Heart failure (HF) is categorized arbitrarily based on the left ventricular ejection fraction (LVEF) in HF with reduced , mildly reduced , or preserved ejection fraction . In this opinion paper, based on (patho)physiological considerations, we contend that the neurohormonal overactivity syndrome (NOHS), which is present in all symptomatic HF patients irrespective of their LVEF, not only contributes to the development of signs and symptoms but it is also a major determinant of patients’ outcomes. In this regard, NHOS is the only currently available treatment target in HF and should be combatted in most patients with the combined use of diuretics and neurohormonal inhibitors . Unfortunately, despite the advances in therapeutics, HF mortality remains high. Probably machine learning approaches could better assess the multiple and higher-dimension interactions leading to the HF syndrome and define clusters of HF treatment efficacy. Heart failure (HF) is a clinical syndrome related to high morbidity and mortality . AccordiRisk factors  always precede the development of HF and are associated with a high HF incidence, whereas comorbidities  may precede or develop after HF and usually co-exist with HF in groups of two or more (multi-morbidity) . The comTraditionally, the principal hemodynamic mechanisms following cardiac damage have included low cardiac output at rest or even at exercise (“forward failure”) as well as elevated (left and/or right) cardiac filling pressures (“backward failure”) . Rarely The detrimental consequences of the prolonged activation of the RAAS and SNS are partly counteracted by the activation of neurohumoral factors such as natriuretic peptides , brain (BNP), and C-type natriuretic peptides (CNP)), which exhibit cardioprotective effects  ,22. UnfoThe advanced stage of NHOS is characterized by the development of multiorgan dysfunction due to the development of an abnormal bidirectional relationship between the heart and several organs such as the brain  , the kidFinally, sudden cardiac death (SCD) is a cardinal manifestation of the NHOS syndrome . Heart dNHOS is the only currently available treatment target in HF and should be combatted in most patients with the combined use of diuretics and neurohormonal inhibitors  ,37,38,39Most symptomatic HF phenotypes converge on the NHOS which is an important outcome predictor and one of the rare rewarding treatment targets in HF. As the NHOS is present throughout the HF spectrum of phenotypes, the LVEF-based HF classification and treatment guidelines should be abandoned as this strategy has deprived HF patients of years of potentially lifesaving treatments. As HF mortality remains high despite the advances in therapeutics, machine learning approaches could better assess the multiple and higher-dimension interactions leading to HF syndrome and define clusters of HF treatment efficacy. This strategy has already been successfully used in HF both for more accurate phenotyping  and the


Background: We sought to evaluate the diagnostic accuracy of post-mortem cardiac magnetic resonance (PMCMR) of explanted hearts to detect the cardiac causes of sudden death. Methods: PMCMR was performed in formalin-fixed explanted hearts of 115 cases of sudden death. Histological sampling of myocardium was performed using two different approaches: (1) guideline-based sampling; (2) guideline-based plus PMCMR-driven sampling. Results: Forensic diagnosis of cardiac cause of death was ascertained in 72 (63%) patients. When the guideline-driven histological sampling was used, the PMCMR interpretation matched with final forensic diagnosis in 93 out of 115 cases (81%) with sensitivity of 88% (79–95%), specificity of 65% (47–80%), PPV of 84% (78–90%), NPV of 73% (58–84%), accuracy of 81% (72–88%), and AUC of 0.77 (0.68–0.84). When a PMCMR-driven approach was added to the guideline-based one, the matching increased to 102 (89%) cases with a PMCMR sensitivity of 89% (80–94%), a specificity of 86% (67–96%), PPV of 95% (89–98%), NPV of 73% (59–83%), accuracy of 89% (81–93%), and AUC of 0.88 (0.80–0.93). Conclusions: PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement or demonstrating signs of myocardial ischemia. Sudden death is defined as a natural, unexpected, fatal event occurring in an apparently healthy individual within 1 h of symptoms’ onset or, for unwitnessed deaths, as a sudden event occurring in individuals observed alive within 24 h before death. Sudden cardiac death (SCD) is the most frequent cause of sudden death. SCD is a major health problem, accounting for 50% of cardiovascular deaths and 20% of natural deaths in Western countries [Postmortem pathology and forensic medicine with their ancillary examinations  together with clinical history are regarded as the gold standard to determine the cause of SCD.Postmortem radiology is increasingly used in forensic practice as a complementary tool to conventional autopsy investigations. Over the last decade, post-mortem cardiac magnetic resonance (PMCMR) imaging was introduced in forensic investigations of natural deaths related to cardiovascular diseases ,3,4,5,6.The potentiality of PMCMR was demonstrated in studies evaluating individual cardiac disease such as myocardial infarction, acute ischemia, cardiomyopathies or myocardial toxic damage ,9,10,11.However, the effectiveness of PMCMR was never evaluated in a systematic study.The aim of the present study was to evaluate the diagnostic accuracy of PMCMR of explanted hearts to detect cardiac disease in consecutive patients with sudden death and to evaluate its effectiveness in different cardiac conditions.We performed PMCMR of hearts explanted from autopsies of 115 consecutive subjects, aged 15–80 years, with sudden death which occurred from April 2017 and January 2021 in the northwestern provinces of the Tuscany Region and in the metropolitan area of Rome .Autopsy investigations were performed by experienced cardiovascular pathologists in two tertiary institutions: The Department of Surgical, Medical and Molecular Pathology and Critical Medicine of the University of Pisa, Italy and the Department of Anatomical, Histological, Medico-Legal and Locomotor Sciences of the Sapienza University of Rome, Italy.Conventional autopsy included macroscopic, histologic and toxicology investigations; when appropriate, further laboratory analyses such as chemistry and genetic testing were performed according to the Recommendations on the Harmonization of Medico-Legal Autopsy Rules produced by the Committee of Ministers of the Council of Europe. A whole-body standard autopsy was performed and the heart was explanted in an en bloc removal, according to the current guidelines for autopsy investigation of sudden death . The heaAfter PMCMR was performed, gross transverse sections and histological and ancillary examinations of the heart were carried out.PMCMR was performed in all the cases with negative extra-cardiac findings at autopsy  and also in cases of individuals with ascertained extracardiac cause of death at whole-body autopsy (non-cardiac death group). PMCMR was performed by investigators blind to the results of the gross autopsy and of clinical data.Cases of inadequate body preservation (signs of early putrefaction and gas formation at autopsy) at autopsy were ruled out prior to PMCMR to avoid gas-related MR signal interferences.®, Milwaukee, WI, USA). A dedicated 16-channel cardiac coil and a heart rate simulator with a set heart rate of 60 bpm was present. After the acquisition of triplane conventional localizer images, a 4-chamber localizer view was acquired using a single-shot steady-state free precession sequence (SSFP). Then, a whole-heart 3D-Fat Sat prepared SSFP pulse sequence was acquired with the following parameters: slice thickness of 0.9 mm (1.8 mm interpolated), no gap, FOV 22 × 22 cm, phase FOV 1, matrix 256 × 256, reconstruction matrix 512 × 512, flip angle of 45°, and a TR/TE ratio approximated = 2, slices acquired 184. From the 4-chamber SSFP view, a set of left ventricular short axis views covering both ventricles was acquired using a matrix of 22 × 22 cm and a slice thickness of 8 mm, no gap, and the following pulse sequences:PMCMR was carried out with a 1.5 Tesla MRI scanner T1 mapping with modified lock-locker (MOLLI) pulse sequence with a 3(3)3(3)5 setting.(2)T2 mapping using a multi-echo spin-echo (MESE) pulse sequence with 4 different echo times .(3)T2* mapping using the multi-echo T2* GRE STARMAP pulse sequence, with 8 different echo times from 2.5 to 16.7 msec.(4)Cine-IR (lock-locker) pulse sequence with 30 images with different inversion times.Finally, a MAGIC pulse sequence with 22 × 22 cm FOV, 256 × 256 matrix and 4 mm slice thickness with no gap was acquired, with reconstruction of a complete dataset of T1-, T2- and proton density (PD) mapping, T2-weighted fast spin echo (FSE), T1-weighted FSE, PD, Fat Sat-PD and short-tau inversion recovery (STIR) synthetic images. The MR acquisition time of the entire protocol was 25 min.Use of the image data for the present study was approved by the local ethics committee. PMCMRs were analyzed by blinded MR board-certified investigators, who were unaware of the circumstances of death and of the patient’s medical history.®, Calgary, AB, Canada) software. All measurement and image interpretation was performed on a picture archiving and communication system (PACS) workstation .Image post-processing was performed using a CVi42  was measured as previously reported . LV WT wAs previously validated, a cut-off of >2.4 of the standard deviation of LV WT was used to identify hypertrophic cardiomyopathy .Fat infiltration was identified as intramyocardial “India ink” signs in 3D-SSFP and confirmed using the PD FSE and STIR approach.A summary of PMCMR algorithms for diagnostic suspicion of cardiac conditions is shown in According to the guidelines , gross e(1)The evaluation of pericardium;(2)The assessment of: coronary arteries’ size, shape, position, number, and patency of the coronary ostia; and the size, course, and “dominance” of the major epicardial arteries by multiple transverse cuts at 3 mm intervals along the course of the main epicardial arteries, including branches such as the diagonal and obtuse marginal;(3)A complete short axis cut of the heart at the mid-ventricular level, and then further parallel transverse slices of ventricles at 1 cm intervals towards the apex. The remainder of right and left ventricles in the basal half of the heart were dissected in the direction of flow of blood.(4)Examination of atrial and ventricular septa, atrio-ventricular valves, ventricular inflows and outflows, and ventricular valves.(5)The wall thickness of mid-cavity free wall (both LV and RV) and of interventricular septum were measured. The transverse dimensions of both ventricles and atria were also measured.Tissue sampling was performed with two different approaches:(1)With guideline-oriented sampling;(2)With PMCMR-driven sampling of tissue.In order to perform histological analysis, 9 blocks of myocardium were collected from the apex, the free wall of the LV , the LV septum (anterior and posterior), and from the free wall of the RV.Additionally, samples from any area with macroscopic or instrumental alteration were collected.In the setting of coronary artery disease, relevant atherosclerotic lesions and endoluminal clots were sampled.Additional PMCMR-driven samples from any area with PMCMR alterations were collected.All samples were stained with hematoxylin and eosin (H&E). If necessary, histochemical and immunohistochemical staining techniques for the characterization of inflammatory infiltrates or for detecting early ischemic lesion and molecular screening were performed. When needed, histomorphometry analysis served to calculate the extent of fibrofatty replacement in the myocardium. The final diagnosis was defined according to the current guidelines .Diagnostic performance of PMCMR was compared with autopsy. Values are presented as the mean ± standard deviations (SD) or as the median (25th–75th percentiles) for variables with normal and non-normal distributions, respectively. Values with non-normal distribution according to the Kolmogorov-Smirnov test were logarithmically transformed for parametric analysis. Qualitative data are expressed as percentages. Categorical variables were compared by the chi-squared test or the Fisher exact test when appropriate. Continuous variables were compared by the ANOVA t test and analysis of variance or by the Wilcoxon nonparametric test when appropriate. Bonferroni correction was used when needed.2 (IQR 23–31). Sixteen deceased had multiple cardiovascular risk factors; 10 deceased had only one known risk factor for CAD: 5 subjects were active smokers; 2 had type 2 diabetes mellitus; 1 subject had systemic hypertension; 1 had