End Diastole Research Articles

(235) False Negative Penile Duplex Sonography: Results of Cavernovenous Leakage Surgery in 41 Patients with Normal End-Diastolic Velocity. The Need for Venous Leak Hemodynamic Criteria Re-Evaluation?

Abstract Introduction In cavernovenous leakage (CVL), blood entering corpora cavernosa escapes too early due to abnormal venous network, for erections to develop or maintain. CVL diagnosis relies on persisting blood flow velocity in cavernosal arteries at the end of diastole (EDV), with a consensus 5 cm/s cut-off value at pharmacologically-challenged penile duplex sonography (PC-PDS). Objective We present clinical, hemodynamic characteristics, and response to surgery of 41 patients with severe ED resistant to PDE5Is, with EDV5 cm/s at PC-PDS, considered non pathologic, but with CVLs identified by gold standard pharmacologically-challenged penile CT-cavernography. Methods Prospectively collected data from 41 consecutive patients with ED resistant to PDE5Is, with cavernosal artery EDV5 cm/s (Group A), were compared to data from 130 patients with EDV>5 cm/s (Group B). CVLs in Group A were detected by PC-PDS on deep dorsal vein or penile superficial veins after intracavenosal injection of Prostaglandin E1 plus Papaverine. All patients had refused a penile implant and underwent CVL intervention consisting in open surgery and embolization during the same procedure. Inter-group comparison used a T-test of means, pre- and post-operative data comparison a paired t-test. Results Patients in Group A were younger than in Group B (mean age 38.2±14.0 and 45.9±11.6 years, respectively, p<.0022). Pharmacologic Erection Hardness Score (EHS) was higher (2.9±.7 vs. 2.4±.6, p<.0001), EDV velocity was less (1.6±2.2 vs. 15.1±2.2 cm/s, p<.0001) in Group A than B, respectively. Pre-operative IIEF5 score was higher in Group A than in B (13.3±5.3 and 9.4±4.8, respectively, p<.0181). Other pre-operative erection parameters were otherwise similar in the two groups (morning erection EHS and frequency, masturbation and sexual intercourse EHS, percentage of successful penetration (p<.498, .543, .682, .510, .289, respectively). Patients in Group A and B responded similarly to surgery, with a similar pharmacologic EHS increase at systematic three-month post-operative PC-PDS (0.77±.94 vs. .81±.67, p<.80). Mixing Group A and B 171 patients, at the end of the 29.8±20.4-month follow-up, a significant improvement on all clinical parameters was observed: IIEF-5 score had increased from 9.7±5.1 to 15.5±6.0 (p<.0001), clinical EHS during sexual intercourse from 2.0±.7 to 3.3±.7 (p<.0001), penetration success rate from 22.3±31.7 to 70.1±37.2% (p<.0001), mean EHS during masturbation from 2.11±.67 to 3.04±.75 (p<.0001), morning erection EHS from .95±1.24 to 2.12±1.37 (p<.0001), before and after surgery, respectively. There was no statistically significant difference between Group A and B regarding all these parameters, demonstrating similar clinical responses to surgery. Conclusions Patients with EDV5 cm/s may have CVL evidenced by PC-PDS flow analysis directly on veins, and gold standard PC-PCTC. Their erection disability is severe. They respond well to combined open and embolization surgery, a confirmation that they suffer CVL. EDV criterium misses CVL in as much as one patient out of four with actual CVL in our series. Since false negative diagnosis has severe, life-long, patient and partner implications, hemodynamic criteria for CVL diagnosis should be debated in the field of sexual medicine. Disclosure No.

MSC exosomes attenuate sterile inflammation and necroptosis associated with TAK1-pJNK-NFKB mediated cardiomyopathy in diabetic ApoE KO mice.

Diabetes is a debilitating disease that leads to complications like cardiac dysfunction and heart failure. In this study, we investigated the pathophysiology of diabetes-induced cardiac dysfunction in mice with dyslipidemia. We hypothesize diabetes in ApoE knockout (ApoE-/-) mice induces cardiac dysfunction by increasing inflammation and necroptosis. ApoE-/- mice were divided into experimental groups: Control, Streptozotocin (STZ), STZ + MSC-Exo (mesenchymal stem cell-derived exosomes), and STZ+MEF-Exo (Mouse embryonic fibroblast derived exosomes). At Day 42, we assessed cardiac function, collected blood and heart tissues. Heart tissue samples were analyzed for inflammation, necroptosis, signaling mechanism, hypertrophy and adverse structural remodeling using histology, immunohistochemistry, western blotting, RT-PCR, cytokine array and TF array. STZ treated ApoE-/- mice developed diabetes, with significantly (p<0.05) increased blood glucose and body weight loss. These mice developed cardiac dysfunction with significantly (p<0.05) increased left ventricular internal diameter end diastole and end systole, and decreased ejection fraction, and fractional shortening. We found significant (p<0.05) increased expression of inflammatory cytokines TNF- a, IL-6, IL-1a, IL-33 and decreased IL-10 expression. Diabetic mice also exhibited significantly (p<0.05) increased necroptosis marker expression and infiltration of inflammatory monocytes and macrophages. MSC-Exos treated mice showed recovery of diabetes associated pathologies with significantly reduced blood glucose, recovered body weight, increased IL-10 secretion and M2 polarized macrophages in the heart. These mice showed reduced TAK1-pJNK-NFKB inflammation associated expression and improved cardiac function with significantly reduced cardiac hypertrophy and fibrosis compared to diabetic mice. Treatment with MEF-Exos did not play a significant role in attenuating diabetes-induced cardiomyopathy as these treatment mice presented with cardiac dysfunction and underlying pathologies observed in STZ mice. Thus, we conclude that cardiac dysfunction develops in diabetic ApoE-/- mice, arising from inflammation, necroptosis, and adverse tissue remodeling, which is ameliorated by MSC-Exos, a potential therapeutic for diabetes-induced cardiomyopathy.

