To investigate the clinical value of acoustic cardiography in the diagnosis of coronary artery disease (CAD) and post‐percutaneous coronary intervention (PCI) early asymptomatic left ventricular systolic dysfunction.n = 315); including 180 patients with angina pectoris and 135 patients with acute anterior wall myocardial infarction after emergency PCI did not present with signs and symptoms of heart failure. Color Doppler echocardiography, brain natriuretic peptide, acoustic cardiography examination were performed. The patients were divided into four groups: non‐CAD group (n = 60), CAD group (n = 120), MIREF group , and MINEF group .Inpatients in the department of cardiology were included in the research (p < .05), and the MINEF group was higher than CAD group (p < .05). S3 strength  and S4 strength  are useful in the diagnosis of CAD. S3 strength  was superior to other indicators in the diagnosis of early left ventricular systolic dysfunction after myocardial infarction.Acoustic cardiography parameters EMATc, systolic dysfunction index, S3 strength and S4 strength in the MIREF group were higher than those in MINEF group (S4 combined with STT standard change can improve the diagnosis of CAD. Acoustic cardiography can be used as a non‐invasive, rapid, effective, and simple method for the diagnosis of asymptomatic left ventricular systolic dysfunction in the early stage after myocardial infarction. Moreover, advanced investigations, such as coronary CT angiography (CTA) and coronary angiography are invasive and expensive making them difficult to apply comprehensively. As a result, diagnosis of myocardial ischemia may be delayed in some cases. Early ventricular remodeling can occur within 24–72 h after acute myocardial infarction. This remodeling may be characterized by left ventricular enlargement, decreased left ventricular ejection fraction (LVEF) and abnormal regional wall activity, which are the main factors determining the development of further cardiac events and long‐term prognosis after acute myocardial infarction (AMI). Asymptomatic left ventricular systolic dysfunction (LVSD) is a major manifestation of early ventricular remodeling, with a prevalence of up to 30%–60% after AMI. Some experts suggest that patients with asymptomatic LVSD after myocardial infarction with an LVEF less than 50% can be diagnosed with ventricular remodeling.As a result, acoustic cardiography has attracted the attention of researchers as rapid, simple and non‐invasive alternative method for the diagnosis of myocardial ischemia and heart failure. Acoustic cardiography has been reported to have clinical value in the diagnosis of heart failure. For example, some studies have shown that cardiac electromechanical activation time (EMAT), left ventricular systolic time (LVST), and S3 are superior to BNP in the diagnosis of LVSD.Therefore, we conducted a clinical experimental study to explore the clinical value of acoustic cardiography in the diagnosis of myocardial ischemia and early asymptomatic LVSD in patients with AMI after percutaneous coronary intervention.22.1n = 331, these patients were chosen a priori and patient recruitment stopped after the enrollment goals were met,16 patients were excluded due to poor ECG quality). Among them, 180 patients with angina pectoris were examined by acoustic cardiography, cardiac doppler ultrasound, ECG and troponin I on admission in order to exclude myocardial infarction . After elective coronary angiography (CAG), the patients were divided into two groups: 60 cases without CAD  and 120 cases with CAD . Another 135 patients with asymptomatic acute anterior wall myocardial infarction after emergency PCI were included . Color Doppler echocardiography, BNP and acoustic cardiography were performed after 72 h. According to EF%, study subjects were divided into two groups: those with LVSD  and those with normal left ventricular systolic function .Inpatients in the Department of Cardiology of the third affiliated Hospital of Chongqing Medical University and Haikou people's Hospital from March 05, 2019 to September 30, 2020 were included , valvular heart disease, congenital cardiovascular disease, pericarditis, myocarditis, cardiomyopathy, severe liver and kidney disease, mechanical ventilation, cardiac pacemaker. Written informed consent was obtained from each patient prior to participation. The study was approved by the local ethics committees of the participating institutions.2.2Each subject underwent acoustic cardiography examination in a supine position Figure . AcoustiEMAT: the time from the Q wave onset to the mitral component of the first heart sound (S1). EMATc indicates the proportion of the cardiac cycle occupied by EMAT Figure .Fourth heart sound (S4) strength: the measurement of the intensity and consistency of the S4; one value between 0 and 10 is reported Figure .Third heart sound (S3) strength: the measurement of the intensity and consistency of the S3; one value between 0 and 10 is reported Figure .SDI: The SDI value is a mathematical combination of QRS duration, QR interval, EMAT, and the RR interval; it undergoes a nonlinear transformation and is mapped onto a scale of 0–10.The following acoustic cardiography parameters were evaluated in this study:2.3Echocardiography was performed according to American Society of Echocardiography guidelines . We used the biplane Simpson's method to calculate end‐diastolic and end‐systolic volumes, and these volumes were used to calculate LVEF.2.4p value <.05 was considered statistically significant. Data were described as means and standard deviations for continuous variables and frequency and proportions for categorical variables. Comparisons between groups were tested using student's t test for normally distributed data and Mann–Whitney U test for skewed data. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR−) for predicting ischemia and AMI with early asymptomatic LVSD (EALVSD). Binary logistic regression analysis was used to identify independent risk factors for AMI with EALVSD.Statistical analyses were performed using SPSS, version 20 . A two‐sided 33.1Basic demographics, medication use and clinical characteristics of study subjects are summarized in Table 3.2p = .000). With an optimal cutoff point of 3.05, S3 strength produced a sensitivity of 70% and a specificity of 58%. The AUC for S4 was 0.617 . With an optimal cutoff point of 4.25, S4 strength produced a sensitivity of 48% and a specificity of 80%. The sensitivity and specificity to detect ischemia was 69% and 80%, respectively, when S4 strength was added to ST‐T wave criteria.ROC curves analysis was used to determine the value of various acoustic cardiographic parameters for predicting CAD. As shown in Figure 3.3Figure 4Our experimental evidence in this study indicates that acoustic cardiography may have clinical value in the diagnosis of coronary heart disease. The sensitivity of S3 Strength, S4 Strength and ST‐T change for the diagnosis of CAD respectively is 70%, 48%, and 38%, respectively, with specificity of 58%, 80%, and 90% respectively. The sensitivity and specificity of S3 Strength combined with ST‐T change is 69% and 80%, respectively. Acoustic cardiography combined ECG could improve the clinical diagnosis rate of coronary heart disease in patients with angina. Many other researchers have studied the diagnostic value of acoustic cardiography in coronary heart disease. One study found that in 40% of patients with myocardial ischemia or reperfusion model during PCI developed an S3 and S4 earlier than ST segment changes. After myocardial ischemia reperfusion, the duration of S4 and S3 were longer.In clinical practice, AMI often causes heart failure, in particular within the week following the acute event. Although emergency PCI can reduce the incidence of arrhythmia, cardiogenic shock and heart failure following AMI, there are still some patients who suffer from heart failure. When signs and clinical symptoms are obvious, doctors can diagnose and treat efficaciously. However, some patients with early LVSD and atypical clinical symptoms may be missed by the doctor. Moreover, it is difficult to monitor heart failure in real time using color Doppler ultrasound and BNP. The results of this study suggest that S3 strength is superior to other parameters in the diagnosis of early LVSD after myocardial infarction. The sensitivity and specificity of S3, EMAT%, SDI, BNP refers to the results section for the detailed numbers. The specificity of acoustic cardiography to detect LVSD in this study was higher than that of BNP, and the combination of S3 and BNP would further improve the sensitivity. Therefore, in the early diagnosis of asymptomatic LVSD after PCI, acoustic cardiography was superior to BNP. Moreover, it was easier to acquire results and could be monitored dynamically at any time. In conclusion, acoustic cardiography is a fast, effective, and simple method for monitoring cardiac function after myocardial infarction.There are several clinical studies that support the value of acoustic cardiography in the diagnosis of heart failure; some studies suggest that SDI >5 correlated with a LVEF <50%, whereas SDI >7.5 correlates with EF <35% and elevated left ventricular filling pressure.In the follow‐up observation of patients with chronic heart failure, the patients with SDI ≥5 or S3 strength ≥4 had increased mortality. Acoustic cardiography can predict the prognosis of patients with chronic heart failure, and be used for adjustment of the patient's treatment plan based on the results of EMAT to significantly reduce adverse events. The monitoring of night time EMAT is a method to predict adverse events of acute heart failure with results better than hemodynamic monitoring.In conclusion, S4 strength combined with ST‐T changes of the ECG can improve the diagnosis of coronary heart disease; Acoustic cardiography can be used as a fast, simple, inexpensive and effective method to diagnose asymptomatic LVSD in the early weeks after AMI.5The sample size of this study was small; larger studies are needed to confirm these findings. Only the ejection fraction was recorded during echocardiographic examination which did not allow exploration of other cardiac parameters. We did not use FFR as a diagnostic criterion for myocardial ischemia. It is the limitation of our experiment, in subsequent experiment, we will improve the evaluation and diagnostic criteria of myocardial ischemia.The authors declare that they have no conflicts of interest.


Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD).Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease.Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain , were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as “ischemic.” All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint.Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint . Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% . In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes .Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration. Cardiovascular diseases are the main cause of morbidity and death in the world, annually claiming more lives than all forms of cancer together . Non-invCurrently, the detection of inducible ischemia during vasodilator stress CMR is mostly based on the visual assessment of perfusion defects –8, whichTherefore, we sought to determine the diagnostic and prognostic value of SENC during vasodilator stress in patients with known or suspected CAD. Global LS (GLS) and CS (GCS) and average global strain (GS), as well as segmental LS (SLS) and CS (SCS) and combined information from SLS or SCS, referred to as segmental aggregate strain (SAS) were compared with perfusion data.Our patient cohort consisted of patients who underwent adenosine stress CMR between September 2017 and July 2019 in the Marien Hospital Hamburg, Hamburg, Germany and had verified follow-up outcomes. Patients were referred for stress CMR due to known or suspected CAD based on current guidelines  equipped with cardiac phased-array receiver coils. Data acquisition was triggered on the R-wave using a 4-lead vector ECG. Cine images were obtained using a breath-hold segmented-k-space balanced fast-field echo sequence (SSFP), employing retrospective ECG gating in long-axis planes  and contiguous short-axis slices covering the whole ventricles, with typically reconstructed 30 phases per cardiac cycle with 50 and 67% acquired heart phases, respectively, for short and long-axis images.®- gadoterate meglumine in a dosage of 0.05 mmol/kg). Three short-axis slices were acquired using a single-shot saturation recovery gradient echo sequence . Fast-SENC acquisitions were performed at baseline, and repeated acquisitions were performed in identical planes during infusion of adenosine after meeting the criteria mentioned above and before the administration of gadolinium for the acquisitions of first-pass perfusion scans. The rest perfusion was performed after 10 min using identical planes and the same dosage of the contrast agent. Afterward, late gadolinium enhancement (LGE) acquisitions were performed in three long-axis and multiple short axes, covering the entire left ventricle.A standard protocol for adenosine stress CMR was used, which is described in detail elsewhere . In shorAll analyses were performed on a commercially available workstation . Results for ventricular volumes, left- and right-ventricular (LV and RV) ejection fraction (%), and myocardial mass were derived from short-axis slices. The presence of myocardial perfusion defects was performed visually in three short-axis images. A perfusion defect was defined as a region in the myocardium exhibiting hypo-enhancement by visual criteria that persists after peak myocardium enhancement for at least 4 RR intervals and corresponds to a coronary territory . In addi1 = Normal Perfusion,2 = Perfusion Deficits With <50% Transmurality and3 = Perfusion Deficits With ≥50% Transmurality During Adenosine StressCorresponding images in a patient with normal perfusion during stress, with a subendocardial and with a transmural perfusion defect during vasodilator stress are provided in our As described previously, fast-SENC is based on the acquisition of high- and low-tuning image sequences with different frequency modulation. Fast-SENC image sequences were analyzed using the MyoStrain software , as described previously .With fast-SENC, bright regions in the two frequency modulation images represented static and fully contracted tissues, respectively. Circumferential and longitudinal strain within a range from 5 to −30% were encoded, with negative values translating into active myocardial contraction. In our study, a single heartbeat, a fast-SENC variant with single-shot spiral readouts was employed. Typical imaging parameters were as follows: field-of-view = 256 × 256 mm, slice thickness = 10 mm, voxel size = 4 × 4 × 10 mm, reconstructed resolution = 1 × 1 × 10 mm, single-shot spiral readout with acquisition time TA = 10 ms, flip angle = 30°, effective echo time (TE) = 0.7 ms, repetition time (TR) = 12 ms, temporal resolution = 36 ms, the typical number of acquired heart phases = 22, spectrally selective fat suppression (SPIR), and total acquisition time per slice < 1 s. Data were acquired in three long-axis  views, and three short-axis views of the LV .Global circumferential strain by fast-SENC is extracted from 3 long-axis views, whereas GLS is extracted from the 3 short-axis images. The endocardial and epicardial borders were drawn at the end-systolic cardiac phase and are traced throughout the cardiac cycle, using an automatic tissue tracking algorithm. Tracking is then verified and manually corrected if necessary. A 16-segment model was used for the GLS and a 21-segment model for the GCS. For the analysis, GLS and GCS were expressed as the average value of all 16 and 21 segments, respectively. In addition, a GS was calculated by averaging LS and CS in all available segments , 20.Global circumferential strain, GLS, and GS were measured both at baseline and during adenosine stress. In addition, segments with relevant segmental LS and/or CS strain (SAS) impairment during stress were defined as ischemic. The number of such “ischemic” segments was calculated for SLS, SCS, and SLS or SCS which was referred to as SAS in each patient.Because myocardial shortening occurred in both longitudinal and circumferential directions during systole, the strain values were consequently negative and were so reported. However, throughout the text, and in keeping with most of the literature on the subject, we refer to the absolute values, i.e., higher strain values meaning more deformation and consequently more “negative” values.Personnel unaware of the CMR results contacted all patients or relatives of patients who underwent stress CMR studies during follow-up. All-cause mortality, the occurrence of non-fatal myocardial infarction, and urgent coronary revascularization by PCI or CABG were selected as the combined primary endpoint of our study. We used all-cause and not only cardiovascular mortality as an endpoint since the prior is free of potential subjectivity, clinically compelling, and therefore most relevant to the patients . In addiM ± SD for continuous variables and as absolute values and percentages for categorical values. A paired t-test was used to compare two groups of normally distributed values. The ANOVA test was used for comparing three or more normally distributed groups with the Scheffé test for post-hoc analysis , we calculated that a minimum of 70 patients would be necessary for our study for a comparison between strain and conventional first-pass perfusion imaging. The MedCalc software version 20.009  was used throughout. All p < 0.05 were considered statistically significant.Data were presented as analysis . The Mananalysis . SurvivaComplete CMR and follow-up data were available in 111 individuals who underwent vasodilator stress perfusion CMR for clinical reasons. Demographic, clinical, and CMR data are provided in During the adenosine stress test, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. Patients with inducible perfusion abnormalities had similar demographic and baseline CMR data to those with negative stress results, except for LV-mass, which was increased in patients with inducible perfusion abnormalities. However, significant differences were observed with the average perfusion score index and for global strain parameters during stress in patients with vs. without perfusion abnormalities .p < 0.05 for all) compared with patients without perfusion defects, whereas all baseline strain values were similar between the 2 groups  reduction during vasodilator stress was selected as best indicative for the presence of segmental myocardial ischemia by perfusion analysis. Thus, the number of ischemic segments with inducible SLS, SCS, or SAS decrease ≥6.5% were all indicative for the presence of inducible perfusion defects, with SAS exhibiting the highest accuracy, followed by SCS and SLS  and significantly higher absolute SAS decrease during adenosine stress (p < 0.001)  . In addin = 15) or CABG (n = 5).During a mean follow-up duration of 1.94 ± 0.65 years, 2 patients died, 3 had a non-fatal myocardial infarction and 20 underwent urgent coronary revascularization by PCI . The perfusion score index was significantly higher in patients with vs. without cardiac endpoints . Similarly, the perfusion score index performed as well as the number of ischemic segments by SAS, predicting the combined endpoint  per patient.A 58-year-old female patient with arterial hypertension, hyperlipidemia and suspected CAD due to atypical angina underwent adenosine stress CMR, which did not show abnormal findings (not shown). Normal strain response was seen by fast-SENC in the short axis views . HoweverIn this analysis of 111 patients with complete perfusion, segmental strain analysis, and follow-up outcomes, we found that:Myocardial perfusion abnormalities during vasodilator administration were associated with clinical outcomes.Evaluation of segmental myocardial strain during baseline and vasodilator stress using fast-SENC was feasible with high reproducibility and within reasonable time-spent.An inducible absolute SAS decrease ≥6.5% during adenosine stress in one or more myocardial segments was associated with inducible perfusion abnormalities during first-pass perfusion imaging.Perfusion and strain abnormalities during vasodilator stress predicted future cardiac outcomes in patients with ischemic heart disease. Overall, perfusion defects showed numerically higher predictive values for future events, which was an expected finding since perfusion is a well-established marker for the prediction of future events , 7. HoweWe and others had previously described the incremental value of SENC both for the diagnostic classification and for the risk stratification of patients with suspected and known CAD , 12. QuaFunctional stress testing has been the non-invasive gold standard for the diagnostic work-up of patients with suspected and known CAD within the last decades, whereas its role in the diagnostic classification and risk stratification is widely accepted in patients with chronic coronary syndromes (CCS) based on current guidelines . ParticuFrom a pathophysiologic point of view, myocardial strain is more sensitive to disturbances of the myocardial metabolism or perfusion, which may be seen in the early stages of many cardiovascular disorders, including CAD and heart failure . In thisa priori ROC analysis, as best indicative for the presence of myocardial ischemia by perfusion analysis, which may overestimate the association between perfusion defects and strain. However, the same cut-off was then independently applied for the prediction of cardiac events, exhibiting significant prognostic value. In addition, a certain overlap was observed for strain values in patients with and without perfusion abnormalities, so that average strain values may not be useful on an individual scale. However, by a selection of a cut-off value for the strain on a segmental level, clinically acceptable accuracy rates could be achieved for the estimation of perfusion abnormalities and clinical endpoints on a patient-by-patient level. Furthermore, we cannot evaluate the accuracy of strain or perfusion abnormalities for CAD detection by comparing these variables to invasive data in conjunction with FFR measures. However, most of our patients had negative stress test results, which helped defer invasive angiography, and this is clinically meaningful.Our cohort was relatively small and heterogeneous with a high percentage of patients with known CAD. This limits the extrapolation of our findings to lower risk cohorts. In addition, the follow-up duration was quite short and only 25 endpoints were recorded. Especially the small number of hard endpoints such as death and non-fatal myocardial infarction and the inclusion of only patients with CMR and complete follow-up data are limitations, that need to be accounted for when interpreting our results. In addition, patients who underwent elective revascularization within the first 90 days after abnormal stress perfusion by CMR were excluded from analysis, and no repeated CMR was performed after the revascularization procedures, which would have helped define the impact of residual ischemia on clinical outcomes. Furthermore, the cut-off value of SS decrease ≥6.5% during vasodilator stress was selected by Fast-SENC during vasodilator stress was non-inferior compared with standard visual perfusion analysis for the diagnosis of ischemia and the risk stratification of patients with ischemic heart disease. This may bear clinical implications since fast-SENC relies on purely quantitative analysis, which is reproducible and can be performed within reasonable time-spent. Thus, fast-SENC can obviate the need for contrast agent injections in this regard, in the interest of time and costs and potentially patient safety. Now prospective larger-scale trials are warranted to test the ability of fast-SENC to predict hard cardiac outcomes.