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Abstract Echocardiographic assessment of left ventricular function is crucial in NICU. The study aimed to compare the accuracy and agreement of global longitudinal strain (GLS) with conventional measurements. Real-life echocardiograms of neonates receiving intensive care were retrospectively reviewed. Shortening fraction (SF), ejection fraction (EF) and S’ measurements were retrieved from health records. GLS was calculated offline from stored images. The association with stroke volume indexed for body weight (iSV) was evaluated by regression analysis. The diagnostic ability to identify uncompensated shock was assessed by ROC curve analysis. Cohen's κ was run to assess agreement. 334 echocardiograms of 155 neonates were evaluated. Mean ± SD gestational age and birth weight were 34.5 ± 4.1 weeks and 2264 ± 914 g, respectively. SF, EF, S’ and GLS were associated with iSV with R2 of 0.133, 0.332, 0.252 and 0.633, (all p

Echocardiographic assessment of left ventricular function is crucial in NICU. The study aimed to compare the accuracy and agreement of global longitudinal strain (GLS) with conventional measurements. Real-life echocardiograms of neonates receiving intensive care were retrospectively reviewed. Shortening fraction (SF), ejection fraction (EF) and S' measurements were retrieved from health records. GLS was calculated offline from stored images. The association with stroke volume indexed for body weight (iSV) was evaluated by regression analysis. The diagnostic ability to identify uncompensated shock was assessed by ROC curve analysis. Cohen's κ was run to assess agreement. 334 echocardiograms of 155 neonates were evaluated. Mean ± SD gestational age and birth weight were 34.5 ± 4.1 weeks and 2264 ± 914 g, respectively. SF, EF, S' and GLS were associated with iSV with R2 of 0.133, 0.332, 0.252 and 0.633, (all p <.001). Including all variables in a regression model, iSV prediction showed an adjusted R2 of 0.667, (p <.001). GLS explained 73% of the model variance. GLS showed a better ability to diagnose uncompensated shock (AUC 0.956) compared to EF, S' and SF (AUC 0.757, 0.737 and 0.606, respectively). GLS showed a moderate agreement with EF (κ =.500, p <.001) and a limited agreement with S' and SF (κ =.260, p <.001, κ =.242, p <.001). GLS was a more informative index of left ventricular performance, providing the rationale for a more extensive use of GLS at the cotside. [ABSTRACT FROM AUTHOR]

Background Single photon emission computed tomography (SPECT) has been extensively used to evaluate left ventricular (LV) systolic function. However, there are few studies comparing diastolic parameters based on SPECT with established reference values for the assessment of LV diastolic function. Objective To evaluate the sensitivity of SPECT-estimated LV diastolic parameters in coronary heart disease with left ventricular end-diastolic pressure (LVEDP) examined by left cardiac catheterization as the gold standard for comparison. Methods Totally 97 patients with suspected or comfired coronary artery disease were prospectively selected from Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University from September 2021 to January 2022. All of them performed echocardiography, coronary angiography with left cardiac catheterization〔estimating LVEDP, left ventricular end-systolic volume (LVESV) , left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) 〕, SPECT〔estimating LVESV', LVEDV', LVEF', peak filling rate (PFR) , the first third filling fraction (1/3FF) , the first third filling rate (1/3FR) , mean filling rate (MFR) , and peak filling time (TPF) 〕within one to three days of admission. Based on coronary angiography data, all patients had at least one sub-epicardial coronary artery stenosed to over 50%. The general data, laboratory indices, and indices of left heart function were compared between patients with normal LV diastolic function (n=50, LVEDP

Purpose: The new version of EchoPAC platform was recently developed by General Electronics (GE) to provide 'vendor-independent' full-myocardial-layer left ventricular (LV) global longitudinal strain (LV-GLS). The agreement of the LV-GLS by two vendor-independent software platforms was investigated under diverse clinical situations. Methods: Two-dimensional speckle-tracking LV-GLS was separately measured by two software platforms. LV-GLS values were compared as default setting of each software platform (GE full-myocardial-layer [GE-Full], and TomTec endocardial-layer [TomTec-Endo]). Agreements according to various conditions and type of echocardiography vendors were evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC). Inter-observer reproducibility of each software platform was assessed, and agreements were further evaluated in various subgroups. Results: One hundred five subjects were initial candidates for the current study (normal LV function without any cardiac pathology [n = 25], hypertrophic cardiomyopathy [n = 40], dilated cardiomyopathy [n = 25], or restrictive cardiomyopathy [n = 15]). After excluding seven subjects with inadequate tracking quality, 98 subjects were finally analyzed. The average LV-GLS was lower in GE-Full than in TomTec-Endo. Agreement between GE-Full and TomTec-Endo was excellent in general; while the greatest bias was observed in the hypertrophic cardiomyopathy group, with TomTec-Endo exhibiting greater LV-GLS values than GE-Full (bias -1.71, limits of agreement -6.02 to 2.59). Both platforms showed excellent inter-observer reproducibility (GE-Full, ICC 0.99; TomTec-Endo, ICC 0.91), and were in good agreements regardless of the echocardiography vendors or subgroups according to age, heart rate, myocardial wall thickness, or LV ejection fraction. Conclusions: LV-GLS by GE-Full showed excellent agreement with that by TomTec-Endo under various cardiac conditions. [ABSTRACT FROM AUTHOR]

Background: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear., Methods and Results: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort., Conclusions: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Aims: Cardiac energy metabolism is perturbed in ischaemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure., Methods and Results: C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and β-hydroxybutyrate (β-OHB) (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. Mice with heart failure exhibited a 56% drop in ejection fraction, which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet, no increase in overall cardiac energy production was observed, and instead, there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet., Conclusion: We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischaemic heart and a decrease in insulin-stimulated glucose oxidation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms., Methods and Results: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T-cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation., Conclusion: Our findings revealed that LIPUS uses an EVs-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM., Competing Interests: Conflict of interest: none declared, (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance. NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.