hypercholesterolemia; and 1 had family history of premature CAD. Seven subjects had previous history of ischemic heart disease, and one of valvular heart disease. The median time from death to autopsy was 2 days (IQR 1–4 days).PMCMR was performed in 115 consecutive cases of sudden death. The mean age at death was 50 ± 19 years (range: 18–81 years). In total, 71 patients were male and 103 patients were white European . As shown in The final forensic diagnoses, based on a guideline-driven sampling, identified a cardiac cause of death in 72 cases (63%): ischemic heart disease in 45 cases; ARC in 3; hypertrophic cardiomyopathies in 9; diffuse non-specific myocardial damage in 8 ; acute myocarditis in 2; and other cardiac conditions in 5 . In 37 (32%) cases, no signs of cardiac involvement were found. Finally, in six patients, advanced decomposition did not allow a complete heart evaluation. At autopsy, the median weight of the heart was 460 g (IQR 362–543); the median heart diameters were 11 cm (10–13) × 12 cm (11–13) × 4 cm (4–5). The median septal wall thickness was 1.5 cm (1.3–1.8). The median LV and RV wall thicknesses were 1.5 cm (1.4–1.8) and 0.5 cm (0.4–0.8), respectively.The median time from death to PMCMR was 23 days (11–31 days). The median time between autopsy and PMCMR was 21 days (8–29 days). At PMCMR, the median LV myocardial mass was 130 g (103–171). The median septal and LV inferolateral wall thicknesses were both 1.6 cm (1.3–1.9 cm).PMCMR interpretation matched with the final forensic diagnosis in 93 out of 115 cases (81%): 43 with ischemic heart disease, 3 with ARC, 9 with HCM, 2 with myocarditis, 1 with diffuse myocardial damage (acute idarubicin toxicity), in 1 case with septal neoformation, 2 traumatic heart damage, and 24 cases with non-cardiac death . Yet, PMOverall, PMCMR had a sensitivity of 88% (79–95%), specificity of 65% (47–80%), positive predictive value of 84% (78–90%), negative predictive value of 73% (58–84%), and accuracy of 81% (72–88%), with respect to autoptic diagnosis. The PMCMR area under the curve (AUC) was 0.77 (0.68–0.84).The PMCMR-driven histologic sampling of the myocardium was performed in addition to the guideline-based approach. With the addition of PMCR-driven sampling, the final forensic diagnosis changed in nine patients. Non-cardiac death decreased to 28 cases. Interestingly, the PMCMR-driven sampling permitted detecting nine more cases of ARC, which would otherwise have gone unnoticed. The final matching between the PMCMR and autopsy was obtained in 102 (89%) cases. PMCMR showed a sensitivity of 89% (80–94%), a specificity of 86% (67–96%), a positive predictive value of 95% (89–98%), a negative predictive value of 73% (58–83%), and an accuracy of 89% (80–94%). The AUC of PMCMR was 0.88 (0.80–0.93).As evident in Ischemic heart disease was diagnosed at autopsy in 45 cases, accounting for 48% of causes of sudden cardiac death. Among them, PMCMR identified ischemic cardiopathy  in 43 hearts (95%). PMCMR was falsely positive in one case , and missed two cases of final forensic diagnosis of ischemic heart disease . An example of PMCMR and histology findings in a case of ischemic heart disease is shown in The overall sensitivity of PMCMR in diagnosing ischemic heart disease was 96% (84–99.9%), with a specificity of 98% (92–99.9%), PPV of 97% (85–99.6%), NPV of 97% (89–99%), and accuracy of 97% (93–99%). The AUC of PMCMR for ischemic heart disease was 0.97 (0.93–0.99).Evaluating coronary artery anatomy, PMCMR missed CAD diagnosis in two cases (6%) and falsely identified significant coronary artery disease in two.PMCMR identified 12 cases with myocardial fatty infiltration of right, left or both ventricles. Most ARC had biventricular involvement , followed by left-dominant  and right ventricular abnormalities . As mentioned above, through guideline-based histologic sampling, the autopsy identified myocardial fibrofatty infiltration only in 3 out of 12 hearts (18%). In contrast, using an additional PMCMR-guided approach to perform histologic sampling in those anatomic regions where MR identified cardiac abnormalities attributable to fatty infiltration, a further nine cases could be diagnosed . An example of a case of biventricular ARC is shown in p = 0.39 and 17 ± 5 mm vs. 16 ± 3, p = 0.54). However, the standard deviation of LV WT of HCM cases diagnosed was significantly higher than in those without . The absolute difference between the maximal and minimal LVWT (max-minD) in HCM cases was 10 ± 5, and in others, 5 ± 2 (p < 0.001). The previously reported cut-off of standard deviation of LV WT (>2.4) allowed the identification of all the cases of HCM. Secondary HCM features  were also found in five out of nine cases.PMCMR and forensic diagnoses matched in all nine cases of HCM , then remained stable in the time window between the first week and the first 60 days after formalin fixation. In patients with cardiac death, abnormalities of regional myocardial T1 and T2 were consistent with the signal abnormalities of the T1-weighted and T2-weighted pulse sequence.The average values of myocardial T1, T2 and T2* for different cardiac conditions are shown in In this study, the result of PMCMR of explanted hearts was compared to the standard forensic procedures for the evaluation of cardiac diseases in a cohort of cases of sudden death. The histological evaluation of the forensic procedure was performed following different approaches:(1)Performing guideline-oriented sampling of myocardial tissue;(2)Performing PMCMR-driven tissue sampling.PMCMR demonstrated a good matching with the standard forensic procedure with the guideline-oriented approach (matching in 80% of cases), which increased by adding the PMCMR-driven approach (matching in 88% of cases). Interestingly, the PMCMR-driven approach allowed performing a further nine diagnoses of ARC that would have been missed using the guideline-based approach.PMCMR demonstrated 88% sensitivity and 65% specificity in detecting cardiac disease in this cohort of sudden death. Applying also the PMCMR-driven approach, sensitivity remained almost unchanged (89%) but specificity increased to 86%. PMCMR was particularly effective in the diagnosis of conditions with focal myocardial abnormalities such as cardiomyopathy (ARC and HCM) or ischemic heart disease. In contrast, PMCMR failed to identify most of the cases with diffuse myocardial involvement because the imaging aspect of such conditions, mostly involving the mid-wall layer, could mimic fixation defects.In living patients, CMR represents the gold-standard imaging tool to evaluate cardiac morphology and function and to characterize tissues through the assessment of myocardial magnetic properties and the use of gadolinium-based contrast-enhanced sequences. CMR is considered the gold-standard imaging technique to diagnose myocarditis, and cardiomyopathy such as HCM and dilated cardiomyopathy. It is also able to distinguish between ischemic and non-ischemic myocardial disease and to detect signs of myocardial damage such as fat infiltration, edema and myocardial fibrosis. Compared to CMR, PMCMR has several advantages: the high image quality and spatial resolution, resulting from the absence of cardiac motion or breathing-related artefacts, as well as the absence of scan time limitations and of specific absorption rate restrictions. On the other hand, PMCMR cannot rely on contrast enhancement pulse sequences and may be negatively affected by post-mortem phenomena of the deceased bodies, such as autolysis/putrefaction, cooling or rigor mortis. Two different approaches of PMCMR are currently used: (a) whole-body and (b) explanted-heart PMCMR. Whole-body PMCMR has the main advantage of allowing the contemporary evaluation of other organs but it is more susceptible to post-mortem phenomena, to the temperature-dependent changes in myocardial T1 and T2 passing from cooling to an ambient temperature, and to practical issues correlated with the complexity of a procedure, including logistic problems such as transportation of bodies, time constraints, and disturbance to routine clinical casework . PMCMR oIn our population, with male preponderance and a mean age of 50 years, ischemic heart disease was found as the cause of almost half of sudden cardiac death cases. The diagnosis of ischemic heart disease was made by the identification of obstructive CAD and/or of ischemic myocardial damage. Overall, PMCMR was able to identify 95% of cases with ischemic heart disease. The mismatch between PMCMR and the final forensic diagnosis referred mostly to the identification of obstructive CAD: PMCMR was falsely positive in two cases, as well as missing CAD in two. The spontaneous formation of post-mortem thrombi, the presence of air bubbles, or the extrinsic compression of the coronary lumen could explain the false-positive results of PMCMR, whereas small vessel diameters could be the cause of false-negative responses.However, the advantage of PMCMR in ischemic heart disease is the capability to identify early signs of myocardial ischemia . Indeed,One of the most important findings of the present study was the demonstration of the role of PMCMR in the diagnosis of ARC. Overall, ARC was eventually diagnosed in 12 patients of this population, but in only 3 of them, the final diagnosis was achieved by using only the guideline-oriented sampling of myocardial tissue. Myocardial sampling driven by PMCMR was able to detect signs of fat infiltration in nine more patients. The explanation of this result is linked to the high spatial resolution of PMCMR and to its capability to evaluate soft-tissue abnormalities and, particularly, fat infiltration. For this purpose, a 3D fat saturation SSFP was used, resulting in the acquisition of 184 slices of 0.9 mm thickness, without gap, and a final voxel size of 0.9 × 0.9 × 0.9 mm. In these images, regions of fat infiltration were detected as well-defined hypointense regions within apparently normal myocardium. In contrast, for histology, ventricles were cut using 1cm-thickness short axis slices and blocks of myocardium were sampled as indicated in the current guidelines for histologic analysis. Indeed, this great difference in “spatial resolution” might explain the high effectiveness of PMCMR in detecting the region of intramyocardial fat infiltration as well as the significant improvement in the PMCMR-driven approach over guideline-oriented tissue sampling. The present study was conducted in Italy where ARC was the first non-ischemic cause of sudden cardiac death , particuPMCMR was also able to detect HCM as the cause of death using both morphological and tissue features. Despite the rigor mortis condition, the identification of asymmetrical hypertrophy could be made by evaluating the standard deviation of wall thickness that was significantly higher in HCM than in other conditions . SecondaFrom the technical point of view, in this large cohort of explanted hearts, we found that myocardial T1, T2 and T2* remained relatively stable over time, after an initial drop-out occurring in the first 7 days following formalin fixation. A recent study by Ebata and coworkers found the same pattern of myocardial relaxation times . These fNoteworthily, myocardial T1 and T1-index  were lower in ARC than in other conditions. This lower T1 could be explained by the presence of intramyocardial fat that decreases T1 or by the increased permeability of formalin in the interstitial spaces because of desmosomial abnormalities of the gap junction. However, these findings need to be confirmed by further evidence.Some study limitations should be mentioned. First, our population did not include all the cardiac conditions that potentially could cause SCD. However, this was a real-life study and the distribution of cardiac disease found reflects the prevalence of the causes of SCD in Italy .Second, inadequate body preservation with signs of early myocardial putrefaction, not permitting the identification of the cause of death, was found in a not-negligible percentage of cases. This may be explained by the fact that in 45% of cases, death occurred at home and we decided to include consecutive cases without excluding those with a possible long time gap between death and autopsy.This study demonstrated that PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement (as in ARC) or to demonstrate signs of myocardial ischemia when death occurs in the peracute or acute phase. In contrast, PMCMR is less effective in conditions causing diffuse myocardial damage. PMCMR of an explanted heart is useful for the detection of cardiac alterations that may be missed by visual examination and random microscopic evaluation, and can be proposed as a complementary guide for histological analysis in sudden death cases, without evident cardiac macroscopic abnormalities.


