.At the very end of the scan, between 10 and 20 min from the time of injection of the gadolinium-based contrast agent, the late gadolinium enhancement (LGE) sequences are acquired, allowing for the detection of the presence and extent of myocardial fibrosis. These sequences should be performed in cases of heart failure symptoms or arrhythmias. LGE imaging is the gold standard for assessing myocardial fibrosis, relaying on the different washout kinetics of a gadolinium-based contrast agent in healthy and fibrotic myocardium. In the latter, the higher interstitial volume increases the washout time, letting the myocardium appear brighter when the images are acquired. In Fontan patients, fibrosis can be due to endocardial fibroelastosis, previous open-heart surgery (scarring), or mid-wall fibrosis (myocarditis or ventricular sheer stress) ,42.The possibility of obtaining detailed information on anatomy, function, and haemodynamics is paramount to identify, rule out, and understand the pathophysiological background of many complications of the Fontan system.bSSFP images permit the assessment of regional wall motion abnormalities and myocardial systolic impairment. bSSFP images can also calculate the end-diastolic and end-systolic volume of the uni-ventricle or both the main and rudimentary ventricles. The end-diastolic volume index is an important, strong predictor of death and transplant-free survival ,43.As already mentioned, atrioventricular valve regurgitation is a frequent complication in Fontan failure. It can be visually detected through bSSFP sequences and quantified via flow sequences. Nevertheless, the regurgitation fraction can also be precisely derived by the difference between the stroke volume of a single functional ventricle and the systemic forward flow .bSSFP can also lead to the suspicion of the ventricle’s in- and outflow obstructions, and in-plane flow sequences can help in identifying accelerations and estimating peak velocity. The obstruction and stenosis of pulmonary arteries, systemic veins, and pulmonary veins can also be present and must be excluded every time a CMR is performed, bearing in mind that small flow acceleration can have important consequences in Fontan patients and on the lymphatic circulation and can lead to a further increase in other organs’ venous pressure. Flow imaging presents the flow distribution patterns of caval flows and pulmonary arteries, giving important information in support of potential transcatheter or surgical reinterventions. Thromboembolic complications are another frequent and life-threatening complication. Early gadolinium enhancement (EGE) is a sequence developed to assess clotting, as thrombotic avascular structures appear low in signal compared with the surrounding vascular structures. In comparison to LGE, EGE are acquired before in time after gadolinium administration. In patients with AP Fontan, especially in atrial arrhythmias, the presence of a clot should always be suspected and ruled out.Desaturation is a frequent finding in Fontan patients, and this can be due to different conditions.It can be associated with conduit fenestration leading to a right-to-left shunt at the atrial level. It can be due to pulmonary-to-systemic venous collaterals leading to desaturation and a right-to-left shunt. It can also be due to the presence of an arterial venous malformation at the lung level ; this is usually not characterised by a shunt. The CMR allows fora precise calculation of the contribution that the venovenous collaterals flow to the systemic cardiac output. The identification of a large collateral can lead to a cardiac catheter intervention, if the desaturation is significant . Fontan-associated liver disease and lymphatic dysfunction can be investigated through CMR, though these do not enter the standard heart protocol and necessitate ad hoc protocols. However, awareness of the long-term detrimental effects on other systems of a passive Fontan circulation is increasing, and in the future more extensive studies are warranted.Due to ionizing radiation exposure, CCT has been historically overlooked in CHD patients, particularly in those requiring serial imaging evaluation. However, the introduction of new generation scanners and the new strategies adopted to minimise both radiation exposure and acquisition time have significantly increased the role of CCT even in this clinical scenario. The use of dual-source or wide-detector scanners, as well as sucrose oral administration and immobilisation devices in neonates, allows for obtaining good quality images even in the youngest of patients, without the need for sedation or general anaesthesia . The latIn patients