End-diastolic Left Ventricular Research Articles

Perioperative outcomes of video-assisted versus right anterior thoracotomy mitral valve replacement: an observational study

BackgroundMinimally invasive mitral valve surgery has been introduced as a safe alternative to full sternotomy through smaller chest wall incisions to reduce the potential sternal complications in addition to the favorable aesthetic effect. This observational study has been designed to evaluate and compare operative and short-term postoperative outcomes of video-assisted versus right anterior thoracotomy mitral valve replacement. The study was conducted on 40 cases and divided into two groups: group 1, comprised of 20 patients who underwent video-assisted mitral valve replacement (VAMVR), and group 2, comprised of 20 patients who underwent right anterior mini-thoracotomy mitral valve replacement (ATMVR). Preoperative data, intraoperative procedures, and early postoperative results have been compared between both techniques.ResultsIntraoperative parameters showed no statistical difference between the two groups. Wound length in the VAMVR group was statistically smaller than the ATMVR group, 5.33 ± 0.96 cm versus 7.08 ± 1.24 cm, respectively (P < 0.001). The intraoperative assessment by TEE showed a well-suited, well-functioning prosthetic valve, and no paravalvular leak in the two groups. In both groups, there were statistically significant reductions in left ventricular end diastole, left atrial diameter, and pulmonary artery systolic pressure in the 3-month postoperative ECHO in comparison to the preoperative ECHO (P < 0.001). There was a statistically significant decrease in left ventricular end-systole in the VAMVR group in the 3-month postoperative ECHO in comparison to the preoperative ECHO (P < 0.001). ICU visual analog scale (VAS) was significantly lower in the VAMVR group than in the ATMVR group (P = 0.049). There was a gradual reduction in VAS in both groups along the period of 3 months postoperatively without significant differences between the two groups in 2 weeks and 3 months postoperatively.ConclusionsVAMVR and ATMVR could be considered safe, feasible approaches with favorable perioperative surgical and echocardiographic results. VAMVR showed statistically significant smaller wounds and less postoperative pain than ATMVR, which may offer potential advantages in terms of reduced postoperative discomfort and cosmetic appearance for the thoracoscopic technique. Further randomized studies with larger cohorts and longer follow-ups are recommended to evaluate the long-term benefits and safety of both techniques.

Differences in athlete’s left ventricular morphology by sex and sports discipline categories in elite Japanese athletes

ABSTRACT Objectives The cardiac morphology of elite athletes is related to sports disciplines and race; however, no studies have examined the effects of sports discipline on East Asian athletes. Therefore, this study aimed to assess left ventricular (LV) remodeling using transthoracic echocardiography in elite Japanese athletes and establish standard values for the indicators of the cardiac morphology of elite athletes in East Asia, considering the influence of body size. Methods We retrospectively evaluated 1,363 elite Japanese athletes who underwent electrocardiography and transthoracic echocardiography between January 2011 and December 2021. The athletes were assigned to four sports discipline categories (skill, power, mixed, and endurance). We evaluated the differences in LV volume and mass between the groups for each sex. Results The LV end-diastolic volume (LVEDV) and LV mass indexed to the body surface area (BSA) in the endurance group (LVEDV/BSA: 72.3 ± 11.4 mL/m2 in males and 68.7 ± 11.0 mL/m2 in females, LV mass/BSA: 121.1 ± 19.1 g/m2 in males and 106.5 ± 18.0 g/m2 in females) were significantly larger than those of any other groups. Both values were affected by sex, BSA, and endurance sport type, whereas only LV mass was affected by age. Conclusion Cardiac remodeling is proportional to the sport type, with a significantly greater effect in athletes playing endurance sports. The remodeling is particularly evident in the left ventricle; however, the corresponding remodeling is also observed in other heart chambers. Cardiac remodeling in elite Japanese athletes is similar to that observed in elite athletes of other races, except for the changes in LV wall thickness.

Effect of additional dimensions and views in the echocardiographic determination of 3-dimensional left ventricular volume in myxomatous mitral valve disease in dogs.

Left ventricular (LV) volumes can be calculated from various linear, monoplane, and multiplane echocardiographic methods, and the same method can be applied to different imaging views. However, these methods and their variations have not been comprehensively evaluated against real-time 3-dimensional echocardiography (RT3D). To identify the LV volumetric approaches that produce the least bias and the best agreement with RT3D, and to assess interoperator reproducibility between an experienced and an inexperienced operator. Fifty-nine client-owned dogs with myxomatous mitral valve disease (38 Stage B1, 13 Stage B2, 8 Stages C/D) received echocardiograms, with a subset of 28 dogs (14 Stage B1, 10 Stage B2, 4 Stages C/D) imaged by 2 operators. Prospective method comparison study. Body weight-indexed end-diastolic and end-systolic LV volumes using linear methods in long- and short-axis views (Teichholz, cube, modified cube), monoplane methods in right parasternal and left apical views (area-length and Simpson's method of discs), biplane Simpson's method of discs, and real-time triplane (RT3P) were compared against RT3D. The RT3P method exhibited no bias and demonstrated the highest agreement with RT3D. The linear methods showed significant bias and lower agreements for end-diastolic volumes, end-systolic volumes, or both. Volumes derived from different imaging views using the same method showed poor agreement. Both RT3P and RT3D methods demonstrated poor interoperator reproducibility. Incorporating additional dimensions improves bias and agreement in LV volume quantification, but comprehensive clinical experience with RT3P and RT3D is needed to improve consistency across all operators.

