Does myocardial viability testing identify patients with ischemic left ventricular dysfunction who benefit from percutaneous coronary intervention?In this prespecified subgroup analysis of a randomized clinical trial of 610 participants with ischemic left ventricular dysfunction 35% or less, myocardial viability testing with cardiovascular magnetic resonance imaging or stress echocardiography did not identify a population of patients who benefit from percutaneous coronary intervention. The extent of nonviable myocardium was associated with a higher risk of death or hospitalization for heart failure and a lower chance of improvement in left ventricular function.Findings suggest that the extent of dysfunctional yet viable myocardium was not associated with revascularization outcomes. In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear.To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function.Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years . A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023.Percutaneous coronary intervention in addition to optimal medical therapy.Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months.The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome  or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome , all-cause death, cardiovascular death, and improvement in left ventricular function.This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function.NCT01920048ClinicalTrials.gov Identifier:  This secondary analysis of a randomized clinical trial assesses whether myocardial viability testing identifies patients with ischemic left ventricular dysfunction who benefit from percutaneous coronary intervention. These tests typically characterize myocardial tissue into 3 distinct states: healthy myocardium contracting normally at rest, viable or hibernating myocardium that contracts abnormally at rest where improvement in function is expected, and nonviable scarred myocardium that contracts abnormally at rest but where improvement is not expected. Historically, viability has been regarded in a binary manner, and when classified in this way, observational, nonrandomized data suggest that patients with extensive myocardial viability might experience left ventricular recovery and improved survival after revascularization.We recently completed the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, a randomized comparison of percutaneous coronary intervention (PCI) vs optimal medical therapy (OMT) alone for patients with ischemic cardiomyopathy who had undergone mandatory viability testing. We report the prespecified analysis of clinical and left ventricular outcomes in relation to the extent of viable and nonviable myocardium to determine their associations with prognosis and functional recovery and the interaction with revascularization.6 Participants for this subgroup analysis were recruited from 40 sites in the United Kingdom between August 28, 2013, and March 19, 2020 (eAppendixes 1 and 2 in NCT01920048), and is available in CONSORT) guideline for reporting of randomized clinical trials.REVIVED-BCIS2 was a prospective, multicenter, open-label randomized clinical trial, the design and preliminary results of which have been published previously.7 and evidence of myocardial viability. The qualifying threshold for viability was defined as at least 4 myocardial segments that were dysfunctional at rest, judged by recruiting centers to be viable and supplied by coronary arteries that were severely diseased but amenable to revascularization by PCI. Key exclusion criteria were myocardial infarction fewer than 4 weeks before randomization, decompensated heart failure, and sustained ventricular tachycardia or ventricular fibrillation less than 72 hours before randomization. Participants were randomized in a 1:1 ratio to a strategy of either PCI plus OMT (PCI group) or OMT alone (OMT group) via an online randomization system .8 All clinical outcomes were adjudicated by an independent clinical events committee, and left ventricular ejection fraction was measured by an independent echocardiography core laboratory blinded to treatment assignment, outcome data, and the temporal sequence of scans.6Participants were eligible for enrollment if they had a left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease (British Cardiovascular Intervention Society jeopardy score ≥6),Viability assessment could be obtained by cardiovascular magnetic resonance (CMR) imaging, dobutamine stress echocardiography, single-photon emission computed tomography, or positron emission tomography. For this analysis, participants who had viability assessed with CMR imaging or dobutamine stress echocardiography were included, with CMR imaging data used when both were available. Given the small number of participants assessed only by single-photon emission computed tomography or positron emission tomography, these participants were excluded because the results would not be generalizable to these nuclear imaging techniques. Any participants for whom viability study results could not be obtained or who were unsuitable for core laboratory analysis were also excluded.9 Segmental wall motion was classed as normal or dysfunctional, with dysfunctional myocardial segments classified as viable or nonviable based on a 25% late gadolinium enhancement transmural threshold by CMR imaging or the presence of contractile reserve by dobutamine stress echocardiography . The left ventricle was described with a 17-segment American Heart Association model.iography .10,11 PeIn the CMR imaging cohort, per-participant ischemic scar burden was determined semiquantitatively by visual consensus of expert readers in pairs  and expressed as a percentage of the total left ventricular myocardial volume . This deThe primary outcome was a composite of all-cause death or hospitalization for heart failure during a minimum follow-up period of 24 months. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improvement in left ventricular function at 6 months, defined as a greater than the median absolute change in left ventricular ejection fraction from baseline, detected by echocardiography, measured by a blinded core laboratory at Guy’s and St Thomas’ NHS Foundation Trust.The statistical analysis plan was finalized before unblinding of viability data. A formal power calculation was not performed for this secondary analysis. A Cox proportional hazards model was used to assess the association between the extent of viable myocardium, nonviable myocardium, scar burden, and the primary outcome across the whole population, adjusted for baseline factors, including age, sex, previous heart failure hospitalization, presence of diabetes, chronic kidney failure, left ventricular ejection fraction, extent of coronary disease, and the modality of viability testing. The interaction between randomized assignment, independent variables , and major outcomes was assessed with a Cox proportional hazards model containing the following covariates: viability characteristics (treated as a linear effect), assigned treatment, their interaction, and baseline risk factors. The results were calculated by considering each viability characteristic as a continuous variable (expressed as hazard ratios [HRs] and 95% CIs), but for illustrative purposes, Kaplan-Meier curves and forest plots were stratified by tertiles of these parameters. Logistic regression models were also created to explore the association between viability characteristics and improvement in left ventricular function, defined dichotomously by the median change in left ventricular ejection fraction adjusting for baseline variables.P values, with P < .05 used to indicate statistical significance.Finally, a landmark analysis was performed including participants who survived at least 6 months from randomization to test the association between improvement in left ventricular function and the primary outcome, using Cox proportional models. Missing values of left ventricular ejection fraction were imputed with a multiple imputation model with chained equations that included randomized treatment, age, sex, and baseline, 6-month, and 12-month left ventricular ejection fractions. A sensitivity analysis was performed and was restricted to observed values, without imputation. All analyses were conducted with Stata, version 17.0 (StataCorp LLC), from March 31, 2022, to May 1, 2023. Two-sided Wald tests were used to calculate Of the 700 participants randomized in the REVIVED-BCIS2 trial, 610 were included in this prespecified analysis, 295 assigned to the PCI group and 315 to the OMT group . The meaP = .93) at a median of 3.4 years , consistent with the results in the whole trial population  (P = .048)   or any o = .048) . Results = .048) .Sensitivity analyses based on a late gadolinium enhancement transmural threshold less than or equal to 50% also showed no association between the extent of viability and primary outcome, as well as no interaction with assignment to PCI vs OMT (eTable 5 in P = .009), all-cause death, and cardiovascular death across the whole trial population , but increasing volumes of nonviable myocardium  and scar  were associated with a lower likelihood of improvement in left ventricular function  at 6 months (eTable 6 in P = .003).In the landmark analysis of participants surviving more than 6 months, improvement in left ventricular function by at least 4.7% was associated with a 38% relative risk reduction for the primary outcome compared with that of those who did not have an improvement  , length of follow-up is unlikely to have affected our findings.The traditional concept of myocardial hibernation, an adaptive state of decreased contractility that can be reversed by relieving the ischemic substrate through medical therapy and revascularization, appears at odds with our findings.18 it is notable that scar burden remained strongly associated with the incidence of the primary outcome after adjusting for baseline left ventricular ejection fraction.In contrast, the extent of nonviable myocardium was associated with an increased likelihood of the primary outcome independent of whether participants were assigned to have revascularization or not. This effect was driven by increased mortality rather than more heart failure hospitalization, with a clear relationship between nonviable myocardial mass and cardiovascular death. When scar burden was semiquantitatively assessed on CMR imaging, agnostic to resting wall motion, the prognostic association was stronger. Whether the negative association between scar and event-free survival is mediated by an increased incidence of fatal ventricular arrhythmia, as well as whether scar burden and morphology could be used to stratify risk and guide management, warrants further investigation. Given that current international guidelines recommend that arrhythmic risk stratification be primarily based on left ventricular ejection fraction,19 the STICH trial investigators did not find that improvement in left ventricular function affected survival.20 The discordance may be due to differences in trial methods because assessment of left ventricular function was protocol mandated for all participants in REVIVED-BCIS2 and continued to 12 months (rather than 4 months in STICH), as well as the observation that mean change in ejection fraction was lower in STICH, which may in turn reflect improvements in optimal medical and device therapy between the trials.Finally, our results demonstrate that patients who experience improvement in left ventricular function by 6 months have markedly better event-free survival than those who do not. Although this association has been reported in nonischemic left ventricular dysfunction,Apart from mandated viability testing, randomized assignment to revascularization, and high rates of guideline-directed medical and device therapy, our study had 2 key strengths compared with previous observational data. First, we characterized participants in terms of viable and nonviable myocardium, each of which relates to a distinct pathophysiologic determinant of outcome in ischemic cardiomyopathy. Second, all these viability characteristics were analyzed as continuous rather than binary variables, which better captures biological heterogeneity and enhances our ability to detect potential interactions.21Our study does have some limitations. We used data from only 87% of the trial population, although the baseline characteristics and clinical outcomes were similar to those of the overall trial population, so this loss of data is unlikely to have affected the results. Enrollment in the REVIVED-BCIS2 trial required participants to have at least 4 segments of viable myocardium according to local adjudication, and consequently the exclusion of patients without viable myocardium means the results cannot be generalized to the entire viability continuum; however, given the consistency of our results with those of the STICH trial, it is unlikely that the primary findings would be affected. Participants for whom viability was assessed with positron emission tomography or single-photon emission computed tomography were excluded, and we cannot extrapolate the results to these modalities. The accuracy of CMR imaging–based scar measurement might be improved by quantitative analysis, but automated methods are not yet in widespread clinical use, and our method best reflects the current way in which CMR imaging studies are interpreted in this patient population. Because we did not mandate paired ischemia testing, it is not possible to link clinical outcomes and improvement in left ventricular function to change in ischemic burden , and hence any comments on the mechanisms of hibernation remain speculative. Finally, differentiating ischemic left ventricular dysfunction from nonischemic cardiomyopathy with bystander coronary artery disease can be challenging in the absence of a definitive test. This issue might influence the results, although the REVIVED-BCIS2 population was phenotyped with advanced cardiac imaging during viability testing and a threshold British Cardiovascular Intervention Society jeopardy score that is highly specific for ischemic left ventricular dysfunction.In conclusion, in this subgroup analysis of a randomized clinical trial of PCI vs OMT alone, viability testing did not identify participants for whom PCI would confer a prognostic benefit or improve left ventricular function. In this population with ischemic left ventricular dysfunction, the extent of viable myocardium as estimated by CMR imaging or dobutamine stress echocardiography did not correlate with event-free survival or the likelihood of improvement in left ventricular function of 5% or greater, although the extent of nonviable myocardium (by CMR imaging or dobutamine stress echocardiography) and the total left ventricular scar burden (by CMR imaging) were associated with both outcomes.