Background: Non-ST-segment elevation myocardial infarction (NSTEMI) is more common than ST-segment elevation myocardial infarction (STEMI), consisting of 60-70% of myocardial infarctions. When left ventricular (LV) pressure increases during early systole, regionally ischaemic myocardium with a reduced active force exhibit stretching. The aim of this study was to evaluate the role of this parameter in determining high risk angiographic territory involvement in NSTEMI patients., Results: This study was a descriptive correlational research that was conducted on 96 patients with NSTEMI and a left ventricular ejection fraction ≥ 50% who underwent coronary angiography (CAG). Patients were divided into two groups based on having or not having high risk angiographic territory involvement in CAG. All patients underwent a transthoracic echocardiography during the first day of hospitalization and early systolic lengthening (ESL), duration of ESL (DESL), left ventricular global longitudinal strain (LVGLS), pulsed-wave Doppler-derived transmitral early (E wave) and late (A wave) diastolic velocities, and tissue-Doppler-derived mitral annular early diastolic (e') and peak systolic (s') velocities were determined. The results of this study showed DESL, DESL LAD , and DESL LCX were longer in high risk angiographic territory group than other one (P value 0.016, 0.044, and 0.04, respectively). The logistic regression analysis showed among different variables, only age and ESL LAD had an independent association with high risk angiographic territory involvement (P = 0.01, odds ratio [OR] 1.09, 95% CI 1.021-1.164, and P = 0.024, odds ratio [OR] 1.243, 95% CI 1.029-1.50, respectively)., Conclusions: Assessment of myocardial ESL LAD by speckle-tracking echocardiography may be helpful in predicting high risk angiographic territory involvement in patients with NSTEMI. Indeed, a higher value can be considered as a high risk parameter which may show benefit of an early invasive strategy versus a conservative approach., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Objective: To explore the correlation between left ventricular global longitudinal strain (LVGLS) and major adverse cardiovascular event (MACE) occurrence in patients with end-stage renal disease (ESRD)., Methods: From January 2019 to December 2023, ESRD patients undergoing maintenance dialysis and LVGLS measurement admitted to the First People's Hospital of Lanzhou City were selected as subjects. They were followed up for 12 months to record the occurrence of MACEs, and divided into MACE group and non-MACE group according to MACE presence or absence., Results: A total of 158 ESRD patients were included, with 32 patients in the MACE group and 126 patients in the non-MACE group. In the MACE group, high-sensitivity C-reactive protein (hs-CRP) level, peak troponin T (TNT) and the ratio of early diastolic mitral inflow velocity to early diastolic septal mitral annulus velocity (E/e') were higher, while hemoglobin, left ventricular ejection fraction (LVEF) and absolute LVGLS were lower compared with the non-MACE group (P < 0.05). Multivariate COX regression analysis revealed that LVGLS (HR = 1.06, 95% CI 1.02-1.10) and hs-CRP (HR = 1.17, 95% CI 1.23-1.31) were independent predictors of MACE occurrence in ESRD patients (P < 0.05). The area under the ROC curve (AUC) for MACE occurrence within 12 months was 0.83 (95% CI 0.74-0.95), with a sensitivity of 89.9% and a specificity of 76.8%. The MACE-free survival rate in the high LVGLS group was higher compared to the low LVGLS group (P < 0.05)., Conclusion: Reduced LVGLS is an independent risk factor for MACE occurrence in ESRD patients within 12 months and a good prognostic indicator., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Postsystolic shortening (PSS) is one of the proposed quantitative measures to predict myocardial ischaemia in the stress echocardiographic (SE) evaluation. It is previously known that hypo-/akinesia (HA) correlates well with coronary stenosis. However, some patients undergoing SE only present with PSS, and their risk of significant coronary stenosis is less clear. This study aimed to evaluate the association between PSS and significant coronary stenosis compared with HA., Methods: This was a retrospective cohort study at the hospital of S:t Görans, Stockholm, Sweden. All patients who underwent SE to investigate inducible ischaemia between 1 January 2018 and 15 October 2021 were eligible for inclusion. Exclusion criteria were normal SE and inconclusive test. Pathological SE were divided into two groups, patients with HA and those with PSS. Outcome was significant coronary artery stenosis visualized by invasive coronary angiography., Results: The final study population consisted of 108 patients (73 PSS, 35 HA). The presence of HA was associated with a higher risk of significant stenosis compared to those with PSS (63% vs. 23%, p < 0.001). This relationship was observed among males (p < 0.001), but not among females (p = 0.133). Nonsignificant stenosis trended to be more common among patients with PSS (21% vs. 6%, p = 0.053) CONCLUSIONS: The finding of PSS without HA was associated with a lower risk of significant coronary stenosis than HA. However, patients with PSS still often had nonsignificant coronary stenosis and PSS in the evaluation for nonobstructive coronary artery disease (CAD) should be further investigated., (© 2024 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Aims: Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and clinical outcomes of patients with AF vary depending on its subtype. While AF progression characterized by the transition from paroxysmal AF to persistent AF is sometimes observed, the incidence and clinical impact of AF progression in patients with HFpEF remain to be explored., Methods and Results: We enrolled patients with HFpEF and paroxysmal AF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. AF progression was defined as the transition from paroxysmal AF to persistent AF. A total of 718 patients (median age: 72 years, 36% were female) were enrolled. For a median follow-up of 6.0 years (interquartile range: 3.0-10.2 years), AF progression occurred in 105 patients (14.6%), with a cumulative incidence of 16.7% at 10 years. In the multivariable Cox proportional hazards model, previous hospitalization for heart failure [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.16-2.60; P = 0.007] and left atrial diameter (per 5-mm increase) (HR 1.37, 95% CI 1.20-1.55; P < 0.001) were significantly associated with AF progression. Furthermore, AF progression was significantly linked to worsening heart failure (adjusted HR 1.68, 95% CI 1.18-2.40; P = 0.004). Notably, 27 cases (26%) of worsening heart failure occurred within 1 year following AF progression., Conclusion: In patients with HFpEF, AF progression is significantly associated with adverse outcomes, particularly worsening heart failure. An increased risk is observed in the early phases following progression to persistent AF., Registration: Clinical Trials.gov Identifier: NCT00418041., Competing Interests: Conflict of interest: H.S. has received lecture fees from Bayer Yakuhin (Osaka, Japan) and Daiichi Sankyo (Tokyo, Japan). S.Y. has received lecture fees from Bristol-Meyers (Tokyo, Japan), Bayer Yakuhin (Osaka, Japan) and Daiichi Sankyo (Tokyo, Japan). T.N. has recieved Grants-in-Aid for Scientific Research (22K08092) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and personal fees from Bayer Yakuhin (Osaka, Japan), Medtronic Japan (Tokyo, Japan), and Biotronik Japan (Tokyo, Japan). The remaining authors have no conflicts of interest to be disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The application of z-scores in normalizing the cardiac size function and structural dimension will be of immense benefit to the clinician, especially in evaluating children with cardiac anomalies. However, heterogeneity in the obtained z- score results is high, thus a subgroup analysis by region (or continent) to assist healthcare practitioners is necessary., Objectives: The review aimed to ascertain the overall mean z-scores for cardiac structures and function., Methods: A thorough search of several databases, EMBASE, PubMed/MEDLINE, and Google Scholar was made. Articles published between January 1999 and December 2023 were recruited, of which the last search was done in December 2023. Keywords used in the search were "z-scores", Children; echocardiography; cardiac structures; cardiac function; and body surface area (BSA)". We restricted our search to children. Besides, additional relevant articles were manually searched. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to highlight selected studies using a pre-defined search protocol. The I 2 statistics were used to ascertain statistical heterogeneity., Results: Two hundred and forty citations were identified in our search strategy, of which a total of 34 studies were identified. Twenty-four were excluded from the thirty-four studies. A total of 11 studies met our inclusion criteria shown in the PRISMA. Apart from different z scores reading obtained from various countries and regions, some authors focused on few cardiac parameters while others were exhaustive. The mean z-scores of the cardiac structures from various countries/regions range as follows; The range of Z scores obtained by different studies and regions above are as follows; MV;-1.62-0.7 AV: -1.8 -0.5 TV: -2.71 -0.7; PV ; -1.52- (-0.99) MPA; -1-81 -0.8 LPA;-1.07-0.4; RPA;-0.92- 0.1 IVSD; -0.1.77-1.89 LVPWD; -0.12-1.5 LVPWS; -0.1-0.15 LVPWS; 0.03-0.18 LVIDD; -1.13- (-0.98) LVIDS; -0.84-10.3 respectively. The mean z-score from the pooled studies showed mitral valve diameter as -0.24 ± 0.9 and pulmonary valve annuls as -1.10 ± 0.3. The left ventricular end diastolic diameter is -0.93 ± 0.3 while the left ventricular end systolic diameter is -0.05 ± 0.5. The total pooled sample size of the eleven included studies was 9074 and the mean at 95% interval was 824.9 ± 537.344. The pooled mean is presented under the model of the Mean raw (MRAW) column. The heterogeneity discovered among the selected studies was statistically significant., Conclusion: Due to heterogeneity involved in the reportage of the z-scores of cardiac structures and function, it may be necessary for every region to use their z-scores domiciled in their locale. However, having a pooled mean z-score of cardiac structures and function may be useful in the near future., (© 2024. The Author(s).)