Pressure-volume analysis by three-dimensional echocardiography: an accurate non-invasive alternative for assessing left ventricular contractility

Abstract Introduction Accurately assessing left ventricular (LV) contractility is vital for diagnosing and managing cardiac conditions like heart failure, cardiomyopathies, and ischemic heart disease. LV contractility assessment by traditional invasive pressure-volume (PV) analysis necessitates invasive measurements, introducing significant risks and limitations. However, three-dimensional (3D) echocardiography and non-invasive LV pressure curve estimation enables accurate PV-loop estimation, presenting a harmless and widely available alternative for LV contractility assessment. Aim Validate indices of LV contractility by PV analysis using 3D echocardiography by comparing them to gold-standard invasive measurements. Methods In 10 open-chest canines, invasive LV pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Echocardiography provided non-invasive 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting a reference curve to the valve events and measured peak LV pressure. Invasive LV end-systolic elastance (Ees) was obtained from multiple PV -loops during preload reduction through least square regression of the points on the PV-loops in the upper left corner with longest normalized distance from loop center. Non-invasive Ees was estimated using a simplified one-beat approach as the slope of a line drawn from this PV-loop point to the origin (Figure 1A). Invasive and non-invasive Ees, along with contractility indices peak LV pressure (Pmax)/end-diastolic volume (EDV) and LV pressure at end-systole (Pes)/EDV, were compared during baseline and during dobutamine infusion. Results As shown in the representative experiment illustrated in Figure 1A, non-invasive Ees captured changes in LV contractility in a similar manner as compared to invasive Ees. Indeed, this was consistent across all experiments, resulting in significant increase in non-invasive Ees in parallel with invasive Ees during dobutamine infusion (p &amp;lt; 0.001 for both) (Figure 1B). Consequently, there was a strong correlation and good agreement between the two methods (r = 0.63, p = 0.003; mean difference – 1.5, SD 2.4) (Figure 1C). For LV contractility indices Pmax/EDV and Pes/EDV, results were comparable: both increased significantly during dobutamine infusion, similar to invasive Ees. This was consistent across all experiments, without exceptions (Figure 2A). Consequently, there were strong correlations between Pmax/EDV and Pes/EDV and invasive Ees (r = 0.77, p = 0.0001 and r = 0.79, p &amp;lt; 0.0001, respectively) (Figure 2B). Conclusions 3D echocardiography provides a reliable and non-invasive method for assessing LV contractility, with good agreement with traditional invasive gold standard Ees. These findings support the use of 3D echocardiography as an accurate and easily accessible alternative for evaluating LV contractility in clinical settings. Invasive vs non-invasive LV Ees Pmax/EDV and Pes/EDV

Artificial intelligence for automatic echocardiography image view detection and left ventricle segmentation and ejection fraction prediction

Abstract Background Left-ventricular (LV) border segmentation is key to assess LV size and function. Current assessment has relatively large inter-observer variability, possibly impacting patients care. Artificial intelligence (AI) may permit faster and more reproducible assessment, possibly suitable to be used by non-experts. Purpose To train and test AI algorithms for (i) the identification of views, (ii) the segmentation of the LV in 2, 3 and 4-chamber views, and (iii) the computation of LV ejection fraction (EF). Methods Fifteen thousand echocardiography studies acquired in the Vall d’Hebron University Hospital (VH) for patients care were retrieved and anonymized. LV wall was identified via commercial clinical software in 619 videos with 2-, 3- and 4-chamber views (14082 frames) and 3 masks were created: LV cavity (within endocardial border), overall LV (within epicardial border) and LV wall. Annotated frames were split into independent training (465 videos) and testing (154) sets and performances were evaluated in terms of DICE score. End-diastolic and end-systolic LV volumes of 4-chamber views were identified and used to compute LV EF, which was compared with clinical reports in 488 patients. An external validation on CAMUS dataset was performed. Results A total of 6831 videos from 488 VH subjects were available for this analysis (Table 1). AI model identified image views with high accuracy (93%). AI performance on the segmentation of the LV cavity, overall LV and LV wall were satisfactory in 2- (0,86[0,79;0,90], 0,91[0,86;0,93], 0,79[0,74;0,83]), 3- (0,88[0,84;0,91], 0,91[0,90;0,93], 0,81[0,77;0,83]) and 4-chamber (0,90[0,86;0,93], 0,92[0,88;0,94], 0,82[0,79;0,85]) views. Segmentation performances were similar between sexes but were lower in case of atrial fibrillation and in images with low quality. In an external validation in 500 CAMUS patients performances were satisfactory, with DICE score of 0,91[0,87;0,94] and 0,80[0,73;0,84] for whole LV and LV cavity in 2 and 4-chamber views, respectively. In VH data EF predictions were in line with expected inter-observer reproducibility, with a good linear association (R=0.39, p&amp;lt;0.001) but remarkable underestimation (mean error = 12%). Models performed similarly in the external validation set, with a good linear association (R=0.31, p&amp;lt;0.001) and minimal underestimation (mean error = 2.2%). Conclusions AI models can identify echocardiography views, segment the LV in 2, 3 and 4-chamber views and use the segmentation to quantify EF. Care should be taken to avoid biases in AI performances, particularly in case of atrial fibrillation and limited image quality. Demographic and clinical information