Half of the population had a meal during saline infusion (food/fluid), and the other half were kept fasting (fasting/fluid). We analyzed end-diastolic (EDV) and end-systolic (ESV) volumes and feature tracking (FT) using CMR, LV global longitudinal strain (GLS), and RV longitudinal strain (LS) using TTE. (3) Results: CO assessed using CMR increased significantly in both groups, and the increase was significantly higher in the food/fluid group: LV-CO (ΔLV-CO: +2.6 ± 1.3 vs. +0.7 ± 1.0 p < 0.001), followed by increased heart rate (HR) (ΔHR: +12 ± 8 vs. +1 ± 6 p < 0.001). LV and RV achieved increased stroke volume (SV) through different mechanisms. For the LV, through increased contractility, increased LV-EDV, decreased LV-ESV, increased LV-FT, and GLS were observed. For the RV, increased volumes, increased RV-EDV, increased RV-ESV, and at least for the fasting/fluid group, unchanged RV-FT and RV-LS were reported. (4) Conclusions: Preload augmentation and food intake have a significant impact on hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake of fluid and food before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.(1) Background: To investigate how food intake and preload augmentation affect the cardiac output (CO) and volumes of the left ventricle (LV) and right ventricle (RV) assessed using cardiac magnetic resonance (CMR) and trans-thoracic echocardiography (TTE). (2) Methods: Eighty-two subjects with ( Assessment of hemodynamic and systolic function of the heart is fundamental for diagnosis, follow-up, and prognosis in patients with or at risk of cardiac dysfunction ,2,3,4. TPrevious studies have examined the effect of food intake on left ventricular (LV) hemodynamic parameters, such as cardiac output (CO), stroke volume (SV), and heart rate (HR), using conventional TTE and Tissue Doppler Echocardiography (TDE). These demonstrated that food intake significantly alters the hemodynamics and function of the LV ,9,10,11.Accurate assessment of cardiac function and hemodynamics is important in patients scheduled for sequential examinations, such as monitoring medical therapy in heart failure, and assessments prior to or during cancer treatment, such as chemotherapy or immunotherapy ,15,16,17While patients scheduled for stress testing by CMR are instructed to abstain from caffeine intake, patients scheduled for echocardiography, CMR without stress testing, and right heart catheterization do not routinely receive recommendations regarding oral intake prior to the assessment of cardiac function. Food intake and preload vary throughout the day and between days, so they may potentially affect the results and precipitate inappropriate changes in care.The purpose of this study is to investigate how food intake and preload augmentation affect the function and volumes of the LV and RV assessed using CMR and strain by TTE.All subjects scheduled for routine TTE at the Echocardiography Laboratory at the Department of Cardiology, Rigshospitalet, Denmark, were sequentially invited to participate in the study over a period of 15 months. The only inclusion criteria were age ≥18 years and sinus rhythm on the examination day. Exclusion criteria were heart failure with New York Heart Association (NYHA) class III–IV, pregnancy, breastfeeding, or any contraindication to CMR. The study design is an observational cross-sectional study and is summarized in The patients were divided into two subgroups: (1) food/fluid and (2) fasting/fluid. The first 50% of the patients were categorized in the food/fluid group, and the last 50% in the fasting/fluid group. The food/fluid group had a meal representing a normal lunch immediately after the pre-examinations during the fluid infusion. The infusion and food period for the food/fluid group lasted 30–45 min. The fasting/fluid group was not allowed any oral intake and kept fasting before and during the entire examination.All subjects were instructed to abstain from any oral intake and cigarette smoking five hours prior to the examination. In this way, the baseline for all the patients was as equal as possible, and we avoided the risk that cigarette smoking could affect the hemodynamics, hence the results ,23. The To investigate the impact of food intake on cardiac function and hemodynamics, the patients were divided into two subgroups: (1) food/fluid and (2) fasting/fluid. The food/fluid group had a meal representing a normal lunch consisting of a sandwich, soda, and coffee/tea during the fluid infusion. The fasting/fluid group was not allowed any oral intake and kept fasting before and during the entire examination.The second CMR and echocardiography were performed immediately after the infusion of 1.5 L saline, while the remaining 0.5 L was infused at a slower rate during the CMR. All examinations were performed within 1.5 h after the saline infusion. HR was measured at 4 points: before the examination, during the main fluid infusion, right after the second CMR, and right after the last TTE. The saline infusion index was calculated as the ratio of saline infusion to the BSA. The investigation conforms with the principles outlined in the Declaration of Helsinki and was approved by the local ethics committee of the Capital Region of Denmark . All subjects provided written, informed consent.CMR images were recorded using a 1.5 T Imaging System  and a phased-array cardiac coil. Cine images were acquired during breath-hold and steady-state free precession cine sequences with retrospective gating. Slice thickness was 8 mm, there were no gaps, the field of view was 300–360 mm, and there were 25 phases/cardiac cycles. Offline analysis was performed using CVI42  and blinded for all other information, including fluid and food status. End-diastole and end-systole were identified as the phases with the largest and smallest volumes, respectively. For volumetric measurements of the LV, the endocardial contours were manually delineated in the short-axis stack and for the RV in the transversal stack. The LV papillary muscles were considered part of the LV volume. Feature tracking (FT) was performed in the long-axis views using two-chamber, three-chamber, and four-chamber views. The adequacy of FT was assessed by visual evaluation of strain curves and whether the contours followed the myocardium. Cardiac output was calculated as SVxHR. Indexed CO was calculated by dividing measured CO with BSA. LV geometry was assessed by dividing patients into four groups: normal, hypertrophic, dilated, and dilated + hypertrophic based on the CMR examination .Two-dimensional (2D) TTE images were acquired by one experienced sonographer using a Vivid E95 ultrasound scanner  and a M5Sc-D matrix phased array transducer (1.5–4.6 MHz). A dataset including TTE of both LV and RV for GLS analysis was obtained. TTE examinations were stored externally and analyzed offline using EchoPac software version 201 . LV GLS was evaluated from basal, mid, and apical segments of apical two-, three-, and four-chamber  views. RV strain was obtained in the 4CH view, assessing strain for both the free wall and for all six segments, including the septum. Adequate image quality for LV strain was defined as ≥4 trackable segments in each view, whereas adequate RV strain quality was defined as ≥5 trackable segments for the complete RV strain analysis and all three segments for the free wall analysis .t-tests for normally distributed variables. To test the effects of food intake and fluid infusion on the LV and RV CO and FT on CMR and echocardiographic strain, multiple linear regression was performed. Friedman’s test was used to test changes in HR over time. To assess the risk of underestimating or overestimating GLS at subsequent examinations if the patient eats/drinks at first and not at the second examination, the post-examination was defined as baseline, and differences between post-GLS and pre-GLS were tested with a chi-square test and compared with current cardio-oncology guidelines. Statistical significance was defined as p < 0.05.Statistical analysis was performed using SPSS Statistics for Macintosh . Continuous variables are presented as mean ± SD, and categorical variables as frequencies and percentages. Comparisons between groups were performed using two-tailed paired and unpaired The baseline characteristics of the two study groups, the fasting/fluid group and the food/fluid group, are summarized in 2) and oral intake of food (+/−), only food intake had a significant impact on LV-CO . In the multiple linear regression model, only food intake had a significant impact on indexed RV-CO   .The effect of preload augmentation and food intake on HR at four different time points showed a significant increase after both fluid alone and fluid plus food. This effect decreased over time, ending with a non-significant post–pre difference in the fasting/fluid group. 