Background: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell-derived exosome nebulization therapy (SCENT)., Methods: Stem cell-derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging., Results: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC- Cd36 fl/- conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall., Conclusions: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC- Cd36 fl/- mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets., Competing Interests: Dr Li is currently an employee of Xsome Biotech Inc. Dr Cheng is a cofounder and equity holder of Xsome Biotech Inc. The remaining authors report no conflicts.

Background: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR)., Methods: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain., Results: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values., Conclusions: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD., (© 2024. The Author(s).)

Background: Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear., Methods and Results: We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP., Conclusions: Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

Aims: The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce., Methods and Results: Consecutive patients with HFmrEF [i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of heart failure (HF)] were retrospectively included at one institution from 2016 to 2022. Patients with AF were compared with patients without with regard to the primary composite endpoint of all-cause mortality and HF-related rehospitalization at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses, and propensity score matching. A total of 2148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with a higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months [hazard ratio (HR) = 2.068; 95% confidence interval (CI) 1.802-2.375; P = 0.01], which was confirmed after propensity score matching (HR = 1.494; 95% CI 1.216-1.835; P = 0.01). AF was an independent predictor of both all-cause mortality (HR = 1.340; 95% CI 1.066-1.685; P = 0.01) and HF-related rehospitalization (HR = 2.061; 95% CI 1.538-2.696; P = 0.01). Finally, rhythm control may be associated with lower risk of all-cause mortality compared with rate control for AF (HR = 0.342; 95% CI 0.199-0.587; P = 0.01)., Conclusion: Atrial fibrillation affects 43% of patients with HFmrEF and represents an independent predictor of adverse long-term prognosis., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population., Methods and Results: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1000 accepted. The following red flags were searched: interventricular septal thickness ≥ 12 mm, any echocardiographic, electrocardiographic or clinical hallmark of CA, or high-sensitivity troponin T ≥ 14 ng/L. Individuals with at least one red flag (n = 346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (Grade 3), left ventricular (LV) wall thickening, Grade 2 and 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 1000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a Grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP < 300 ng/L. The prevalence of ATTR-CA in subjects ≥ 65 years was calculated as 0.46% (i.e. 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2)., Conclusion: Wild-type transthyretin cardiac amyloidosis is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease., Competing Interests: Conflict of interest: M.F. has consulting income from Intellia, Novo Nordisk, Pfizer, Eidos, Prothena, Alnylam, Alexion, Janssen, and Ionis. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The overarching goal of cardiogenic shock (CS) therapy is ensuring long-term survival. In recent years, increasing emphasis has been placed on analyzing mechanisms to improve outcomes in CS. This includes averting in-hospital mortality, modifying the disease process by promoting heart recovery while avoiding multiorgan failure, and circumventing complications related to both CS and treatment strategies deployed to treat CS. Heart replacement therapies represent a viable strategy for long-term survival but are restricted to a small, select percentage of patients. In this review we focus on pathophysiology of the shock state, with an emphasis on addressing reversible etiologies contributing to the decompensated state, optimizing physiological factors for recovery, and identifying therapeutic targets to promote recovery. We also review the known predictors of myocardial recovery, regardless of the etiology of CS. Lastly, we highlight the current gaps in knowledge in this field and support additional high-quality studies focusing on myocardial recovery in CS., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Despite significant advancements in managing acute ST-segment elevation myocardial infarctions, the prevalence of heart failure has not decreased. Emerging paradigms with a focus on reducing infarct size show promising evidence in the improvement of the incidence of heart failure after experiencing acute coronary syndromes. Limiting infarct size has been the focus of multiple clinical trials over the past decades and has led to left ventricular (LV) unloading as a potential mechanism. Contemporary use of microaxial flow devices for LV unloading has suggested improvement in mortality in acute myocardial infarction complicated by cardiogenic shock. This review focuses on clinical data demonstrating evidence of infarct size reduction and highlights ongoing clinical trials that provide a new therapeutic approach to the management of acute myocardial infarction., Competing Interests: The other authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) is a morbid and life-threatening disease, arising secondary to abnormalities of cardiac structure and function that lead to adverse LV remodeling. Implementation of medical and device therapies results in significant improvements in patient outcomes that are associated with reverse LV remodeling and improved LV ejection fraction. This review provides an overview of the pathobiology of reverse LV remodeling in animal models and in HFrEF patients. We emphasize the differences between myocardial recovery and remission as well as the fragile nature of maintaining a state of myocardial remission., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Competing Interests: Dr. Bhimaraj is a consultant for Abiomed and Abbott. Dr. Young has no competing interests to declare.