EVALUATION OF THE RELATIONSHIP BETWEEN IRON LOAD, AGE, AND CARDIAC FUNCTION IN CHILDREN AND YOUNG ADULTS WITH THALASSEMIA MAJOR: A PULSED-WAVE DOPPLER AND TISSUE DOPPLER IMAGING STUDY

Objective: To determine the structural and functional cardiac differences in children and young adults with thalassemia major (TM) compared to healthy subjects using pulsed-wave Doppler and tissue Doppler imaging methods and determine the relationship between iron overload and these differences. Materials and Methods: We analyzed the data of pediatric and young adult TM patients (n = 44) aged 4–22 years and an age- and gender-matched control group (n = 40) in our hospital data system between Oct.01.2023 and Oct.01.2024. Height, weight, body mass index (BMI), systolic–diastolic blood pressure measurements, complete blood count, ferritin, cardiac T2* magnetic resonance imaging (MRI) values, and echocardiography results were recorded. In addition to comparisons between the two groups, correlation analysis was performed between ferritin–cardiac T2* MRI results and echocardiographic parameters and age in TM patients. Results: Our study showed growth retardation (low height standard deviation score (SDS), low weight SDS and low BMI SDS), dilatation of the left cavities (high left ventricular internal diameter end diastole (LVIDd)), increased left ventricular muscle mass (high left ventricular mass index (LVMI)), cardiac distinctive diastolic (restrictive pattern: left ventricular (LV) peak early diastolic flow (E)/peak late diastolic flow (A) and E/early diastolic myocardial peak flow (E') high), and subclinical systolic (LV peak systolic flow low and LV Tei index high) dysfunction. In addition, iron load (ferritin and cardiac T2* MRI) was correlated with LVMI, and cardiac diastolic and systolic function indicators. As age increased, ferritin value did not change, but cardiac T2* MRI value decreased and diastolic–systolic parameters worsened. Conclusion: Periodic cardiac T2* MRI and Doppler echocardiography examinations of patients with TM may detect subclinical myocardial dysfunction at an early stage, thus providing a window of opportunity for intervention.

Establishment of a HFpEF model using female Dahl salt-sensitive rats: a valuable tool for elucidating the pathophysiology of HFpEF in women.

The pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains unclear, and effective treatments are limited. HFpEF is more prevalent in females, indicating potential gender differences in its pathogenesis. However, no female HFpEF model animals have been established. Hypertension is a major contributor to HFpEF, and sympathetic activation is thought to play a role in both conditions. This study aimed to establish a female HFpEF model using hypertensive Dahl salt-sensitive rats and to assess the presence of sympathetic activation. Seven-week-old female Dahl salt-sensitive rats were fed an 8% high-salt diet (HS group, n = 6), while a low-salt diet group (LS group, n = 9) served as controls. The HS group exhibited increased systolic blood pressure and heart rate. Echocardiography revealed an increased left ventricular (LV) wall thickness, a decreased E/A ratio, and an increased E/e' ratio, all indicative of diastolic dysfunction without reduced LV ejection fraction. Additionally, the HS group showed elevated LV end-diastolic pressure, LV weight, and lung weight, along with histological cardiomyocyte hypertrophy and interstitial fibrosis. Gene expression markers for cardiac hypertrophy and fibrosis were also increased. Renal function was significantly impaired, and plasma norepinephrine levels were elevated, consistent with heightened pre-sympathetic neuronal activity in the brain. In conclusion, high salt loading from 7 weeks of age in female Dahl salt-sensitive rats induced hypertensive HFpEF phenotypes with LV hypertrophy and fibrosis, and sympathetic activation by 16 to 19 weeks of age. This model provides a valuable tool for studying HFpEF pathophysiology in women.

Abstract 4137854: Effect of Sacubitril/valsartan on Left Ventricular Tissue Characterization in Heart Failure with Left Ventricular Ejection Fraction Below 50%

Background: The effects of sacubitril/valsartan (ARNI) on myocardial tissue characterization in heart failure (HF) with left ventricular ejection fraction (LVEF) &lt;50% are still unclear. Objective: The present study investigated the effects of 9 months of ARNI treatment on LV structure and myocardial tissue characteristics in HF with LVEF &lt;50% using cardiac magnetic resonance (CMR). Methods: This study was a prospective, 2-arm, randomized, open-label clinical trial (SAVE-HF). Sixty-four HF outpatients with LVEF&lt;50% were randomized 1:1 from ACE inhibitor/ARB to ARNI (ARNI group) or control group (continued ACE inhibitor/ARB). CMR was performed to evaluate LV structure and tissue characteristics, including changes in LV extracellular volume fraction (delta ECV) before and after the 9-month period. The primary endpoint was difference in ECV between the two groups. Secondary endpoints included changes in LV volumes and mass, LVEF, extracellular mass (ECM) calculated as LV mass times ECV/100, and intracellular mass (ICM) calculated as LV mass minus ECM. Results: A total of 59 of 64 stable patients (68±12 years; 52 men) completed the 9-month intervention followed by repeated CMR. ARNI decreased systolic BP levels from the first month by approximately 10 mmHg. ARNI group exhibited significant reductions in LV end-diastolic and end-systolic volumes and LV mass. While LVEF and ECV remained unchanged (31.6±5.0 vs. 31.9±5.0%, p=0.26), both ECM and ICM significantly decreased after ARNI. In the control group, systolic BP, LV volumes and LV mass, ECV, ECM and ICM were unchanged. Comparing the two groups, while delta ECV was not significantly different, delta ECM was greater in ARNI group than control group (-3.6±7.3 vs. 0.2±5.3 g, p=0.025), indicating improved LV tissue characteristics. Conclusions: ARNI reduced LV volume and LV mass, accompanied with reduction of both ECM and ICM, and consequently unchanged ECV. These findings may suggest that ARNI may improve LV tissue characteristics and protect from LV remodeling in HF patients with their LVEF&lt;50%.