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the General Medical Council Hamburg. The patients/participants provided their written informed consent to participate in this study.GK and HS designed the study, performed the analysis, wrote and reviewed the manuscript, and provided important intellectual input. MM performed the acquisitions, reviewed the manuscript, and provided important intellectual input. SK, SE, AS, and SG reviewed the manuscript and provided important intellectual input. All authors contributed to the article and approved the submitted version.HS, SK, and GK received research grants from Myocardial Solutions. SK owns stock options of Myocardial Solutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Noncompaction cardiomyopathy (NCCM) has gained increasing attention over the past twenty years, but in daily clinical practice NCCM is still rarely considered. So far, there are no generally accepted diagnostic criteria and some groups even refuse to acknowledge it as a distinct cardiomyopathy, and grade it as a variant of dilated cardiomyopathy or a morphological trait of different conditions. A wide range of morphological variants have been observed even in healthy persons, suggesting that pathologic remodeling and physiologic adaptation have to be differentiated in cases where this spongy myocardial pattern is encountered. Recent studies have uncovered numerous new pathogenetic and pathophysiologic aspects of this elusive cardiomyopathy, but a current summary and evaluation of clinical patient management are still lacking, especially to avoid mis- and overdiagnosis. Addressing this issue, this article provides an up to date overview of the current knowledge in classification, pathogenesis, pathophysiology, epidemiology, clinical manifestations and diagnostic evaluation, including genetic testing, treatment and prognosis of NCCM. When the World Health Organization (WHO) published the first definition of cardiomyopathy in 1980, noncompaction cardiomyopathy (NCCM) was not yet known ,3,4,5,6.A real breakthrough in diagnosis of this myocardial anomaly in vivo could be achieved through 2D echocardiography as was described in 1984 and is presented in In 1990, Chin et al. suggested the term “isolated noncompaction of the left ventricular myocardium (INVM)”, assuming that the myocardial anomaly occurred as a result of an arrest of the normal compaction process during embryonal endomyocardial morpho- genesis [Eventually, recent observations suggest, that LV noncompaction (LVNC) may not be the result of an arrest in the compaction process, but instead results from the compacted myocardium of the ventricular wall, growing into the ventricular lumen in a trabecular fashion .Initially, the term isolated NCCM was used for cases without congenital or other structural heart defects. Today, some groups use the term for cases with areas of LVNC and normal LV function . Table 1During the years, a wide range of morphological variants could be observed. Some authors, therefore, propose to consider a differentiation in several subtypes, especially in the pediatric population .In the last five years, a number of studies described the usefulness of contemporary diagnostic tools, including echocardiographic imaging techniques, magnetic resonance (CMR), computed tomographic (CT) imaging and genetic testing, and revealed that some cases seemed to occur in patients with neuromuscular disease ,15,16,17Of major interest are results from CMR imaging studies, which detected the phenotype of LVNC in healthy athletes and pregnant women, suggesting a physiologic adaptation ,20. The The classification and definition of cardiomyopathies have been developed in the last six decades with more precise and elaborated recommendations due to increasing abilities in diagnostic and therapeutic modalities.In 1957, the term cardiomyopathy was proposed for uncommon, noncoronary heart muscle diseases . In 1972The WHO/ISFC updated its classification in 1995 as diseases of the myocardium associated with myocardial dysfunction and now included arrhythmogenic right ventricular cardiomyopathy. The cardiomyopathies were classified by “the dominant pathophysiology or, if possible, by etiological/pathogenetic factors” . Once moIn 2006, the AHA defined cardiomyopathies as diseases of the myocardium associated with mechanical and/or electrical dysfunction, which usually exhibit inappropriate ventricular hypertrophy or dilation due to a variety of causes that frequently are genetic, classified as primary or secondary. This classification presented the first attempt to classify primary cardiomyopathy by origin  and NCCM was assigned a genetic cardiomyopathy . The 200Today, NCCM is classified as a genetic cardiomyopathy by the AHA, while the ESC working group for myocardial and pericardial disease and the WHO classified it a familial/genetic unclassified cardiomyopathy ,24,25.D: dilated cardiomyopathy; MH: hypertrophic cardiomyopathy; MA: arrhythmogenic right ventricular (RV) cardiomyopathy; MR: restrictive cardiomyopathy; MLVNC: Noncompaction Cardiomyopathy) [LVNC.D) or with LV hypertrophy (MLVNC.H) from pure LVNC (MLVNC) [In 2013 a nosology for cardiomyopathies was proposed with a descriptive genotype–phenotype system, the MOGE(S) nosology . This clyopathy) . In the  (MLVNC) .LVNC remains a heterogeneous morphological anomaly of the heart with multiple possible concomitant phenotypes. Initially, isolated NCCM was characterized by the absence of an additional structural heart disease, especially congenital heart disease; later this definition was changed to those with normal systolic LV dimensions.In 2015, LVNC was considered to consist of nine distinct subtypes in the pediatric population, whereas another classification was suggested in 2016 ,27. Thesn = 95 (27%); NCCM/HCM n = 47 (13%); NCCM/DCM n = 195 (56%) and NCCM/HCM/DCM n = 12 (3%) [In the literature, the most cohorts were analyzed as a whole, and only a few were divided into subgroups for analysis; for example, the isolated NCCM form that met the echocardiographic criteria, but did not have LV dilatation or hypertrophy, or the subtypes with concomitant dilatation or hypertrophy of the LV. Van Waning et al. described four subtypes in their cohort of 349 patients: Isolated NCCM  12 (3%) .Right ventricular noncompaction cardiomyopathy is a challenging diagnosis due to an increased physiological trabeculation of the right ventricle. Nevertheless, there are some cases reported in the literature ,30.NCCM in the pediatric and adult population probably has a different background. The National Australian Childhood Cardiomyopathy study documented 9.2% of the primary cardiomyopathies in children younger than 10 years of age as NCCM ,32. JeffThe percentage in adults seems lower: 4.1% in the EORP Cardiomyopathy registry and 5% in the German Torch registry ,35.In men, NCCM is twice to three times more common than in women. The diagnosis can be achieved in adults, adolescents, children, newborns and even prenatal ,37. The Left ventricular noncompaction is estimated to affect 8 to 12 per one million individuals per year, but the condition is likely more common because asymptomatic individuals are not diagnosed. Increased awareness of this condition and improvements in noninvasive cardiac imaging have led to a higher detection rate.Familial occurrence is seen in up to 40% of the cases. The clinical phenotype is very variable, even in a single family. In a systematic family screening, a quarter of the examined relatives showed echocardiographic abnormalities, including LV dysfunction with and without noncompaction [In experienced echocardiography departments NCCM has a prevalence of 0.014% to 0.26% ,41,42,43There is a broad spectrum of clinical presentations with primarily heart failure symptoms, different forms of arrhythmias and thromboembolic events. Between the onset of symptoms and the diagnosis there can be a delay of up to 3 to 4 years .Heart failure symptoms can be mild, but severe symptoms with need for heart transplantation or LV assist device implantation can arise. In the German NCCM registry, 61% of patients showed heart failure symptoms at the time of initial diagnosis of NCCM and 15% developed heart failure symptoms during the follow-up of 27 months or deteriorated .Arrhythmias are frequent in NCCM, ventricular as well as supraventricular arrhythmias. In the German NCCM registry 26% of the patients presented with arrhythmias and were subsequently diagnosed with cardiomyopathy. In 17%, atrial fibrillation was found. Atrial fibrillation was more often observed in patients with reduced LV function. Bradycardia requiring pacemaker implantation was seen in 5% of the cohort. Supraventricular arrhythmias occurred in 4%, WPW syndrome was observed in 1.5%, AV nodal reentry tachycardia in 1% and typical atrial flutter in 1.5%. Sustained ventricular tachycardia and ventricular fibrillation were observed in patients with severely reduced LV function. In patients with an LV ejection fraction above 35%, sudden cardiac deaths were found only rarely ,48. In cThromboembolic events mainly occur in patients with NCCM and atrial fibrillation. Stasis of blood flow can appear in the deep intertrabecular recesses notably in reduced LV function. Neurologic departments occasionally diagnose NCCM in patients with otherwise not explained stroke. In cohorts with NCCM, a percentage of about 10–15% suffer from stroke .There are several case reports of patients with NCCM and specific neuromuscular disorders or hereditary neuropathy such as Charcot–Marie–Tooth, Becker muscular dystrophy, Emery–Dreifuss muscular dystrophy, myotonic dystrophy, Leber’s hereditary optic neuropathy, and Barth syndrome, and also with neuromuscular problems not specified in more detail ,51. ThesSeveral congenital heart defects were described with NCCM ,54. A paCoronary heart disease is uncommon in NCCM, but severe coronary heart disease that needs revascularization therapy has been found in some patients with NCCM ,59,60,61Up to now, the diagnostic criteria of LVNC are far from being perfect . The difEchocardiography with its widespread availability, low