with a Fontan anatomy, CT could be the preferred imaging modality when a concomitant evaluation of the coronary anatomy is required or in the presence of cardiac devices (either contraindicated or the source of unpredictable artefacts in CMR) ,33,34. TWhen discussing the role of cardiovascular imaging in the follow-up of patients with a Fontan circulation, it is crucial to also mention cardiac catheterisation. Cardiac catheterisation is an invasive procedure in which a catheter is guided through a blood vessel to the heart, not only allowing for the haemodynamic assessment of the circulation but also determining the cardiovascular anatomy, which permits the possibility of intervening in any eventual complications. Through this catheter, the following parameters can be measured: central venous pressure, cardiac output (CO), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), and the hepatic venous pressure gradient (HVPG) . KnowledAfter Fontan completion, ventricular volume corresponds to superior vena cava (SVC) return, which is connected to the pulmonary arteries, and the systemic venous return from the IVC. The conduit could be initially fenestrated, creating a right-to-left shunt, improving the ventricular preload by reducing the total systemic venous vascular resistance, and improving the overall cardiac output. Understanding this pathway and physiology is fundamental for interpreting the haemodynamic data and where these are collected during this examination. Indeed, pressures are sampled in all the parts of the circuit together with a pull-back gradient across the eventual reconstructed aortic arch, to exclude any obstruction that should be addressed by transcatheter balloon angioplasty if the rise is equal or more than 10 mmHg. The transpulmonary gradient is the most critical pressure measurement in the whole circuit assessment, which equals the difference between the Fontan pressure and the pulmonary venous atrial mean pressure. The expected value is considered 3 mmHg; while it can reach 5 mmHg, which is already high, 20 mmHg is strongly associated with poor outcomes ,60. SatuIt has been almost 54 years since Fontan and his team started to perform the palliative procedure, now named after him, which revolutionised the natural history of patients with a single-ventricle physiology . The oriWhen discussing the role of multimodality imaging in patients with Fontan circulation, it is necessary to mention that such imaging is fundamental in all the stages before TCPC, guiding clinicians to select good candidates for the Fontan pathway and identifying the right timing for the different steps ,65. IndeIn the follow-up of patients with TCPC, the choice of imaging modalities will vary according to the patients’ factors , availability of imaging technologies, and clinicians’ skills. In any case, an at-least-annual clinical and imaging surveillance in specialised adult congenital heart disease centres, involving different professional figures, is mandatory. Indeed, imaging interpretation in these patients requires familiarity with a wide range of anatomical abnormalities and with different surgical techniques .Two-dimensional echocardiography remains the first-line imaging to assess the patency of the Fontan circuit, single-ventricle and valves’ function, and aortic outflow obstruction . The useWhen available, CMR is usually considered the more appropriate choice for further assessment, since it avoids iodate contrast and radiation. It is usually reasonable to perform CMR every 3–5 years, starting from the age of 8, unless an urgent assessment is necessary , and a bLastly, CCT is a valid alternative to CMR thanks to its high spatial and temporal resolution and rapid acquisition time, making this imaging modality ideal for acute situations and a powerful tool for the comprehensive anatomical evaluation of cardiac and extracardiac vascular structures and of vascular stents and to guide surgical or percutaneous interventions ,75. OtheThe evolution of cardiovascular imaging in the assessment of a Fontan circulation has been characterised by a shift from a singular technique to an integrated multimodality approach. Imaging follow-up should be performed in specialised centres and requires the integration of different professional figures. Imaging guidelines help clinicians identify the best technique for a specific clinical question, highlighting the advantages and drawbacks of different cardiovascular imaging modalities. However, physicians should keep in mind that a customised approach may be preferable, to achieve an evaluation as accurate as possible for each patient, to guide their therapy and clinical decisions.