Accuracy of Pediatric Interventricular Septal Thickness Measurement Obtained Via Point-of-Care Ultrasound: A Prospective Study.

Hypertrophic cardiomyopathy is a genetic, life-threatening cardiovascular disease that often goes unidentified in pediatric patients. Patients are often asymptomatic and neither history or physical examination are reliable to detect the disease. The only reliable method to diagnose hypertrophic cardiomyopathy is with echocardiography to look at interventricular septal thickness. Emerging literature has shown that cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians is as effective and accurate compared with cardiac echocardiography performed by pediatric cardiologists. The objective of the study was to determine the diagnostic accuracy of POCUS performed by ultrasound-trained PEM physicians in measuring the interventricular septum end diastole (IVSd) thickness in the pediatric emergency department. We conducted a prospective, single-center, observational, diagnostic accuracy study to examine the diagnostic accuracy of POCUS in measuring IVSd thickness in pediatric patients who presented to the pediatric emergency department with symptoms that prompted a cardiac POCUS. Cardiac POCUS findings were interpreted by a PEM physician at the bedside and retrospectively by a pediatric cardiologist. Diagnostic concordance of the measurements obtained by the PEM physician and cardiologist was assessed. Forty-eight patients were enrolled. Median patient age was 13.4 years. There was excellent diagnostic agreement on the measurement of the IVSd thickness between PEM physicians and the pediatric cardiologist (81.25% of cases; 39/48). Disagreement was seen in 18.75% of the cases (9/48). The mean error of disagreement was -0.32, with a 95% confidence interval of -0.37 to -0.28. Overall, the mean error of both agreement and disagreement was -0.046, with 95% confidence interval of -0.08 to -0.01 and P value of 0.008. Point-of-care ultrasound performed by ultrasound-trained PEM physicians to measure pediatric IVSd thickness has a high diagnostic accuracy with excellent agreement with a pediatric cardiologist.

Prognostic Implications of Septal Hypertrophy in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

Cardiac remodeling is frequently observed in patients with heart failure (HF) and serves as an indicator of disease progression and severity. Septal hypertrophy represents an aspect of remodeling that can be easily assessed via an echocardiographic measurement of the interventricular septal end diastole (IVSd), but it has not been evaluated for its prognostic value, particularly in patients with heart failure with mildly reduced ejection fraction (HFmrEF). We retrospectively included 1881 consecutive patients hospitalized with HFmrEF (i.e., a left ventricular ejection fraction of 41-49% and signs and/or symptoms of HF) at one institution during a study period from 2016 to 2022. Septal hypertrophy, defined as an IVSd > 12 mm, was prevalent in 34% of the HFmrEF patients. Although septal hypertrophy was not associated with all-cause mortality at 30 months (median follow-up) (HR = 1.067; 95% CI: 0.898-1.267; p = 0.460), it was associated with an increased risk of hospitalization due to worsening HF at 30 months (HR = 1.303; 95% CI: 1.008-1.685; p = 0.044), which was confirmed even after multivariable adjustment (HR = 1.340; 95% CI: 1.002-1.792; p = 0.049) and propensity score matching (HR = 1.399; 95% CI: 1.002-1.951; p = 0.048). Although septal hypertrophy was not associated with the risk of all-cause mortality in patients with HFmrEF, it was identified as an independent predictor of long-term HF-related rehospitalization.

Automatic segmentation of 2D echocardiography ultrasound images by means of generative adversarial network.