Partial or complete imaging resolution of left ventricular (LV) systolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) has gone by many names in the past few decades, including LV recovery, remission, reverse remodeling, and, most recently, improvement. This phenomenon has been described in a variety of clinical scenarios, including removal of an acute myocardial insult, unloading with durable LV assist devices, and treatment with various devices as well as pharmacotherapies, termed guideline-directed medical therapy (GDMT). Irrespective of definition, systolic improvement is associated with improved clinical outcomes compared to persistent systolic dysfunction. In the past few years, systolic improvement has been distinguished from HFrEF as a new clinical entity referred to as HF with improved EF (HFimpEF). Given the relative novelty of this condition, there is a paucity of data with regard to the clinical trajectory and management of this population. In this review, we describe the history of myocardial improvement terminology and explore notable findings that have led to the delineation of HFimpEF. Additionally, we highlight the importance of understanding LV trajectory and the potential opportunity for new GDMT management for clinicians when treating patients with HFimpEF., Competing Interests: Dr. Wilcox is a consultant for Abbott, Abiomed, Astra Zeneca, and Boehringer Ingelheim. The other authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Reverse remodeling, the overarching concept behind myocardial recovery, describes the process in which the maladaptive cardiac structural and functional alterations are reversed by removing the underlying etiology or by therapy. This review addresses different imaging modalities and biomarkers as possible predictors for reverse remodeling in patients with chronic heart failure. Although echocardiography remains the imaging modality of choice in daily practice, the presence and amount of fibrosis on cardiac magnetic resonance is a better predictor and inversely correlated with the likelihood for reverse remodeling. A decrease in NT-proBNP levels and serum soluble ST3 during follow-up is associated with better clinical and structural outcomes. The role of troponins and galectine-3 is less clear. There is a promising role for microRNAs in the future, although more research is necessary. Accurate predictors of reverse remodeling could help identify patients with an increased likelihood for reverse remodeling and, in turn, improve patient-tailored medicine., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Children hospitalized with acute decompensated heart failure (ADHF) frequently require intravenous vasoactive (IVV) support drugs and are at risk for adverse cardiovascular (ACV) outcomes. We wished to assess whether serial changes in B-type natriuretic peptide (BNP) levels are associated with successful weaning off IVV support and/or prespecified ACV outcomes in children hospitalized with ADHF., Methods and Results: Children hospitalized with ADHF from 2005 to 2021 at our institution were assessed for serial changes in BNP, weaning off of IVV support, and ACV outcomes. Changes in BNP level were evaluated using linear mixed-effects modeling. Bonferroni correction was used to adjust for multiple hypothesis testing. In 131 hospitalizations of children with ADHF, the median age was 4.8 years, with 74% receiving IVV support. ACV outcomes occurred in 62 children. IVV support was associated with lower admission left ventricular ejection fraction (26.7% versus 32%, P =0.002), more severe left ventricular dilation (left ventricular internal diastolic dimension Z score 5.9 versus 3.1, P =0.021) moderate or more mitral regurgitation (41.3% versus 20.6%, P =0.038), and qualitative right ventricular systolic dysfunction (in 45.4% versus 11.8%, P <0.001). Decline in BNP levels was more rapid in patients who were successfully weaned from IVV support (-0.20 versus -0.03 2log pg/mL per day, P <0.001) and in the non-ACV group (-0.17 versus -0.03 2log pg/mL per day, P <0.001). Right ventricular systolic dysfunction was an independent risk factor for ACV (odds ratio, 2.49; P =0.045)., Conclusions: The declining rate of serial BNP levels was associated with weaning from IVV support and no ACV outcomes in children hospitalized with ADHF. Right ventricular systolic dysfunction was associated with ACV outcomes.

Background: Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press-strain loop (LV-PSL)., Methods: Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL < Hb < 9 g/dL. Thirty-three healthy individuals were used as the control (Group A). The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global waste work (GWW), global work efficiency (GWE) were derived using LV-PSL analysis. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal left ventricular systolic function in IDA patients., Results: Compared to group A, GWI and GCW were reduced in group B (both P < 0.01). Compared with groups B and A, GLS, GWI, GCW and GWE, and E/A were all diminished, and GWW, LVEDV, LVESV, and E/mean e' were all increased in group C (all P < 0.01). GLS was positively correlated with GWI, GCW, and GWE (r = 0.679, 0.681, and 0.447, all P < 0.01), and negatively associated with GWW (r = - 0.411, all P < 0.01). For GWI, area under the ROC curve (AUROC) was 0.783. The optimal GWI threshold for detecting abnormal LV systolic function in IDA was1763 mmHg%, with sensitivity of 0.71 and specificity of 0.78., Conclusions: LV-PSL allows noninvasive quantitative assessment of early impaired LV systolic function in IDA patients with preserved LV ejection fraction, and GWI has high sensitivity and specificity compared with other parameters., (© 2024. The Author(s).)