Prognostic yield of echocardiographic measures of cardiac structure and function in HFrEF patients with vs without an ICD or CRT-D

Abstract Background Selected echocardiographic measures of cardiac structure and function are known to be associated with mortality in patients with Heart Failure with reduced Left Ventricular (LV) Ejection Fraction (HFrEF). Whether the predictive ability of measures of cardiac structure and function remain after implantation of an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy-Defibrillator (CRT-D) is unknown among patients with HFrEF. Purpose To compare the predictive ability of echocardiographic measures of cardiac structure and function in HFrEF patients with or without an ICD/CRT-D. Methods Echocardiographic examinations were performed between 2003 and 2013 and retrieved from 2168 patients with HFrEF. Patients that had an ICD or CRT-D implanted during follow-up were identified through registries. The endpoint was all-cause mortality and follow-up was 100% to date. Images were analyzed offline in accordance with current guidelines. Associations were assessed by Cox multivariable regression and Cox univariable interaction models. Results After a median of 169 days, 677 patients had an ICD or CRT-D implanted. In total, 68% vs 80% of patients with and without an ICD, respectively, were men (p&amp;lt;0.001) and the median age were 70 vs 71 years (p=0.192). There was a significant difference in resting heart rate (median 74 vs 69, p&amp;lt;0.001) and frequency of ischemic heart disease (64% vs 81%, p&amp;lt;0.001) between the groups. Patients with an ICD had a higher mortality rate (69 per 1000 people/year vs 92 per 1000 people/year, p&amp;lt;0.001) and died significantly faster (median 9.3 vs 8.2 years, p&amp;lt;0.001). Patients with an ICD had higher Left Atrial (LA) End Systolic Volume (59.2 vs 67.3, p&amp;lt;0.001), LA Volume Index (28.5 vs 33.9, p&amp;lt;0.001), LV End Diastolic Volume (137.7 vs 153.7, p&amp;lt;0.001), and LV Mass Index (114.5 vs 124.5, p&amp;lt;0.001), as well as lower LA strain (9.8 vs 6.3, p&amp;lt;0.001) and TAPSE (2.0 vs 1.7, p&amp;lt;0.001). In patients without an ICD, Right Ventricular strain was associated with mortality (HR = 1.05 per 1% decrease mm/m2 [1.005, 1.11] when adjusting for covariates whereas in patients with an ICD, LA Volume Index (HR 1.14 per 1 increase [1.03, 1.25], and LV Ejection Fraction (HR 0.96 per 1% increase [0.92, 0.99]) were associated with mortality when adjusting for covariates. ICD/CRT-D implantation significantly modified the prognostic yield of LV End Diastolic Volume (HR per 1 ml increase: 0.99 without vs 1.01 with an ICD/CRT-D, p=0.005) and LV Mass Index (HR per 1 g/m2 increase: 1.00 without and 1.01 with an ICD/CRT-D, p=0.031). Conclusion Different echocardiographic measures were stronger prognosticators in HFrEF patients with and without an ICD or CRT-D, respectively, and ICD implantation modified the prognostic yield of LV End Diastolic Volume and LV Mass Index in HFrEF patients.Table 1Forest plot

Cardiac remodeling in rheumatoid arthritis: assessing the influence of anti-CCP and rheumatoid factor

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF), markers of Rheumatoid Arthritis (RA) activity, are associated with adverse cardiovascular outcomes, suggesting a potential link between RA and cardiac remodeling. Purpose Our study aimed to explore the correlation between antibody levels (anti-CCP and RF) and left ventricular (LV) remodeling in RA patients without known heart disease. Additionally, it sought to identify other disease-related factors that correlate with LV remodeling. Methods A cross-sectional study of 124 RA patients aged ≥ 18 years, classified per the 2010 ACR/EULAR criteria, collected blood samples for CRP, and antibody levels (RF ≥ 20 IU/ml and anti-CCP ≥ 5 IU/ml via ELISA). Transthoracic echocardiography (TTE) was conducted using a linear method in a long-axis parasternal 2D window. Sixty-two patients exhibited LV remodeling and were matched with 62 patients without it. Echocardiographic variables included were those to calculate the relative wall thickness (RWT, cut-off value 0.42) and left ventricular mass index (LVMI, cut-off values of 43-95 g/m2 in women and 49-115 g/m2 in men) along with left ventricular end diastolic (LVIDd), and systolic volumes (LVIDs), and left ventricular ejection fraction (LVEF). Statistical analyses employed the Chi-square test, Student's t-test, or Mann-Whitney U test as applicable, with correlations assessed using Spearman's rho, an analysis was conducted on the area under the curve (AUC) and a significance level of p ≤ 0.05. Results The most common type of LV alteration in our study was concentric remodeling (74.2%). A statistically significant difference was observed in the levels of Anti-CCP titers 193.85 IU/ml (p &amp;lt; .001), RF IgM 200.00 IU/ml (p &amp;lt; .001) and IgA 185.5 IU/ml (p &amp;lt; .001) in patients with LV remodeling. Anti-CCP and RF IgA antibody levels exhibited a moderate correlation with the presence of LV remodeling, with rho 0.387 (p &amp;lt; .001) and rho 0.344 (p &amp;lt; .001), respectively. The RWT showed a moderate correlation with anti-CCP titers with rho 0.298 (p .001). AUC analysis anti-CCP titers demonstrated better diagnostic performance for the existence of cardiac remodeling (0.722, 95% CI 0.628-0.816, p &amp;lt; .001), RF IgA (0.696, 95% CI 0.602-790, p &amp;lt; .001) and IgM (0.650, 95% CI 0.563-755, p .002). Conclusion In summary, among RA patients without heart failure (HF), LV remodeling and elevated RWT correlate with antibody levels independently of traditional cardiovascular risk factors. Patients with altered LV geometry exhibit higher antibody titers, highlighting the need for RA-related biomarkers that correlate with changes in LV structure and function Recognizing association between autoimmunity and HF development holds significant implications for both prevention and treatment strategies in RA patients.