21 or ESMO22 guidelines are used, respectively, 17% (1 patient with an absolute GLS drop ≥ 5% and 13 patients with a relative GLS drop ≥ 12%) and 7% (6 patients with a GLS drop > 15%) of patients manifested clinically significant GLS deterioration when the post-examination was used as a baseline.Depending on whether the ESCIn this study, we investigated the effects of food intake and preload augmentation on cardiac volumes and function assessed using feature tracking by CMR and GLS by echocardiography.(1)CO and LV contractility  are significantly increased by preload augmentation and further increased by food intake.(2)Fluid infusion and food intake may falsely improve GLS, which may affect follow-up.(3)The LV and RV seem to act through different mechanisms when increasing CO: the LV through increased contractility and the RV through augmented EDV and ESV, which are indirectly driven by the effects of the LV.Cardiac assessment of hemodynamic and systolic function are important measures for diagnosis, prognosis, and decision-making in patients with, or at risk of, cardiac dysfunction. Currently, there are no widely accepted guidelines regarding fluid or food intake before cardiac assessments using echocardiography, CMR, or right heart catheterization ,2,3,4.Previous studies ,26 foundWe found a significant increase in HR between the baseline and second CMR in both groups, with the fasting/fluid group reverting to baseline more rapidly and only the food/fluid group maintaining a persistently increased HR at the end of the study day. Similar patterns have also been demonstrated before ,11,27.We observed significantly increased CO with preload augmentation and significantly larger increases when adding food. However, the mechanism behind the increase seems different between the two ventricles. The LV responds to preload augmentation and food intake by increasing HR and contractility, with an attendant decrease in LVESV. The RV responds with increasing volumes, indicated by an increase in RVEDV and an unchanged/trend towards increasing RVESV . Our finThe physiological explanation for the different mechanisms to increase CO could be the thinner wall, lower volume-to-mass ratio, and smaller cardiomyocytes of the RV that make the RV more compliant and able to dilate . In addiIn our study, the RVEF increased when adding food intake to preload augmentation; however, the RVEF decreased with only preload. A possible explanation is that LV contraction contributes 20–40% of the RV SV and, thus, pulmonary flow. Therefore, increased LV contractility after food intake indirectly affects the RVEF .In all patients where serial measurements of cardiac function are necessary, it is important that all external conditions are equal at every examination to avoid inaccuracies. A theoretical example of this importance is in the field of cardio-oncology.Cardiovascular diseases in patients with cancer are a major challenge since the considerable improvements in cancer treatment are at the cost of short- and long-term cardiovascular adverse effects. Cancer-therapy-related heart failure is a leading cause of morbidity and mortality in cancer patients ,32. TherThe scenarios described above are relevant not only in oncocardiology but also in all other patients where multiple follow-up examinations are performed. The scenarios underline and support our recommendations that patients should not eat or drink before a cardiac evaluation, or at least ensure there is equivalent intake before all examinations.First, the TTE and CMR were performed non-blind to food status. However, all examinations were anonymized and completely blinded during the post-processing analysis. Second, the meals in the food group consisted of both a standardized food intake and coffee/tea/soda with potential caffeine. The effects of food intake may wholly or partly represent the effects of caffeine or oral fluid intake. Our meal represents a usual lunch and was chosen to mimic a normal situation. For future studies, a standardized meal with exact energy intake and nutritional information, with/without caffeine, would be preferable. Third, CMR was always performed right before and right after fluids and food (when not fasting). Consequently, the second TTE was performed last, and there might be a risk that the effects of fluid or food have subsided. There are some limitations that need to be highlighted. Preload augmentation and food intake significantly impact the hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.


Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of heart failure and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CA, which is now possible without recourse to endomyocardial biopsy in around 70% of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CA and more accurate prognostic stratification. Therapies able to slow or halt ATTR-CA progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional heart failure medications. A wide horizon of possibilities is unfolding and awaits discovery. During the last decade, perception of cardiac ATTR amyloidosis has been radically transformed through major diagnostic advances in cardiovascular magnetic resonance (CMR) and bone tracer scintigraphy, and the development of treatments designed to ameliorate its natural history . The floIn this issue of the Global Heart Journal, Brito et al. present the World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy which provides a comprehensive review of ATTR-CM, prioritizing patients’ needs, including treatment accessibility, and the role of Patient Advocacy Groups, and highlighting the importance of multidisciplinary patient management, emphasizing the key role of specialized amyloidosis centers.To achieve this aim, a panel of 18 expert clinicians specialized in ATTR amyloidosis from 13 countries was assembled along with a representative from the Amyloidosis Alliance, a patient advocacy group. Such a breadth of expertise is required since ATTR amyloidosis is highly heterogeneous with significant variation worldwide in terms of clinical phenotype at presentation, presence and consequence of the vast number of TTR gene mutations, diagnostic pathways, outcomes and treatment strategies. Identification of patients with early ATTR-CM has afforded the opportunity to broaden our understanding of its natural history and the factors influencing its clinical course such as the fibril type (ATTRwt vs. ATTRv amyloidosis), particular TTR gene mutations , severitUntil recently, most patients with ATTR-CM were diagnosed with severe advancements already progressed throughout the disease, with characteristic echocardiographic features including severely increased wall thickness, restrictive LV filling pattern, atrial dilatation, and reduced ejection fraction . However10The use of CMR and repurposed bone scintigraphy for diagnosing ATTR-CM represents a milestone advance in the field, which has led to an exponential increase in the number of patients identified worldwide, and a much greater proportion being diagnosed at an earlier stage . Brito eATTR-CM is now treatable, making early diagnosis all the more important. Remarkably, a number of very different therapeutic strategies have been developed, with theoretical potential to be used together. Small molecule drugs that bind to circulating TTR, the liver-derived amyloid precursor protein, can enhance its stability with the aim of reducing its propensity to misfold and aggregate into ATTR amyloid fibrils. The TTR stabiliser tafamidis, was the first ever drug to be approved for any kind of amyloidosis; in the ATTR-ACT trial for ATTR-CM , treatmeA quantum leap beyond gene silencing is permanent one-shot interference of the TTR gene by means of CRISPR-Cas9  gene editing. Long applied in plant biology, current trials in ATTR amyloidosis represent its first in vivo use in humans. This treatment approach achieves near sustained up to 95% knockdown of TTR serum concentrations in patients with hereditary ATTR-PN , and it These remarkable advances in therapy for ATTR-CM have between them shed substantial light on the continuously dynamic nature of cardiac amyloidosis, i.e. the interplay between amyloid production and amyloid clearance 2223, bot22