Recent study has shown that the transient receptor potential vanilloid 2 (TRPV2) channel was exclusively upregulated in patients with atrial fibrillation (AF), and that this overexpression might be detrimental for occurrence and maintenance of AF. We aimed to characterize the expression levels of TRPV2 mRNA in peripheral blood mononuclear cells (PBMCs) with/without early recurrence of atrial fibrillation (ERAF) after radiofrequency catheter ablation (RFCA), and to find a reliable predictor for ERAF.65 patients of AF, who underwent RFCA successfully, then divided into two groups according to ERAF during following 3 months. PBMCs were isolated from whole blood by Ficoll gradient centrifugation before and after RFCA. Gene set enrichment analysis was performed to evaluate TRPV channels expression levels and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping was used for pathway enrichment analysis.There was no significant difference in the TRPV2 mRNA expression level between the two groups before RFCA, while without ERAF group of TRPV2 expression was markedly reduced compared to ERAF group after RFCA. Moreover, the number of TRPV2 expression was confirmed as an independent predictor for the first time through receiver operating characteristic and Kaplan–Meier survival curve analysis. It should be pointed out that the above results were only used to predict ERAF, and have no predictive significance for late recurrence of atrial fibrillation according to the current data. Additionally, ERAF was inversely correlated with P wave dispersion. KEGG mapping further clustered 41 pathways, revealing that ‘‘cyclic guanosine monophosphate-protein kinase G signaling pathway’’ was significantly enriched.We firstly assume that downregulated expression of peripheral TRPV2 appear in patients without ERAF after RFCA. TRPV2 may thus represent a novel predictor of early phase after successful radiofrequency ablation.The online version contains supplementary material available at 10.1186/s12872-022-02992-0. Two radiologists measured the anterior and posterior diameters, left and right diameters, upper and lower diameters of the left atrium in diastole, and the anterior and posterior diameters of the pulmonary veins in cross section. The left atrial volume index (LAVI) is the product of /body surface area(BSA).All patients underwent trans-thoracic echocardiograph  prior to RFCA, and a few patients have undergone cardiac ultrasound reexamination after RFCA. Recommendations of the American Society of Echocardiography were followed to measure echocardiographic indexes. The left atrial diameter  was obtained in the parasternal long axis view during end-systole, and left atrial area was calculated by the product of “anterior–posterior diameters” × “left–right diameters”. Left ventricular ejection fraction (LVEF) was measured by modified Simpson’s method. Late diastolic peak velocity of mitral inflow(A) and early diastolic peak velocity of mitral inflow(E) were measured, which used to calculate the E/A ratio. We measured them from the mean value of 10 cardiac cycles during AF state. Trans-esophageal echocardiography was performed to exclude intracardiac thrombi.Prior to the procedure, all patients received oral anticoagulation (warfarin or rivaroxaban) for at least 1 months, and rule out the presence of LA thrombus by transesophageal echocardiogram within 24 h before RFCA. During the procedures, heparin was administered as continuous pumping at an intraprocedural activated clotting time > 300 s. PentaRay , a star shaped mapping electrode, was sent to the left atrium for modeling and matrix mapping after successful puncture of atrial septum under the guidance of a Carto 3 electroanatomic mapping system . After modeling, the cold saline perfusion ablation catheter STSF  was sent to the left atrium for the positioning of the pulmonary vein, and the power mode was selected for ParAF ablation under the guidance of ablation index (AI). The parameters were: posterior wall power 45 W, AI = 380; top and bottom power 45 W, AI = 400; anterior wall power 50 W, AI = 450. The left and right pulmonary veins were isolated along the vestibular potential. For PerAF, in addition to the ablation line of ParAF, the left atrial roof line ablation  and the mitral isthmus line ablation  were performed. If cavotricuspid isthmus (CTI)-dependent atrial flutter was induced during the procedure, the cavotricuspid isthmus line  and the atrial flutter originating from the superior vena cava were performed for superior vena cava isolation . The stimulation mapping of corresponding positions was performed under sinus rhythm pacing to verify whether the left atrial roof line, mitral isthmus line and cavotricuspid isthmus line were successfully blocked. Successful RFCA was defined as exit block in pulmonary veins and entrance block in left atria was reconfirmed 30 min after PVI, as well as no atrial arrhythmia was induced after procedure. The maps of RFCA were included in Additional file Peripheral blood samples were collected from patients before radiofrequency ablation of AF and then again when all patients recovered sinus rhythm at the end of radiofrequency ablation. All blood samples were collected by centrifugation of chemistry tubes. PBMCs were acquired through Ficoll gradient centrifugation of complete blood tubes followed by two washes with phosphate-buffered saline (PBS).−△△Ct method (versus β-actin). All data were analyzed by the Applied Biosystems SDS 2.3 software using the threshold cycle (Ct) relative quantification method with β-actin as an endogenous control.RNA from PBMCs was extracted using the high pure RNA isolation kit  and transcribed by Verso RT-PCR kits . Quantitative PCR was performed using the SYBR Green SuperReal PreMix Plus qRT-PCR Kit . The primers used were as follows: human TRPV2: forward, 5′AGTCAGTGCCCATGGA3′ and reverse, 5′GCCGATGGTGAATTTGAAGAG3′; human β-actin reference gene: forward, 5′CTGGAACGGTGAAGGTGACA3′ and reverse, 5′CGGCCACATTGTGAACTTTG3′. Each sample was measured three times, and the relative quantitative of TRPV2 mRNA expression was calculated using the 2https://david.ncifcrf.gov/). The function charts of DEGs are built by using DAVID. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were applied for the DEGs, with the threshold of p value < 0.05. The rich factor is calculated as the ratio of the numbers of DEGs enriched in this pathway, to the numbers of all genes annotated in the same pathway. The Q-value is the corrected P-value with threshold < 0.05. Heatmap and scatter were plotted by https://www.bioinformatics.com.cn, a free online platform for data analysis and visualization.To obtain a global view of the TRPV expression, hierarchical cluster was constructed to characterize changes across 10 samples  from GEOp-value < 0.1 on univariate analysis were considered in the multivariate model. Time to recurrence and event-free survival curves were analyzed using the Kaplan–Meier method with a 3-month ERAF and log-rank significance testing. The predictive effectiveness evaluation of influencing factors is expressed by the ROC curve. Missing values were minimal (except in the case of the ECG parameters after RFCA) and roughly equivalent between groups for all variables and were thus omitted. Statistical analysis was performed using SPSS version SPSS 26.0 , and significance was set at p-value < 0.05.The numerical variables with normal distribution are expressed as the mean ± standard deviation. The t-test was used for intergroup comparison. The numerical variables that did not obey the normal distribution are represented by the median (25th and 75th percentile). The nonparametric rank sum test was used for intergroup comparison. Categorical variables are expressed as the number of cases (%) and the χ2 test for comparison between groups. Correlation was tested by two-tailed Spearman analysis. Binary logistic regression analysis was used to screen out the influencing factors of the indexes with statistical significance. Factors with a p = 0.016, 0.0079, and 0.016, respectively). However, the TRPV3, TRPV5, and TRPV6 expression was not statistically significant in control and AF samples. The heatmap of the DEGs is shown in Fig. By comparing individuals with and without AF through Wilcoxon tests, it was found that the TRPV1, TRPV2, and TRPV4 mRNA expression from the LA tissue of individuals with AF was significantly upregulated (p > 0.05). In terms of the indicators of cardiac color Doppler ultrasound, the LA area of the ERAF group was higher than without ERAF group, although not statistically significant. The mitral flow diagram consists of the peak E, representing early filling, and peak A, representing late filling. The indicator of E/A < 1 reflected left ventricular diastolic dysfunction and increased LA pressure. As expected, the number of E/A < 1 after RFCA in the no ERAF group was markedly lower compared to that of the ERAF group , indicating that RFCA could alleviate LA pressure after sinus rhythm conversion. Due to the small number of postoperative cardiac color Doppler ultrasounds, larger sample data are needed to support this result. PWD has been reported to be related to ERAF or LRAF. In line with this, we found that the PWD in the ERAF group was significantly higher than no ERAF group .Overall, as is shown in Table ] vs. 21 , 31; p =p < 0.001), PWD . There were moderately strong Spearman correlations between TRPV2 mRNA expression after RFCA and E/A after RFCA . Patients with AF after RFCA could improve LV diastolic dysfunction and LA pressure, which may contribute to suppress the expression of TRPV2 mRNA. However, the Spearman correlation between TRPV2 mRNA expression after RFCA and LRAF was not significant (p = 0.96).Spearman’s Rho test was used to analyze the correlations between ERAF and related variables Fig. . There wp = 0.002) and PWD  were independent positive predictors of ERAF. Taking the median TRPV2 mRNA expression after RFCA (0.6) and PWD (25.5 ms), survival analysis using the Kaplan–Meier method and log-rank test showed significant differences in ERAF after RFCA in both. As shown in Fig. p < 0.001). As shown in Fig. p = 0.006).The results of univariate and multivariable binary logistic regression model analyses are summarized in Table p < 0.001). We chose the optimal cut-off value of ≥ 0.26 according to Youden’s index; the sensitivity and specificity of the optimal cut-off value were 80% and 68.9%, respectively . We chose the optimal cut-off value ≥ 0.35 according to Youden’s index; the sensitivity and specificity of optimal cut-off value were 78.9% and 84.4%, respectively  and combined TRPV2 mRNA expression after RFCA and PWD (model 2). The area under the ROC curve of the model 1 curve was 0.78 , which is produced most readily in patients with PerAF, less readily in ParAF, and even less in sinus-rhythm controls [2+, which causes increased magnitude and spatial dispersion of susceptibility to Ca2+—and repolarization-alternans, and finally leads to reentrant rotor formation and enhanced vulnerability to the initiation and maintenance of AF [It was found that TRPV2 mRNA was significantly upregulated in LA tissue  from patce of AF . Greiserdy state . Ca2+-hacontrols . In dogsce of AF .2+ waves triggered by L-type Ca2+ channels at the cell boundary might activate Ca2+-overloaded sarcoplasmic reticulum (SR) sites at the cardiomyocyte center, leading to large triggered Ca2+ waves (TCWs) during the AP. This causes delayed afterdepolarizations (DADs) to reach the threshold of ectopic lesion discharge, and sustained delayed