costs and nearly zero complications is the first-choice procedure in diagnosis of LVNC. Echocardiography can detect the pathognomonic features of a thick, bilayered myocardium with prominent trabeculations and intertrabecular recesses communicating with the LV cavity . If convLVNC can be mainly observed at the cardiac apex and in the mid-inferior, mid-anterior, and mid-lateral areas of the LV wall . A low-NAlthough the first echocardiographic diagnosis of NCCM was published more than 37 years ago and the term noncompaction was introduced more than 30 years ago, there are no globally accepted diagnostic criteria ,68. Chin2 on an apical 4-chamber view, with three categories: mild, moderate and severe [Frischknecht recommended the combination of criteria as specific, and Belanger in 2008 proposed different criteria with an additional classification of the severity derived from the noncompaction/compaction ratio and the affected planimetered area in cmd severe ,72.In the last decade of the last century and the first decade of this century, the diagnosis of NCCM was confirmed mainly in heart failure patients, and underdiagnosis of the disease was of major concern. Since more common recognition of the disease and introduction of newer imaging techniques occurred, the problem of overdiagnosis arose. To overcome these problems, additional criteria were introduced by the Swiss group in 2012: the compacta thickness; a compacta thickness of below 8 mm being a discriminator between the groups . SabatinThe Rotterdam group was the first to show that the absence of twist in speckle tracking tissue Doppler echocardiography can be a marker for NCCM. They demonstrated the loss of LV twist in 83% of 34 adults with NCCM . The radArunamata et al. investigated the speckle tracking strain results in a pediatric study group with NCCM, with and without congenital heart defects. Segmental radial, circumferential, and longitudinal strain decreased in NCCM compared with control subjects. Strain measurements were lowest in those with adverse compared with favorable outcomes. In NCCM, deformation was affected in all regions, including compacted myocardial segments .Sabatino et al. assessed global and regional longitudinal strains in a pediatric population using apical 4-chamber, 3-chamber, and 2-chamber views; radial and circumferential strains were measured using LV short-axis views at different levels. LV twist was calculated as the difference between peak apical rotation and basal rotation at a time interval corresponding to the ejection phase of the systole. The measurements could discriminate between a normal counterclockwise pattern with reduced apical rotation peak values in LVHT and NCCM with rigid body rotation presenting with a sensitivity of 82% and a specificity of 92% . In contThe World Heart Federation MOGE(S) classification graded LVNC as a morphological entity with an excessive trabeculation of the LV on echocardiography or cardiac magnetic resonance imaging. The noncompacted ventricular muscle layer was substantially thicker than the compact layer. No ratio was specified .Even in experienced groups the interobserver agreement of the echocardiographic diagnosis was limited, with about 11% of questionable cases ,82. Meas2), a noncompacted to compacted myocardium ratio of ≥3:1 in at least one of the segments 1–3 or 7–16 excluding the apical segment 17 and trabeculation in segments 4–6 ≥ 2:1 (noncompacted to compacted ratio) [NCCM can be diagnosed using CMR . There ad ratio) . Dreisbad ratio) ,91. The A combination of different echocardiographic criteria and, if appropriate, a combination with an additional diagnostic technique should help to diagnose NCCM definitely or reject the diagnosis. However, there may be some borderline cases with a possible, but not definite, diagnosis of NCCM. In these cases, the imaging approach has to integrate clinical findings, family history and genetic data. However, at this time, a negative genetic test is not a marker, that diagnosis of NCCM is unlikely ,93.Diagnosis of NCCM can also be performed by LV angiography. Sometimes it is a diagnosis at a glance, but there are no definite criteria for the diagnosis of NCCM by LV angiography ,62.Cardiac CT is an imaging tool with increasing significance. In patients with dilated cardiomyopathy, cardiac CT is used to exclude coronary heart disease . Conces An ECG does not show specific alterations in cases with NCCM. Alterations in the ST segments and T waves are common, as also are different types of bundle branch blocks. Some publications reported that nearly 90% of the patients presented with ECG alterations . ConductNTproBNP is a marker for heart failure. High NTproBNP levels were investigated for being an indicator for death and heart transplantation in patients with NCCM . An elevEndomyocardial biopsy continues to be the gold standard in the detection of myocardial inflammation. Myocarditis is a potential differential diagnosis in cases with NCCM. Biopsy findings can offer clear therapeutic recommendations, especially in cases with giant cell myocarditis or sarcoidosis.Prominent LV trabeculation can be found in healthy hearts, as well as in hypertrophic cardiomyopathy (HCM) and in LV hypertrophy secondary to dilated, valvular, or hypertensive cardiomyopathy. Thus, the differentiation between variants and LVNC may often be challenging . DiffereIn 25% of normal pregnancies, an increase in LV trabeculations can be assessed ,103. A LSome persons affected with noncompacted areas do not have any symptoms and are diagnosed by chance. A major number of these persons are athletes, and noncompaction perhaps may be a physiological remodeling process in these persons . Luijkx A noncompaction pattern can be a myocardial response to acquired triggers, Loria et al. discussed chemotherapy with drug toxicity as a possible trigger . A reporIn the first series of patients with NCCM, the disease was familial to a large extent. Noncompaction areas resembled the fetal heart and the hypothesis of an arrest in the normal compaction process of the heart seemed adequate.The development of the heart is a complex, precisely regulated molecular and embryogenetic process. The different steps of the development are triggered by specific signaling molecules and mediated by tissue-specific transcription factors ,111. TraThe NOTCH pathway is required for proliferation, differentiation and tissue patterning in various tissues, including the heart . The NOTIn 2016, Jensen in contrary described the excessive trabeculations in noncompaction not to have the embryonic identity and drew the conclusion that noncompaction is probably not the result of failed compaction, but likely the result of abnormal growth of the compact wall . This mePathoanatomical studies of NCCM revealed a marked trabecular meshwork with many intertrabecular recesses in the involved mural segments of the LV myocardium  8,43,12,1243,122Burke examined hearts in cases with NCCM by autopsies and found poorly formed papillary muscles in the LV, a distinct noncompacted zone in the LV and, often, in the right ventricle . The patIn histological examinations the trabeculations were covered with excessive fibrous tissue and elastin deposits, perhaps suggestive of some degree of subendocardial ischemia ,125. OecUltrastructural investigations could give additional impact on the discussion of pathogenesis of noncompaction areas. Ultrastructural investigations of hearts with noncompaction/hypertrabeculation demonstrated alterations in the shape and number of mitochondria, sarcomeric alterations, and other morphological abnormalities such as lipid-like inclusions and enlarged interstitial spaces . The finFamilial cumulation of NCCM assumes a genetic background. Basic research showed that trabeculation is regulated by genes and that mutations in the NOTCH pathway regulator MIB1 cause noncompacted myocardium .The genetic pathogenesis of NCCM is heterogeneous. In a majority of the adult patients with noncompaction cardiomyopathy, it is an autosomal dominant disorder. X-linked disorders, autosomal recessive, and mitochondrial  inheritance have also been described. The first genetic cause of isolated NCCM was initially described by Bleyl et al., when they identified mutations in the X-linked G4.5-Gen encoding for Tafazzin, the gene also responsible for Barth syndrome . AffecteGene mutations have been identified, that cause congenital heart disease with noncompaction; in patients with hypoplastic left heart syndrome and noncompaction a DTNA (α- dystrobrevin) mutation was identified. Dystrophin mutations are also involved in boys with Duchenne and Becker muscular dystrophies . WhereasNCCM is often familial with an autosomal dominant inheritance but with variable penetrance and a high intrafamilial variability . StudiesChildren more frequently had an X-linked or mitochondrial inherited defect or chromosomal anomalies. In multivariate analysis MYBPC3, TTN, arrhythmia—non-sarcomere non-arrhythmia cardiomyopathy—and X-linked genes were genetic predictors for MACE. The presence of pathogenic variants was an independent risk factor for adverse outcomes in other cohorts as well and may aid in risk stratification in patients. Biallelic mutations and double pathogenic variants were found to have a worse prognosis ,137.Current investigations in more than 800 patients showed a genetic overlap indicating that NCCM often represents a phenotypic variation of DCM or HCM, but also variants uniquely associated with NCCM .Up to 40% of NCCM cases may be familial, so family screening is recommended when the diagnosis of NCCM is assessed in a child . NCCM isHRS/EHRA in 2011 recommended mutation specific testing of family members and appropriate relatives following the identification of a NCCM causative mutation in the index case (Class I). NCCM genetic testing can be useful (Class II a) for patients in whom a cardiologist has established a clinical diagnosis of NCCM, based on an examination of the patient’s clinical history, family history, and electrocardiographic/echocardiographic phenotype . The GerIn the pediatric population, genetic testing should be considered in individuals with cardiomyopathy co-occurring with NCCM. The actual database does not suggest an indication for cardiomyopathy gene panel testing in individuals with isolated noncompaction in the absence of a family history of cardiomyopathy phenotype with dilatation or hypertrophy .With no underlying common diagnostic criteria, the comparison of different cohorts is difficult. The prognosis of the patient populations with NCCM is dependent on the occurrence of heart failure, death and on the need for heart transplantation. Systolic function is an important risk factor; heart failure with a reduced ejection fraction (HFrEF) with an LV ejection fraction below 35% has a worse prognosis. Several MR imaging studies demonstrated a good prognosis in preserved LV function ,144,145.Long term survival of patients with isolated apical noncompaction and preserved ejection fraction was shown to be comparable with the general population . The endMurphy et al. found that 62% of the patients developed heart failure symptoms. The death rate was found to be only 2% in a follow-up time of up to 15 years with regular visits . In chilGenetic testing also has an impact on the prognostic stratification (see genetics).2/m2. Left atrial dilatation was present in half of the patients. Among the patients with left atrial dilatation 25% died, compared to 8% without left atrial dilatation. However, the patients with left atrial dilatation were significantly older, showing a greater frequency of hypertension, congestive heart failure, and atrial fibrillation [Romano et al. demonstrated global longitudinal strain (GLS) derived with CMR to be a prognostic factor even in NCCM . The exiillation . Regressillation .There is no specific