Background: Patients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve., Methods: This study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM-HFpEF (n = 74) and the T2DM-non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain., Results: Patients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P < 0.05). Furthermore, LV longitudinal PSSR, LA reservoir, and LA conduit strain were notably impaired in patients with T2DM without HFpEF compared to controls (all P < 0.05), but LV torsion, LV radial PSSR, and LA booster strain compensated for these alterations (all P < 0.05). Multivariate linear regression analysis demonstrated that LA reservoir and LA booster strain were independently associated with global MPRI (β = 0.259, P < 0.001; β =  - 0.326, P < 0.001, respectively). Further, the difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI. Global stress PI, LA booster, global rest PI, and global MPRI showed high accuracy in diagnosing HFpEF among patients with T2DM (areas under the curve [AUC]: 0.803, 0.790, 0.740, 0.740, respectively)., Conclusions: Patients with T2DM and HFpEF exhibited significant LV systolic and diastolic deformation, decreased LA reservoir strain, severe impairment of myocardial perfusion, and elevated LA booster strain that is a compensatory response in HFpEF. Global MPRI was identified as an independent influencing factor on LA reservoir and LA booster strain. The difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI, suggesting a possible mechanistic link between microcirculation impairment and cardiac dysfunction in diabetes. Myocardial perfusion and LA strain may prove valuable for diagnosing and managing HFpEF in the future., (© 2024. The Author(s).)

Background: A relatively common complication of COVID -19 infection is arrhythmia. There is limited information about myocardial deformation and heart rate variability (HRV) in symptomatic post COVID patients presented by ventricular arrhythmia., Aim of the Study: Our goal was to assess 2D-ventricular strain and heart rate variability indices (evaluated by ambulatory ECG monitoring) in post-COVID-19 patients suffering from ventricular arrhythmia., Methods: The current observational case-control study performed on 60 patients one month after they had recovered from the COVID-19 infection. Thirty healthy volunteers served as the control group. Each participant had a full medical history review, blood tests, a 12-lead surface electrocardiogram (ECG), 24-h ambulatory ECG monitoring, and an echo-Doppler examination to evaluate the left ventricular (LV) dimensions, tissue Doppler velocities, and 2D-speckle tracking echocardiography (2D-STE) for both the LV and right ventricular (RV) strain., Results: Symptomatic post-COVID patients with monomorphic premature ventricular contractions (PVCs) showed a substantial impairment of LV/RV systolic and diastolic functions, LV/RV myocardial performance (MPI) with reduced indices of HRV. Patients with higher versus lower ventricular burden had poorer functional status, higher levels of inflammatory biomarkers and reduced parameters of HRV (New York Heart Association (NYHA) class: 2.1 ± 0.9 vs. 1.5 ± 0.6, p < 0.001, C-reactive protein (CRP): 13.3 ± 4.1 vs. 8.3 ± 5.9 mg/L, p < 0.0001, low frequency/high frequency (LF/HF): 3.6 ± 2.4 vs. 2.2 ± 1.2, p < 0.002, the root mean square of the difference between successive normal intervals (rMSSD): 21.8 ± 4.7 vs. 29.3 ± 14.9 ms, p < 0.039 and the standard deviation of the RR interval (SDNN): 69.8 ± 19.1 vs.108.8 ± 37.4 ms, p < 0.0001). The ventricular burden positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.33, p < 0.001), CRP (r = 0.60, p < 0.0001), while it negatively correlated with LV-global longitudinal strain (GLS) (r = -0.38, p < 0.0001), and RV-GLS (r = -0.37, p < 0.0001)., Conclusions: Patients with post-COVID symptoms presented by ventricular arrhythmia had poor functional status. Patients with post-COVID symptoms and ventricular arrhythmia had subclinical myocardial damage, evidenced by speckle tracking echocardiography while having apparently preserved LV systolic function. The burden of ventricular arrhythmia in post-COVID patients significantly correlated with increased inflammatory biomarkers and reduced biventricular strain., (© 2024. The Author(s).)

Background: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF., Methods: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA 2 DS 2 -VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF., Results: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA 2 DS 2 -VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05)., Conclusions: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group., (© 2024. The Author(s).)

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here., Methods: Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing., Results: Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats., Conclusions: In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities., (© 2024. The Author(s).)

Background: Owing to a lack of data, this study aimed to explore the effect of cardiac preload on myocardial strain in patients with sepsis., Methods: A total of 70 patients with sepsis in intensive care unit (ICU) of a tertiary teaching hospital in China from January 2018 to July 2019 and underwent transthoracic echocardiography were enrolled. Echocardiographic data were recorded at ICU admission and 24 h later. Patients were assigned to low left ventricular end-diastolic volume index (LVEDVI) and normal LVEDVI groups. We assessed the impact of preload on myocardial strain between the groups and analyzed the correlation of echocardiographic parameters under different preload conditions., Results: Thirty-seven patients (53%) had a low LVEDVI and 33 (47%) a normal LVEDVI. Those in the low LVEDVI group had a faster heart rate (121.7 vs. 95.3, p < 0.001) and required a greater degree of fluid infusion (3.67 L vs. 2.62 L, P = 0.019). The left ventricular global strain (LVGLS) (-8.60% vs. -10.80%, p = 0.001), left ventricular global circumferential strain (LVGCS) (-13.83% vs. -18.26%, p = 0.006), and right ventricular global longitudinal strain (RVGLS) (-6.9% vs. -10.60%, p = 0.001) showed significant improvements in the low LVEDVI group after fluid resuscitation. However, fluid resuscitation resulted in a significantly increased cardiac afterload value (1172.00 vs. 1487.00, p = 0.009) only in the normal LVEDVI group. Multivariate backward linear regression showed that LVEDVI changes were independently associated with myocardial strain-related improvements during fluid resuscitation. The baseline LVEDVI was significantly negatively correlated with the LVGLS and RVGLS (r = -0.44 and - 0.39, respectively) but not LVGCS. LVEDVI increases during fluid resuscitation were associated with improvements in the myocardial strain degree., Conclusions: Myocardial strain alterations were significantly influenced by the cardiac preload during fluid resuscitation in sepsis., (© 2024. The Author(s).)