Automated cardiac segmentation from two-dimensional (2D) echocardiographic images is a crucial step toward improving clinical diagnosis. Anatomical heterogeneity and inherent noise, however, present technical challenges and lower segmentation accuracy. The objective of this study is to propose a method for the automatic segmentation of the ventricular endocardium, the myocardium, and the left atrium, in order to accurately determine clinical indices. Specifically, we suggest using the recently introduced pixel-to-pixel Generative Adversarial Network (Pix2Pix GAN) model for accurate segmentation. To accomplish this, we integrate the backbone PatchGAN model for the discriminator and the UNET for the generator, for building the Pix2Pix GAN. The resulting model produces precisely segmented images, thanks to UNET's capability for precise segmentation and PatchGAN's capability for fine-grained discrimination. For the experimental validation, we use the Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) dataset, which consists of echocardiographic images from 500 patients in 2-chamber (2CH) and 4-chamber (4CH) views at the end-diastolic (ED) and end-systolic (ES) phases. Similarly to state-of-the-art studies on the same dataset, we followed the same train-test splits. Our results demonstrate that the proposed GAN-based technique improves segmentation performance for clinical and geometrical parameters compared to the state-of-the-art methods. More precisely, throughout the ED and ES phases, the mean Dice values for the left ventricular endocardium reached 0.961 and 0.930 for 2CH, and 0.959 and 0.950 for 4CH, respectively. Furthermore, the average ejection fraction correlation and Mean Absolute Error obtained were 0.95 and 3.2ml for 2CH, and 0.98 and 2.1ml for 4CH, outperforming the state-of-the-art results.

Cardiac Valve Event Timing in Echocardiography Using Deep Learning and Triplane Recordings.

Cardiac valve event timing plays a crucial role when conducting clinical measurements using echocardiography. However, established automated approaches are limited by the need of external electrocardiogram sensors, and manual measurements often rely on timing from different cardiac cycles. Recent methods have applied deep learning to cardiac timing, but they have mainly been restricted to only detecting two key time points, namely end-diastole (ED) and end-systole (ES). In this work, we propose a deep learning approach that leverages triplane recordings to enhance detection of valve events in echocardiography. Our method demonstrates improved performance detecting six different events, including valve events conventionally associated with ED and ES. Of all events, we achieve an average absolute frame difference (aFD) of maximum 1.4 frames (29 ms) for start of diastasis, down to 0.6 frames (12 ms) for mitral valve opening when performing a ten-fold cross-validation with test splits on triplane data from 240 patients. On an external independent test consisting of apical long-axis data from 180 other patients, the worst performing event detection had an aFD of 1.8 (30 ms). The proposed approach has the potential to significantly impact clinical practice by enabling more accurate, rapid and comprehensive event detection, leading to improved clinical measurements.

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-β1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

Optical Flow-Guided Cine MRI Segmentation With Learned Corrections.

In cardiac cine magnetic resonance imaging (MRI), the heart is repeatedly imaged at numerous time points during the cardiac cycle. Frequently, the temporal evolution of a certain region of interest such as the ventricles or the atria is highly relevant for clinical diagnosis. In this paper, we devise a novel approach that allows for an automatized propagation of an arbitrary region of interest (ROI) along the cardiac cycle from respective annotated ROIs provided by medical experts at two different points in time, most frequently at the end-systolic (ES) and the end-diastolic (ED) cardiac phases. At its core, a 3D TV- L1 -based optical flow algorithm computes the apparent motion of consecutive MRI images in forward and backward directions. Subsequently, the given terminal annotated masks are propagated by this bidirectional optical flow in 3D, which results, however, in improper initial estimates of the segmentation masks due to numerical inaccuracies. These initially propagated segmentation masks are then refined by a 3D U-Net-based convolutional neural network (CNN), which was trained to enforce consistency with the forward and backward warped masks using a novel loss function. Moreover, a penalization term in the loss function controls large deviations from the initial segmentation masks. This method is benchmarked both on a new dataset with annotated single ventricles containing patients with severe heart diseases and on a publicly available dataset with different annotated ROIs. We emphasize that our novel loss function enables fine-tuning the CNN on a single patient, thereby yielding state-of-the-art results along the complete cardiac cycle.

An attention-based deep learning method for right ventricular quantification using 2D echocardiography: Feasibility and accuracy.

To test the feasibility and accuracy of a new attention-based deep learning (DL) method for right ventricular (RV) quantification using 2D echocardiography (2DE) with cardiac magnetic resonance imaging (CMR) as reference. We retrospectively analyzed images from 50 adult patients (median age 51, interquartile range 32-62 42% women) who had undergone CMR within 1 month of 2DE. RV planimetry of the myocardial border was performed in end-diastole (ED) and end-systole (ES) for eight standardized 2DE RV views with calculation of areas. The DL model comprised a Feature Tokenizer module and a stack of Transformer layers. Age, gender and calculated areas were used as inputs, and the output was RV volume in ED/ES. The dataset was randomly split into training, validation and testing subsets (35, 5 and 10 patients respectively). Mean RVEDV, RVESV and RV ejection fraction (EF) were 163±70mL, 82±42mL and 51%±8% respectively without differences among the subsets. The proposed method achieved good prediction of RV volumes (R2 =.953, absolute percentage error [APE]=9.75%±6.23%) and RVEF (APE=7.24%±4.55%). Per CMR, there was one patient with RV dilatation and three with RV dysfunction in the testing dataset. The DL model detected RV dilatation in 1/1 case and RV dysfunction in 4/3 cases. An attention-based DL method for 2DE RV quantification showed feasibility and promising accuracy. The method requires validation in larger cohorts with wider range of RV size and function. Further research will focus on the reduction of the number of required 2DE to make the method clinically applicable.