therapy for NCCM today. Therapy has to address the clinical symptoms and to cover prognostic aspects. Heart failure therapy in patients with NCCM and reduced LV systolic function can be applied according to the heart failure guidelines . CardiacAntiarrhythmic therapy depends on the clinical situation, the use of ablation therapy in supraventricular and ventricular tachycardia, pacemaker and ICD systems have been reported ,161,162.The 2008 ACC/AHA guidelines graded ICD implantation a Class II b indication in NCCM independent of the systolic LV function . The curAnticoagulation with VKA is recommended in cases with NCCM and reduced ejection fraction with LVEF < 40%, as proposed in the literature ,62. The Recently, there were case reports on resection of the noncompacted myocardium that showed recovery of the cardiac function. Long term follow-up is recommended .Regular physical activity, including systematic exercise, is an important component of prevention and therapy for most cardiovascular diseases and is associated with reduced mortality . The 202Today, we know that the morphological noncompaction pattern is not restricted to the genetically determined NCCM. LVNC can occur in both, physiologic and pathologic remodeling. However, the same is true for other structural features such as dilatation of the LV or for LV hypertrophy, which can also be detected in a variety of clinical settings and require a differentiated approach.Nevertheless, we need diagnostic consensus criteria to streamline future research efforts and be able to better compare patients’ subgroups with statistical meaningful volume. A big international registry could be the basis for more evidence-based recommendations to avoid unnecessary diagnostic testing and to formulate specific treatment options for this elusive cardiomyopathy.There are ample areas of need for future research to help unravel the mysteries of this rare disease, NCCM. Future basic research should investigate the role of genetics as well as the ultrastructural features of cardiomyocytes to help discover targeted treatments. Future clinical studies need to focus on improving diagnostic imaging and laboratory testing. In the meantime, patients with NCCM should receive early diagnosis, counselling and optimal treatment, while avoiding overdiagnosis and overtreatment in those with only a physiologic remodeling.


The interventricular septum contributes to the pumping function of both ventricles. However, unlike the ventricular wall, its mechanical behavior remains largely unknown. To fill the knowledge gap, this study aims to characterize the biaxial and transmural variation of the mechanical properties of the septum and compare it to the free walls of the left and right ventricles (LV/RV). Fresh hearts were obtained from healthy, adult sheep. The septal wall was sliced along the mid-line into two septal sides and compared to the epicardial layers of the LV- and RV-free walls. Biaxial tensile mechanical tests and constitutive modeling were performed to obtain the passive mechanical properties of the LV- and RV-side of the septum and ventricular walls. We found that both sides of the septum were significantly softer than the respective ventricular walls, and that the septum presented significantly less collagen than the ventricular walls. At low strains, we observed the symmetric distribution of the fiber orientations and a similar anisotropic behavior between the LV-side and RV-side of the septum, with a stiffer material property in the longitudinal direction, rather than the circumferential direction. At high strains, both sides showed isotropic behavior. Both septal sides had similar intrinsic elasticity, as evidenced by experimental data and constitutive modeling. These new findings offer important knowledge of the biomechanics of the septum wall, which may deepen the understanding of heart physiology. Heart failure is the leading cause of death worldwide . Among tThe septum has been traditionally viewed as a single entity and a part of the LV chamber , having a similar contribution to LV function as the LV free wall . HoweverFurthermore, in vivo evidence suggests that the septum wall is a layered structure with transmural variations. For instance, Boettler et al. reported from echocardiography an abrupt change in echogenicity (acoustic reflectance) down the middle of the septum, suggesting a shift in the tissue density dividing the left and right sides. In the left side of the septum, the longitudinal strain and strain rate were larger than those of the radial direction, and the opposite was observed in the right side of the septum . Their fNevertheless, the full ex vivo characterization of the transmural biomechanical variation of the septum is lacking. To date, only two studies reported the ex vivo mechanical properties of the septum from canine or human samples. These studies tested either the mid-layer  or non-sThe aims of this study are to characterize the biaxial and transmural variation of the passive mechanical properties of the septum and compare them to their respective ventricle free walls in healthy adult ovine. Sheep were chosen because of the similarities between human and ovine cardiovascular anatomy, physiology, and function ,17. Becan = 12) with no known cardiovascular diseases from unrelated studies at the Colorado State University Veterinary Teaching Hospital. Within 30 h after harvest, the hearts were placed into cardioplegic solution (CPS)  on ice or at 4 °C to maintain tissue viability. The epicardial layer was extracted from the LV and RV free walls. Next, the septal wall was cleaned with the removal of the trabeculae and papillary muscles, and then sliced approximately down the middle into two halves to elucidate transmural differences between the LV and RV sides of the septum. The ventricle and septal sections were then cut into square sections  with a thickness of ~3 mm and kept in CPS and 30 mM of 2,3-butanedione 2-monoxime (BDM)  at body temperature (37 °C) for at least 10 min to prepare for the passive mechanical tests on physiological conditions. The long axis (apex-to-base) was defined as the longitudinal direction (90°) and the perpendicular axis was defined as the circumferential direction (0° for LV-side or 180° for RV-side) in the septum. The outflow tracts were defined as the longitudinal direction in the ventricular free wall samples [n = 9)  . After mounting on an in-house biaxial tester, the samples were preloaded with approximately 0.1 N and underwent 10–15 cycles of equibiaxial stretch for preconditioning. An additional 5 cycles of equibiaxial stretch at a quasi-static testing frequency (ventricle: 0.01 Hz and septum: 0.02 Hz) were performed and the data from the last cycle were used for the mechanical analysis. All the preconditioning and tests were performed in a tissue bath of CPS and 30 mM of BDM at 26–37 °C to ensure that the cardiomyocytes were relaxed, and passive biomechanical behavior was obtained ,24. All S)  were derived as the slope of the stress–strain curve in the low and high strain ranges  [The Second Piola-Kirchhoff (P-K) stress—Green strain curves were then derived from the loading curve of the last testing cycle. The formulas were as follows: Second P-K stress (ctively) ,27.From our experimental data, we calculated the shear deformation and presented the average normal strains and shear strains in E) components were calculated by using the following equations:Green strain tensor  for an incompressible tissue were calculated using the following equation:F is the gradient tensor, C is the right Cauchy-Green tensor, and p is an unknown hydrostatic pressure to enforce det(C) = 1.The Second P-K stress and Cauchy stress  was calculated to assess the fitting results.The Fung strain energy function was fitted to the experimental data for each specimen. The fitting was performed with a Levenberg-Marquardt least-squares algorithm with a tolerance of 10K:In order to further quantify tissue anisotropy, the stress–strain curves were numerically converted to the equibiaxial stretch condition, where K value . Three regions of interest to represent the overall tissue were randomly selected. To quantify the collagen content, the areas that were positive for collagen (dark red) were identified using a color thresholding function in ImageJ , and the collagen area fraction (%) was calculated as the ratio of the collagen area to the total tissue area. All images were analyzed by the same observer, who was blinded to the group information. Since the ventricle and septum tissues were stained in different batches, the non-specific staining in the background was different, and thus different thresholding values were set for these batches. However, this did not affect the identification of the positive staining of collagen fibers, and the images from the same batch were acquired at the same setting.M and collagen data. p < 0.05 was considered statistically significant.Data are presented as mean ± SEM. The Mann–Whitney U-test was used for the myofiber angle and mechanical comparisons in the septum. One-way ANOVA and Tukey post-hoc tests were performed between directions, and between the septal and ventricular From the myofiber angle measurements, we observed a change in the fiber angle from the LV-side to the RV-side of the septum. As shown in The average stress–strain curves of the ventricular free walls and both sides of the septum are presented in M) between the groups and between the directions at low and high strains  between the two sides of the septum  anisotropy in the LV-side of the septum compared to the RV-side (p = 0.049). At high strains, however, both sides of the septum presented isotropic behavior. Next, we compared the elastic moduli (M) of the two sides from the same direction. There was no difference in the M between the two sides of the septum in all strain ranges or in both directions, although there was a trend of a stiffer RV-side septum compared to the LV-side in the high strain range in the circumferential direction (p = 0.06).Similar anisotropies are shown from the low-strain elastic modulus  derived from the model fitting in each ventricle type, and in different directions. This parameter serves as an indicator of myofiber stiffness. As shown in p = 0.08), indicating that the LV-side was more anisotropic and stiffer in the longitudinal direction than the circumferential direction , which indicated a stiffer behavior in the longitudinal direction. These results agreed with our experimental data, especially at the low strain range , indicating a marked reduction of collagen in the septal wall compared to the ventricular free walls , but the degree of anisotropy was stronger in the LV-side. The intrinsic elasticity was similar between the two sides of the septum, and in both directions. Our results suggest that the septum should not be treated as a part of the LV or RV, and the unique transmural distribution of the biomechanical properties of the septum will assist in the understanding of left and right ventricular function.The two ventricles have different embryological origins. The early heart ventricles, which are formed from bilateral tubes, fuse to form the septum during cardiac development ,19,20. TOur study is the first to examine the biaxial mechanical behavior of the septum wall in two halves and compare each side of the septum to its respective ventricular free wall. We found significantly stiffer ventricular free walls than the corresponding side of the septum, and the stiffer behavior was more pronounced in the higher stretch (strain) regions. It is known that collagen is a load-bearing protein and that more collagen is correlated with stiffer elastic behavior . The larOur data partly agreed with the previous reports noted above. For example, it is found that the outer and inner layers of the LV free wall tended to be