T2 mapping of the liver is a potential diagnostic tool, but conventional techniques are difficult to perform in clinical practice due to long scan time. We aimed to evaluate the accuracy of a prototype radial turbo-spin-echo (rTSE) sequence, optimized for multi-slice T2 mapping in the abdomen during one breath-hold at 3 T.2 and 80 subjects  were investigated. A radial turbo-spin-echo (rTSE) sequence with and without fat suppression, a Cartesian turbo-spin-echo (Cart-TSE) sequence, and a single-voxel multi-echo STEAM spectroscopy (HISTO) were performed in phantom, and fat-suppressed rTSE and HISTO sequences were performed in in vivo measurements. Two approaches were used to sample T2 values: manually selected circular ROIs and whole liver analysis with Gaussian mixture models (GMM).A multi-sample (fat: 0–35%) agarose phantom doped with MnClR2 = 0.988) and with HISTO-T2s of water (R2 = 0.972) in phantom with an offset between rTSE and Cart-TSE maps (mean difference = 3.17 ± 1.18 ms). The application of fat suppression decreased T2 values, and the effect was directly proportional to the amount of fat. Measurements in patients yielded a linear relationship between rTSE- and HISTO-T2s .The rTSE-T2s values exhibited a strong correlation with Cart-TSE-T2s (The fat-suppressed rTSE sequence allows for fast and accurate determination of T2 values of the liver, and appears to be suitable for further large cohort studies.Radial turbo-spin-echo T2 mapping performs comparably to Cartesian TSE-T2 mapping, but an offset in values is observed in phantom measurements.•Fat-suppressed radial turbo-spin-echo T2 mapping is consistent with T2 of water as assessed by MRS in phantom measurements.•Fat-suppressed radial turbo-spin-echo sequence allows fast T2 mapping of the liver in a single breath-hold and is correlated with MRS-based T2 of water.• Magnetic resonance (MR) has been used to non-invasively diagnose and characterize different pathological conditions of the liver. By assessing MR parameters, conditions such as steatosis , iron ovTo increase patient compliance and clinical throughput, the assessment of all parameters needs to be fast. Desired elimination of breathing artifacts in the abdominal examinations underlines the need for optimized accelerated scan protocols. Whereas most of the methods from the multi-parametric protocols are fast enough , the data acquisition for the assessment of tissue-specific T2 relaxation times with the use of conventional multi-spin-echo techniques  is consiIn animal models, T2 mapping was suggested to be a marker of hepatic fibrosis , 11, witIt has been proposed that long acquisition times and sensitivity to body motion of conventional T2 mapping can be overcome by radially sampled techniques combined with turbo-spin-echo (TSE) imaging and a tiered reconstruction . Radial Among fibrosis and iron overload, fat accumulation is another pathology involving liver diffusely. It has been shown that fat is a confounder in T2 measurement by direct comparison of fat-suppressed and non-fat-suppressed multi-echo T2 acquisitions in iron-overloaded patients . While tTherefore, the goal of this study was to evaluate a fat-suppressed radial TSE (rTSE) sequence for accuracy of T2 mapping and feasibility in clinical protocol. The parameters were optimized for measurement in the liver at 3 T during single breath-hold, while keeping sufficient in-plane resolution and volume coverage (number of slices = 5). MRS-based T2 measurement taken as quantitative gold standard in both in vitro and in vivo conditions was complemented by Cartesian T2 mapping in phantom measurements.(eff) times. The radial sequence used here generates individual TE(eff) images via echo-sharing. The general idea of echo-sharing is to use only the views with given TE in the center of the k-space, which determines the image contrast, and views at other TEs are included in the outer part of the k-space. The inclusion of the views with other TEs can be done in several ways; in this study, a “full-tier” method  was used [T2 relaxation times are being calculated by exponential fit to multiple images with different TEwas used .To reduce the streaking artifacts arising from T2 decay and object motion, schemes that distribute the views from different TR periods were proposed . Here, aThe sequence was first tested in phantoms for its accuracy, and the effect of fat suppression on the T2 values was investigated. Finally, the sequence was evaluated in a cohort of patients and volunteers under clinical settings.2 (in concentration 0.28–0.48mM) to mimic human liver in vivo T2 values  with peanut oil (0–35%) and lecithin as emulsifiers, doped with MnCl4 ± 4 ms ). All saDatasets of 78 patients undergoing abdomen MR examination between October 2018 and June 2019 were selected for the study  equipped with a 64-channel body coil and a 32-channel