ALK1 Deficiency Impairs the Wound-Healing Process and Increases Mortality in Murine Model of Myocardial Infarction.

The functional role of TGFβ type I receptor, activin-like kinase (ALK)-1 in post-myocardial infarction (MI) cardiac remodeling is unknown. We hypothesize that reduced ALK1 activity reduces survival and promotes cardiac fibrosis after MI. MI was induced in wild-type (WT), and ALK+/- mice by left coronary ligation. After 14 days ALK1+/- mice had reduced survival with a higher rate of cardiac rupture compared to WT mice. ALK1+/- left ventricles (LVs) had increased volumes at the end of systole and at the end of diastole. After MI ALK1+/- LVs had increased profibrotic SMAD3 signaling, type 1 collagen, and fibrosis as well as increased levels of TGFβ1 co-receptor, endoglin, VEGF, and ALK1 ligands BMP9 and BMP10. ALK1+/- LVs had decreased levels of stromal-derived factor 1α. These data identify the critical role of ALK1 in post-MI survival and cardiac remodeling and implicate ALK1 as a potential therapeutic target to improve survival after MI.

Effect of photobiological modulation therapy on cognitive impairment and cardiovascular structure in an APP/PS1 mouse model of Alzheimer’s Disease

AbstractBackgroundPhotobiological modulation (PBM) therapy, a form of low‐dose light therapy, is beneficial in treating various disease conditions including Alzheimer’s disease (AD). Double‐transgenic mice (APPswe/PS1dE9) develop progressive accumulation of amyloid‐β (Aβ) plaques, cognitive impairment, and alterations in cardiovascular structure and function, and represent a model of AD. Prior studies have shown that PBM therapy reduces the size and number of Aβ plaques in the neocortex and hippocampus in the mouse models of AD. The aim of this study was to investigate the effects of PBM on cardiovascular structure and function and cognitive function in the aged AD mice.MethodsSix‐month old female AD (APPswe/PS1dE9; AD‐PBM, n = 8) and wild type mice (WT‐PBM, n = 8) were exposed to near‐infrared light (wavelength 850 nm, 4.5 J/cm2, 3min/day, 5 days/week) for 6 months. Control mice (AD‐CNT, n = 6; WT‐CNT, n = 6) were placed under the PBM apparatus without turning the light on for 3min/day, 5 days/week. Cardiac parameters were measured by echocardiography. Gait analysis (DigiGait), home cage activity (HCA), and spatial working memory (indicated by alternation rate in cross maze test, CM) were assessed after 6 months of treatment. Group differences were identified by two‐way ANOVA.ResultsIn HCA test, the AD‐CNT mice exhibited circadian locomotor hyperactivity at night‐time relative to WT‐CNT mice (Figure 1A, B), which was reduced by PBM. AD‐CNT mice had lower alternation rates in CM, indicating spatial working memory impairment. PBM had minimal effect on this parameter (Table 1). The AD‐CNT vs. WT‐CNT mice manifested differences in several gait parameters, specifically, they demonstrated a lower fore propel time than WT‐CNT. PBM normalized this parameter in AD‐PBM mice to the level of WT‐CNT (Figure 1C). Both WT‐PBM and AD‐PBM mice had improved cardiovascular structure, which was demonstrated by lower relative wall thickness of left ventricle (LV) and LV mass, and higher LV volume at the end of diastole in PBM‐treated vs. correspondent CNT groups (Table 1, Figure 2).ConclusionPBM improved cardiovascular structure and AD‐associated cognitive impairment in the APP/PS1 mouse model. It is possible that more effective cardiovascular structure and function contributes to Aβ removal from the brain after PBM treatment. Supported by NIA/NIH/IRP

Maternal Cardiac Functional and Structural Changes in Preeclampsia: an Echocardiographic Study