stiffer than the midwall of the septum , and theThe stark differences in the elasticity between the free walls and septum can explain in vivo findings of the different contributions of the septum and free walls to the overall ventricular function. Assuming the similar mechanical properties and contractility of the septum and LV free wall, we would expect 16–35% of the cardiac work to be contributed by the septum , based on its volume fraction from the sheep and human data ,32. HoweIt has been reported that the ventricular free walls exhibit a transmural fiber orientation shift ,35. In tIn the present study, we had a preliminary examination of the transmural change of fiber orientation in the septum, and we originally found that the average fiber orientation shifted from 78 ± 3° (LV-side) to 9 ± 2°  and, finally, to 108 ± 8° (RV-side). Our data showed ~150° for the main myofiber angle transmural shift through the entire septum. The transmural change may be related to the individual support of the pumping demand for each ventricle. For instance, the longitudinal myofiber orientation on each endocardial side are, potentially, better aids in blood ejection along the outflow tracts of each ventricle.As we mentioned above, the ex vivo mechanical properties of the septum reported in prior studies used the main fiber and cross-fiber directions as the testing axes. It is not surprising that these studies reported similar anisotropy, i.e., a stiffer behavior in the fiber direction than cross-fiber direction, probably due to the aligned myosin–actin cross-bridge, and titin in the ‘fiber direction’ (direction of myofiber shortening). However, such measurement cannot provide the anatomic relations between the tissue anisotropy and the ventricular deformation in systole and diastole, thus preventing an investigation of the relation between the biaxial mechanical behavior and the physiological function of the myocardium. Furthermore, using the main fiber and cross-fiber coordinate system for biaxial tests can be problematic for tissues that have a significant transmural change in the fiber orientation. The myocardium tissue  is composed of helical and heterogenous myofibers that vary in orientations transmurally ,39; simip < 0.05, p < 0.01), whereas that in the RV-side of the septum was marginal (p = 0.049). The different degrees of anisotropy between the two sides have been evidenced by the different in vivo strains (a surrogate of elasticity) between the longitudinal and radial axes of each septum side. Boettler et al. found the global longitudinal and radial strain difference was larger in the septal LV-side than the RV-side , indicating a more anisotropic behavior of the left-side of the septum than the right-side [M0), which tended to be larger than that of the RV-side. Given that the two septal sides have different strains and different degrees of anisotropy, it is reasonable to anticipate different elastic resistances in the different axes or septum sides, which results in varied impacts on the LV and RV diastolic functions. Therefore, a further investigation of the relations of septum mechanics and ventricular function is needed. In all septum tissues, we observed stiffer behavior in the longitudinal direction in the low strain range (ght-side . In the M0) predicted from the constitutive model, which suggests that the myofiber stiffness is comparable between the two sides. The examination of the collagen fraction also showed no significant difference between the two sides. Therefore, the main transmural change in the septum is related to the orientation of the myofibers (anisotropy), not the material properties or tissue composition.We also compared the strain-dependent elastic moduli and modeling parameters of elasticity between the two sides of the septum. We did not observe any difference in the intrinsic mechanical property. We further examined the potential differences in the myofibers and collagen fibers in the septum sides. There was no difference in the zero-load elastic modulus (In this study, we sliced the septum into approximately two equal halves after cleaning the endocardial surfaces. To our knowledge, there is no anatomic mark to distinguish the LV- and RV-side of the septum, although the two sides share distinct embryologic origins ,20. The In summary, this original study investigates the transmural variation of the ex vivo passive mechanical properties of the septum in healthy adult ovine. The septum sides were significantly softer than their corresponding ventricular free walls, and the collagen content was less than that of the ventricular walls. At low strains, there was similar anisotropic behavior between the two sides, but the degree of anisotropy was stronger in the LV-side than the RV-side. At high strains, both sides were isotropic. Our results suggest that the septum should not be treated as a part of the LV or RV, and that the tissue presents distinct structure–function relationships from the ventricular free wall. The investigation of septum biomechanics will further reveal the biomechanical mechanism of ventricular function and the dysfunction in heart failure progression.


The CardioMEMS HF system is used to measure pulmonary artery (PA) pressures of patients with heart failure (HF). The goal of this study was to determine the impact of time in the daily PA pressure measurements, considering variance and influence of circadian rhythms on cardiovascular pathophysiology.The study included 10 patients with HF with reduced ejection fraction . Individual daily PA pressures were obtained by CardioMEMS sensors, per protocol, measured up to six times throughout the day, for a period of 5 days. Differences between variation of morning versus evening PA pressures were compared with Wilcoxon signed-rank test.p = 0.01). The same daily pattern of pressure variability was observed in diastolic (p = 0.01) and systolic (p = 0.04) pressures, with diastolic pressures being more variable than systolic at all time points.Mean PA pressures (mPAP) increased from a morning value of 19.1 ± 2 mm Hg  to 21.3 ± 2 mm Hg late in the evening . Over the course of 5 days, evening mPAP exhibited a significantly higher median coefficient of variation than morning mPAP (14.9 (interquartile range [IQR] 7.6–21.0) and 7.0 (IQR 5.0–12.8) respectively; Morning PA pressure measurements yield more stable values for observing PA trends. Patients should thus be advised to consistently perform their daily PA pressure measurements early in the morning. This will improve reliability and interpretation of the CardioMEMS management, indicating true alterations in the patient’s health status, rather than time-of-day-dependent variations.The online version of this article (10.1007/s12471-021-01590-7) contains supplementary material, which is available to authorized users. Pulmonary artery pressures are most stable in the morningsHighest pulmonary artery pressures are observed late in the eveningDaily pulmonary artery pressures are advised to be measured early in the morningStandardised CardioMEMS measurements will improve reliability of the pressure valuesHeart failure (HF) has become a major socio-economic burden as it is characterised by episodes with acute decompensation, requiring hospitalisation, and is associated with increased morbidity and mortality , 2. The Currently, HF patients with a CardioMEMS sensor are instructed by the manufacturer to measure PA pressures in the morning. However, it has not yet been investigated whether morning indeed yields the most precise PA pressure measurements, while some patients may prefer a different time for practical reasons, or may vary the time of their measurement considerably. Additionally, while daily patterns of PA pressures measured in a consistent manner are currently not available, CardioMEMS provides the opportunity to study them. Previous studies on PA pressures in HF suggest the existence of diurnal rhythms , 10. GivA total of 10 consecutive patients (New York Heart Association [NYHA] class III), who had received a CardioMEMS sensor according to the current guidelines , particiThe CardioMEMS sensor was used to obtain individual daily measurements of PA pressures at six time points throughout the day  for a period of two consecutive days, followed by three time points  for the next three consecutive days. Measurements were downloaded for analysis using the CardioMEMS online system (merlin.net).p-value of < 0.05 was considered statistically significant. All analyses were performed in IBM SPSS Statistics (v. 23).The coefficient of variation (CV) was used as a measure of relative variability of mean (mPAP), systolic (sPAP), and diastolic (dPAP) PA pressures, either within-day or between-day. The CV was calculated as the ratio of the standard deviation to the mean, and expressed as a percentage. Wilcoxon signed-rank test was used to compare differences between CVs of PA pressures, and Student’s t‑test was used to compare differences between morning and evening heart rate. A A total of 10 patients  were enrolled in this study. Patient characteristics are summarised in Tab. Within a 24‑h period, in 7 out of 10 patients mPAP values increased from morning to evening. The mean mPAP value was 19.1 ± 2 mm Hg in the morning  and 21.3 ± 2 mm Hg in the evening  . Intriguingly, patients who exhibited the highest PA pressure variation in the evenings scored as either moderate morning or pronounced morning chronotypes on the VOA questionnaire (data not shown), pointing to the influence of individual diurnal rhythms.Since clear reproducible differences between morning and evening measurements were observed, we investigated whether it is relevant to strictly prescribe morning versus evening PA pressures in daily practice using the between-day CV. Interestingly, the between-day CV of mPAP, sPAP and dPAP was significantly higher in the evening than in the morning measurements , with a follow-up measurement in the evening (= highest PA pressure), it could indicate a deterioration of the patient’s condition, while it actually only reflects a mere circadian fluctuation. If the pressure is always measured in the morning, any deviating recording of PA pressures would be a clear indication that an intervention is needed. Secondly, as previously mentioned, PA pressures may be affected by patient’s activity during the day, including exercise, and food, fluid, and medication intake. The susceptibility of PA pressures to these daily changes could explain why evening PA pressures were least stable in the majority of subjects during a course of five days. Combined with their diurnal properties, highest and least consistent PA pressures are observed in the evening. Thus, morning PA pressure measurements are more reliable and better reflect the true changes in the patient’s condition (e.g. worsening of heart failure), rather than showing the influence of daily activities  which will reset until the next day. In conclusion, morning PA pressure measurements, as opposed to evening measurements that are prone to external influences, will give a clear indication for intervention if relevant increase in values is observed.N = 10), however, this was sufficient to show consistent changes in daily PA pressures. A large set of time points per patient was provided, both within the 24 h and during the course of five days. This gives a better representation of the individual PA pressure fluctuations, substantiating derived conclusions about morning PA pressure stability.Our study included a relatively low number of patients (Given the pronounced variation in ambulatory PA pressures during the day, standardised morning PA pressure measurements will improve reliability and interpretation of the values provided by the CardioMEMS sensor (see Take-home Fig. Table overview of between-days variation of sPAP, dPAP, and heart rate in heart failure patients.