spine coil.All measurements were performed on a 3-T MR system   allowingThe fat-suppressed rTSE-T2 map was integrated into the multi-parametric abdomen protocol targeted at patients undergoing abdomen examination at our clinic. The data for 5 slices of the T2 map were acquired across the largest partition of the liver during a 17-s breath-hold. The protocol included HISTO sequence as well, serving for FF and water T2 assessment, which were evaluated inline. The spectroscopic voxel was placed in the liver parenchyma avoiding large vessels, biliary tracts, and liver boundaries.n = 7), the examination was repeated on the same examination date and the subject was taken out of the magnet and asked to sit up, and the coil was unplugged between the measurements.For the evaluation of T2 mapping variability in test-retest measurements on healthy volunteers  analysis by a single operator with 2 years of experience in liver mapping. In the phantoms, circular ROIs as large as the sample permitted, excluding the borders, were placed on the slice through the middle of the sample. In vivo liver data were evaluated with two approaches. First, the simpler approach  was to draw two to three circular ROIs placed in the liver parenchyma, excluding large vessels, ducts, and streaking artifacts, and to calculate T2 as the mean of the ROI values. In the second approach , the slice with the largest liver cross-sectional coverage was selected, and a free-hand ROI encompassing the whole liver was drawn manually. Since the ROI included sections other than pure liver parenchyma, like vessels and lesions, the ROI T2 values were fit to a Gaussian mixture model implementing the expectation-maximization (EM) algorithm. The Gaussian mixture model (GMM) is a soft-clustering method, which allows a pixel to belong to more than one type of tissue with a certain probability , 22. TheR square was reported. Bland-Altman analysis was performed between radial and Cartesian acquisition in phantom, in test-retest study, and between the ROI and GMM approach. One-sample t-test on the differences against zero was carried out to test for statistical difference. For test-retest study, coefficients of variation (CoV) were calculated. Statistical analysis was performed in SPSS 24.0 and p < 0.05 was considered statistically significant.Data were presented as counts for categorical variables and as mean ± standard deviation (SD) for normally distributed variables and as median ± interquartile range (IQR) for non-normally distributed continuous variables. For the comparison of the methods and approaches, regression analysis was performed and adjusted R2 = 0.972, p < 0.001, Fig. R2 = 0.988, p < 0.001, Fig. p < 0.001).Table R2 = 0.273, p = 0.165 and R2 = 0.170, p = 0.490, respectively).The HISTO FFs of the samples ranged from 0.1 to 36.0% Table . The fatThe exclusion criteria for the in vivo analysis were severe streaking artifacts (4) and inadequate liver coverage with rTSE 1), leaving 73 patients to evaluate. Clinical characteristics of patients and summary of primary indications for MR exams are given in Table , leavingR2 = 0.943 (p < 0.001) for ROI analysis and R2 = 0.831 (p = 0.003) for GMM analysis with small differences that were not statistically significantly different from zero  with a slope of 1.12 (p < 0.001) and intercept 7.49 ms (p = 0.32) for ROI analysis and with a slope of 1.01 (p < 0.001) and intercept 10.16 ms (p < 0.001) for GMM analysis  and were in a good agreement with mean difference of 0.45 ms that was not statistically significant (p = 0.079), and upper and lower limits of agreement 4.87 and − 3.97 . Note that the analyzed range of R2 (1/T2) values was much broader than in our study, which might be the source of stronger correlation compared to our study  for the iron assessment in the liver . Regressnding to  vs ROI/GSome authors studied liver T2s as a marker of disease using only dual-echo TSE sequences, which introduces lower statistical certainty in the fitting algorithm . DespiteAs the limitations of our study, we should certainly name: (i) missing of direct comparison to a “gold standard” for in vivo liver T2 mapping, and it is yet unclear which method that could be. The theoretical equivalence of spectroscopy (HISTO) and imaging has not been established yet, and has to be further investigated . (ii) ThIndirect (stimulated) echoes can confound T2 values, and approaches to correct for this have been proposed, also for estimation of T2s from highly under-sampled data . This coIn conclusion, the radial T2 mapping with short acquisition times, thus enabling breath-hold acquisition, presented here compares favorably to other methods both in phantoms and in vivo, works reliably in a clinical protocol, and appears to be suitable for further studies of diffuse liver disorders and to be a part of multi-parametric protocols.