Background &amp; objective: Preeclampsia is a pregnancy-induced multi-organ syndrome of acute cardiovascular manifestations with significant short and long-term sequelae. However, there is a relative lack of knowledge with respect to cardiac functional and structural changes in women with preeclampsia Therapeutic interventions used in the management of preeclampsia may cause iatrogenic adverse consequences due to this lack of knowledge. The present study was therefore designed to evaluate the echocardiographic changes in cardiac structural and functional indices in pregnant women with PE. Methods: This cross-sectional study was carried out in the Department of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Medical College Hospital (DMCH), and Shaheed Suhrawardy Medical College Hospital (SSMCH) in collaboration with National Institute of Cardiovascular Diseases (NICVD), Dhaka over a period of one year from July 2013 to June 2014. A total of 30 single-tone pregnant women of 20-40 weeks gestation with preeclampsia were taken as cases. An equal number of gestationally-matched healthy pregnant (HP) women of similar age cohorts having no history of preexisting hypertension were included as controls. Preeclampsia was defined as SBP ≥140and/or DBP ≥ 90 mmHg after 20 weeks gestation in a woman with previously normal blood pressure and with proteinuria≥1 + in the dipstick test. Pregnant women with systolic and diastolic blood pressures within the normal range (&lt; 140mmHg and &gt; 90 mmHg respectively), trace or absence of proteinuria by dipstick test were defined as controls. All thesubjects were investigated with ECG, standard two-dimensional, M-mode, and Doppler transthoracic echocardiography. The cardiac functional and structural changes were measured in terms of interventricular septal thickness (IVSTd),posterior wall thickness (PWTd), left ventricular internal diameter at the end of diastole (LVIDd), ejection fraction (EF), transmitral velocity (MV E/A ratio), MV deceleration time (MV DecT). Result: Half of the women with preeclampsia were primigravidae and there was no association between gravidity and the occurrence of preeclampsia. Prepregnancy overweight or obesity (in terms of BMI) was found to be strongly associated with preeclampsia. One in 10 PE women had a previous history of preeclampsia as opposed to none in the HP women. A substantial proportion (56.7%) of PE women had a family history of hypertension in comparison to healthy pregnant women (16.3%). The women with PE had significantly higher SBP, DBP, &amp; MAP than the HP women. Parameters of diastolic dysfunction, like mitral E/A ratio was reduced and deceleration time was prolonged in PE with diastolic dysfunction (mean E/A ratio &lt; 0.73 and mean DceT &gt;178 ms respectively) than those in PE with normal diastolic function (mean E/A ratio 1.2 and mean DceT 192.4 ms respectively) healthy pregnant women (mean E/A ratio 1.3 and mean DecT 186.5 ms respectively). Over one-third (36.7%) of women with PE met the criteria of diastolic dysfunction compared to none in healthy pregnant women. The LVH appears to be a frequent occurrence in pregnancies complicated by preeclampsia (43.3%) as compared to none in healthy pregnant women. In the present study, the systolic function was assessed with the help of EF, which was well-preserved both in PE and HP with no significant intergroup difference. Conclusion: Preeclampsia is associated with left ventricular diastolic dysfunction and hypertrophy preserving the systolic function. These structural and functional changes are primarily adaptive in nature for maintaining cardiac systolic function. Ibrahim Card Med J 2022; 12 (2): 32-39

Prediction of genetic cardiomyopathy by whole exome sequencing and myocardial strain in patients with concentric left ventricle hypertrophy

Abstract Introduction Genetic cardiomyopathies (CMP) are a group of inherited diseases that can lead to heart failure and sudden cardiac death. Left ventricular hypertrophy (LVH) is common findings in these diseases, but the diagnosis can be challenging due to their heterogeneous clinical presentations. Myocardial strain and whole exome sequencing (WES) are a powerful tool for early detection of genetic CMP. Purpose We aim to investigate the utility of the combination of myocardial strain and WES in the diagnosis of genetic CMP in patients with LVH. Methods We performed WES with buccal swab test on a total of 65 patients who had concentric LVH and decreased global average strain (GAS) by echocardiography between July 2021 and December 2022. The genetic data was analyzed to identify disease-causing genetic variants, and the clinical data and echocardiographic findings were collected and analyzed. Logistic regression analysis was performed to identify the predictive factors of genetic cardiomyopathy, and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of these factors. Results Of the 65 patients, we identified 10 patients with genetic cardiomyopathy by WES, including hypertrophic CMP, cardiac amyloidosis, and Fabry disease. The diagnostic yield of WES was 15.4% for genetic CMP. Logistic regression analysis showed that sex, diastolic blood pressure, interventricular septal thickness at end diastole (IVSd) and end systole (IVSs), posterior wall thickness at end diastole (PWd), and GAS were significant predictors of genetic CMP (p&amp;lt;0.05 for all). ROC curve analysis showed that IVSs had the highest area under the curve (AUC) value of 0.711 (p=0.037), with a sensitivity of 60.0% and a specificity of 67.3%. Conclusion Our study highlights the utility of WES and myocardial strain with echocardiographic data in diagnosing genetic CMP, especially in patients with concentric LVH. These findings support the integration of genetic testing and advanced imaging techniques in the diagnostic approach for patients with suspected genetic cardiomyopathies.