Introduction: The left (LV) and right (RV) ventricles are linked biologically, hemodynamically, and mechanically, a phenomenon known as ventricular interdependence. While LV function has long been known to impact RV function, the reverse is increasingly being realized to have clinical importance. Investigating ventricular interdependence clinically is challenging given the invasive measurements required, including biventricular catheterization, and confounding factors such as comorbidities, volume status, and other aspects of subject variability.Methods: Computational modeling allows investigation of mechanical and hemodynamic interactions in the absence of these confounding factors. Here, we use a threesegment biventricular heart model and simple circulatory system to investigate ventricular interdependence under conditions of systolic and diastolic dysfunction of the LV and RV in the presence of compensatory volume loading. We use the end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, Frank Starling curves, and cardiac power output as metrics.Results: The results demonstrate that LV systolic and diastolic dysfunction lead to RV compensation as indicated by increases in RV power. Additionally, RV systolic and diastolic dysfunction lead to impaired LV filling, interpretable as LV stiffening especially with volume loading to maintain systemic pressure.Discussion: These results suggest that a subset of patients with intact LV systolic function and diagnosed to have impaired LV diastolic function, categorized as heart failure with preserved ejection fraction (HFpEF), may in fact have primary RV failure. Application of this computational approach to clinical data sets, especially for HFpEF, may lead to improved diagnosis and treatment strategies and consequently improved outcomes. While the left (LV) and right (RV) ventricles are distinct embryologically, structurally, and functionally , they arHeart failure with reduced ejection fraction  represents nearly 50% of heart failure cases worldwide and is characterized by LV SD . The impPreclinical studies have addressed some of these knowledge gaps. Early isolated heart studies in large animals showed that due to VVI, LV contraction contributes to 60%–70% of RV systolic function . IschemiComputational modeling is aptly positioned for investigating VVI because the influence of specific contributors to these interactions can be interrogated individually. For example, the impact of the pericardium, shared myofibers, interventricular septum, and LV and RV preload and afterload as determined by the characteristics of the cardiovascular system (CVS) can be varied independently. In addition, the absence of subject variability and potential species differences simplifies interpretation. Numerous CVS models have been used to explore ventricular dysfunction; however, few account for VVI without computationally and time intensive finite element modeling. Additionally, volume loading as a surrogate for HF compensation is computationally expensive with high order models. Thus, we employ the Lumens et al. three-segment (TriSeg) biventricular model of the heart (2009) because it accounts for differences in RV and LV geometry and captures VVI through shared myofibers and the septum while remaining computationally simple. Previously this model has been used to investigate biventricular mechanics including septal dynamics in primary RV dysfunction due to pulmonary hypertension and pulmonary arterial hypertension .To develop a predictive mechanistic understanding of interventricular interactions under conditions of HFrEF, HFpEF, and heart failure with moderately reduced ejection fraction (HFmrEF) with compensatory volume loading, we combine the TriSeg model with a closed-loop lumped-parameter circulation model. Our simulations reveal that: 1) RV SD and DD induce an apparent LV stiffening that is due to VVI and not to intrinsic changes in the properties of the LV or pericardial constraints; 2) LV dysfunction causes a compensatory increase in RV CPO to supply sufficient LV preload when volume loading is sufficient to maintain normal systemic pressures; and 3) RV dysfunction contributes to LV dysfunction via impaired Frank-Starling mechanism in the LV. The model codes, which are parameterized to simplify the use of potentially subject-specific data, are freely distributed to facilitate further independent exploration of the mechanisms investigated here.We establish a hypothetical ideal subject that represents a healthy adult (weight −70 kg). Normative values for systemic, LV, and RV chamber pressures and volumes as well as total blood volume for this hypothetical subject were based on literature values . End-sysThe TriSeg model is adapted from In the TriSeg model, the midwall is defined as a theoretical surface radially half-way between the inner and outer surfaces of the ventricular wall   is a unit conversion factor, ex vivo and computed approximations of the volume when the EDP is −0 and 30 mmHg. Thus, with a single end-diastolic pressure and volume point, we predict the entire EDPVR. Although the Klotz experiments were performed on LV only, we assume the RV has similar material properties to the LV, and hence, apply the same behavior to the RV. We optimize parameter Here, we simplified the Lumens et al.  formulatmization .For the active stress component, we havehe heart  given ase length . Thus, tBased on DP as in  to the Tdiastole . We assu canines , 1.9 μm  canines ; we chos canines .Similarly, the active stress scaling factor relates the ESP as in  to the TThe three walls of the TriSeg model are mechanically coupled through a tension balance at the shared junction point where all three walls meet. The ventricular volumes are then used to calculate the chamber pressures. Given a model of wall mechanics for each segment, the axial and radial tension components are calculated at the shared junction point. All Triseg cardiac model euqations are listed in the .We implement a pericardial constraint, The healthy (H) case is defined based on normative hemodynamic data including LV and RV pressures and volumes  and card studies , by scalr the LV . For theAs a VVI challenge, we increased circulating blood volume from 100% to 350%. In this study, we volume loaded to achieve a mean systemic arterial pressure  and B (RV) at a normal circulating blood volume. Panels C and D show end-systolic pressure volume (ESPVR) and EDPVR curves, respectively, during volume loading. The ESPVRs show physiological nonlinearity  and dysfunction cases, including LVSD, LVDD, RVSD, and RVDD –8 with tinearity . The bolpute CPO  at the bReducing VR curve . WhereasVR curve . The areVR curve ; LV and VR curve . At fullVR curve . As a reVR curve . The impVR curve .Increasing uces ESP . As in tuces ESP . Under vuces ESP  is obseruces ESP ; the impuces ESP . RV systuces ESP . LV EDP uces ESP  that resuces ESP . The RV uces ESP apparent stiffening due to mechanical interactions between the ventricles. The slope of the RV EDPVR curve decreases slightly with dysfunction as the flattening of the septum allows for more RV filling given the same pressure. At full compensation, the LV pressure-volume loop is mostly maintained from healthy  . Only inregions) . Figure regions) . LVDD sh−1, and during diastole curvature decreases, reaching a minimum of about 0.25 cm−1. For severe LVSD, septal flattening can be visualized during systole both spatially  exhibited phenotypes seen in HFpEF, suggesting multiple modes of heart failure in HFpEF, which is consistent with and may help to explain the clinical heterogeneity of HFpEF. More defined diagnostic sub-categories of HFpEF will allow for the development of targeted treatments and improved outcomes of this disease.


Left atrial dissection is a rare event, typically associated with cardiac manipulation. We report the first case of a left atrial dissection caused by parasitic infectious endocarditis, which required the use of patch repair for the damaged mitral annulus and valve.To treat heart failure in a 43-year-old man with left atrial dissection, we performed a patch repair of the mitral annulus and valve using autologous pericardium.We encourage novel surgery for complicated infectious endocarditis. Left atrial dissection (LatD) is an extremely rare condition characterized by a false blood-filled cavity or lumen extending from the mitral annulus (MA) to the left atrium (LA) , 2. It i9/L with 37.8% eosinophils. Transthoracic echocardiogram (TTE) showed a 5.4 × 6.0 cm mass containing thrombus in the posterior wall of the left atrium (LA), causing functional mitral insufficiency and MV obstruction. In addition, there was a suspicious endocardial orifice beneath the root of the posterior mitral leaflet (PML) on the left ventricle (LV). Enhanced Computed tomography (CT) revealed the contrast filling the mass cavity, indicating intramural hematoma.  and catheter-based interventions , 2. CaseTransesophageal echocardiography (TEE) is the preferred method for diagnosing LatD, but its efficacy and diagnostic value are still limited . EchocarHemodynamic instability is mainly secondary to obstruction of MV inflow or pulmonary vein orifice and eventually becomes congestive heart failure and low-output syndrome, making conservative management impractical. Surgery was necessary for our patient .To achieve successful repair, three main keys are the following: (a.) to gain adequate evacuation of the hematoma; (b.) obliteration of the false lumen; and (c.) addressing the entry point, if identified. If the communication is not repaired, the dissection may recur under persistent pressurized inflow , 2. TherBy introducing this rare parasitic infestation of LatD and its surgical details, we aim to encourage novel surgery for complicated infective endocarditis.