According to traditional Chinese medicine (TCM), chronic heart failure has the basic pathological characteristics of “heart-kidney yang deficiency.” Chronic heart failure with heart- and kidney-Yang deficiency has good overlap with New York Heart Association (NYHA) classes III and IV. Traditional Chinese medicine classical prescriptions for the treatment of chronic heart failure often take “warming and tonifying kidney-Yang” as the core, supplemented by herbal compositions with functions of “promoting blood circulation and dispersing blood stasis.” Nowadays, there are still many classical and folk prescriptions for chronic heart failure treatment, such as Zhenwu decoction, Bushen Huoxue decoction, Shenfu decoction, Sini decoction, as well as Qili Qiangxin capsule. This review focuses on classical formulations and their active constituents that play a key role in preventing chronic heart failure by suppressing inflammation and modulating immune and neurohumoral factors. In addition, given that mitochondrial metabolic reprogramming has intimate relation with inflammation, cardiac hypertrophy, and fibrosis, the regulatory role of classical prescriptions and their active components in metabolic reprogramming, including glycolysis and lipid β-oxidation, is also presented. Although the exact mechanism is unknown, the classical TCM prescriptions still have good clinical effects in treating chronic heart failure. This review will provide a modern pharmacological explanation for its mechanism and offer evidence for clinical medication by combining TCM syndrome differentiation with chronic heart failure clinical stages. The word “heart failure” has been recorded in the ancient Chinese medicine book “Huangdi Neijing” more than 2,300 years ago. According to the combination of different traditional Chinese medicine (TCM) syndrome elements, TCM can divide chronic heart failure into 4–6 TCM syndromes , which aThe occurrence and development of chronic heart failure includes a variety of processes, which are related to inflammation of heart tissue, participation of immune cells , regulation of neurohumoral factors, and programmed cell death , myocardial hypertrophy, and cardiac fibrosis –8. ExperThe levels of circulating pro-inflammatory biomarkers are closely related to disease severity and prognosis in patients with heart failure. Despite disappointing clinical trial results inflammation is still considered to be a major pathophysiological factor contributing to chronic heart failure, including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction , 22. Mor+ T lymphocytes are progressively augmented and broadly activated in circulation, failing heart and spleen, and are also necessary for pathological left ventricular remodeling in chronic heart failure . HFrEF happens because of chronic low-grade inflammation and immune activation, tissue fibrosis, and remodeling, decreased ventricular compliance caused by chronic myocardial machinery overwork. The importance of inflammation in heart failure has been summarized, analyzed, and prospected by many excellent reviews –34, and  failure . Treg, C failure . The plahe heart . Otherwihe heart .+CD25+Foxp3+Treg and CD4+ T cells were suppressed, while the low level of IL-10 was elevated , neobavisoflavone, and isobavachalcone. It has been reported that bakuchiol in studies can attenuate myocardial ischemia-reperfusion injury, pathological myocardial hypertrophy, and heart failure , 66. BakEpimedium, Eucommia, Cistanche, and Cnidium are all important herbs for warming and tonifying kidney-Yang. Many studies have revealed that their active ingredients, such as icariin, icariside II, aucubin, echinacoside, and osthole improved myocardial hypertrophy, remodeling and fibrosis induced by pressure overload –73, or mSympathetic hyperactivity is an identified hallmark of chronic heart failure. Cardiac sympathetic afferent reflex (CSAR), a sympathetic excitatory reflex with positive feedback characteristics, can be activated by endogenous substances during chronic heart failure, such as Ang II, AT1 receptor, NF-κB, and NADPH oxidase pathways –88. The in vivo (Corticotropin-releasing hormone (CRH) is one of a variety of neuroendocrine hormones secreted by PVN. The expression of CRH in PVN of rats with ischemia-induced heart failure is elevated with the increased expression of pro-inflammatory cytokines and pro-inflammatory genes, even up to two times , 100. Coin vivo –117 and in vivo , 118  with heart failure and kidney-Yang deficiency have higher plasma AngII level, slightly lower left ventricular ejection fraction (EF) and fractional shortening (FS), and much lower left ventricular diastolic function (E/A ratio) than heart failure patients with non-kidney-Yang deficiency , 5, 134.+/K+-ATPase and Ca2+-ATPase are important pumps to maintain the homeostasis of intracellular sodium and potassium levels and the excitability of cardiomyocytes, and they are also the main energy consumers of myocardium. A lot of evidence shows that glycolysis and Na+/K+-ATPase pumps are coupled in function, which provides ATP fuel for the pump .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.