Reduced left ventricular elastance as a novel marker of cardiac dysfunction in patients with severe liver disease

Abstract Introduction Left ventricular (LV) elastance reflects the contractility of the myocardium and is an index of cardiac performance. Liver cirrhosis is characterized by reduced systemic vascular resistance, leading to reduced afterload on the LV. This, combined with increased blood volume, results in increased preload, increased stroke volume and remodeling of the LV. The latter may result to alterations in end-systolic LV elastance (Ees) a parameter that has not been extensively studied in cirrhotics. Purpose To investigate the relationship between Ees and the severity of liver cirrhosis. Methods We conducted a cross-sectional study in which transthoracic echocardiography was performed in 75 patients with liver cirrhosis (mean age 58.9±8.5 years, 74.7% males). A verified noninvasive single-beat formula was used to calculate Ees. Specifically, Ees was calculated employing systolic and diastolic blood pressures, echo-derived stroke volume (SV), ejection fraction (LVEF) and the estimated normalized ventricular elastance at arterial end-diastole (ENd). The ENd was estimated from a group-averaged value adjusted for individual contractile/loading effects. The Model for End-Stage Liver Disease-Sodium (MELDNa) score, a widely used tool for assessing liver disease severity was also calculated. We compared Ees between patients with MELDNa scores above and below 15, which is the cutoff commonly used to indicate severe liver disease. Results Mean Ees in the cohort of the 75 patients was 2.34±0.81mmHg/ml. Ees was correlated with end-systolic LV volume (rho=-0.448, p&amp;lt;0.001), SV (rho=-0.568, p&amp;lt;0.001) and systolic blood pressure (rho=0.283, p=0.014), but not with LVEF. Mean MELDNa score was 15.5±7.3 and 32 (42.7%) of patients had MELDNa score ≥ 15. Mean Ees in patients with MELDNa score above 15 was significantly lower than in patients with MELDNa score below 15 (2.08±0.61mmHg/ml vs 2.54±0.89mmHg/ml, p=0.015). The association remained significant in a multivariate model after adjusting for age, sex, and body surface area (B=-0.426, p=0.015). Conclusion Our study demonstrates that patients with severe liver disease have lower Ees, indicating impaired LV function. Ees could be a useful marker for identifying patients with liver cirrhosis who are at increased risk of cardiovascular complications. Further research is needed to better understand the mechanisms underlying this association and to propose therapeutic interventions aimed at improving LV function in this special population.

Atrial cardiomyopathy by strain predicts atrial fibrillation in young Lamin A/C patients

Abstract Introduction Cardiac laminopathy is a malignant and highly arrhythmogenic form of dilated cardiomyopathy caused by variants in the lamin A/C (LMNA) gene. Atrial fibrillation (AF) is common during disease progression and often occurs at a young age, before evident structural cardiac changes and therefore, decision making on anticoagulation for AF is challenging. Whether atrial cardiomyopathy is present at this early stage of LMNA disease has not yet been explored. Purpose We aimed to evaluate for atrial cardiomyopathy in LMNA genotype positive subjects without prior atrial arrhythmias and assess whether atrial cardiomyopathy would be associated with the occurrence of AF during follow-up. Methods We prospectively recruited LMNA genotype-positive patients in a cohort study. Patients without prior documented atrial arrhythmias were evaluated for atrial cardiomyopathy by echocardiography. Atrial cardiomyopathy was evaluated by left atrial (LA) volume index (LAVI) and LA strain (peak reservoir strain and peak conduit strain). LA strain was assessed by 2D speckle-tracking echocardiography, averaged from apical four- and two-chamber views using a LA strain dedicated software with R-wave at end diastole as zero-reference point. Results We evaluated 129 LMNA genotype positive patients (51% women, age 40±15 years), of whom 57 patients (44%) had previous AF. Hence, we included 72 patients (32±14 years old, 49% female, left ventricular ejection fraction 53±11%) for assessment of atrial cardiomyopathy. The mean LA reservoir strain was 35±14%, conduit strain 25±13% and LAVI 38±23 ml/m2. During 7.7±5.0 years of follow-up, 28 (39%) patients developed AF after a median of 2.2 years. Patients with AF during follow-up had larger LAVI (47±30 vs. 32±10ml/m2, p=0.01) and worse LA reservoir strain (29±12% vs. 38±14%, p=0.02) at baseline than those who did not develop AF. LA reservoir strain and LAVI at baseline were both predictors of AF during short-term follow-up (HR 0.95 [CI 0.90-0.99], p=0.025 and HR 1.02 [CI 1.01-1.03], p=0.009, respectively), whereas LA conduit strain was not (HR 0.98 [CI 0.94-1.03], p=0.45). ROC analysis identified LA reservoir strain better than 32.5% as the best discriminating value for survival free of AF (log rank p=0.05) (Figure). Conclusion Atrial cardiomyopathy was common in LMNA genotype positive patients without previous atrial arrhythmias. LA volume and and LA reservoir strain predicted new onset AF during follow-up and may be used as markers for detecting short term risk of AF and potentially guide anticoagulation treatment in LMNA disease.LA reservoir strain and AF in LaminA/C

Left atrial appendage geometry and function using transesophageal three-dimensional echocardiography in atrial fibrillation: a new approach to characterize left atrial thrombogenic milieu