Multi-vendor validation of automated left ventricular analysis from 3D echocardiography using artificial intelligence

Abstract Background Accurate echocardiographic assessment of left ventricular (LV) function is dependent on both image acquisition and analysis. Although 3D echocardiography (3DE) is increasingly recommended for volume quantification, manually derived volumes are limited by operator subjectivity, variable image quality, and the lengthy duration of analysis. Consequently, several automated approaches based on artificial intelligence (AI) have been proposed to segment the LV cavity from 3DE and have demonstrated better accuracy and reproducibility compared to human experts. While the utility of AI models in the clinic depends on their ability to generalise to different populations and ultrasound vendors, the external validation of developed models remains limited. Purpose This study evaluates the ability of an existing AI model trained using data from a single vendor to accurately estimate routine 3DE LV indices in an independent external dataset acquired using equipment from a different vendor. Methods A previously published and internally validated deep learning model for segmentation of the LV cavity and myocardium from 3DE was used to automatically derive LV indices including end-diastolic volume (EDV), end-systolic volume (ESV), LV mass, and ejection fraction (EF) [1]. A second independent dataset consisting of paired 3DE and CMR images from 65 marathon runners from a different centre (using equipment from a different vendor) was subsequently used for external validation. Images from both datasets were subjectively scored from 1 (poor) to 5 (excellent) as a measure of image quality. Agreement with CMR as the reference was assessed using a two-way mixed effects intraclass correlation coefficient (ICC), supplemented by Bland-Altman analysis, to determine the model bias (between 3DE and CMR) and 95% limits of agreement (LOA). To assess whether performance could be improved by inclusion of multi-vendor data during training, the initial model was fine-tuned using a small subset (n=9) of images from the second centre. Results The mean image quality score from the second dataset was 2.5 (± 1.1), which was significantly lower than the mean of 3.4 (± 1.0) from the first dataset. Despite vendor and image quality differences, the initial model produced good agreement with CMR in EDV, ESV, and LV mass but only poor agreement in EF (Fig 1). Fine tuning greatly improved agreement in EF with reduced bias and narrower 95% LOA (Fig 2). Conclusion With the addition of a small number of cases for fine-tuning, AI models for automated LV analysis can achieve good performance analysing 3DE images acquired from a different vendor and population. Advancing model generalisability through more sophisticated data augmentation strategies may enable truly vendor-agnostic automated LV analysis from 3DE.

Lipin1 prevents ischemic heart disease by regulating lipid homeostasis

Abstract Background Lipid metabolism plays a crucial role in the pathophysiology of cardiovascular diseases. Lipin1 plays a pivotal role in lipid metabolism regulation. In the nucleus, Lipin1 acts as a transcriptional co-stimulatory molecule, interacting with peroxisome proliferator–activated receptor–gamma coactivator 1 alpha (PGC1α) and peroxisome proliferator–activated receptor alpha (PPARα). In the cytoplasm, Lipin1 functions as a phosphatidate phosphatase, converting phosphatidic acid to diacylglycerol to regulate lipid metabolism. Low expression of Lipin1 has been implicated in the severity of cardiac dysfunction in mice. Purpose This study aimed to investigate the role of Lipin1 in the cardiac remodeling after myocardial infarction (MI), revealing its impact on lipid metabolism and molecular pathway associated with cardiac dysfunction. Methods Two types of transgenic mice, cardiomyocyte-specific Lipin1 knockout (cKO) and overexpression (cOE) mice were used in this study. Eight to ten-week-old male mice were subjected to MI by coronary artery ligation. Cardiac lipid droplets were quantified, and triacylglycerol and free fatty acid levels were measured one week after MI surgery. Four weeks after MI, cardiac morphology and function were evaluated using echocardiography, alongside measurements of body weight (BW) and heart weight (HW). Additionally, gene expression analysis and histological evaluation were conducted to assess fatty acid metabolism, cardiac fibrosis, inflammation, and oxidative damage. Results Before MI surgery, there were no differences in HW/BW ratio, left ventricular end-diastolic diameter (LVDd) or LV fractional area change (LVFAC) among cKO/ cOE mice and their littermate controls. After MI, cKO mice exhibited significant cardiac dysfunction with larger LVDd, lower LVFAC and increased HW/BW ratio compared to littermate controls. This was accompanied by exacerbated cardiac fibrosis, increased inflammation, and augmented reactive oxygen species accumulation compared with their controls. Conversely, cOE mice displayed improved LVFAC, reduced cardiac fibrosis, inflammation, and reactive oxygen species accumulation compared to their littermate controls. Notably, the transgene of Lipin1 induced changes in the number of cardiac lipid droplets (LDs). cKO mice hearts showed a reduction in cardiac LDs with decreased levels of triacylglycerol and free fatty acids compared to the littermate controls. In contrast, cOE mice displayed increased cardiac LDs and upregulated expression of fatty acid metabolism–related genes after MI. Conclusion These results suggested that Lipin1 has a protective role against ischemic injury through controlling lipid metabolism in ischemic cardiomyocytes. Thus, Lipin1 emerges as a potential therapeutic target for myocardial infarction.