Objective. Instantaneous, non-invasive evaluation of left ventricular end-diastolic pressure (LVEDP) would have significant value in the diagnosis and treatment of heart failure. A new approach called cardiac triangle mapping (CTM) has been recently proposed, which can provide a non-invasive estimate of LVEDP. We hypothesized that a hybrid machine-learning (ML) method based on CTM can instantaneously identify an elevated LVEDP using simultaneously measured femoral pressure waveform and electrocardiogram (ECG). Approach. We studied 46 patients (Age: 39-90 (66.4 ± 9.9), BMI: 20.2-36.8 (27.6 ± 4.1), 12 females) scheduled for clinical left heart catheterizations or coronary angiograms at University of Southern California Keck Medical Center. Exclusion criteria included severe mitral/aortic valve disease; severe carotid stenosis; aortic abnormalities; ventricular paced rhythm; left bundle branch and anterior fascicular blocks; interventricular conduction delay; and atrial fibrillation. Invasive LVEDP and pressure waveforms at the iliac bifurcation were measured using transducer-tipped Millar catheters with simultaneous ECG. LVEDP range was 9.3-40.5 mmHg. LVEDP = 18 mmHg was used as cutoff. Random forest (RF) classifiers were trained using data from 36 patients and blindly tested on 10 patients. Main results. Our proposed ML classifier models accurately predict true LVEDP classes using appropriate physics-based features, where the most accurate demonstrates 100.0% (elevated) and 80.0% (normal) success in predicting true LVEDP classes on blind data. Significance. We demonstrated that physics-based ML models can instantaneously classify LVEDP using information from femoral waveforms and ECGs. Although an invasive validation, the required ML inputs can be potentially obtained non-invasively., (Creative Commons Attribution license.)

Background: Patients with concomitant type 2 diabetes mellitus (T2DM) and aortic regurgitation (AR) can present with right ventricular (RV) dysfunction. The current study aimed to evaluate the impact of AR on RV impairment and the importance of ventricular interdependence using cardiac magnetic resonance feature tracking (CMR‑FT) in patients with T2DM., Methods: This study included 229 patients with T2DM (AR-), 88 patients with T2DM (AR+), and 122 healthy controls. The biventricular global radial strain (GRS), global circumferential strain (GCS), and global longitudinal peak strain (GLS) were calculated with CMR‑FT and compared among the healthy control, T2DM (AR-), and T2DM (AR+) groups. The RV regional strains at the basal, mid, and apical cavities between the T2DM (AR+) group and subgroups with different AR degrees were compared. Backward stepwise multivariate linear regression analyses were performed to determine the effects of AR and left ventricular (LV) strains on RV strains., Results: The RV GLS, LV GRS, LV GCS, LV GLS, interventricular septal (IVS) GRS and IVS GCS were decreased gradually from the controls through the T2DM (AR-) group to the T2DM (AR+) group. The IVS GLS of the T2DM (AR-) and T2DM (AR+) groups was lower than that of the control group. AR was independently associated with LV GRS, LV GCS, LV GLS, RV GCS, and RV GLS. If AR and LV GLSs were included in the regression analyses, AR and LV GLS were independently associated with RV GLS., Conclusion: AR can exacerbate RV dysfunction in patients with T2DM, which may be associated with the superimposed strain injury of the left ventricle and interventricular septum. The RV longitudinal and circumferential strains are important indicators of cardiac injury in T2DM and AR. The unfavorable LV-RV interdependence supports that while focusing on improving LV function, RV dysfunction should be monitored and treated in order to slow the progression of the disease and the onset of adverse outcomes., (© 2024. The Author(s).)

Background: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM)., Methods: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression., Results: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (β = - 6.05, P < 0.001) and impaired global longitudinal strain (β = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (β = - 45.81, P = 0.008), LV global circumferential strain (β = 18.25, P = 0.003), LA reservoir strain (β = - 59.20, P < 0.001) and strain rate (β = - 2.90, P = 0.002)., Conclusions: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients., (© 2024. The Author(s).)

Background: Septic shock is associated with increases in end-diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown., Methods and Results: Purpose-bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular-arterial coupling, and circumferential strain. Early during sepsis, (0-24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes., Conclusions: The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

Background: Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow-up to treat drug-refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center., Methods and Results: PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post-PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty-one patients returned to the hospital for follow-up 6 to 30 (median, 14) months after the procedure. At the last follow-up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5-26.4) to 19.1 (interquartile range, 16.0-22.1) mm ( P <0.001) and the left ventricular outflow tract peak gradient at rest decreased from a median of 70.0 (interquartile range, 29.1-107.5) to 20.0 (interquartile range, 10.8-48.8) mm Hg ( P <0.001). The percentage of patients with symptoms of New York Heart Association functional class III/IV decreased from 51% to 0%. Of all 76 patients, there was no in-hospital or 30-day death, no right or left branch block, and no permanent pacemaker implantation. Six (8%) patients had pericardial effusion, with 1 experiencing cardiac tamponade and ventricular fibrillation, and 1 (1%) patient developed septal branch aneurysm that was treated with coil occlusion., Conclusions: PIMSRA allows for the reduction in the left ventricular outflow tract gradient and enhances symptomatic improvement, with a limited incidence of adverse events and complications among patients with hypertrophic obstructive cardiomyopathy.

Background: Gene therapy has been proposed as a strategy to induce cardiac regeneration following acute myocardial infarction (AMI). Given that Tbx20, a transcription factor of the T-box subfamily, stimulates cell proliferation and angiogenesis, we designed a baculovirus overexpressing Tbx20 (Bv-Tbx20) and evaluated its effects in cultured cardiomyocytes and in an ovine model of AMI., Methods and Results: Cell proliferation and angiogenesis were measured in cardiomyocytes transduced with Bv-Tbx20 or Bv-Null (control). Subsequently, in sheep with AMI, Bv-Tbx20 or Bv-Null was injected in the infarct border. Cardiomyocyte cell cycle activity, angioarteriogenesis, left ventricular function, and infarct size were assessed. Cardiomyocytes transduced with BvTbx20 increased cell proliferation, cell cycle regulatory and angiogenic gene expression, and tubulogenesis. At 7 days posttreatment, sheep treated with Bv-Tbx20 showed increased Tbx20 , promitotic and angiogenic gene expression, decreased levels of P21 , increased Ki67- (17.09±5.73 versus 7.77±7.24 cardiomyocytes/mm 2 , P <0.05) and PHH3 (phospho-histone H3)-labeled cardiomyocytes (10.10±3.51 versus 5.23±2.87 cardiomyocytes/mm 2 , P <0.05), and increased capillary (2302.68±353.58 versus 1694.52±211.36 capillaries/mm 2 , P <0.001) and arteriolar (146.95±53.14 versus 84.06±16.84 arterioles/mm 2 , P <0.05) densities. At 30 days, Bv-Tbx20 decreased infarct size (9.89±1.92% versus 12.62±1.33%, P <0.05) and slightly improved left ventricular function. Baculoviral gene transfer-mediated Tbx20 overexpression exerted angiogenic and cardiomyogenic effects in vitro., Conclusions: In sheep with AMI, Bv-Tbx20 induced angioarteriogenesis, cardiomyocyte cell cycle activity, infarct size limitation, and a slight recovery of left ventricular function, suggesting that Bv-Tbx20 gene therapy may contribute to cardiac regeneration following AMI.