Background: In patients following complete repair of the tetralogy of Fallot, the duration of the QRS complex is associated with the size and mechanical function of the right ventricle, which are contemporarily assessed by cardiac magnetic resonance (CMR). Methods: 38 patients aged 18.0–54.9 years (median age 24.9 years) who had undergone complete repair of the tetralogy of Fallot were examined using CMR and concomitant 24 h ambulatory electrocardiography monitoring. We used statistical analysis to investigate the correlations between electrocardiographic parameters  and CMR results  for patients after early and late repair. Results: The ECG-based parameters were not correlated with time since repair. There were significant correlations between QRS duration and RVEF (r = −0.61), RVEDVI (r = 0.56), and RVESVI (r = 0.54) for early operated patients but not for late-operated patients. No other substantial correlations were reported. Conclusion: Despite its role in screening for arrhythmias, electrocardiography has a limited role as a predictor of morphology and function of the right ventricle in patients after repair of the tetralogy of Fallot. The pathophysiology of a repaired tetralogy of Fallot (rTOF) is an interplay between the anatomy of the heart and its electrical and mechanical function. Persistent pulmonary regurgitation results in dilatation of the right ventricle (RV) and fibrosis. Consequently, the diastolic compliance of RV decreases, leading to the elevation of end-diastolic pressure in RV and a further increase in the pulmonary regurgitation fraction. On the other hand, the scar surrounding the RV outflow tract (RVOT) patch, combined with impaired histological structure of the RV wall due to volume and pressure overload, are a substrate for conduction delay and ventricular arrhythmias. As a result, the typical electrocardiogram (ECG) features in rTOF are wide QRS complexes with a right bundle branch block (RBBB) pattern, and arrhythmias are among the most frequent causes of death in patients who survive rTOF, together with heart failure and myocardial infarction ,2.Routine screening of these patients therefore includes a standard ECG and echocardiography. Additionally, a 24 h Holter ECG recording is performed periodically to screen for asymptomatic arrhythmias. Cardiac magnetic resonance (CMR) is also performed, which is currently the gold standard for volumetric and functional assessment of the RV. It is recommended that CMR should be performed before therapeutic interventions such as valve replacement or balloon valvuloplasty, and routinely every 2–3 years from adolescence in rTOF patients .Given that the electrical anomalies are partly explained by RV enlargement, in the present study, we aimed to investigate the utility of ECG in evaluating RV morphology and function in rTOF patients by investigating the correlation between results of concomitant ECG diagnostics with Holter monitor and CMR.We performed a retrospective study on patients who were followed up in our unit following complete TOF repair. The inclusion criteria were primary diagnosis of tetralogy of Fallot, regular screening visits in our unit, at least one CMR performed between February 2013 and July 2021, age ≥ 18 years at time of CMR, and sinus rhythm on ECG. Where a patient had more than one CMR examination during the timeframe, only the most recent examination was taken into consideration.CMR was performed on a 1.5 T scanner . All subjects underwent routine cine imaging for functional assessment of the left ventricle . Three standard long axis cines as well as short axis and transverse cine stacks were obtained every 10 mm (slice thickness 7 mm) from the base to apex and from the level of the diaphragm up to the level of the major arteries. The in-plane resolution was typically 1.4 × 1.4 mm. Next, 2D phase-contrast gradient echo (GRE) sequences were used to measure flow in the main, right, and left pulmonary arteries and in the ascending aorta, carefully checking for aliasing. Then, late gadolinnium enhancement (LGE) images were acquired 8–15 min after contrast administration (gadobutrol 0.1 mmol/kg) using both segmented and single-shot IR-GRE sequence with inversion time adjusted as needed. A simplified scoring system was applied to assess LGE. Considering that the foci of LGE in rTOF patients can be found in four main sites  patch, at the insertion points of the RV on to the LV, and in the LV free wall), the patients in whom LGE was limited to VSD and RVOT were assigned LGE value of 1, 2 points if a focus was found at the insertion points, and 3 points for LGE outside the insertion points.Additionally, data from 24 h Holter ECG recordings obtained as a part of concurrent ambulatory visits were collected. The time interval from Holter ECG to CMR was less than 12 months. After general analysis and manual correction of the recordings, automatic measurements were collected including average heart rate (HR) and heart rate variability (HRV) as well as the percentages of supraventricular and ventricular arrhythmias in the recording. The following indices of HRV were calculated: the average of all five-minute standard deviations of NN intervals (ASDNN), the standard deviation of all five-minute averages (SDANN), the standard deviation of all NN intervals (SDNN), and the square root of the mean squared differences of successive NN intervals (RMSSD). Interval measurements (PQ and QRS) were obtained from a fragment of ECG, in which the HR was rhythmic and equal with the average HR from the 24 h recording. After the formation of a five-electrode 12-lead vector-based ECG reconstruction (EASI), the PQ interval was measured semi-automatically in lead II and the QRS was measured in a lead where its length from the onset to the crossing with the isoelectric line was maximal. All of the interval measurements were obtained by a single investigator, blinded to the results of CMR. The average of two independent measurements was taken for statistical analysis. Considering the importance of QRS duration in risk stratification and its potential dependence on momentary HR, we decided to correct the QRS for HR according to a formula created by previous authors :QRSc = QVentricular and supraventricular arrhythmias during the recording were recognized where the number of inappropriate beats exceeded 0.1% of the 24 h recording. Non-sustained ventricular tachycardia (nsVT) was diagnosed as an episode of three or more consecutive ventricular beats at a rate of greater than 100 beats per minute with a duration of less than 30 s.t-test after testing for normality using the Shapiro–Wilk method. Where the distribution of a variable differed from normal, the Mann–Whitney U test was used. Relationships between continuous variables were analyzed using Spearman’s correlation coefficient, and Pearson’s chi-squared test was used for testing relationships between categorical variables. For all analyses, a value of p < 0.05 was considered statistically significant. Statistical analysis was performed using Statistica software, version 13 .The data were expressed as mean +/− SD. Comparisons between independent groups were made with Student’s A total of 39 patients met the inclusion criteria, out of whom one was excluded due to insufficient quality of the CMR results. The final group therefore consisted of 38 subjects  aged 18.0–54.9 years (median age 24.9 years) who had undergone a complete TOF repair at the age of 16 days to 15.1 years (median age 2.4 years). A palliative procedure had been performed in 10 of them (26.3%) prior to complete correction. Fifteen of the patients (39.5%) had their repair within the first 12 months of life (early repair), and the remaining 23 patients (60.5%) had the procedure later in life (late repair). RVOT was reconstructed in 16 subjects (42.1%) with a transannular patch (TAP) and in 6 of them (26.1%), RVOT was reconstructed with a homograft. In the remaining 16 patients (42.1%), pulmonary comisurotomy was performed along with infundibulectomy and non-transannular patch insertion . The timIn terms of ECG results, 28 patients (80.0%) had RBBB and 7 (20.0%) had incomplete RBBB (IRBBB) features; 12 patients had a single ventricular arrhythmia on their 24 h recording, 21 had a benign supraventricular arrhythmia, and four had at least one episode of nsVT. All patients who developed nsVT had undergone late repair: a 45-year-old male with TAP at the age of 13.1 years, a 40-year-old patient with nontransannular patch through ventriculotomy at the age of 3.7 years, a 36-year-old operated with the same method at the age of 8.5, and a 35-year-old with pulmonary homograft implantation at 8.2 years. QRS prolongation was observed in three of them, whereas the remaining one had normal QRS duration. The relative intraobserver variability of the two QRS measurements was 2.0% (6.1 ms) on average. p < 0.001); however, there were no substantial differences in terms of indexed RV measurements or the ECG parameters. The type of surgical repair had no substantial influence on the presence of ventricular arrhythmia (p = 0.239), on the percentage of ventricular beats in the Holter recording (p = 0.553), or on the QRS duration (p = 0.093)  .In the analysis of correlations between the results of 24 h Holter ECG and CMR for the whole group, PQ duration corresponded with a right ventricular ejection fraction (RVEF) (r = −0.34), and longer QRS duration was associated with a higher right ventricular end-systolic volume index (RVESVI) (r = 0.32). The measurements of HR variability were not associated with RV size; however, substantial negative correlations were found between two of the HRV indices and pulmonary ejection fraction. Furthermore, there was a substantial correlation of pulmonary regurgitation fraction (PRF), with RVEDVI and RVESVI but not with the ECG parameters. Similarly, older age at CMR was associated with greater RVEDVI and RVESVI but not with greater QRS duration . The anap = 0.448) according to the assigned LGE score. The data regarding LGE analysis can be found in the There were no substantial differences in QRS duration (The results suggest that hemodynamic and electrical functions of the RV do not correlate precisely with each other in all rTOF patients. Among the ECG parameters considered in this study, solely the QRS duration in early operated patients was affected by RV size, as estimated by CMR. This finding implies that QRS prolongation in TOF patients results from a combination of factors of varying impact, depending on the time since repair. Noticeably, PRF, which is known to be a major determinant of RV size in patients with corrected TOF, was not correlated with QRS duration in any of the groups.Widening of the QRS complex with a RBBB pattern on the ECG, is a feature observed in the vast majority of patients with rTOF ,8. TypicSimilarly, data from CMR deliver important information in terms of prognosis and risk stratification. According to current guidelines, severely impaired RV and LV function is associated with life-threatening ventricular arrythmias, such as polymorphic ventricular tachycardia and ventricular fibrillation . In a coThe relation between RV morphology and QRS duration was also investigated previously. Abd El Rahman et al. showed a positive correlation between RVEDV and RVESV absolute values as estimated by 3D echocardiography with QRS duration  on an agFurthermore, pulmonary valve replacement has been found not only to limit further elongation of QRS  but alsoAlthough RV dilatation is the most remarkable sign of volumetric overload and the major determinant of QRS prolongation in rTOF subjects, other concomitant factors that contribute to the impairment of RV mechanics have been identified. Among them, RV fibrosis, ischemia, formation of aneurysms, and RV wall stress are the most important . NotablyrTOF patients were found to have lower HRV parameters obtained from 24 h Holter recording in comparison with healthy controls [Some authors claim that the morphology of the QRS complex has a superior role over its duration in risk stratification in patients with repaired TOF ,9,25. ApConsidering that the rapid advancement in cardiac surgery over the past decade has enabled TOF repair in younger children, patients with early and late TOF repairs differ by age. We cannot exclude that the discrepancy between them in terms of ECG–CMR correlation results from age difference at the time of screening rather than from the time of repair. Since our oldest rTOF patients operated on in infancy are currently young adults, a comparison of age-matched groups is, to date, infeasible. Our study demonstrated no significant differences in QRS duration and presence of ventricular arrhythmia in regard to the surgical technique. Considering that the sample number was relatively small for this analysis, we leave this issue for further investigation in future studies.In conclusion, the ECG parameters have a poor predictive value for assessing the RV morphology and function in rTOF patients. In the era of advanced image diagnostics, QRS prolongation has limited sensitivity as a marker of RV enlargement and cannot be adequately used in clinical practice as a single parameter. HRV analysis from a 24 h ECG recording provides no conclusive data on the hemodynamic status of rTOF patients either. Considering the complexity of mechanoelectrical interactions after TOF repair, a regular multimodal assessment of these patients is necessary for adequate risk stratification. The prognostic factors encompass a patient’s surgical history, and ventricular dimensions and function assessed by CMR, together with the ECG parameters. Importantly, Holter ECG monitoring is a valuable tool in screening for heart rhythm disturbances, which are responsible for a substantial proportion of deaths in this population.


Anorexia nervosa (AN) is accompanied by bradycardia, low blood pressure (BP) and cardiac morphological remodeling. Systolic and diastolic functions are relatively preserved when assessed by standard ultrasound methods. However, novel advances based on speckle tracking echocardiography (STE), that could detect subtle and early alterations of left ventricular (LV) function, remained poorly used in AN patients.The aim of this study was to assess the cardiac function of AN patients by evaluating LV myocardial strains, myocardial work (MW) and LV mechanical dispersion. We hypothesized that LV strains and global myocardial work would be decreased and LV twisting mechanisms enhanced to preserve the systolic function.Fifty-nine adolescents including 26 women AN patients (14.6 ± 1.9 yrs. old) with a mean duration of AN of 19 ± 9 months and 33 controls (14.1 ± 2.0 yrs. old) underwent STE to assess LV morphology and myocardial regional strains.p = 0.006). The area under the pressure-strain loop, representing the global MW was not altered but was shifted to the left and downwards in AN patients, due to their lower BP and higher GLS. Intraventricular mechanical dispersion was similar in both groups. Circumferential strains, twisting/untwisting mechanics were preserved.The global longitudinal strain (GLS) was higher in AN patients compared to controls (−18.8 ± 2.0 vs. −16.9 ± 2.8%, Our results strongly support that the cardiac morphological remodeling observed in our AN patients was associated with normal ventricular regional myocardial functions. Only GLS was higher in AN patients, but its clinical significance remains to be demonstrated. Anorexia nervosa (AN) is characterized by important weight loss, severe malnutrition and body composition abnormalities . Most caMyocardial strain analyses from speckle tracking echocardiography (STE) have emerged as a reliable technique for studying myocardial mechanics . AlthougNon-uniform contractions of LV myocardial walls due to a decline of synchronicity affect myocardial performance. In AN patients, previous studies showed structural myocardial abnormalities with possible presence of fibrosis –12. SincAnother important factor influencing LV myocardial performance is LV twist. During systole, contraction of the cardiomyocytes induced not only LV longitudinal, but also circumferential and radial strains , 19. MorIn this context, the objective of the study was to compare the cardiac function of AN patients with healthy controls using novel advances in STE. We hypothesized that (1) LV strains and LV GMW would be decreased in AN patients, (2) LV intraventricular mechanical dispersion would be increased, and (3) LV twisting mechanisms would be enhanced to preserve their systolic function.The study, prospective, included female patients with AN who had been diagnosed in a pediatric department of a university hospital in France between March 2019 and January 2020. All patients ranged from 10 to 18 years and fulfilled the DSM V criteria for AN (American Psychiatric Association) . The con−2 and body surface area (BSA) was calculated according to Boyd  using a 3.5-MHz transducer (M4S probe). Cine loops were recorded in parasternal long axis and apical  views and saved for blinded offline analysis . Grayscale images were saved at a frame rate of 80–90 frames.seciography . All ech2.7 as recommended in the pediatric population  and twist mechanics  were obtained as previously detailed , circumferential strains (CS), diastolic longitudinal strain rate (LSrdetailed . Data welaxation  and peak17S).From a 17-segments model from apical 4, 3 and 2 chamber views to assess LV regional strains and time to peak (TTP) strains , LV mechMyocardial work (MW) and related parameters were estimated using the Automatic function imaging of the EchoPac software . MW was MW was calculated from mitral valve closure until mitral valve opening. During LV systole, segmental shortening contributes to the final LV ejection, whereas segmental stretch or lengthening does not contribute to LV ejection. As a result, the work performed by the myocardium during segmental shortening represents MCW, whereas the work performed by the myocardium during stretch or segmental lengthening represents energy loss, which is defined as MWW . During p < 0.05.All values were expressed as mean ± SD. Statistical analyses were performed using Medcalc . One-way analysis of variance (ANOVA) was used to compare groups, after checking the normality of distribution of each variable by Shapiro-Wilk test. In the absence of normal distribution, the nonparametric Kruskal-Wallis test was used. Statistical significance for all analyses was assumed at Twenty-six female AN patients, with an illness duration of 19 ± 9 months, and 33 controls were included. 2.7 were lower in AN patients compared to controls. There was no difference in the LV septum thickness, relative wall thickness (RWT), LV end-diastolic and end-systolic volume. AN patients presented with lower CO index, lower A wave with higher E/A ratio. Stroke volume index and EF were not different between groups. Systemic vascular resistances were higher in AN patients compared to controls.Data of LV morphology and function are presented in LV strains and MW are presented in 17S, an overall marker of intraventricular mechanical dispersion, was similar between groups . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.JP: design, methodology, investigation, analysis, and writing initial manuscript. EM: investigation and supervision. DT: methodology and investigation. AC: analysis and supervision. ER: supervision. PO: methodology and analysis. SN: design, methodology, investigation, analysis, writing, and supervision. All authors contributed to the article and approved the submitted version.This work was supported by the Platform 3A, funded by the European Regional Development Fund, the French Ministry of Research, Higher Education and Innovation, the Provence-Alpes-Côte-d'Azur region, the Departmental Council of Vaucluse and the Urban Community of Avignon.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.