Pulmonary atresia and tetralogy of Fallot can require palliative surgery in the neonatal period due to severe hypoxia; however, limitations of established techniques include high failure rate and need for cardiopulmonary bypass. Herein, right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter is described.A retrospective review of patients who underwent right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter at our institution between September 2018 and March 2022 was completed. During the procedure, a Foley balloon catheter was used to occlude the blood from the right ventricular inflow tract.Eight patients with pulmonary atresia and intact ventricular septum underwent an off-pump right ventricular outflow tract reconstruction. One patient with pulmonary atresia and ventricular septal defect, and two patients with tetralogy of Fallot underwent an on-pump right ventricular outflow tract reconstruction on a beating heart. The procedures were successful in all patients. Patent ductus arteriosus ligation without modified Blalock-Taussig shunt placement was performed in three patients with pulmonary atresia with intact ventricular septum and two patients with tetralogy of Fallot, ductus arteriosus was left open in four patients with pulmonary atresia with intact ventricular septum. All patients remained clinically well without serious complications.Right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter for pulmonary atresia and tetralogy of Fallot is a feasible alternative to catheter-based interventions or traditional surgical treatment, especially in patients with muscular infundibular stenosis or hypoplastic pulmonary annulus. Further studies with more cases are needed to verify feasibility and superiority of this approach. Pulmonary atresia (PA) and tetralogy of Fallot (ToF) are cyanotic congenital heart diseases that can require early establishment of additional pulsatile pulmonary flow, using either surgical or catheter-based interventions, to improve hypoxia and promote growth of the right ventricle (RV) and pulmonary vascular beds –3. To daThis study was approved by the institutional review board of the ethics committee in Qingdao women and children’s hospital (QFELL-YJ-2022-72) on 1 October 2022. Informed consent was obtained in all cases. Between September 2018 and March 2022, a composite group of patients was treated at our institution, comprising 8 cases of PA-IVS, 1 case of PA-VSD [n = 2) or PA-VSD (n = 1). Great attention was paid to tricuspid regurgitation and the Z-value of tricuspid valve was performed before surgery in patients with ToF (ntinotti ), presen-VSD n = . Great aAll the patients were administered prostaglandin E1(PGE1) to maintain patent ductus arteriosus(PDA) after referral to the intensive care unit (ICU). Eight patients with PA-IVS initially underwent the catheter-based procedure; however, the procedures were unsuccessful despite several attempts to puncture the atresic pulmonary valve. Subsequently, modified hybrid therapy, namely TBPV and RVOT reconstruction without CPB, was performed on these eight patients to depressurize the right ventricle  was estimated in all the other cases at the end of the procedure by temporarily blocking the PDA. This manoeuvre also helped to decide the strategy of PDA ligation and mBT shunt placement. For patients whose PDA was left open, PGE1 was progressively discontinued after surgery.Except in the first patient with PA-IVS who routinely underwent ligation of the ductus arteriosus and simultaneous mBT shunt placement due to lack of experience, saturation of hemoglobin with oxygen from 72.5 ± 9.2% . The median mechanical ventilation time was 108.1 ± 82.0 h , and median postoperative ICU stay was 12.7 ± 5.2 days . The median max velocity in the RVOT was 1.4 ± 0.2 m/s  and median max velocity of pulmonary valve was 2.7 ± 0.7 m/s .The median procedure duration was 136.7 ± 41.0 min . Median postoperative SpO2 value of 86% with room air, without other interventions, was achieved on day 32 after surgery. Other patients in whom the PDA was left open were successfully weaned from PGE1 in less than one week. Although residual stenosis of the pulmonary valve was common, it was tolerable. Mild pulmonary regurgitation was present in all cases, including in two patients who underwent a transannular patch augmentation procedure.Minor complications occurred in some patients, e.g., PGE1 discontinuation was delayed in one paitent with PA-IVS due to repeated hypoxemia during reduction of pump speed. Nevertheless, PGE1 treatment was finally stopped when a stable SpOPatients were followed-up for a median time of 18.6 ± 11.6 months . Out-patient follow-up included echocardiography, electrocardiography, transcutaneous oxygen monitoring, and electroencephalography. A gradual increase in the pressure gradient across the pulmonary valve and consequent hypoxemia were detected in three PA-IVS patients; hence, percutaneous balloon pulmonary valvuloplasty (PBPV) was performed at six months to one year after palliative surgery in them. Unexpectedly, a RVOT aneurysm was detected during PBPV in the first patient with PA-IVS but no apparent worsening of the aneurysm has been observed to date. A closed ductus arteriosus was confirmed by echocardiography at less than one year after the procedure in all patients with PA-IVS. Tolerable maximum pressure gradient at the pulmonary valve, mild regurgitation of the tricuspid valve, and no obvious RVOT obstruction were also detected in all cases. As CTA confirmed well-developed distal pulmonary arteries, definite repair was performed in patients with TOF and PA-VSD at four to twelve months after surgery. Mono-cusp outflow tract patch was used in both cases who underwent the transannular patch augmentation to prevent further pulmonary regurgitation. As CTA revealed local stenosis of right pulmonary artery around the junction with mBT shunt in the patient with PA-VSD, additional patch augmentation of the right pulmonary artery was performed. All patients are doing well clinically without neurological complications.Neonatal palliative surgery is sometimes essential for relieving cyanosis and for boosting the growth of the native pulmonary arteries in patients with PA or ToF. Different options, typically PBPV, TBPV, mBT shunt, and surgical treatment under CPB, can be considered based on anatomical features and associated anomalies.2, which may result in shunt-related complications, such as high risk of occlusion and shunt thrombosis due to the small size of the grafts used, or systemic steal and subsequent heart failure due to overshunting. All of these ultimately result in higher interstage mortality in infants [PBPV is associated with various drawbacks, including high procedure failure rate and reintervention rate, several complications such as cardiac perforation and early pulmonary regurgitation , 12–15.  infants , 19. Add infants .Theoretically, RVOT reconstruction with transannular patch augmentation or pulmonary valvuloplasty under direct vision yield better anatomical results than catheter-based procedures or traditional hybrid procedures, especially in patients with muscular stenosis of the RVOT or hypoplastic PV annulus. However, the surgical approach requires neonatal CPB, which necessitates a period of cardiac arrest that has both acute consequences related to the systemic inflammatory response and long-term effects on end-organ development and neurocognitive and psychomotor function , 22. HypThus, a new approach to both the off-pump modified hybrid therapy in PA-IVS and the on-pump RVOT reconstruction with transannular patch augmentation or pulmonary valvuloplasty under direct vision on a beating heart for ToF and PA-VSD  is described.The most critical aspect of this new approach is the use of a Foley balloon catheter to block blood flow from the right ventricular inflow tract. Using 2–3 ml saline to inflate the balloon and achieve appropriate traction of the catheter results in less bleeding and a bloodless operative view, and prevents air ingression into the left heart. This economical new approach may reduce the likelihood of simultaneous mBT placement, decrease the possibility of early reintervention by achieving better anatomical results, and help avoid CPB or cardiac arrest. These aspects would be especially advantageous for patients from low-income countries who suffer from infundibular muscular stenosis or hypoplastic PV annulus.CPB as a standby for PA-IVS and cerebral oxygenation monitoring are recommended for all. And continuous administration of PGE1 during the procedure are of great importance to ensure adequate supply to the pulmonary artery. Guidance under TEE during the insertion or dilation of the Foley balloon catheter is essential to prevent injuries of tricuspid valve. Mild regurgitation of the tricuspid valve was noted at the latest follow-up for all patients. At the initial stages of a modified hybrid procedure for PA-IVS, a bovine pericardial patch or a glutaraldehyde-treated autogenous pericardial patch previously sutured over the anterior wall of the RVOT is recommended instead of a fresh autogenous pericardial patch because the latter may increase the risk of RVOT aneurysm. An RVOT aneurysm was detected in one patient with PA-IVS in our cohort during catheter reintervention at six months after surgery, which was suspected to be associated with the use of a fresh autogenous pericardial patch. Close follow-up of the RVOT aneurysm continues and further intervention may be inevitable. Therefore, in the subsequent patients, bovine pericardial patches were used as an alternative to cover the anterior wall of the RVOT, and no more RV aneurysms have been detected at one year after surgery. During the RVOT dredging, attentions should be paid to protect the Foley balloon catheter from accidental injury, which is easily avoidable under direct vision. To prevent from pulling out the Foley balloon catheter with excessive resection of the hypertrophic muscles of the RVOT, our experience suggests that it is safe to stop RVOT dredging when about two-thirds of the balloon is visible from the incision.2 was higher than 85% during temporary occlusion of the PDA. If SpO2 was between 75% and 85%, the PDA was left open without mBT placement. Ligation of PDA with simultaneous mBT placement was performed only if SpO2 was lower than 75% during occlusion.Further, despite prolonged hospital stays due to sustained PGE1 requirement, it is recommended to avoid mBT placement to prevent the occurrence of associated complications. Hence, our experience was to evaluate the degree of hypoxia during deployment of the PDA snare. Specifically, ligation of PDA without mBT placement was performed if SpOThe study presented has a few limitations that should be taken into account. Firstly, the sample size is relatively small, which may limit the generalizability of the findings. Additionally, there is a lack of a concurrent traditional TBPV cohort as a comparison group, which could have provided valuable insights into the effectiveness of the intervention being studied. Furthermore, while all patients were successfully weaned from PGE1, it is important to note that there remains a risk that patients with a reserved PDA may not be able to dissociate from PGE1 and may require further intervention. As such, future studies should aim to address these limitations and explore the potential impact of these factors on the outcomes observed.A novel approach to RVOT reconstruction on a beating heart using a Foley balloon catheter in patients with PA-IVS, PA-VSD  and ToF is described. This procedure showed encouraging results, is economical, may reduce the likelihood of simultaneous mBT placement, and decrease the possibility of early reintervention due superior anatomical results compared to catheter-based interventions or traditional hybrid therapy. These advantages are especially true in neonatal patients with muscular infundibular stenosis or hypoplastic pulmonary annulus. As our results are limited by small sample size and the retrospective approach, further studies with more cases are needed to verify feasibility and superiority of this novel approach.