Abstract Background Little data is available on the evaluation of left atrial appendage (LAA) geometry and function using three-Dimensional (3D) transoesophageal echocardiography (TEE). Purpose We hypothesized that 3D LAA geometry evaluated using dedicated TEE software could be integrated in the evaluation of the thromboembolic milieu in patients hospitalized for atrial fibrillation (AF). Methods We prospectively studied 206 hospitalized patients with AF with two-dimensional transthoracic echocardiography (TTE) and 3D TEE of the LAA within 24 hours of admission. 3D parameters were analysed off-line using Tomtec software (4D Cardio-View, Generic Volume, Philips) (Figure 1). Patients were divided into two groups according to the presence (n = 35) or absence (n = 171) of LAA sludge/thrombus on admission. Results Patients with LAA sludge/thrombus had more frequently a history of heart failure together with higher values of BNP, CRP and hemoglobin. These patients received less frequently angiotensin II receptor antagonist treatment on admission. Concerning the echocardiographic characteristics, patients with LAA sludge/thrombus exhibited higher left atrial (LA) volume, lower left ventricular ejection fraction (LVEF) and cardiac output. In the 2D TEE study they had lower LAA emptying and filling flow velocities compared to those without sludge/thrombus. 3D TEE showed overall higher 3D end-systolic (ES) and end-diastolic (ED) LAA measurements (ostium area, length, volume), and more frequently the absence of a chicken wing morphology. There were no intergroup differences regarding the number of LAA lobes (Table 1). Conclusion 3D characterization of LAA geometry and function depicts a degree of appendage remodeling in AF that appears to be associated with the degree of thrombogenicity. Further investigation is needed to determine the impact of this remodeling on outcomes in these patients.

Abstract 16590: Left Ventricular Remodelling Following Transcatheter Mitral Valve Replacement With the Innovalve System

Introduction: Transcatheter Mitral Valve Replacement (TMVR) using a trans-septal approach is a new therapeutic option for patients with severe mitral regurgitation (MR). However, both surgical as well as currently under-testing trans-catheter approach, are shown to cause decrease in LV function. The Innovalve TMVR is a novel self-expandable transcatheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intravalvular posterior position after subvalvular anchoring by rotation of 6 circumferential arms Hypothesis: TMVR procedure (Innovalve system) leads to LV anatomical and functional changes Methods: CT was performed before the Innovalve TMVR procedure, and after 3 to 6 months. CT protocol included retrospective ECG gating with full cardiac cycle coverage. LV end diastolic and end systolic diameters (LVEDD, LVESD) were measured in the left ventricular outflow tract orientation at the most basal level. Tip to tip papillary muscle distance was measured in the short axis orientation at the most basal slice demonstrating the papillary muscle tips. LV ejection fraction (LVEF) was calculated using the end systolic and end diastolic volumes. All measurements were performed at end systole and end diastole before MTVR and after 3-6 months using a dedicated platform (3Mensio). Results: Ten patients (7 males) average age 69+/-10 years, underwent the Innovalve TMVR procedure. Average LVESD decreased from 52±15 mm at baseline to 44±15mm (P=0.016) at 3-6 months. Similarly, LVEDD decreased from 60±14 mm at baseline, to 52±13mm at 3-6 months (P=0.039). Average papillary muscle tip to tip distance at end diastole (ED) decreased from 31.7±7mm at baseline to 28.4±6.5mm at 3-6 months (P=0.047).A trend of LVEF improvement was evident with an increase from 35%±12 average at baseline compared with 39%±12 average after 3-6 months (P=0.346). Conclusions: These preliminary results show that the TMVR procedure using the Innovalve system may result in favourable LV reverse remodelling changes including reduction of LVESD, LVEDD and ED papillary muscle distances, with improved LVEF. This encouraging data might suggest favourable postprocedural structural LV change.

Abstract 13816: Clearing P16+ Cells Prevents Cardiac Dysfunction and Death in Mice With Acute Myocardial Infarction

Introduction: Cellular senescence, a stress and age-related response, is often characterized by p16 expression in p16 positive (p16 + ) senescent cells. Senescent cells secrete profibrotic and proinflammatory factors as parts of a “senescence associated secretory phenotype”. The role of cellular senescence in myocardial infarction (MI) is unclear. Aims: To study the effect of p16 + cell clearance on survival, cardiac remodeling and function after MI. Methods: We used INK ATTAC transgenic mice, in which p16 + cells undergo targeted apoptosis upon exposure to a dimerizer, AP20187 (AP). MI mice were treated with AP or vehicle (V), twice a week for 1 month, beginning 3-4 hours post-MI. Cardiac function and structure were evaluated with echocardiography, hemodynamic parameters with a Millar catheter, infarct area with Masson’s Trichrome, gene expression with qPCR and single-nucleus RNA-sequencing (snRNAseq). Results: Survival post MI was dramatically increased in MI-AP vs MI-V mice (P&lt;0.001, Fig A), primarily via prevention of cardiac rupture (CardRup). Left ventricular (LV) ejection fraction (EF%) and LV anterior wall thickness at end diastole (LVAWd) decreased in MI-V vs Sham and improved in MI-AP mice (Fig B), indicating preservation of cardiac function and structure with p16 + cell clearance. Hemodynamic indices of LV function (max and min dP/dt) improved with AP (Fig C). Fibrosis-related gene expression (Col1a1, Col3a1 and Lox; Fig D) increased with MI and improved with AP, paralleling changes in infarct size (Fig E). snRNAseq showed that genes were principally upregulated in MI-V macrophages and neutrophils; significant responses were seen in TNF-α, inflammatory response pathways and gene programs associated with CardRup (Fig F). Conclusion: These results suggest that p16 + cells play a significant role in the evolution of MI, apparently by modulating inflammatory signaling, pointing to an important pathophysiological role of cellular senescence.