Relation between wearable heart rate monitor derived training load and cardiac adaption in endurance athletes

Abstract Background No studies have effectively measured training load (TL) from wearable heart rate (HR) monitors and determined its relation to exercise induced left and right ventricular (LV, RV) remodeling. A better insight into drivers of exercise induced cardiac remodeling is of clinical relevance to guide training advice in athletes at risk of adverse remodeling. Purpose We determined the TL, based on HR monitoring by commercial wearables[1]. The number and duration of training sessions was quantified during a period of 3 months. Training-intensity was calculated as Edwards TRIMP (eTRIMP) based on the product of training duration in one of 5 HR zones (1=light, 5=very vigorous) and the coefficient related to the respective HR zone. Methods Training data was collected in 2 prospective multicenter studies. Master@Heart comprises endurance trained middle-aged men aged 45 to 70years[2]. Pro@Heart consists of elite athletes aged 16 to 23years[3]. For this analysis, all male athletes with complete training data recorded using a chest-worn HR monitor for 3 months were included. Using an in-house developed pipeline, maximal HR and TL were calculated from raw training data. Cardiac magnetic resonance imaging was performed to measure indexed LV/RV end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume (LVESVi, RVESVi), ejection fraction (LVEF, RVEF) and LV mass (LVMi). Results Pro@Heart athletes (n=69; age 21.9 ± 4.2 years) trained more than Master@Heart athletes (n=82; age 55.2 ± 6.5 years) and their total 3-month TL (eTRIMP) was also higher (9718 ± 3190 vs. 5499 ± 3775min; P&amp;lt;0.05 and 22339 ± 7350 vs. 13438 ± 8880 AU; P&amp;lt; 0.05; Table 1). Considering all athletes, there was a strong correlation between both training duration and eTRIMP and LVEDVi, LVESVi, LVMi, RVEDVi and RVESVi. Training duration in zone 1&amp;2 correlated well with LVEDVi, LVESVi, LVSV, LVMi, RVEDVi and RVESVi (Table 2). We found small significant negative correlations between duration and eTRIMP compared to LVEF and RVEF (Table 2). To filter out individual training factors influencing cardiac remodeling we used a partial least squares method which included time and percentage of time spent in training zones and age. Accordingly, training duration in zone 1&amp;2 and age were the main predictors of cardiac volumes and LVMi. For LVEF, age and time in zone 3 was most predictive, whereas for RVEF zone 3 and to a lesser degree zone 1&amp;2 were the main predictors, irrespective of age. Interestingly, time spent in high intensity zones 4 and 5 was not predictive. Conclusion We prospectively quantified TL in comparison to CMR-derived measures of cardiac remodeling and demonstrated that training duration in low intensity training zones is most predictive for cardiac volumes and mass, whereas LVEF and RVEF are more closely associated to time in zone 3. Very vigorous intensity exercise was not predictive, likely due to limited time training in zone 4 and 5.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation (AF). However, the impact of LVH and LAE and their regression following antihypertensive therapy on AF incidence remains unclear. Purpose This study aimed to investigate the impact of changes in the LVH and LAE status on the occurrence of new-onset AF (NOAF). Methods This retrospective analysis included patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6–18 months. LVH was defined as LV mass index &amp;gt;115 g/m2 (men) and &amp;gt;95 g/m2 (women), and LAE was defined as LA volume index &amp;gt;42 ml/m2. LVH and LAE regression was defined as the absence of LVH and LAE on follow-up echocardiography, respectively. The occurrence of NOAF was assessed in relation to changes in LVH and LAE status. Results Among the 1,464 patients included in the study, 163 (11.1%) patients developed NOAF during a median follow-up of 63.8 months (interquartile range, 35.9–128.5 months). On average, 12 electrocardiograms per patient were reviewed for AF detection. New-onset LVH (adjusted HR 1.88, 95% CI 1.20–2.94, P=0.006) and LAE (adjusted HR 1.89, 95% CI 1.05–3.40, P=0.034) were significant predictors of NOAF. Conversely, regression of LVH (adjusted HR 0.51, 95% CI 0.280.91, P=0.022) or LAE (adjusted HR: 0.30, 95% CI 0.15–0.63, P=0.001) after antihypertensive therapy was associated with a reduced risk of NOAF. The risk of NOAF was higher in patients with LVH and LAE together (adjusted HR 4.30, 95% CI 2.81–6.56, P&amp;lt;0.001) than in those with either LVH or LAE, or those with neither, as determined by follow-up echocardiography. Conclusion In patients with hypertension and sinus rhythm, regression of LVH and LAE following antihypertensive therapy is associated with a decreased incidence of NOAF, whereas newly developed LVH or LAE is associated with a higher risk of NOAF. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Sacubitril/valsartan improves outcome in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LV-EF ≤ 40% were enrolled prospectively. Non-invasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (Ees; a measure of LV contractility), effective arterial elastance (Ea; a measure of afterload), and the ventricular-arterial coupling ratio (Ea/Ees). Mean age was 65±13 years, 30% were female, and 54.7% had ischemic heart disease. During six months of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. 102 patients were included in pressure-volume analyses. After six months of sacubitril/valsartan treatment, Ees increased (0.66mmHg/ml [IQR 0.45-0.94] vs. 0.78mmHg/ml [IQR 0.57-1.10], p=0.001), Ea decreased (1.76mmHg/ml [IQR 1.48-2.13] vs. 1.62mmHg/ml [IQR 1.36-1.96], p=0.014), and the Ea/Ees ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], p<0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both p<0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-minute walking distance. Change in LVEF correlated with change in Ees (r=0.33, p=0.0008), while change in NT-proBNP was associated with change in LVEDP (r=0.42, p<0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF.