Using speckle tracking technology to investigate the effect of hypertriglyceridemia on the global longitudinal strain(GLS) of the left ventricle in patients with coronary heart disease in the early stage, and to explore the value of myocardial strain in early identification of cardiac dysfunction in patients with coronary heart disease in the pre-heart failure stage.A cross-sectional study of 138 participants was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained for all patients. Myocardial strain parameters were compared between the hypertriglyceridemia and normal triglyceride level groups and the effect of hypertriglyceridemia on early left ventricular global longitudinal strain impairment in coronary heart disease patients was evaluated.The overall longitudinal strain of the left ventricle was smaller in the hypertriglyceridemia group than in the normal triglyceride group. After the multivariate Logistic regression model adjusting for the influence of confounding factors, the results remained stable.The risk of impairment of global longitudinal strain of the left ventricle in patients with coronary heart disease is positively correlated with triglyceride levels, and hypertriglyceridemia maybe an independent risk factor affecting early cardiac dysfunction in the pre-heart failure stage of patients with coronary heart disease. Despite revascularization, coronary heart disease patients remain at a high risk for reduced ejection fraction and heart failure many years after the onset –5. HeartAlthough left ventricular ejection fraction (LVEF) is commonly used to evaluate left ventricular systolic function, it has various limitations. It has low sensitivity for local myocardial damage , does noWe used speckle tracking technology to explore the early effects of hypertriglyceridemia on left ventricular myocardial structure and function in coronary heart disease patients and to provide clinical evidence for myocardial remodeling caused by hypertriglyceridemia in the pre-heart failure stage.n = 60) and non-hypertriglyceridemia  groups according to the American Endocrine Association clinical practice guidelines for hypertriglyceridemia  was calculated by dividing the weight (kg) by height (m) squared.Blood samples were obtained from all participants and the following laboratory tests were performed: serum TG, serum high density lipoprotein (HDL-C), serum low density lipoprotein (LDL-C), serum total cholesterol, fasting glucose, glycosylated hemoglobin (HbA1c%), and estimated glomerular filtration rate (eGFR).The GENSINI score was calculated based on the participants' coronary angiography . Based oThe EPIQ7C color Doppler ultrasound diagnostic instrument  was used for the examination with a X5-1 cardiac probe at a probe frequency of 1.0–5.0 MHz. The measurements were repeated twice by an experienced cardiac sonographer in accordance with the American Society of Echocardiography criteria .a.Conventional echocardiographyThe routine cardiac parameters were calculated as the average of three consecutive cardiac cycles. All participants were in sinus rhythm at the time of echocardiography. LVEF, left ventricular end-systolic volume, and left ventricular end-diastolic volume were measured using the Simpson biplane method under hemodynamically stable conditions. Interventricular septal thickness was measured using M-mode ultrasound. Pulse wave Doppler was used to measure the forward flow velocity of the mitral valve E-peak (early diastole) and A-peak (late diastole), and the E/A ratio was calculated.b.Two-dimensional speckle tracking echocardiography analysisAll participants were instructed to hold their breath during image acquisition to obtain high-quality images. While acquiring images, an electrocardiograph was connected to track the left ventricle membrane from the parasternal long-axis and short-axis views and apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) views. Two-dimensional echocardiographic images of 3–5 complete cardiac cycles were obtained. The images were input into the Qlab13.0 workstation to automatically calculate the peak global longitudinal strain (GLS) of the left ventricular global systolic period. The measurements were repeated thrice for each participant and the average was calculated.http://www.R-project.org; The R Foundation for Statistical Computing, Vienna, Austria), Free Statistics software version 1.7.1, and SPSS Statistics version 25.0 , Some graphics were constructed using GraphPad Prism Version 8.0 for Windows . Normally distributed data on Kolmogorov-Smirov test were expressed as means ± standard deviation, and t test was used for comparisons between two groups. Data with skewed distributions were expressed as medians (interquartile range); the rank sum test was used to compare two groups. Count data were expressed as the number of cases (n) and percentages (%), and were compared using the chi-square test. Pearson and Spearman correlation analyses were used to assess correlations between factors. Multicollinearity between covariates was assessed using variance inflation factor and tolerance values.All statistical analyses were performed using R version 3.3.2 . Model 5 was adjusted for the clinically meaningful Gensini scores.We assessed the association between the TG levels and the risk of GLS impairment using a multivariate logistic proportional hazards regression model by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Five models were used to adjust for potential confounders. Model 1 was the crude model. Model 2 was adjusted for age, sex and comorbidities including hypertension. Model 3 was further adjusted for the risk factors when added it to this model, changed the matched odds ratio by at least 10 percent in model 1 . Model 4 further adjusted the risk factors when in univariate analysis, their 2), hypertension (no vs. yes), diabetes (no vs. yes), and hypertriglyceridemia (no vs. yes). Interactions between subgroups were assessed using the likelihood ratio test.In the subgroup analysis, we examined the relationship between GLS impairment and the TG levels according to age (≤ 65 years vs.> 65 years), sex , BMI . Our sample size calculations were based on sample sizes from similar studies , 25 and Of the 138 coronary heart disease patients initially evaluated, 14 with ejection fraction< 50%, five with missing ultrasound data, four with persistent atrial fibrillation, two with dilated cardiomyopathy, six with missing lipid data were excluded, and five with missing blood glucose data. A total of 102 patients met the inclusion criteria. p = 0.037). There were no significant differences between the two groups in terms of gender, age, BMI, and the frequency of diabetes and hypertension. TG and TC were significantly higher in the hypertriglyceridemia group compared to the non-hypertriglyceridemia group (p < 0.001). There were no significant differences in LDL-C, fasting blood glucose, HbA1c, and eGFR between the two groups. In addition, there was no significant difference in the GENSINI scores between the groups.The 102 participants had a mean age of 62.9 years and included 59.8% males; 42 (41.2%) were diagnosed with hypertriglyceridemia. We used single regression imputation to fill in missing values on these covariates. p < 0.05; r = 0.376, p < 0.0001). Resting heart rate , TC , fasting blood glucose , and eGFR  were weakly correlated with GLS.P < 0.05 in the univariate regression analysis; or (3) variables that were considered confounders based on existing literature and clinical judgment. Variables with strong multicollinearity were excluded. Based on the results of the tolerance value and variance inflation factor tests, the variables in the final model did not have multicollinearity. Adjusting for confounding factors did not change the association between the TG levels and impaired GLS . For every 1 unit increase in the TG levels, the risk of GLS impairment increased 2.035-fold, indicating that hypertriglyceridemia maybe an independent risk factor for impaired left ventricular GLS in coronary heart disease patients.P for interaction = 0.002). The association between the TG levels and the risk of GLS impairment was more significant in female patients than in male patients: OR 1.29 (95% CI 1.08–1.55) for female vs. 1.01 (95% CI 0.94–1.07) for male. The subgroup analysis showed that the association between the TG levels and GLS impairment was similar across patient subgroups stratified by age, gender, hypertension, diabetes mellitus, hypertriglyceridemia and BMI .A forest plot of the subgroup analysis is shown in The present study found that CHD patients with hypertriglyceridemia had lower myocardial longitudinal strain levels. There was a correlation between TG levels and GLS reduction in coronary heart disease patients. After adjusting for the effects of confounding factors, such as fasting blood glucose, TC, resting heart rate, GENSINI score, and eGFR, using multivariate logistic regression analysis, the correlation still exists, indicating that hypertriglyceridemia maybe an independent risk factor for myocardial structural changes in pre-HF coronary heart disease patients.p < 0.20); both of them caused myocardial structure and function impairments in pre-HF coronary heart disease patients (p < 0.05). High TG and high fasting blood glucose levels are the main components of metabolic syndrome (The present study also found a potential correlation between high TG and high fasting blood glucose levels (syndrome , indicatsyndrome , 29. Metsyndrome , 31. Inssyndrome .The mechanism by which hypertriglyceridemia causes early changes in the left ventricular structure in coronary heart disease patients is currently unknown. The relationship between hypertriglyceridemia and left ventricular function may be direct, indirect, or a combination. High serum TG levels directly cause myocardial steatosis and lipotoxic injury , 34. SpeMeanwhile, hypertriglyceridemia also acts on the vasculature, leading to heart failure indirectly by mediating vascular remodeling and increasing the risk of ischemic cardiomyopathy . When frCoronary heart disease patients with hypertriglyceridemia also had higher resting heart rates. A hypertriglyceridemic state reduces vagal excitability, which increases the basal heart rate , 47. SomThe present study did not find a correlation between