Abstract 17128: Detection of Hypertrophic Cardiomyopathy From Noisy Single-Lead Electrocardiography

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death among young people and be detected from ECGs using artificial intelligence. Wearable devices could allow for broad AI-based screening but obtain noisy ECGs. We report the development of a wearable-adapted AI-ECG model that retains performance for detecting HCM in noisy single-lead ECGs. Methods: In 11,883 ECGs obtained within 30 days of transthoracic echocardiograms from Yale New Haven Hospital (2015-2021), we defined HCM as interventricular septal wall thickness (end diastole) (IVSd) &gt; 15 mm and moderate to severe left ventricular diastolic dysfunction (LVDD). Standard and noise-adapted models were trained using a 1:10 age-sex matched dataset. For the noise-adapted model, each ECG was included four times in the training set, augmented each time with random gaussian noise within four distinct frequency ranges emulating different real-world noise sources. We evaluated the performance of the noise-adapted and standard models on an independent set of ECGs with four different real-world noisy artifacts, including noise extracted from a portable device ECG, at multiple signal-to-noise ratios (SNRs). Results: In single-lead ECGs without noise, the noise-adapted model outperformed the standard model, with an AUROC of 0.920 and 0.906, respectively for HCM. With the same ECGs augmented with noise ranging from half (SNR 2) to twice (SNR 0.5) the signal, the noise-adapted model maintained their performance across real-world noise signatures (A). At an SNR of 0.5, the noise adapted model had a significantly greater performance in detecting HCM in ECGs augmented with portable device ECG noise (AUROC 0.917 [0.861-0.974] vs 0.609 [0.398, 0.821]) (B). Conclusions: We developed a model which accurately screens for HCM in noisy single-lead ECGs. This approach represents a more accessible and scalable method for screening for HCM using wearable device ECGs.

Abstract 16717: Managing Myxedema Coma: A Challenging Case of Cardiogenic Shock Culminating in Orthotopic Heart Transplantation

Background: Myxedema coma (MC) is a rare manifestation of severe hypothyroidism often seen in elderly female patients. While the sequelae of MC can lead to multi-organ involvement and eventual failure, irreversible Heart Failure (HF) is rarely seen. This case culminated in orthotopic heart transplant (OHT) for definitive treatment. Case Presentation: A 23-year-old male presented with worsening RUQ abdominal pain for 2 weeks. In the ED, he had PEA arrest and with ROSC, he was admitted to the CCU for presumed cardiogenic shock, with labs remarkable for lactate 7.5 mmol/L, pro-BNP 6104 pg/mL, and markedly elevated serum creatinine and LFTs. The patient exhibited HF symptoms for 9 months before admission, manifesting as worsening LE edema, fatigue, and weight gain. He was also noted to have untreated hypothyroidism with repeat TSH of 857 μIU/mL on admission, indicating MC as a potential trigger for worsening HF. TTE revealed severe biventricular dysfunction with global hypokinesis and LVEF of 10-15%. Inotropic support was initiated with dobutamine, with RHC showing CVP 11 mmHg, RV 23/11 mmHg, PA 32/22 mmHg, PCWP 25 mmHg, and CI 2.3 LPM/m 2 . Subsequent deterioration in CI and MVO2 necessitated IABP placement and vasopressor support, and later rescue VA-ECMO with atrial septostomy, aiming for OHT. Endocrine evaluation confirmed primary hypothyroidism, and the patient received high-dose levothyroxine, T3, and stress-dosed steroids. While there have been instances where cardiac consequences of myxedema HF were reversed by thyroid administration, his significantly dilated left ventricular internal dimension at end diastole, as well as complications of ECMO (bleeding) expedited his transplant evaluation. OHT was successfully performed on hospital day 14. Continuous improvement in thyroid function studies was observed throughout the treatment course with levothyroxine therapy. Discussion: Worsening HF in the setting of MC, particularly in a male patient, is an uncommon presentation that requires prompt action. This patient required mechanical support as an eventual bridge to OHT with simultaneous treatment for hypothyroidism, illustrating the complexity of the case and the interventions necessary for a positive outcome in an uncommon clinical scenario.