Atrial function in Fontan patients is unknown. Our goal was to report the relationship of atrial function with the cardiac index and atrial function and clinical outcome through longer follow-up periods.Twelve patients were followed up for over 20 years after their first Fontan operation. Atrial function, including the expansion index, atrial ejection fraction, passive ejection fraction and active ejection fraction, was examined using cardiac computed tomography. The relationship of atrial function with the cardiac index and failing Fontan patients was analysed.P = 0.02), the atrial ejection fraction (P = 0.035), and the active ejection fraction (P = 0.013). The expansion index (39.2 ± 19.6 vs 64.1 ± 3.9), atrial ejection fraction (26.6 ± 10.9 vs 39.0 ± 1.5%), booster pump (15.6 ± 9.0 vs 31.3 ± 3.5) and cardiac index (2.1 ± 0.3 vs 2.5 ± 0.2 L/min/m2) were significantly lower in patients with a history of arrhythmia than in patients without a history of arrhythmia (P < 0.05). The expansion index (23.5 ± 13.5 vs 59.5 ± 8.7), atrial ejection fraction (18.1 ± 8.6 vs 37.1 ± 3.7) and active ejection fraction (7.3 ± 2.7 vs 27.7 ± 5.2) were significantly lower in failing Fontan patients than in non-failing Fontan patients (P < 0.01).Twelve Fontan patients were included. The median follow-up period after the first Fontan operation was 27  years, and the median age of those examined was 33.5  years. There were 6 male patients (50%). The cardiac index showed a significant positive correlation with the expansion index (Patients with atrial arrhythmia and signs of Fontan failure have lower atrial function than those without. The Fontan operation, first reported by Fontan in 1971 for the treatment of tricuspid atresia [1], is currently the standard procedure for patients with single ventricular physiology. The Fontan operation, first reported by Fontan in 1971 for the treatment of tricuspid atresia . The cauet al. [Atrial tachycardia increases in the late phase of the Fontan procedure  Atrial tet al.  clarifieThe Ethics Committee of the Osaka University Hospital approved the design of this study; written informed consent was obtained from all patients. This retrospective study was approved by our institutional review board on 2 November 2016 . All patientsThis retrospective study included 12 patients who had been followed up at the Osaka University Hospital for > 20 years since their first Fontan operation and whose atrial function could be analysed with cardiac computed tomography (CCT) while maintaining sinus rhythm or atrial all-pacing rhythm.Demographic and clinical data were obtained from a review of the medical records, including cardiac anatomy, Fontan type, age at Fontan operation, time from Fontan to CCT, history of arrhythmia and cardiac function obtained from cardiac catheterization. Patient characteristics are shown in Table In all patients, we examined the catheter-related parameters such as cardiac index (CI), cardiac central venous pressure, end-diastolic pressure, ejection fraction (EF), pulmonary artery index, pulmonary vascular resistance and each atrial function.n = 8) and patients with no history of treatment were classified as group NA (n = 4). The cardiac indices of both groups were compared.After a detailed review of the medical records, patients with a history of arrhythmia treatment, including a pacemaker implant, the MAZE procedure and radiofrequency catheter ablation were classified as group A . Cases without such a history were defined as the non-failing Fontan group (group NF). Failed Fontan patients were as follows: 1 patient underwent an atriopulmonary connection (APC) Fontan procedure at the age of 7 years and subsequently an extra-cardiac total cavopulmonary connection (EC-TCPC) at the age of 20 years. She suffered from chronic renal failure, ascites collection and hypoalbuminemia. Pleural effusion and ascites collection were repeatedly collected, and she died at the age of 37 years. One patient underwent the APC Fontan procedure at the age of 38 years and subsequently an EC-TCPC conversion at the age of 52 years. She had chronic renal failure with 2.0 to 3.0 mg/dl of serum creatinine. She died at the age of 63 years of renal failure. These 2 patients died 6 and 12 years after the computed tomography (CT) scan, respectively, and 3 and 6 years after the MRI. One patient, by the time of this study, has chronic ascites collection; as much as 2000 ml every month was drained. One patient had no ascites and pleural effusion, but her symptoms of fatigue and dyspnoea on exertion were severe. She had been hospitalized and discharged repeatedly due to her symptoms.Postoperative atrial volume was evaluated using CCT. Multidetector cardiac CT examinations were performed using a 64-slice CT system  and an