BMI and early ventricular structural and functional changes in coronary heart disease patients. To the best of our knowledge, hypertriglyceridemia and obesity are closely related, and obesity may be an independent risk factor for reduced myocardial strain . A correThe present study also found that in sex-stratified subgroups, the association between TG levels and the risk of impaired GLS in CHD patients was stronger in women than in men. Our findings are consistent with previous studies that have identified sex differences in triglyceride metabolism , 60. TheThis study had some limitations. First, as this was a cross-sectional study with a small sample size, no causal relationships could be established. Unmeasured potential confounding factors may exist when assessing the effect of an increased TG levels on the GLS of the left ventricle in patients with coronary heart disease; however, the results of our sensitivity analysis showed that the results were stable across different subgroups. Meanwhile, this study focused on the effects of hypertriglyceridemia on left ventricular systolic function in coronary heart disease patients. In future research, stratified strain may be considered and left ventricular diastolic function may be further evaluated. In addition, this study used two-dimensional speckle tracking technology to obtain ultrasound images; image quality was limited by the conditions of the acoustic window, which may be difficult to view in the case of a low echo window.In patients with coronary heart disease, hypertriglyceridemia maybe cause early damage to the global longitudinal strain of the left ventricle . An opti


The following parameters decreased significantly from the initial assessment to follow-up: stroke volume , cardiac output , and LV mass index . The 10-year ASCVD risk score also remained unchanged between the two timepoints . (4) Conclusion: Myocardial T1 values and ECVFs were stable over time in the same middle-aged men.(1) Background: Longitudinal changes in myocardial T1 relaxation time are unknown. We aimed to assess the longitudinal changes in the left ventricular (LV) myocardial T1 relaxation time and LV function. (2) Methods: Fifty asymptomatic men  who underwent 1.5 T cardiac magnetic resonance imaging twice at an interval of 54 ± 21 months were included in this study. The LV myocardial T1 times and extracellular volume fractions (ECVFs) were calculated using the MOLLI technique (before and 15 min after gadolinium contrast injection). The 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score was calculated. (3) Results: No significant differences in the following parameters were noted between the initial and follow-up assessments: LV ejection fraction (65.0 ± 6.7% vs. 63.6 ± 6.3%,  Diffuse myocardial fibrosis can manifest in various diseases, such as hypertension, aortic stenosis, cardiomyopathy, myocarditis, diabetes mellitus, and heart failure ,2. The mT1 times and ECVF might change in relation to the progression of diseases or durations of disease, as mentioned above. However, threshold values for myocardial abnormalities have not been established according to age and sex to date. Furthermore, it has not been clearly determined whether alterations in T1 times or ECVF in follow-up examinations suggest disease progression and not a change due to aging.Rosmini et al. revealed that T1 mapping techniques yielded inconsistent results regarding the native T1 time with respect to increasing age, and that the ECVF was independent of age for all mapping techniques . Howevern = 2528), (2) those lacking an optimal sequence for T1 mapping (n = 60), and (3) women .Our Institutional Review Board Center approved this retrospective study. We evaluated the records of asymptomatic individuals who underwent cardiac magnetic resonance (CMR) imaging for the screening of cardiac diseases, including ischemic heart disease, at our institution between March 2012 and March 2021. We excluded the following subjects: (1) those who only underwent one test without a follow-up examination  were finally included in this retrospective study.They underwent 1.5 T CMR imaging  with a 32-channel phased-array receiver coil twice at a mean interval of 54 ± 21 months . The study selection process for the 2639 subjects screened is shown in All subjects were under fasting state without hydration for eight to ten hours before CMR examinations. Beta-blockers were not administered to them before CMR examinations. CMR scanning was performed using the MOLLI technique . Image acquisition and analysis were performed in accordance with the consensus statement by the Society for Cardiovascular Magnetic Resonance . Two carAn observer with 13 years of experience in the data acquisition and analysis of CMR images analyzed the cardiac short-axis cine images  using an Argus workstation  to calculate the global LV function parameters .The ECVF was calculated using the following formula:The hematocrit values were obtained from venous blood samples collected on the same day that CMR imaging was performed .The Atherosclerotic Cardiovascular Disease (ASCVD) 2013 Risk Calculator  was performed to examine the relationship between the T1 times and cardiovascular risk factors. Specifically, a correlation analysis was performed between the myocardial T1 times in the pre-contrast assessment and the following risk factors in the initial and follow-up assessments: age, risk score, LV ejection fraction, end-systolic LV volume (ESV), end-diastolic LV volume (EDV), LV mass index, and LV mass/end-diastolic volume ratio. Additionally, a correlation analysis was also performed on the difference between the myocardial T1 times or ECVF and the following risk factors: age, risk score, LV ejection fraction, ESV, EDV, LV mass index, and LV mass/end-diastolic volume ratio. Finally, changes in the T1 times and ECVF were correlated with changes in the LV function parameters, risk scores, and study duration. We performed a Bonferroni correction to adjust p-values to account for potential spurious significant results when probing for simple relationships with multiple variables.Intra-observer and inter-observer variabilities in two observers were measured by calculating intraclass coefficients (ICCs) for LV function parameters, T1 times, and ECVF in 20 randomly-selected examinations for analyses at one-month intervals.The baseline characteristics of the 50 men and their status with respect to the cardiovascular risk factors are summarized in Significant late gadolinium enhancement, indicative of old myocardial infarction or cardiomyopathy, was not present in all subjects.p = 0.12), LV mass/end-diastolic volume ratio , native T1 times , post-contrast T1 times with 15 min delay , and ECVF  (p = 0.01), cardiac output , and LV mass index . The 10-year ASCVD risk score did not change significantly during follow-up .No significant differences were noted between the initial and follow-up assessments with respect to the LV ejection fraction  . Howevern = 27) and the long-term follow-up group  with respect to the change (Δ) in the native T1 mapping values , Δpost-contrast T1 value , and ΔECVF .Group difference analysis using the follow-up interval based on the mean follow-up interval of 54 months  revealedn = 29) and the higher-aged group  with respect to the Δnative T1 value , Δpost-contrast T1 value , and ΔECVF   .p = 0.006), and EDV (p < 0.001) at the initial assessment. No significant correlation was observed between the myocardial T1times and the cardiovascular risk factors and LV function parameters at the initial and follow-up assessments. Additionally, no significant correlation was observed between the myocardial ECVF and the cardiovascular risk factors and LV function parameters at the follow-up assessments.Results of the analysis of the correlation between the myocardial T1 values/ECVF and the risk factors are summarized in p < 0.001), while the correlations were insignificant between other LV function parameters and changes in T1 times or ECVF.Correlation analysis showed a significant negative correlation (r = −0.47) between changes in the myocardial T1 time and changes in the EDV  by Rosmini et al. , Kim et In some studies, the T1 time decreased with increasing age in women, whereas the ECVF was not influenced by aging. Rosmini et al. reported that the native myocardial T1 time decreased slightly, while the ECVF remained unaffected, with increasing age . AccordiIn a study on healthy individuals, Piechnik et al. observed no age dependency of the myocardial T1 values in individual and age group-based regression analyses . In theip < 0.1 for all) but not at 3 T; this association was stronger in the male cohort .In one study, the T1 values were similar across the age groups regardless of the field strength used (1.5 T vs. 3 T) . In anotAs for the left ventricular function parameters, according to a meta-analysis of normal reference ranges, men have larger EDV and ESV indices and a higher LV mass than women . The LV According to our analysis, stroke volume and cardiac output were found to decrease with aging. One study reported a significant relationship between age and cardiac output, showing a reduction of approximately 1 percent per year . They exOnly age and LVEDV were seen to be correlated negatively with ECVF at the initial assessment, while ASCVD risk scores, LVEF, LV mass, ESV, and LV mass/EDV ratio were not correlated with T1 times or ECVFs. Again, only changes in LVEDV were seen to be negatively correlated with changes in T1 values. Our study results suggest that most LV function parameters do not change over time regardless of changes in T1 times or ECVF in asymptomatic middle-aged men in less than 5 years. According to a meta-analysis , both meThis study had several limitations. First, it was performed retrospectively at a single center. Therefore, our findings should be validated in a larger prospective study. Second, due to the low rate of examinations in women, our study only included men. The higher native T1 time and ECVF in women than in men in several studies suggest the influence of sex hormones on the myocardial structure and function ,15,18,19The myocardial T1 relaxation times and ECVF were stable over time in the same individuals. Changes in the EDV were negatively correlated with changes in the myocardial T1 times.