depolarization potential can also cause AF [2+ release-promoting triggered activity is considered an important mechanism of AF initiation [2+ signaling through failure of subcellular-propagated Ca2+ release is a protective mechanism against the massive Ca2+ overload that occurs during chronic AF [2+ flow in cardiomyocytes. Catheter ablation offers a greater chance of achieving and maintaining SR; however, it is unclear how long the benefits are sustained, and whether early restoration of SR will result in better long-term outcomes [2+ evokes PV triggers after RFCA, and the regulatory proteins of Ca2+ handling are important contributors to an SR Ca2+ overload, diastolic membrane instability, and AF occurrence [2+ current (ICaL), and shortening of APD and effective refractory period (ERP). The Ca2+ loading leads to ICaL (Ca2+) channel inactivation, reduces the APD, and causes atrial structural and electrical remodeling, which may set off an AF trigger in both the PV and non-PV areas, initiating a vicious cycle. Therefore, the key to reduce the recurrence of atrial fibrillation caused by calcium overload is successful PVI. It was demonstrated that AI-guided catheter ablation is associated with high effectiveness and good safety of RFCA [Moreover, Cacause AF . In addiitiation . A trialronic AF . The recoutcomes . Abnormacurrence . Yue et currence  examined of RFCA . In this of RFCA . Actuall of RFCA  found th of RFCA , 32. The2+ and lead to dilated cardiomyopathy [Recently, it was revealed that LA pressure was increased during the onset of AF, which was linked to TRPV2 expression . Animal myopathy . Elevatemyopathy . The resmyopathy , 38, and. reported that more than 50% of patients had symptomatic and asymptomatic AF before RFCA, while only 38% of patients with AF were accurately identified; within the first 3 months after RFCA, asymptomatic arrhythmia recurrence (mainly ERAF) reached to 38% [According to our study, it was found that there was no difference in the expression level of TRPV2 between ParAF and PerAF. In addition, the level of TRPV2 measured in 29 healthy people was almost equal to that of the above patients (Additional files d to 38% . Therefod to 38% , 42. Pred to 38% , 44. Li d to 38%  demonstrDEG analysis suggested that TRPV1 and TRPV4 mRNA expression was consistent with TRPV2 in LA tissue. Therefore, we will explore the detection of TRPV1 and TRPV4 mRNA expression levels from PBMCs to identify whether they also have value in predicting ERAF after RFCA. Nevertheless, the role of TRPV2 channels in the pathogenesis of ERAF after RFCA remains unknown. KEGG mapping implies that several signaling pathways are highly enriched, which provides a possible research direction for the study of the mechanism of ERAF. Finally, TRPV2 signal regulation would provide a new idea for developing potential novel therapeutic targets for ERAF after RFCA.First, it is undeniable that the sample size of the ER group was relatively small and unequal to that of the without ER group, which may lead to bias in statistical analysis. For discharged patients, although we can detect asymptomatic ERAF as much as possible through the patient's regular follow-up ECG examination and their own evaluation of pulse rhythm, there may still be a possibility of missing diagnosis of asymptomatic AF. Second, we found no association between left atrial size, AF duration, or type of AF and ER occurrence, while the correlation of both had been confirmed in previous studies . In addiWe assume that downregulated expression of peripheral TRPV2 appears in patients without early recurrence of AF after radiofrequency ablation. Therefore, TRPV2 may represent a novel predictor of the early phase after successful radiofrequency ablation.Additional file 1. Maps of RFCA.Additional file 2. TRPV2 mRNA expression before RFCA of AF patients and health individuals.


Mean PR was 41.5 ± 7.1% of the Doppler‐derived pressure gradient (Pmax), which resulted in a markedly increased homograft orifice area . PR significantly reduced homograft resistance and transvalvular stroke work . When PR was considered, the correlations of the parameters used were significantly better, and 11 of 18 patients (61%) in the group with severe homograft stenosis (EOAI <0.6 cm2/m2) could be reclassified as moderate stenosis. Our results showed that the Doppler measurements overestimated the degree of homograft stenosis and thus the right ventricular load, when PR was neglected in the pulmonary artery. Therefore, Doppler measurements that ignore PR can misclassify homograft stenosis and may lead to premature surgery.Relevant pressure recovery (PR) has been shown to increase functional stenotic aortic valve orifice area and reduce left ventricular load. However, little is known about the relevance of PR in the pulmonary artery. The study examined the impact of PR using 2D‐echocardiography in the pulmonary artery distal to the degenerated homograft in patients after Ross surgery. Ninety‐two patients with pulmonary homograft were investigated by Doppler echocardiography . PR was measured as a function of pulmonary artery diameter determined by computed tomography angiography. Homograft orifice area, valve resistance, and transvalvular stroke work were calculated with and without considering PR. PR decreased as the pulmonary artery diameter increased ( The presented results showed that the Doppler measurements overestimated the degree of homograft stenosis and thus the right ventricular load when the energy loss concept with pressure recovery (PR) in the pulmonary artery was neglected. Doppler measurements that ignore PR can misclassify the severity of homograft stenosis and may lead to premature surgery. The sum of kinetic and potential energy is therefore significantly reduced in the pulmonary artery compared to the RVOT and vena contracta. This difference is caused by the EL. When considering the potential energy alone (P1), the pressure gradient between RVOT and pulmonary artery is referred to as net pressure gradient (Pnet = P1 − P3) 2 × π  :C can be calculated by the ratio of EOA and PA:According to Voelker et al.  C can beC) depends only on the ratio of valve opening area (EOA) and vessel CSA or in this case, the pulmonary CSA (EOA/PA) and mathematically describes the relationship between the two variables as an inverted parabola. The summit of PRI of 50% can be attained by EOA/PA of 0.5. Smaller and higher ratios of EOA/PA result in lower values of PRI indicated by the parabolic function. The EOA/PA ratio covers the entire range of all possible degrees of valve stenosis and vessel CSAs. Interestingly, other factors such as flow and turbulence have no effect on this function. Absolute PR is also influenced by Pmax : EOAI.Energy loss coefficient index   were routinely investigated by echocardiography between 2012 and 2018 as part of the Ross registry follow‐up protocol . Details of echocardiographic evaluation have been previously described  were assessed by using the CW‐Doppler signal across the pulmonary homograft. Stroke volume was assessed using the diameter of the RVOT as well as pulsed wave Doppler VTI of RVOT. SV = D2/4 × π × VTIRVOT where D is the diameter of RVOT. The dimensionless velocity index (DVI) was calculated by the ratio of VTIRVOT and transvalvular VTI collected by CW‐Doppler. The diameter of the pulmonary artery was measured 2 cm beyond the mobile parts of the homograft using parasternal short axis. The ventricular ejection time (t) was measured by assessing the time between the R‐wave of ECG and the end of the pulsed‐waved Doppler RVOT‐VTI signal  could also be measured using the tricuspidal regurgitation Doppler signal as a reliable approximation of total right ventricular afterload. Additionally, in 26 healthy patients with native pulmonary valves, RVSP and 2.6All CT angiographies were performed during apnea, using identical settings  . Most of these patients were male and had normal left and right ventricular function with only a minority of patients showing the typical cardiovascular risk factors. The main Doppler‐hemodynamic parameters of the cohort with or without correction for PR are shown in Table Table Pmax was small (<5 mmHg) in the homograft subgroup, but large in healthy controls (>17 mmHg). The difference between RVSP and EL  was significantly higher and corresponds exactly to the difference of RVSP‐Pmax of healthy controls as a reference point  . The difference between RVSP and Pmax indicates the calculated pure pulmonary vascular resistance in mmHg. The difference between RVSP and ) Figure ; Table 2r = −0.69, p < 0.001). Echo‐ and CT‐derived diameter measurements of the pulmonary artery showed good agreement  . Both parameters are significantly reduced compared to Pmax (p < 0.001).A significant inverse correlation between PR and the diameter of pulmonary artery (CT scan) is depicted in Figure ) Figure , Table 22/m2, respectively  and reveals an implied parabolic function. The parabolic curve of calculated PRI values  shows an optimum effect for the relative PR of 50% with a ratio of EOA to PA of 0.5 . The biggest difference between ELCOI and EOAI was noted in the EOAI range of 1.0  and indicates the highest PRI results of the studied cohort. Higher grade  and lower grade stenoses (>0.6 green colored points) show smaller differences.ELCOI and EOAI showed a significant correlation with the correlation line shifted above the identity line Figure . The meay Figure  Additiony Figure . The dif5 Figure   was noted when the standardized homograft orifice area was ≤0.6 cm2/m2 (severe stenosis) compared to >0.6 cm2/m2  than when it was <7 cm2 , which indicates systematically higher ELCOI values . The seven patients with an EOAI value <0.5 cm2/m2 remained in the group of severe homograft stenoses even after PR correction   Figure .PR with 1/ELCOI (r = −0.86) was significantly better  compared to the correlation of Vr with 1/EOAI [r = −0.56  and was significantly better  than the correlation of Pmax with 1/EOAI (r = −0.39)  Figure .r = 0.84) as well as for ELCOI was tested. In this case, the correlation between DVI and ELCOI (r = 0.91) was significantly better as well  . If the cutoff value for high‐grade stenoses of the ELCOI of 0.6 cm2/m2 is inserted in this equation, a DVI value of 0.23 (95% CI: 0.20–0.26) is calculated. This value roughly corresponds to a VTI ratio of  1 to 4, similar to that for severe aortic valve stenosis  which resulted in a reclassification of 61% (11 out of 18 patients) from severe to moderate homograft stenosis. This result can be explained by the high mean PRI (33 ± 5%) found in this group, which is well above the clinically relevant PRI value of >20% .Based on the EL concept, the PR is of higher magnitude if the vessel diameter downstream of a stenotic valve lesion is relatively small  depends on the ratio of the valve orifice area and the CSA of the downstream vessel root. This relationship describes mathematically the interaction or “crosstalk” , the total resistance (approx. 180 dyne × s × cm−5), and the diameter of the pulmonary artery (<2.5 cm) are significantly lower than in the left system.Loss of energy is a normal feature of the circulation when mechanical energy of the flowing blood is converted into heat by the friction of the vessel wall  is inserted in the equation . Ingo Eitel: Critically reviewing the final manuscript. Stephan Ensminger: Critically reviewing the final manuscript. Efstratios I. Charitos: Statistical analysis, critically reviewing the final manuscript. Gert‐Hinrich Reil: Conception of the study, interpreting data, drafting the manuscript. Ulrich Stierle: Conception of the study, performing echoes, interpreting data, critically reviewing the final manuscript.Written informed consent of all subjects participating in the research comprising the manuscript was obtained. The procedures were in accordance with the ethical standards of the responsible committee on human experimentation  and with the Helsinki Declaration of 1975, as revised in 2008.All authors declared no conflict of interest.