The Management Outcome of Heart Failure Reduced Ejection Fraction with or without Angiotensin Receptor Neprilysin Inhibitor

INTRODUCTION: Heart failure is associated with recurrent admission, higher mortality and low quality of life. Angiotensin receptor neprilysin inhibitor (ARNI) is a novel agent that has been used for treating heart failure reduced ejection fraction (HFrEF) patients. Thus, it is interesting to evaluate the effect of ARNI on the reverse cardiac remodelling, rehospitalization, cardiac biomarker and quality of life in HFrEF patients. MATERIALS AND METHODS: A case controlled study was conducted to assess the treatment outcome of HFrEF with or without ARNI. During the study, the patients’ basic demography, co-morbidities, baseline echocardiography (ECHO) findings, NYHA classification, NT-pro BNP levels and KCCQ score were evaluated. The patients’ admission history within 90 days from initiation of ARNI or non ARNI were obtained retrospectively. A follow up ECHO was obtained after at least 3 months of intervention. RESULTS: A total of 81 patients were recruited in which 54 patients were on ARNI and 27 were on non ARNI treatment. There was a statistically significant improvement of ejection fraction, left ventricular internal diameter end diastole and systole, and left ventricular end-systolic volume in ARNI group. The NYHA class was also noted to improve after ARNI treatment. The NT-proBNP value was lower whereas the KCCQ score was higher in ARNI group compared to non ARNI group. CONCLUSION: HFrEF patients with ARNI treatment had better reverse cardiac remodelling effect, cardiac biomarker and quality of life compared to non ARNI treatment. Furthermore, patient received ARNI demonstrated improved heart failure classification after treatment

Epicardial Fat in Heart Failure with Preserved Ejection Fraction Compared with Reduced Ejection Fraction.

Background: The role of epicardial adipose tissue (EAT) in heart failure with preserved ejection fraction (HFpEF) remains to be defined. Methods: A consecutive series of outpatients with chronic heart failure-heart failure with reduced ejection fraction (HFrEF) and HFpEF and/or diastolic dysfunction-had EAT assessed by echocardiographic measurement and related to indices of cardiac structure and function. Results: Epicardial fat thickness was significantly (p < 0.05) greater in HFpEF (N = 141) with a mean of 6.7 ± 1.6 mm compared with a mean of 5.1 ± 1.0 mm in HFrEF (n = 40). After adjusting for the relationship with BMI, in HFpEF, epicardial fat was significantly (p < 0.05) negatively correlated with left ventricular internal diameter end diastole (LVIDd), left ventricular internal diameter end systole (LVIDs), left ventricular (LV) end-diastolic volume (EDV) index, lateral e', septal e', right atrial (RA) volume index, and hemoglobin (Hgb). The association with Hgb was no longer significant after adjusting for the effect of age. HFpEF was associated with smaller LVIDd, LVIDs, LV EDV indexes, and left atrial (LA) and RA volume indexes. Conclusions: Epicardial fat is significantly (p < 0.05) greater in HFpEF than HFrEF. Epicardial fat is associated with smaller cardiac chamber sizes in HFpEF suggesting that epicardial fat acts as a constraint to cardiac dilation.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension.

Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation. However, the impact of LVH and LAE and their regression following antihypertensive therapy on atrial fibrillation incidence remains unclear. This retrospective analysis included consecutive patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6-18 months between 2006 and 2021 at tertiary care centres in Korea. LVH was defined as LV mass index greater than 115 g/m2 (men) and greater than 95 g/m2 (women), and LAE was defined as LA volume index greater than 42 ml/m2. The occurrence of new-onset atrial fibrillation (NOAF) was assessed in relation to changes in LVH and LAE status. Among the 1464 patients included, 163 (11.1%) developed NOAF during a median 63.8 [interquartile range (IQR) 35.9-128.5] months of surveillance period. New-onset LVH [adjusted hazard ratio (aHR) 1.88, 95% confidence interval (CI) 1.20-2.94, P = 0.006] and LAE (aHR 1.89, 95% CI 1.05-3.40, P = 0.034) were significant predictors of NOAF. Conversely, regression of LVH (aHR 0.51, 95% CI 0.28-0.91, P = 0.022) or LAE (aHR 0.30, 95% CI 0.15-0.63, P = 0.001) was associated with a reduced risk for developing NOAF. Patients with both LVH and LAE at follow-up echocardiography had a higher risk for NOAF (aHR 4.30, 95% CI 2.81-6.56, P < 0.001) than those with either LVH or LAE or those with neither. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