The application value of T2 mapping in evaluating endometrial carcinoma (EMC) features remains unclear. The aim of the study was to determine the quantitative T2 values in EMC using a novel accelerated T2 mapping, and evaluate them for detection, classification,and grading of EMC.Fifty-six patients with pathologically confirmed EMC and 17 healthy volunteers were prospectively enrolled in this study. All participants underwent pelvic magnetic resonance imaging, including DWI and accelerated T2 mapping, before treatment. The T2 and apparent diffusion coefficient (ADC) values of different pathologic EMC features were extracted and compared. Receiver operating characteristic (ROC) curve analysis was performed to analyze the diagnostic efficacy of the T2 and ADC values in distinguishing different pathological features of EMC.p < 0.05). The T2 and ADC values were significantly different between endometrioid adenocarcinoma (EA) and non-EA (both p < 0.05) and EMC tumor grades  but not for EMC clinical types (both p > 0.05) and depth of myometrial invasion (both p > 0.05). The area under the ROC curve (AUC) was higher for T2 values than for ADC values in predicting grade 3 EA . When combined T2 and ADC values, the AUC for predicting grade 3 EA showed a significant increase to 0.947 (p = 0.03) compared with those of ADC values. The T2 and ADC values were negatively correlated with the tumor grades .The T2 values and ADC values were significantly lower in EMC than in normal endometrium (bothl Quantitative T2 values demonstrate potential suitability in discriminating between EMC and normal endometrium, EA and non-EA, grade 3 EA and grade 1/2 EA. Combining T2 and ADC values performs better in predicting the histological grades of EA in comparison with ADC values alone. The treT2 mapping is a quantitative MRI method that measures the transverse relaxation time (T2) of various tissues, which is displayed as image voxels on parametric maps . The T2 This study aimed to determine the quantitative T2 values for endometrial cancer and normal endometrium using a novel accelerated T2 mapping, and their evaluation with regard to detection, classification, and grading of endometrial cancer in comparison to the corresponding apparent diffusion coefficient (ADC) value.22.1This prospective study was approved by the institutional review board of our hospital. Written informed consent was obtained from all study participants. This study included 109 patients who were diagnosed with EMC between December 2019 and October 2021 at our hospital. The inclusion criteria were as follows: (1) patients without dilation and curettage, surgery, or other related treatments before the MRI examination; (2) patients suspected of having EMC; (3) patients with data from all MRI sequences relevant to this study; (4) patients that underwent surgical treatment within two weeks after the MRI examination; and (5) patients with a confirmation of EMC based on the histopathologic examination after surgery. The exclusion criteria were as follows: (1) patients with small lesions (n = 15), (2) poor image quality that did not meet the requirements for analysis (n = 12), (3) histologic subtype or pathologic grading that could not be determined by the histopathologic examination (n = 15), and (4) patients treated with radiotherapy and chemotherapy before the MRI examination (n = 11). Finally, 56 patients  were enrolled in the study. Among these, 35.7% (20/56) were premenopausal women, and 64.3% (36/56) were postmenopausal women. The mean time interval between MRI acquisitions and surgery was 7.5 days (range: 2–14 days). The study also included 17 age-matched healthy volunteers during the same period, and none of the volunteers showed any abnormalities in the uterus or adnexa according to the ultrasound or MRI examinations. The mean age of the volunteers was 53 ± 10 years (range: 27–64 years). Among the 17 healthy volunteers, 41.2% (7/17) were premenopausal women, and 58.8% (10/17) were postmenopausal women.2.22. T2 mapping was performed using the prototypic multiecho sequence accelerated 10-fold with the GRAPPATINI technique by using a parallel imaging factor of 2 and an undersampling factor of 5. The apparent diffusion coefficient (ADC) and T2 parametric maps were automatically generated inline after data acquisition. The MRI sequence parameters are shown in The pelvic MRI examinations were performed using a 3T MRI scanner  equipped with an 18-channel phased-array body coil. The patients were scanned in a head-first supine position. All patients of childbearing age and healthy volunteers underwent MRI examinations between days 5 and 14 after the end of menses, whereas the timing of the MRI examination was not restricted for the menopausal patients and the healthy volunteers . The pat2.3syngo.via software . Two radiologists with eight and five years of experience in pelvic MRI independently performed the quantitative analysis by using the double-blinded method. Statistical analysis was performed using the average values of the measurements by the two radiologists. The EMC lesions, junctional zone (JZ), and outer myometrium (OMM) were identified on the ADC and the T2 maps on the basis of the T2-weighted imaging (T2WI) and DWI scans, respectively. The regions of interest (ROIs) were manually drawn for the EMC lesions, JZ, and OMM of all patients with EMC, and each ROI included more than 25 pixels. Furthermore, the shape and position of the ROIs on the ADC and the T2 maps were consistent. The ROIs for the EMC lesions were drawn along the largest cross-section of the lesions. In the case of thin or unclear JZ, the ROIs were drawn around the muscle tissue adjacent to the EMC lesion   . The cys2.4All 56 patients with EMC underwent standard surgery consistent with the current FIGO staging criteria . The his2.5H test and the Mann–Whitney U test, and the Bonferroni correction method was used to obtain the adjusted p values. Receiver operating characteristic (ROC) curve analysis was performed to analyze the diagnostic efficacy of the T2 and ADC values. Each parameter’s discriminating power was quantified using the area under the ROC curve (AUC). The DeLong test was performed to compare the differences in the diagnostic efficacy of each parameter. Pearson’s correlation coefficient was used to evaluate the correlation between the T2 and ADC values. Spearman correlation was applied to analyze the association between the T2 and ADC values with different histological grades. The intraclass correlation coefficient (ICC) was used to evaluate the agreement in the quantitative measurements between the two radiologists, in which ICC ≥ 0.75 was considered a good agreement. Also, a p value < 0.05 was considered statistically significant.SPSS 21.0  and MedCalc  were used for the statistical analyses. The Shapiro–Wilk normality test was used to determine normal or skewed data distribution for each group. The nonnormally distributed data were compared using the Kruskal–Wallis 33.1p = 0.421). The clinical characteristics of the patients are shown in This study enrolled 56 patients with a postoperative pathologic diagnosis of EMC and 17 healthy volunteers. The mean ages of the patients with EMC (55 ± 7 years) and healthy volunteers (53 ± 10 years) were not significantly statistically different  and significantly higher than those for the JZ (p < 0.001); however, significant differences were not observed between the T2 values of the EMC and the OMM (p = 0.845) (p < 0.001) (p < 0.001) (p < 0.001). Further, the ICC analysis showed a good agreement between the two radiologists for the T2 and ADC values of the EMC, normal endometrium, JZ, and OMM ,and between superficial and deep myometrial invasion  did not show any statistically significant differences. The T2 and ADC values of the endometrioid adenocarcinoma (EA) were significantly lower than those of the non-EA tumors . Moreover, a quantitative analysis of the EA tumors with different pathologic grades demonstrated that the T2 values were significantly lower for grade 3 (G3) EA than those for grade 1 (G1) EA or grade 2 (G2) EA (both p < 0.017) (p > 0.05). Furthermore, the ADC values for the G3 EA were significantly lower than those for the G1 EA . When combined T2 and ADC values, the AUC showed a slight increase to 0.992 with no significant difference . The AUC values for the T2 and ADC values in distinguishing between the EA and non-EA tumors were 0.798 and 0.705, respectively (p = 0.395). When combined T2 and ADC values, the AUC showed a slight increase to 0.817 with no significant difference .The AUC values for predicting G3 EA were 0.939 for the T2 values and 0.764 for the ADC values (p = 0.048), that is, however,slightly less significant. When combined T2 and ADC values, the AUC showed a significant increase to 0.947 compared with the ADC values  are listed in 3.5The Pearson’s correlation analysis showed that there was a significant positive correlation between the T2 and the ADC values  and poorly differentiated (G3) EA. The combination of T2 and ADC values resulted in a notable increase in the AUC for predicting grade 3 EA, when compared with ADC values alone. Furthermore, T2 values show a strong inverse correlation with pathologic EA grading.Regarding uterine MRI, conventional pelvic MRI sequences have been used to characterize the signal intensity of normal endometrium, myometrium, and cancerous lesions by visual analysis. However, precise discernment is hindered when the signal difference between the cancerous lesion and adjacent tissue is small. T2 mapping can be used to analyze the changes in the composition of the tissue by measuring the T2 relaxation time, which is related to the water content in the tissue . PreviouOur study demonstrated that quantitative T2 values could differentiate EMC from normal endometrium, which was consistent with tumors in other organs , 16, 17.EMC is classified into EA, serous uterine carcinoma, undifferentiated carcinoma, uterine carcinosarcoma, and clear cell carcinoma by the 2014 World Health Organization Classification of Tumors of Female Reproductive Organs . Among tThe pathologic grade of EMC is a major prognostic factor that affects the survival rates of patients with EMC . In the The T2 values in this study were obtained on the basis of a novel fast imaging technique  with a parallel acquisition factor of two and an undersampling factor of five. The T2 maps were reconstructed with a 10-fold undersampled k-space, which significantly reduced the acquisition time and improved the clinical utility of T2 mapping. The broad clinical application of conventional T2 mapping is limited by long image acquisition times and potential motion artifacts because of patient movements. Previous studies have confirmed that the T2 values obtained with the GRAPPATINI technique are comparable with those obtained using the conventional multiecho spin echo sequence , 11, 23.This study has a few limitations. The sample size of the study cohort was small. Furthermore, the number of cases in the non-EA group were significantly low. Therefore, analysis of the T2 values for rare tumors such as serous uterine carcinoma, uterine carcinosarcoma, and undifferentiated carcinoma was not feasible. Also, future large-scale studies are necessary to confirm our results and characterize different subgroups of EMC.In summary, our study demonstrated that the quantitative T2 values obtained from accelerated T2 mapping were useful for preoperative diagnosis and the pathologic classification and grading of EMC.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by The First Affiliated Hospital of Zhengzhou University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.TH, TK, JZ, FQ: Conceptualization, Methodology, Software, Validation. ZZ, JL, WW: Data curation, Writing- Original draft preparation and Editing. YZ, JC: Supervision.