Mean right ventricular constrictive ratio in patients with double-chambered right ventricle (15%) was significantly smaller than that without (29%). A cut-off value of a right ventricular constrictive ratio less than 20.1% was established to diagnose double-chambered right ventricle with an 89.7% sensitivity and 78. 3% specificity. Right ventricular constrictive ratio can be a valuable asset for the preoperative diagnosis of double-chambered right ventricle with cardiac computed tomography.To introduce image characteristics of double-chambered right ventricle on cardiac computed tomography and set a diagnostic criterion for the diagnosis. We retrospectively collected and measured the right ventricular constrictive ratio on computed tomography images in children who had simple ventricular septal defects in the past 10 years, because double-chambered right ventricle is often associated with ventricular septal defects. The right ventricular constrictive ratio was defined as the subinfundibular cross-sectional intraluminal area during end-systole divided by the area during end-diastole in the same patient. We compared the right ventricular constrictive ratio between subjects with concomitant double-chambered right ventricle and those without. 52 children were included, and 23 (44.2%) of them have concomitant double-chambered right ventricle. In most cases ( The muscular bundles tend to cause right ventricular outflow tract obstruction (RVOTO). It is an entity not to be confused with the spectrum of diseases with pulmonary stenosis, such as Tetrology of Fallot, in which the infundibulum rather than the subinfundibulum is stenotic2. Almost 90% of DCRV cases have associated membranous ventricular septal defects (VSD)4. Some believed the hypertrophied muscular bundles in DCRV are induced by VSD, in order to prevent the pulmonary circulation from overloading5. A right intraventricular pressure gradient of at least 20 mmHg should be measured during transthoracic echocardiography for DCRV to be considered6. When treated properly with surgery, usually myectomy of the hypertrophied muscular bundles, the prognosis is optimal with complications occurring rarely9.Double-chambered right ventricle (DCRV) is a rare congenital heart disease in which muscular bundles growing in the 10. While most prospective ECG-gated cardiac computed tomography (CT) images disclose heart appearances during the diastolic phases, hypertrophied muscular bundles in DCRV are often reasonably more visible when the heart is contracted in systole12. Observation during surgery is also not always straightforward because operated hearts are usually in a state of induced diastolic arrest during cardiopulmonary bypass. All of which may lead to overlooking of underlying DCRV and thus reoperations when RVOTO gets worse14. Correct diagnosis before surgery is thereby crucial.However, the subinfundibulum is not always well visualized in standard planes of transthoracic echocardiography, and measuring the RV pressure gradient is not a routine15 in DCRV. Data regarding its diagnosis via ECG-gated cardiac CT on the other hand is relatively scarce, while CT still remains a popular modality of choice in Asia16. We not only share our experience in diagnosing DCRV with cardiac CT in this study, to our knowledge this is also the first of its kind to gather such a considerable amount of cases and perform quantified measurements.Numerous studies have already explored the diagnostic value of conventional echocardiographyThe National Taiwan University Hospital Research Ethics Committee has approved this retrospective study with survey, waiving the need for informed consent as it does not affect patient safety or clinical outcome. The study protocol strictly adhered to the ethical guidelines of the 1975 Declaration of Helsinki and was conducted in a single tertiary referral hospital.We retrospectively collected information on patients diagnosed with simple VSD and received operations for this cause between March 2008 and October 2018. All patients received transthoracic echocardiography followed by retrospective ECG-gated cardiac CT within 3 months before surgery, as part of the routine in the surgical ward. Final confirmation of a DCRV diagnosis was made using intraoperative transesophageal echocardiography when RV pressure gradient reached 60 mmHg. Confirmed patients with DCRV form the study group, who would then receive subinfundibular myectomy along with VSD repair. The control group consisted of patients who did not have DCRV and only received VSD repair without myectomy.Patients with complex heart diseases, such as Tetralogy of Fallot, transposition of the great arteries, double outlet right ventricle, endocardial cushion defect, hypoplastic left heart syndrome or heterotaxy were completely excluded from this study. Patients who received myectomy in the infundibulum instead of subinfundibulum were also not included in this study.All participants underwent postoperative follow-up transthoracic echocardiography. No residual right ventricular pressure gradient or arrhythmia was noted in any of them in the control or study group.19.A 64-detector scanner  was used since December 2008, and another 320-detector scanner  was used since December 2016. Data were acquired in the caudocranial direction, with a section thickness of 0.625–0.65 mm without gaps. Dynamic changes in the RV mid-cavity were explored using retrospectively gated cardiac CT. A cardiac cycle was divided into 20 phases, which means that each phase image was reconstructed at a 5% interval of the cardiac cycle. The matrix size in the X–Y plane was 512 × 512 pixels. A nonionic iodinated contrast medium  was delivered through a power injector to all patients at 80% of the maximum allowable injection rate. The delay time between the start of the contrast medium administration and the start of imaging was determined using a bolus tracking technique. A region in the ascending aorta was used for bolus-tracking; the threshold level was set at 150 HU. All cooperative patients were asked to hold their breath during scanning. Quiet respiration without crying was deemed acceptable in younger children and infants who could not comply with this request; therefore, patients aged < 5 years were routinely sedated with chloral hydrate (50 mg/kg) during examination. The mAs and kVp were age adjusted in order to reduce the radiation dose, based on the as low as reasonably achievable principleImage reconstruction and quantification were performed at an independent workstation using commercialized CT softwares . Animated myocardial models with the viewer’s side  removed were created for surgeons to better visualize the location of the muscular bundles if they exist . The models we designed are slightly different from common 3D volume renderings in that instead of the contrast-filled intraluminal areas, we rendered the muscular portions instead, leaving chambers hollow.A survey questionnaire was sent out to a group of physicians consisting of cardiologists and cardiovascular surgeons with examples of DCRV cases to clarify whether such reconstructed myocardial models are useful in the eyes of non-radiology physicians. They were asked to rate their confidence in pointing out the whereabouts of hypertrophied muscular bundles with three different image sets from the same DCRV patient on a scale of 1 to 5. The three image sets were a single static CT image, a dynamic cine CT loop, and an animated myocardial model.max and Amin respectively. The right ventricular constrictive ratio was defined as Amin divided by Amax  between interpreters with vast experience differences.p value of < 0.05 was considered significant.Descriptive statistics and Student’s t test were used to compare the mean measurements of the study and control groups. The receiver operating characteristic curve analysis established a diagnostic CR cutoff value for DCRV. The preceding statistical analyses were performed using the commercially available software SPSS . A This is a retrospective pure image analysis study that did not involve patient or public recruitment prior to research and did not affect treatment decisions.We enrolled 52 patients with simple VSD, in which 23 (44.2%) of them have DCRV . The remaining 29 (55.8%) patients  had simple VSD but no DCRV. Preoperative echocardiography diagnosed DCRV in 11 out of 23 patients (48%) with an average middle RV pressure gradient of 44.2 mmHg.  involve or occur just inferior to the level of supraventricular crest in the right ventricle.An extremely high degree of hypertrophied muscular bundles in our DCRV cases  was significantly lower than that in patients without DCRV 29.0%), with 9.0%, wit001 Fig. . A cut-oAccording to our survey questionnaire collected from a group of 35 non-radiology pediatric cardiology specialists, the average confidence to point out the whereabouts of muscular bundles in DCRV on a scale of 1 to 5 (higher ratings for higher confidence) was 2.87 for single static CT image, 4.30 for dynamic cine CT loop, and 4.46 when myocardial models were present.The average radiation effective dose of included patients was estimated to be 1.72 mSv in infants, 3.46 mSv in preschoolers, and 9.87 mSv in school-aged patients performed with our 64-detector CT scanner. Average radiation dosage was reduced to 0.43 mSv in infants and 1.61 mSv in preschoolers with our newly-installed 320-detector CT scanner. No school-aged patients received examinations with the 320-detector CT scanner. No sequelae from chloral hydrate sedation occurred in any of the patients.22. When simple VSD is repaired without simultaneously correcting DCRV, tension could build up in the patched-up ventricle as hypertrophied muscular bundles continue to cause mid-cavity obstruction, but now without a defect to partially release the ventricular pressure9.  While isolated DCRV is extremely rare, associated lesions are by contrast better demonstrated during diastolic phases22. That is the reason why both systolic and diastolic images are essential for DCRV cases. In intricate details, retrospective ECG-gated cardiac CT shows the entire cardiac cycle, both systole and diastole. Identifying perplexity in congenital heart diseases has always been a strong suit for CT1.The heart is a moving organ ever-changing its forms and shapes during a single cardiac cycle. Hypertrophic muscular bundles in DCRV are more easily spotted when contracted and thickened during systolic phasesn = 21; 91.3%) occur just inferior to the level of the supraventricular crest in RV, not just anywhere randomly. The morphology consistency across different patients is surprisingly high. Maron et. al first proposed the idea back in 197324 that DCRV might result from an acquired process in which the supraventricular crest slowly hypertrophied due to increased turbulent flow and shunting from VSD thus the high co-occurrence of DCRV and VSD. Our data supported the hypothesis in that a markedly high degree of our cases had hypertrophied muscle bundles involving or just inferior to the supraventricular crest. Thus it was only reasonable that we chose to measure uniformly close to the level of the supraventricular crest in RV. Other than that, as our myocardial model was able to directly demonstrate muscular thickness and morphology, it enables us to differentiate a normal supraventricular crest, which is supposed to be just an infolding of the RV wall25, from a solid hypertrophied ridge in DCRV. Whereas with usual volume rendering, both show indentations in the luminal area and it wouldn’t be easy to tell if condensed muscles are present or the infolding is simply wider.  