Abstract Tu052: RPN6-Serine14 Phosphorylation by PKA Protects Against Systolic Overload-Induced Cardiac Remodeling and Heart Failure

The ubiquitin-proteasome system is the main proteolytic pathway for quality control (PQC) and regulatory degradation of proteins in living cells. Systolic overload, as seen in hypertension and aortic stenosis, is a leading cause of heart failure (HF). Proteasome functional insufficiency is implicated in HF caused by systolic overload. Previous studies have established that Ser14-RPN6 phosphorylation (pS14-RPN6) mediates the activation of 26S proteasomes by protein kinase A. However, the pathophysiological significance of pS14-RPN6 in systolic overload remains to be established. We hypothesize that pS14-RPN6 helps maintain proteostasis and protects the heart during systolic overload. We observed a significant increase in myocardial pS14-RPN6 and ubiquitin conjugates in human HF of ischemic or non-ischemic etiologies (p=0.020, p=0.034) and similarly in wild type (WT) mice after 2 weeks of transverse aortic constriction (TAC) (p&lt;0.0001, p=0.001). To investigate the role of pS14-RPN6 in vivo, our lab created Rpn6 S14A (S14A) knock-in mice where Ser14-Rpn6 phosphorylation is blocked. Here we have compared the responses to TAC between WT and S14A mice. We found that TAC-induced increases in myocardial proteasome peptidase activities were significantly attenuated, and accumulation of ubiquitin conjugates exacerbated in S14A mice (p&lt;0.0001; p&lt;0.0005). Serial echocardiography revealed that S14A mice displayed significantly greater left ventricular (LV) end-diastolic posterior wall thickness and LV mass to body weight ratios at 1- and 12-week post-TAC (p=0.024, 0.0003; p=0.005, 0.01), and lower ejection fraction at 12-week post-TAC than WT mice (p=0.035). S14A mice also showed greater heart weight to tibial length (TL) and ventricular weight to TL ratios at 1 and 12-week post-TAC (1-week, p=0.043, 0.039; 12-week, p=0.007, 0.006). Wheat germ agglutinin and picrosirius red staining indicated a greater cardiomyocyte cross-sectional area and cardiac fibrosis in 12-week post-TAC S14A mice vs. WT mice (p&lt;0.0001; p=0.005). These novel findings demonstrate compellingly that myocardial pS14-RPN6 helps maintain proteostasis, curtails cardiac hypertrophy and delays heart failure occurrence during systolic overload

Abstract Mo113: An Ovary-Intact Postmenopausal HFpEF Animal Model.

Background: The incidence of HFpEF in women significantly escalates following the age of menopause. This trend cannot solely be attributed to chronological aging, as evidenced by the more gradual increase in prevalence among men with HFpEF. This pattern suggests that menopause is a provocative event for HFpEF. However, the underlying mechanisms remain elusive and challenging to investigate in human subjects; moreover, the attempt to create HFpEF in ovariectomized (OVX) mice was unsuccessful. We aim to create an animal model of postmenopausal HFpEF that resembles the characteristics of HFpEF in women with natural menopause. Methods: We use the 4-vinyl cyclohexene dioxide (VCD) to induce “ovary-intact” menopause, combined with the 2hit regimen (HFpEF inducing regimen elicited by high-fat diet and nitric oxide synthase inhibitor) to model postmenopausal HFpEF. VCD gradually causes ovarian failure, providing the perimenopausal transition and preserving residual ovarian stroma, mimicking natural menopause. The HFpEF phenotypes were studied at the in vivo LV by pressure-volume (PV) analysis and at the single cell level by intact cell force measurement. Results: The Female-VCD-2hit model demonstrates diastolic dysfunction at both the LV and the cellular levels. At the LV level, the increase in the end-diastolic pressure-volume relation (EDPVR) stiffness coefficient and LV end-diastolic pressure (LVEDP) indicates a heightened stiffness of the LV chamber and an elevation in LV filling pressure, an HFpEF-like condition. At the cardiomyocyte level, the female-VCD-2hit model exhibits an increase in cellular diastolic stiffness, suggesting that the observed LV diastolic stiffness is derived from the stiffness of the cardiomyocytes. We compared the female-VCD-2hit mice with the OVX mice subjected to the 2hit regimen. The 2hit-OVX model showed a milder form of diastolic dysfunction, observed as a smaller increase in LV diastolic stiffness (EDPVR) and normal LV filling pressure (LVEDP). Conclusions: Female mice, either premenopausal or ovariectomized, are more resistant to the development of HFpEF, unlike their ovary-intact menopausal (VCD-treated) counterparts, which exhibit a vulnerability to HFpEF, making the VCD-2hit model a suitable model to study postmenopausal HFpEF. The LV diastolic dysfunction observed in the 2hit model is attributed to mechanical dysfunction at the cardiomyocyte level.