Background: Myocardial infarction (MI) is a major disease with high morbidity and mortality worldwide. However, existing treatments are far from satisfactory, making the exploration of potent molecular targets more imperative. The E3 ubiquitin ligase RING finger protein 5 (RNF5) has been previously reported to be involved in several diseases by regulating ubiquitination-mediated protein degradation. Nevertheless, few reports have focused on its function in cardiovascular diseases, including MI., Methods: In this study, we established RNF5 knockout mice through precise CRISPR-mediated genome editing and utilized left anterior descending coronary artery ligation in 9-11-week-old male C57BL/6 mice. Subsequently, serum biochemical analysis and histopathological examination of heart tissues were performed. Furthermore, we engineered adenoviruses for modulating RNF5 expression and subjected neonatal rat cardiomyocytes to oxygen-glucose deprivation (OGD) to mimic ischemic conditions, demonstrating the impact of RNF5 manipulation on cellular viability. Gene and protein expression analysis provided insights into the molecular mechanisms. Statistical methods were rigorously employed to assess the significance of experimental findings., Results: We found RNF5 was downregulated in infarcted heart tissue of mice and NRCMs subjected to OGD treatment. RNF5 knockout in mice resulted in exacerbated heart dysfunction, more severe inflammatory responses, and increased apoptosis after MI surgery. In vitro, RNF5 knockdown exacerbated the OGD-induced decline in cell activity, increased apoptosis, while RNF5 overexpression had the opposite effect. Mechanistically, it was proven that the kinase cascade initiated by apoptosis signal-regulating kinase 1 (ASK1) activation was closely regulated by RNF5 and mediated RNF5's protective function during MI., Conclusions: We demonstrated the protective effect of RNF5 on myocardial infarction and its function was dependent on inhibiting the activation of ASK1, which adds a new regulatory component to the myocardial infarction associated network and promises to enable new therapeutic strategy., (© 2024. The Author(s).)

Background: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear., Methods: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans., Results: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology., Conclusions: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients., (© 2024. The Author(s).)

Introduction: Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown., Methods: In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test., Results: The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E', or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = - 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = - 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = - 0.28; p < 0.001), peak VO 2 (rho = - 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant., Conclusion: Among patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals., Trial Registration: ARISE-HF, NCT04083339 Date Registered August 23, 2019., (© 2024. The Author(s).)

Objective: To summarize the clinical characteristics of patients with end-stage heart failure who receive heart transplant under extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data of 12 pediatric patients who received heart transplant with ECMO support in the Seventh Medical Center of Chinese People's Liberation Army General Hospital and Guangdong Provincial People's Hospital, from January 2019 to December 2023 was collected. The data included sex, age, weight, diagnosis, pre-ECMO lactate level, left ventricular ejection fraction (LVEF), vasoactive-inotropic score (VIS), and preoperative ECMO running time. Surgical data included cold ischemia time of the donor heart, cardiopulmonary bypass time, intraoperative use of immunosuppressant, postoperative use of ECMO, duration of postoperative ECMO, rate of successful weaning from ECMO, and survival discharge rate. The paired t -test was performed to compare cardiac function indices before and after left ventricular decompression. Results: The 12 patients ranged in age from 1.1 to 15.8 years, and weighted from 8 to 63 kg. Ten children were diagnosed with dilated cardiomyopathy, one with myocardial underdensification, and one with a novel heterozygous mutation of the SCN5A gene causing overlap syndrome complicated by fatal arrhythmia. Before ECMO, the lactate ranged from 0.6 to>15.0 mmol/L, the LVEF from 6.5% to 43%, and VIS from 3 to 108. Four patients underwent left ventricular decompression supported by preoperative ECMO, and their pulse pressure was significantly increased after decompression ((17.8±2.1) vs. (9.8±1.5) mmHg, 1 mmHg=0.133 kPa, t =11.31, P =0.001), while there was no apparent change in LVEF ((26.8±4.4)% vs. (24.9±4.9)%, t =1.75, P =0.178). A total of 7 children received a second run of ECMO after surgery and 3 of them successfully weaned off ECMO and survived to discharge. In the entire cohort, 10 were successfully weaned from ECMO and 8 survived to discharge. Conclusions: For children with end-stage heart failure supported by ECMO, left ventricular decompression can significantly improve pulse pressure. These patients will eventually require heart transplantation.