Our questionnaire results confirmed that myocardial models are effective image addendums that subjectively increase physicians’ confidence. It was also during this process that we discovered most hypertrophied muscular bundles in our DCRV cases (26. However, cardiac magnetic resonance is often costly and time-consuming in Asia. For pediatric patients, this means heavy sedation or anesthesia in most cases, which is not always feasible due to tight schedules and shortage of anesthesia manpower. CT is often considered more cost-effective and accessible than cardiac magnetic resonance here, requiring only light sedation in the pediatric population at the cost of acceptable radiation exposure16. We were thereby able to collect such a considerable amount of CT images in DCRV over the past 10 years. Of course, diagnosis of DCRV can always be made with cardiac catheterization, but it would be more invasive and costly than any of the image modalities17.In recent decades, cardiac magnetic resonance has been gaining popularity for the evaluation of pediatric congenital heart diseases with no radiation exposureThe major limitation in our study involves patient selection. We were unable to recruit patients with isolated DCRV due to its rareness and therefore our data only applies to the majority that has concomitant simple VSDs. There is also the possibility of selection bias in that our patients might have exhibited more worrying clinical symptoms than average VSD patients to warrant an operation, which explains the high DCRV occurrence rate. The presence of other cardiac lesions may complicate the process of measurements which is also not investigated in this study. The results of this study, however, still prove CT to be a reliable modality in the diagnosis of DCRV under most circumstances.Image post-processing, especially volume rendering, is a time-consuming process that can only be properly done manually, making it unrealistic to include myocardial models in every examination. Nevertheless, its potential to assist in surgical planning should not be underestimated.In this study, we wish to raise awareness of DCRV in simple VSD cases among cardiologists, cardiothoracic surgeons, and radiologists. Right ventricular constrictive ratio showed promising diagnostic accuracy for the disease, with a cutoff value of less than 20.1%. We share our observations regarding this disease on CT in hopes of enhancing diagnosis before a patient enters the operating room. Our animated myocardial model brings about great potential in providing pediatric cardiology specialists with a better perception of DCRV morphology.Supplementary Information 1.Supplementary Information 2.


Fabry disease is a rare, progressive X-linked inherited disorder of glycosphingolipid metabolism due to a deficiency of α-galactosidase A enzyme. It leads to the accumulation of globotriaosylceramide within lysosomes of multiple organs, predominantly the vascular, renal, cardiac, and nervous systems. Fabry cardiomyopathy is characterized by increased left ventricular wall thickness/mass, functional abnormalities, valvular heart disease, arrhythmias, and heart failure. Early diagnosis and treatment are critical to avoid cardiac or renal complications that can significantly reduce life expectancy in untreated FD. This review will focus on the role of cardiovascular magnetic resonance imaging in the diagnosis, clinical decision-making, and monitoring of treatment efficacy. Fabry disease (FD) is a rare, monogenic X-chromosome-linked lysosomal storage disorder caused by mutations in the GLA gene. It results in an absence or deficiency of the enzymatic activity of α-galactosidase A (α-GAL) . More thThe prevalence of FD is around 1 in 40,000 to 1 in 117,000 , 6. ClasFabry disease is a multisystem disease with frequent misdiagnoses and significant diagnostic delays in females (16.3 ± 14⋅7 years) and males 13.7 ± 12⋅9) , that ad⋅9 , thatThe main diagnostic challenge from a cardiac perspective is distinguishing FD cardiomyopathy from other forms of unexplained LVH, given its infrequent clinical suspicion, especially in the absence of extracardiac manifestations in atypical FD patients and heterozygote females. Increased community awareness will be needed in order to recognize FD as a potential cause of seemingly idiopathic LVH. Confirmation of FD is made by enzyme activity assay and/or genetic testing; tissue biopsy is rarely required. However, genetic testing is the initial screening test in most US centers due to its wide availability. A comprehensive diagnostic approach is needed for early diagnosis and treatment of FD cardiomyopathy, including early recognition of clinical red flags, biomarkers, multimodality cardiac imaging, and assessment for the involvement of other organ systems such as the kidneys, nervous system, etc.Cardiovascular magnetic resonance is an essential imaging modality for the quantitative and qualitative assessment of cardiomyopathies. In contrast to transthoracic echocardiography (TTE), CMR provides anatomical and structural evaluation, myocardial strain analysis, and quantitative tissue assessment using late gadolinium enhancement (LGE) and novel parametric mapping techniques like native T1 mapping and extracellular volume (ECV) measurement. It can detect the majority of genotype-positive patients with mild or subclinical cardiac phenotypes. CMR, with advanced mapping techniques, is a valuable diagnostic tool in asymptomatic carriers and preclinical deposition of GL3 in the myocardium, microvasculature, conduction system, and valves . MultipaCardiovascular magnetic resonance is the gold standard for the assessment of myocardial wall thickness and mass. In comparison, TTE is limited by acoustic windows, overestimating or underestimating wall thickness and mass, dropout artifacts in the basal inferolateral wall and RV myocardium, and lower reproducibility .Left ventricular hypertrophy is the most common structural change reported in FD . Patient2 vs. follow-up 27 ± 7 g/m2, p < 0.05).Right-sided structural changes are common in FD, typically right ventricular hypertrophy (RVH), with preserved systolic function and normal chamber size. However, diastolic dysfunction often exists that may progress to advanced heart failure . NiemannFabry disease is different from other interstitial cardiomyopathies–GL3 accumulation is intracellular, resulting in a true increase in LV myocyte mass and a reactive LVH. It impairs ventricular compliance, increases filling pressures, and restricts diastolic filling, causing heart failure . CMR is p = 0.002), and it was able to discriminate between FD patients without LVH or LGE from healthy controls, endorsing it as an early marker of cardiac involvement in FD. In a study by Roller et al. (p = 0.0009) and correlated with Lyso-GL3 elevation. GLS values increased with worsening LVH and LGE. Another study by Vijapurapu et al.  is a very feasible and highly accurate technique for strain/strain rate analysis in cardiac diseases, especially the assessment of LV-GLS  in LVH has excellent reproducibility . It is mr et al. , GLS wasu et al.  demonstrLate gadolinium enhancement reflects replacement fibrosis and helps differentiate FD cardiomyopathy from ischemic and other hypertrophic cardiomyopathies. LGE is present in almost half of FD patients and typically involves the basal and mid inferolateral myocardium in about 75% of these patients , 29 Fig. About oStandard imaging evaluation of anatomical and functional abnormalities and the presence of replacement fibrosis lack sensitivity or specificity to diagnose FD. Quantifying longitudinal relaxation time (T1) generates a pixel-wise color-encoded map of the myocardium, allowing the detection of very subtle pathological changes at the microscopic level that may be indicative of the preclinical stage. Native myocardial T1 values, obtained without a paramagnetic contrast agent, are higher in fibrosis, edema, and amyloid but lower in iron overload and focal fat infiltration. Accumulation of sphingolipids inside lysosomes in FD significantly shortens the native T1 values. T1 mapping has overcome the limitations of gadolinium contrast agent used in patients with advanced renal disease. In addition, T1-mapping is superior to LGE, with higher diagnostic accuracy, when the myocardium has more uniform and diffuse involvement .Pica et al.  found T1P < 0.0001), which were inversely related to LV wall thickness . In 40% of the FD patients without LVH, T1 values were abnormal due to the early phase of GL3 accumulation in myocytes.In patients with LVH, T1 mapping could differentiate FD from other phenotypes. In a study by Sado et al. , FD patiThompson et al.  comparedT1 mapping parameters, as surrogates for GL3 accumulation, can be reduced in the absence of LVH and basal inferolateral wall (BIFL) LGE. Thus, it may play a potential role in detecting the most appropriate patients for treatment and early quantitative assessment of treatment efficacy.B = 2.4; p < 0.001). All patients with elevated troponin had LGE representing inflammation instead of scar. Chronic T2 elevation in LGE areas and elevations of global T2 values are both associated with poor outcomes  guidelines do not provide FD-specific recommendations for CMR evaluation in the pediatric population . In younMultiparametric CMR has a vital role in differentiating FD cardiomyopathy from other etiologies of LVH and can strongly impact clinical decision-making and prognosis by initiating disease-specific therapies  Table 1Table 1. via lentivirus  or increasing α-GAL enzyme activity inside lysosomes by chaperone therapy. Current ERT options include intravenous agalsidase-α  or agalsntivirus , adeno-a1 dispersion, and left ventricular mass index (LVMi) to provide an accurate estimate of the 5-year risk of adverse cardiac outcomes. CMR-derived myocardial T1 relaxation time with wider distribution may have a greater prognostic value as it can better reflect GL3 accumulation, fibrosis/inflammation, and thus disease severity. LVMi by CMR is independently associated with adverse cardiac events in FD (Cardiomyopathy is the leading cause of death in men (34%) and women (57%) with FD . Early dts in FD . Other cCardiac involvement should be detected promptly in FD patients to prevent disease progression and life-threatening complications. Multiparametric CMR imaging can play a vital role in reaching the correct diagnosis of hypertrophic myocardium and differentiating it from other phenotypes. FT-CMR and parametric mapping are emerging techniques with the potential for preclinical detection of cardiac involvement and monitoring response to therapy. In particular, T1 mapping is a superior technique for detecting GL3 accumulation and diffuse fibrosis. It has the potential for quantitative assessment of treatment efficacy–current data is insufficient, and further research is required to establish this role.Both authors contributed to review conception, design, research, writing, and editing and approved the submitted version.