iodinated contrast agent . After the reformatted images were transferred to a workstation, contiguous multiphase short-axis images were generated using semi-automated interactive software  . The atrThe atrial volume analysis during the entire cardiac cycle length describes atrial functions. The atrium receives blood from the pulmonary veins, increasing its volume from minimum to maximum during the ventricular systole. The atrial endocardial borders were detected by visual inspection using volume rendering and multiplanar two-dimensional (2D) images. We drew a 2D trace of images in 2 directions  and converted the morphology of the atrium into a three-dimensional (3D) image. One radiologist and one cardiac surgeon checked the 2D and 3D images so that the 3D image accurately reflected the atrial volume. The average value of the atrial volume measured for each was adopted as the atrial volume. The atrial volume connected to the systemic chamber was calculated. If the patients have had an intra-atrial conduit, the volume of the conduit was removed. This atrial volume was calculated to be that of the left atrium. The atrial volume was calculated every 10% of the percentage of the RR interval, which was analysed in 1 cardiac cycle. A cycle of the maximum, the minimum and atrial pre-atrial contraction volumes was drawn and calculated.This function is affected by the atrial reservoir function (expansion index) and the atrial global function . The conduit function is influenced by atrial compliance as well as by the passive ejection fraction. The booster pump actively augments the ventricular filling as an active EF during late ventricular diastole , 13. Thet-test. Regression analysis was performed to determine the correlation between the Fontan circulation and atrial function using a univariable model with just 2 factors. All statistical analyses were performed using JMP Pro 14 software , and a P-value of <0.05, which was considered statistically significant.Continuous variables are presented as median (maximum to minimum) or mean ± standard deviation. Categorical variables are reported as frequencies. Intergroup comparisons were performed using an unpaired Student Twelve patients with Fontan were included in this study Table . They unBasic haemodynamic parameters, including catheterization data and atrial function, are shown in Table P = 0.02), the atrial EF (P = 0.04) and the active EF (P = 0.01).The CI was not significantly correlated with other cardiac functions such as central venous pressure, end-diastolic pressure, EF, the pulmonary artery index and pulmonary vascular resistance Fig. . HoweverP = 0.044) and active EF  were significantly lower in group A than in the remaining groups. The CI was also significantly lower in group A  , atrial EF  and active EF  were significantly lower in group F than in group NF. There were no significant differences in the remaining parameters between the groups, except for the CI   and the non-failing Fontan group (group NF) were compared Table . The expThe results of this study have indicated that the atrial function measured using CCT correlated positively with the CI by invasive catheter examination and clinical symptoms. Atrial function, such as the expansion index, atrial EF, passive EF and active EF, were expected to be an important indicator of Fontan circulation.et al. demonstrated a correlation between atrial strain variables by echocardiography with CI and their importance for Fontan circulation [et al. demonstrated that patients with EC-TCPC had higher atrial reservoir function than patients with LT-TCPC, but atrial function did not predict exercise capacity or events [Peck culation . This str events . In thisr events  reportedet al. [Ven et al.  showed tet al. , which iThis study has several limitations. It was a retrospective, single-centre study that included a small number of patients. First, the statistical analysis may not have had sufficient power to permit drawing firm conclusions. In a heterogeneous population with such small numbers, significant caution needs to be exercised when interpreting the data. These patient data were small in number but less variable and tended to be shown. We performed this study as a pilot study to explore the relationship between atrial function and failing Fontan circulation. Second, the evaluation of atrial function and volumetry of both atriums or a single atrium is performed by echocardiography and MRI as reported in references , 8, 13. Fontan circulation, clinical outcomes and atrial function tend to be closely related. In this study, patients with atrial arrhythmia and signs of Fontan failure have lower atrial function. The implications of these findings need to be evaluated in a longitudinal manner to assess the impact on Fontan failure.