Abstract: Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway., Competing Interests: The authors declare that there were no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Positron emission tomography/computed tomography (PET/CT) with 18 F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known., Objectives: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18 F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes., Methods: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18 F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18 F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months., Results: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage., Conclusions: In this first study to link cardiac 18 F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health. Dr Dorbala was supported by grants R01 HL 130563; K24 HL 157648; AHA16 CSA 2888 0004; AHA19SRG34950011. Dr Falk was supported by a grant R01 HL 130563. Dr Liao was supported by grants AHA16 CSA 2888 0004; AHA19SRG34950011. Dr Ruberg was supported by grants R01 HL 130563; R01 HL 093148. Dr Bianchi was partially supported by a grant K08 CA245100; and has received consulting fees from Prothena. Dr Clerc has received a research fellowship from the International Society of Amyloidosis and Pfizer. Dr Cuddy was supported by grants NIH 1K23HL166686-01 and AHA 23CDA857664NIH; and has received an investigator-initiated research grant from Pfizer; and has received consulting fees from BridgeBio, Ionis, AstraZeneca, and Novo Nordisk. Dr DiCarli has received a research grant from Gilead and Alnylam Pharmaceuticals; in-kind research support from Amgen; and consulting fees from Sanofi, MedTrace Pharma, and Valo Health. Dr Kwong has received grant funding from Alynlam Pharmaceuticals. Dr Falk has received consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, Caelum Biosciences; and research funding from GlaxoSmithKline and Akcea. Dr Ruberg has received consulting fees from AstraZeneca, and Attralus; and has received research support from Pfizer, Alnylam, Anumana, and Ionis/Akcea. Dr Dorbala has received consulting fees from Pfizer, GE Health Care, and Novo Nordisk; and investigator-initiated grants from Pfizer, GE Healthcare, Attralus, Siemens, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Global longitudinal strain (GLS) is reported to be more reproducible and prognostic than ejection fraction. Automated, transparent methods may increase trust and uptake., Objectives: The authors developed open machine-learning-based GLS methodology and validate it using multiexpert consensus from the Unity UK Echocardiography AI Collaborative., Methods: We trained a multi-image neural network (Unity-GLS) to identify annulus, apex, and endocardial curve on 6,819 apical 4-, 2-, and 3-chamber images. The external validation dataset comprised those 3 views from 100 echocardiograms. End-systolic and -diastolic frames were each labelled by 11 experts to form consensus tracings and points. They also ordered the echocardiograms by visual grading of longitudinal function. One expert calculated global strain using 2 proprietary packages., Results: The median GLS, averaged across the 11 individual experts, was -16.1 (IQR: -19.3 to -12.5). Using each case's expert consensus measurement as the reference standard, individual expert measurements had a median absolute error of 2.00 GLS units. In comparison, the errors of the machine methods were: Unity-GLS 1.3, proprietary A 2.5, proprietary B 2.2. The correlations with the expert consensus values were for individual experts 0.85, Unity-GLS 0.91, proprietary A 0.73, proprietary B 0.79. Using the multiexpert visual ranking as the reference, individual expert strain measurements found a median rank correlation of 0.72, Unity-GLS 0.77, proprietary A 0.70, and proprietary B 0.74., Conclusions: Our open-source approach to calculating GLS agrees with experts' consensus as strongly as the individual expert measurements and proprietary machine solutions. The training data, code, and trained networks are freely available online., Competing Interests: Funding Support and Author Disclosures Dr Rajani has received speaker fees from Siemens Healthcare and GE Medical; and has provided consultancy to Medtronic and Edwards Lifesciences. Dr Rana has provided consultancy to Philips and Occlutech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The COAPT Trial was the first ever to demonstrate a survival benefit in treating functional mitral regurgitation (FMR). That was achieved through transcatheter mitral repair in selected patients. The exact proportion of patients fulfilling COAPT selection criteria in the real-world is unknown., Aims: To assess the applicability of COAPT criteria in real world and its impact on patients' survival., Methods: We assessed the clinical data and follow-up results of all consecutive patients admitted for FMR at our Department between January 2016 and May 2021 according to COAPT eligibility. COAPT eligibility was retrospectively assessed by a cardiac surgeon and a cardiologist., Results: Among 394 patients, 56 (14%) were COAPT eligible. The most frequent reasons for exclusion were MR ≤ 2 (22%), LVEF < 20% or >50% (19%), and non-optimized GDMT (21.3%). Among Non-COAPT patients, weighted 4-year survival was higher in patients who received MitraClip compared to those who were left in optimized medical therapy (91.5% confidence interval [CI: 0.864, 0.96] vs. 71.8% [CI: 0.509, 0.926], respectively, p = 0.027)., Conclusions: Only a minority (14%) of real-world patients with FMR referred to a tertiary hospital fulfilled the COAPT selection criteria. Among Non-COAPT patients, weighted 4-year survival was higher in patients who received MitraClip compared to those who were left in optimized medical therapy (91.5% [0.864, 0.96] vs. 71.8% [0.509, 0.926], respectively, p = 0.027)., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Cardiovascular dysfunctions complicate 10-20% of pregnancies, increasing the risk for postpartum mortality. Various gestational insults, including preeclampsia are reported to be associated with adverse maternal cardiovascular outcomes. One such insult, gestational hyperandrogenism increases the risk for preeclampsia and other gestational morbidities but its impact on postpartum maternal health is not well known. We hypothesize that gestational hyperandrogenism such as testosterone (T) excess will adversely impact the maternal heart in the postpartum period. Pregnant ewes were injected with T propionate from day 30 to day 90 of gestation (term 147 days). Three months postpartum, echocardiograms, plasma cytokine profiles, cardiac morphometric, and molecular analysis were conducted [control (C) n = 6, T-treated (T) n = 7 number of animals]. Data were analyzed by two-tailed Student's t test and Cohen's effect size ( d ) analysis. There was a nonsignificant large magnitude decrease in cardiac output (7.64 ± 1.27 L/min vs. 10.19 ± 1.40, P = 0.22, d = 0.81) and fractional shortening in the T ewes compared with C (35.83 ± 2.33% vs. 41.50 ± 2.84, P = 0.15, d = 0.89). T treatment significantly increased 1 ) left ventricle (LV) weight-to-body weight ratio (2.82 ± 0.14 g/kg vs. 2.46 ± 0.08) and LV thickness (14.56 ± 0.52 mm vs. 12.50 ± 0.75), 2 ) proinflammatory marker [tumor necrosis factor-alpha (TNF-α)] in LV (1.66 ± 0.35 vs. 1.06 ± 0.18), 3 ) LV collagen (Masson's Trichrome stain: 3.38 ± 0.35 vs. 1.49 ± 0.15 and Picrosirius red stain: 5.50 ± 0.32 vs. 3.01 ± 0.23), 4 ) markers of LV apoptosis, including TUNEL (8.3 ± 1.1 vs. 0.9 ± 0.18), bcl-2-associated X protein (Bax)+-to-b-cell lymphoma 2 (Bcl2)+ ratio (0.68 ± 0.30 vs. 0.13 ± 0.02), and cleaved caspase 3 (15.4 ± 1.7 vs. 4.4 ± 0.38). These findings suggest that gestational testosterone excess adversely programs the maternal LV, leading to adverse structural and functional consequences in the postpartum period. NEW & NOTEWORTHY Using a sheep model of human translational relevance, this study provides evidence that excess gestational testosterone exposure such as that seen in hyperandrogenic disorders adversely impacts postpartum maternal hearts.