Data regarding short- and long-term cardiovascular complications of biological agents is lacking. Herein, the authors reported a case of abrupt onset of acute heart failure induced by ustekinumab treatment for resistant pityriasis rubra pilaris in a young healthy female with no past cardiac history. Although medical management was immediately initiated for cardiogenic shock, the patient passed away. Promising results were shown in patients with various dermatological conditions refractory to traditional therapies.A 21-year-old female presented in 2021 with extensive erythematous skin rash that was provisionally diagnosed as severe eczema. She was treated conventionally with antihistamines and corticosteroids, but her condition did not improve. After referral to the dermatology department, she was diagnosed with pityriasis rubra pilaris and started on dupilumab, which was continued for 8 months with no response. She was then started on ustekinumab and reported improvement of her skin lesions. However, within a few days, she started to complain of gradually worsening shortness of breath and bilateral lower extremity edema. She had no previous medical history of cardiovascular risk factors or family history of heart disease. On clinical examination, she was distressed, tachypneic with a respiratory rate of 25, tachycardiac with a heart rate of 120 beats/minute, and with blood pressure of 90/60 mm Hg. Cardiac examination was significant for jugular venous dilatation, pansystolic murmur over the mitral area, and bilateral lower limb edema. Lung auscultation revealed bilateral diffuse crepitations. Her laboratory workup was significant for markedly elevated pro B-type natriuretic peptide (NT-proBNP), renal and liver functions, lactic acidosis, and slightly elevated troponin levels. Electrocardiogram showed sinus tachycardia 120 beats/minute, right bundle branch block, and left posterior fascicular block . Urgent 2 reversible ustekinumab-induced heart failure for treatment of plaque-type psoriasis was reported in a 46-year-old female patient with no past cardiac history.This is a case of abrupt onset of acute heart failure induced by ustekinumab treatment for resistant pityriasis rubra pilaris in a patient without any family or medical history of cardiovascular disease. Similar to the case reported by Beroukhim et al.,3 Data from phase III clinical trials demonstrated promising efficacy and safety profile with rapid improvement in psoriasis area and severity index.4 Common side effects include upper respiratory tract infections, nasopharyngitis, headache, and arthralgias.4Several biologic agents are available for the treatment of moderate-to-severe psoriasis. Ustekinumab, a human monoclonal antibody targeting the shared p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23), has been recently approved by the FDA for patients with immune-mediated inflammatory diseases, including moderate-to-severe plaque psoriasis and Crohn’s disease.5 The role of IL-17 in atherosclerosis remains controversial.5 Several studies demonstrated its proatherogenic effect, whereas a plaque-stabilizing effect was noted in the setting of enhanced IL-17 production with suppressed interferon-γ.5 According to the French national health insurance database consisting of 9,290 patients treated with ustekinumab, there was a statistically significant correlation between ustekinumab and severe atherosclerotic cardiovascular events—including acute coronary syndrome and ischemic stroke—within 6 months after initiation in those with high cardiovascular risk.6 Also, from a prospective study of 981 patients with acute myocardial infarction, lower serum levels of IL-17 were associated with a higher risk of death and recurrent myocardial infarction.7 The observed findings from both studies were likely attributed to the impaired regulatory and atheroprotective role of IL-17. Additionally, data from an in vivo study of myocardial infarction mice showed that IL-23 deficiency was associated with adverse remodeling and myocardial inflammation.8The mechanism and effects of ustekinumab on the heart remain largely unknown. IL-23, which plays a pivotal role in the differentiation of T helper 17 cells (Th17) and subsequent production of interleukin-17 (IL-17), is inhibited by ustekinumab.6 Data from PHOENIX 2—a multicenter, phase III, randomized, placebo-controlled study of 1,212 patients with moderate-to-severe psoriasis—revealed two cases of new-onset heart failure associated with 90 mg ustekinumab after 806 and 1,217 days of treatment, respectively.9 Previous evidence regarding the use of ustekinumab and cardiovascular events was well summarized and recently published.10 However, most of the studies included either a short follow-up or only focused on a composite of major cardiovascular events that did not involve heart failure. Besides heart failure, venous thrombosis has been reported in 115 patients (0.18%) from a total of 65,635 patients according to a phase IV clinical trial.11 The echocardiographic finding of large right ventricular thrombi in our patient also raises concern for this possible adverse event, although it was more likely secondary to heart failure.In addition to the atherothrombotic events, twelve cases of in-hospital mortality due to heart failure were reported in the French national health insurance database.12 IL-12, a major pro-inflammatory cytokine involved in psoriasis, is elevated in the failing heart; therefore, its cardioprotective effect was presumably due to IL-12 inhibition. The detrimental effect of IL-17 on adverse cardiac remodeling was also demonstrated in animal models,14 so it is plausible that ustekinumab-mediated IL-17 inhibition may contribute to the improved outcomes in this study.Controversial results showing favorable effects to the heart were obtained from a trial of 150 psoriasis patients randomly treated with ustekinumab, etanercept, or cyclosporine. In this trial, IL-12/23 inhibition led to improved left ventricular global longitudinal strain and lower NT-proBNP levels.Given the controversy showing both cardioprotective and detrimental effects secondary to IL-12/23 inhibition, the risks and benefits of initiating ustekinumab, particularly in those with cardiovascular risk factors or established cardiovascular diseases, should be thoroughly assessed until the exact mechanistic relationship can be ascertained. It should be noted that heart failure could also develop in those without prior cardiac history. Although the incidence seems to be low, interval monitoring with echocardiography may be beneficial for early detection of heart failure, thus allowing prompt discontinuation of ustekinumab.


Few patients with coronavirus disease 2019–associated severe acute respiratorydistress syndrome (ARDS) require veno-venous extracorporeal membrane oxygenation(VV-ECMO). Prolonged VV-ECMO support necessitates repeated oxygenatorreplacement, increasing the risk for complications. Transient hypoxemia, inducedby VV-ECMO stop needed for this procedure, may induce transient myocardialischemia and acutely declining cardiac output in critically ill patients withoutresidual pulmonary function. This is amplified by additional activation of thesympathetic nervous system . Immediate reinjection of the primingsolution of the new circuit and induced acute iatrogenic anemia are otherpotentially reinforcing factors. The case of a critically ill patient presentedhere provides an instructive illustration of the hemodynamic relationshipsoccurring during VV-ECMO support membrane oxygenator exchange. This is particularly due to the inflammatory and pro-thromboticstate, with increased coagulation activities and hemolysis observed.7 Accordingly, prolonged VV-ECMOsupport requires repeated membrane oxygenator exchange. This is generally astraightforward procedure; however, in critically ill patients without residualpulmonary function, significant transient hemodynamic impairment may occur.The coronavirus disease (COVID-19) outbreak is characterized by a high rate ofhospitalized patients with respiratory failure. Twenty percent of them develop anacute respiratory distress syndrome (ARDS) requiring ventilation.2/FiO2) was below 80 mmHg for morethan 6 h. A VV-ECMO was implanted. After heparinisation (intra-venous injection of5000 UI unfractionated heparin), a 25 French (Fr) 55-cm inflow multiport cannula(Maquet®) was inserted percutaneously via the right femoral vein and a 17 Fr 23-cmoutflow simple-port cannula (Maquet®) via the right internal jugular vein. Thecannulas were connected to an HLS circuit  and aCardiohelp® device. VV-ECMO support was initiated without problems, and systematicheparinisation was monitored by measuring anti-Xa factor activity(0.3–0.5 units/mL).A 60-year-old previously healthy patient was admitted for ARDS caused by SARS-CoV-2.The patient required oro-tracheal intubation and mechanical ventilation. 9 dayslater, he became refractory to conventional therapies. Despite prone positioning,neuromuscular blockade, and high positive end-expiratory pressure ventilation, theratio of partial pressure of oxygen in arterial blood to fractional concentration ofoxygen in inspired air .This was realized without complications, and hemolysis regressed. However, themembrane oxygenator had to be replaced again on days 16, 24, and 36 because of thesame problem. The ECMO circuit was disconnected during this procedure and replacedby a new one (HLS Maquet®) previously primed with 600 mL of isotonic crystalloids. During one of these changes, after reconnection ofthe previously primed circuit as well as VV-ECMO restart, electrocardiographic (ECG)monitoring showed large, peaked T waves as well as ST segment elevation . Few secThe circuit change was performed rapidly (29 s) and was otherwise technicallyunproblematic. Pre-procedurally, hemoglobin was 112 g/L and then 98 g/L, corresponding to a 15% decrease. High sensitive troponin T did notincrease, and echocardiography showed unchanged normal left ventricular ejectionfraction. After further stabilization, the patient could be weaned off VV-ECMO after45 days. The patient left the intensive care unit on day 85.5 Therefore, it seems notsurprising that accordingly, in COVID-19 patients under VV-ECMO support, repeatedoxygenator changes become necessary.Long-term VV-ECMO patients are known to undergo a number of acute biological changes,including alterations in coagulation activity. In addition, approximately one-thirdof critically ill COVID-19 patients develop coagulopathy, with thrombotic eventspredominating over haemorrhagic events.8 In the early hypoxemic phase of our patient, the ECG showslarge, peaked (hyper-acute) T waves followed by the appearance of ST elevations,indicating acute myocardial ischemia , and systemic vascular resistance, resulting in additional stresson the already weakened myocardium.9The hemodynamic changes observed in this case are most likely triggered by theshort-term severe acute hypoxemia caused by the sudden cessation of VV-ECMO supportin patients with severely impaired residual pulmonary function. The transientdecrease in oxygen delivery leads to depressed myocardial function, wall motionabnormalities, arrhythmias, and corresponding ECG changes similar to cardiacischemia.ischemia . These c2 (Therefore, as a consequence of this transient hypoxemia and subsequent cardiacischemia, there may be a decrease in cardiac output, systemic hypotension, and adecrease in end-tidal CO2 .8 Restarting VV-ECMO at a reducedflow rate could potentially attenuate this “crystalloid flush effect.”Although these mechanisms are effective for a very short time, they are exacerbatedby the connection of the new circuit and the subsequent immediate reinjection of thecrystalloid priming solution because this leads to a rapid decrease in hematocritand hemoglobin concentration that immediately follows the hypoxemia provoked by theVV-ECMO stop. This iatrogenic anemia could therefore be another factor exacerbatinghypoxia-induced myocardial weakness.The hemodynamic changes shown here confirm that membrane oxygenator replacementcarries some risks, especially in patients with severe respiratory failure. Thisknowledge can help to follow certain safety rules and to react adequately.


Endocardial fibroelastosis (EFE), an uncommon congenital heart disorder often occurring in infants, has a poor prognosis. It is of great significance to perform early diagnosis and accurately analyze cardiac function to enable further clinical treatment and prognosis decisions. This study aimed to explore the findings of cardiac magnetic resonance (CMR) in patients with EFE, including morphological changes and cardiac function analyses. Additionally, we compared the difference in the evaluation of the cardiac function between CMR and echocardiography (Echo).’ cardiac function. The correlations between clinical cardiac function classification and MRI- and Echo-derived imaging data were determined.Eleven patients with EFE , treated in our hospital, were analyzed retrospectively. Left ventricular posterior wall thickness (LVPW), anterior wall thickness (LVAW), fractional shortening (FS), ejection fraction (EF), end-systolic diameter (ESD), end-diastolic diameter (EDD), end-systolic volume (ESV), and end-diastolic volume (EDV) were assessed using both Echo and CMR. The Original Ross classification and the New York Heart Association functional classification were used to grade the patientsr = 0.646 > 0.224; FS, r = 0.627 > 0.245, respectively).All patients showed a thickened endocardium and left ventricle globular dilatation on CMR. We observed significant systolic dysfunction and whole or segmental abnormal ventricular movement. Compared with those measured by Echo, the EF, FS, and EDV values were significantly lower when measured using CMR. Compared with Echo measurements, the ESV, ESD, LVAW, and LVPW values were significantly higher when measured using CMR. CMR-measured EF and FS correlated better with the clinical cardiac functional score than those derived from Echo (EF, In patients with EFE, the characteristic morphological changes of the heart could be displayed accurately using CMR. The parameters measured by CMR were more accurate than those of Echo and correlated well with clinical cardiac function scores, mainly because it does not make invalid geometrical assumptions. Collagen and elastic fiber hyperplasia in the endocardium results in endocardial thickening, a characteristic of endocardial fibroelastosis (EFE). Infants and young children more frequently develop EFE, but it can also present rarely in adulthood . ResearcAlthough Echo is commonly performed for patients with EFE, research has shown that cardiac magnetic resonance (CMR) might be more visual and accurate in evaluating morphological and functional changes in patients’ hearts , 9. The This was a retrospective study conducted on 11 patients with EFE. The patients received treatment at our hospital between November 2010 and July 2019. There were nine female and two male patients, aged between 0.3 and 1.9 years (average age = 0.9 ± 0.6). All patients underwent CMR and Echo within 2 weeks after being admitted to the hospital. The diagnosis of EFE was confirmed using clinical signs, Echo, and CMR using the diagnostic criteria of the World Health Organization/International Society and Federation of Cardiology Task Force 12). The In this study, a 1.5 T MR scanner  incorporating a special eight-channel cardiac phased-array coil was used to carry out CMR measurements. An electrocardiography-gated technique and a respiratory-gated technique in real-time instances were used to avoid the influence of rhythm and breath. We obtained fast spin Echo with a double inversion recovery preparatory pulse and fast-imaging employing steady-state acquisition (FIESTA) cine images in one short-axis view and three long-axis views  covering the LV from the base to the apex. Subsequently, 0.2 mmol/kg gadolinium-based contrast agent was injected intravenously. Ten minutes later, we performed myocardial delayed enhancement (MDE) using a T1-weighted inversion recovery gradient Echo sequence. Dedicated software  was used by experienced radiology technicians to carry out the cardiac function analysis. In all scan slices, the endocardial and epicardial borders of the LV myocardium were traced manually at the end of diastole and systole on each cine short-axis image to determine LV fractional shortening (FS), LV ejection fraction (EF), LV end-systolic volume (ESV), and LV end-diastolic volume (EDV). At the end of the diastolic phase, we measured the left ventricular posterior wall thickness (LVPW) and left ventricular anterior wall thickness (LVAW). An ultrasound instrument  using a probe frequency of 2.5 MHz was used to carry out Echo measurements. An EchoPAC workstation  was used for data analysis.P value < 0.05. SPSS version 25.0  was used to conduct statistical analyses.The data were consistent with the skewness distribution and were described by the median and interquartile range (IQR). Statistical differences were tested using the Wilcoxon signed-rank test. Correlations between clinical cardiac functions and CMR/Echo characteristics were calculated using Spearman’s rank correlation analysis. Statistically significant differences were identified by a In all cases, CMR showed a thickened endocardium (mostly larger than 2–3 mm) with increased and hypertrophied myocardial trabeculae. The boundary between the thickened myocardial trabeculae and the compact myocardium was clear, which was located in the inferior wall, posterior wall, and posterior ventricular septum of the left ventricle. In the short-axis position, the lesion range was more than one-third or one-half of the circumferential diameter . The lefP < 0.05; r = 0.646 and r = 0.627, respectively). Meanwhile, Echo-classified EF and FS also correlated with clinical cardiac function classes  , are shown in ctively) .Left ventricular dysfunction caused by EFE sometimes causes fulminant progression to heart failure. Early diagnosis, early treatment, and long-term adherence are the key to a good prognosis . HistoloAdditionally, for patients who are suspected of having EFE, it is sometimes difficult to distinguish EFE from left ventricular noncompaction (LVNC). The best method of diagnosis is endocardial biopsy, which is an invasive method and is not recommended. CMR can clearly show the border of the endocardium and the compact myocardium, which can be used to distinguish these two diseases. Deep trabecular fossae communicating within the LV cavity and multiple prominent trabeculae in the subendocardial area characterize LVNC. LVNC can also be manifested as apparent thickening of the endocardium, similar to EFE. The difference is that the compacted myocardium is significantly thinned in LVNC, but not in EFE . The lefP < 0.05). Compared with those of Echo, CMR-determined EF and FS correlated better with the clinical cardiac functional score . Echo does have some advantages. It is a portable technique and is rapid and cheap. Moreover, Echo is often the first choice for most patients. However, with the development of magnetic resonance imaging (MRI) and the use of electrocardiography and respiratory gating, cardiac MRI can play a more important role in diagnosing EFE. Patients suspected of having EFE should be recommended to receive a CMR for diagnosis and a comprehensive evaluation of their cardiac function  were significantly lower in the CMR group than in the Echo group . Additionally, the boundary between the thickened myocardial trabeculae and the compact myocardium was clear, which can distinguish EFE from LVNC.This study had some limitations. First, this was a single-center retrospective study. Second, the number of cases was relatively low. Therefore, it is necessary to expand the number of samples for further research.CMR can accurately display the characteristic morphological changes of the heart in patients with EFE. In the analysis of cardiac function, the values measured by CMR were more accurate than those measured using Echo and had a good correlation with clinical cardiac function. Of course, CMR also has some limitations such as long examination times and higher costs. With the further development of medical technology, improvements in CMR can be expected in the future.