Left Ventricular Stroke Volume Research Articles

The causality between obstructive sleep apnea and ventricular structure and function: a bidirectional Mendelian randomization study.

Background: Multiple observational studies have discovered a substantial link between obstructive sleep apnea (OSA) and ventricular dysfunction. However, conventional observational studies are vulnerable to causal reversal and confounding, making it challenging to infer the causes of effects and their direction. Methods: With the help of a bidirectional, two-sample Mendelian randomization (MR) study, we assessed the potential causality between OSA and left and right ventricular (LV, RV) structure and function. We conducted our analysis utilizing summary data from genome-wide association studies of OSA (16,761 cases and 201,194 controls) in the FinnGen Study, as well as LV (36,041 participants) and RV (29,506 participants) in the UK Biobank cardiovascular magnetic resonance research. The inverse variance weighted (IVW) was selected as the main strategy, with the MR-Egger and weighted median methods serving as supplements. Other methods were employed as sensitivity analysis tools to look at heterogeneity and pleiotropy, including MR-Egger intercept, Cochran Q statistic, MR-PRESSO, and leave-one-out analysis. Results: In the primary IVW analysis, genetically predicted OSA was strongly causative on LV end-diastolic volume (β = 0.114, 95% CI = 0.034-0.194, p = 0.006) and LV stroke volume (β = 0.111, 95% CI = 0.031-0.191, p = 0.007), and genetically predicted LV ejection fraction was linked to an increased risk of OSA (OR = 1.161, 95% CI = 1.029-1.309, p = 0.015). However, there was no connection found between OSA and any RV parameters. Conclusion: Our genetic analysis raises a potential causative link between OSA and ventricular structure and function, which may improve the knowledge of OSA as a risk factor for cardiovascular disease by demonstrating a direct impact on cardiac structure and function.

Advanced photon counting CT imaging pipeline for cardiac phenotyping of apolipoprotein E mouse models.

Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT). 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac segmentation. Statistical analysis evaluated genotype, diet, sex, and body weight effects on cardiac measurements. Our results showed that PCCT offered high quality imaging with reduced noise. Material decomposition enabled separation of calcified plaques from iodine enhanced blood in APOE KO mice. Deep learning-based segmentation showed good performance with Dice scores of 0.91 for CT-based segmentation and 0.89 for iodine map-based segmentation. Genotype-specific differences were observed in left ventricular volumes, heart rate, stroke volume, ejection fraction, and cardiac index. Statistically significant differences were found between control and high fat diets for APOE2 and APOE4 genotypes in heart rate and stroke volume. Sex and weight were also significant predictors of cardiac measurements. The inclusion of the human NOS2 gene modulated these effects. This study demonstrates the potential of PCCT in assessing cardiac structure and function in mouse models of CVD which can help in understanding the interplay between genetic factors, diet, and cardiovascular health.

Diagnostic capabilities of echocardiographic indicators of acceleration time and the ratio of acceleration time to total left ventricular ejection time in the assessment of severe aortic stenosis in patients with reduced left ventricular ejection fraction

Objectives: 1) to evaluate the diagnostic capabilities of AT and AT/ET in determining severe AS in patients with reduced LV EF and low stroke volume.2) to determine the threshold values for AT and AT/ET in the diagnosis of severe AS in patients with low stroke volume and low transaortic gradient.Materials and methods. This is prospective single center study included 70 patients with low transaortic pressure gradient, reduced LV ejection fraction was and severe aortic stenosis. All patients have been examined from 2017 to 2022. Inclusion criteria for the study are: isolated AV stenosis with, reduced LV RF, low transaortic pressure gradient. Severity of AS was identified based on dobutamine stress echocardiography and aortic valve area (AVA). Severe stenosis was defined as AVA< 1 cm2.Result. A statistically significant and high negative correlation was found between the AVA and AT/ET ratio, (r = 0.77, p < 0.001) and weak correlation with the AT indicator (r = 0.41, p = 0.01). The RoC-analysis showed the greatest predictive ability in the differential diagnosis of severe AS for the ratio AT/ET (AUC = 0.84 ± 0.54, p < 0.001) and the lower predictive ability for the indicator AT (AUC = 0.63 ± 0.72, p < 0.02). The optimal threshold value for determining severe AS for the AT / ET > 0.32 (sensitivity of 92%, specificity of 70%), for AT > 99 (sensitivity of 81%, specificity of 88%). Multiple logistic regression analysis revealed that the AT/ET ratio is the only echocardiographic parameter that has a significant impact on the differential diagnosis of severe AS in patients with reduced LV EF (OR 1.5; 95% CI 1.2–1.9, p = 0.001). There was low interobserver variability in measurements of AT score (intraclass correlation coefficient was 0.93 [95% CI, 0.80-0.97] and AT/ET ratio (intraclass correlation coefficient was 0.88 [95% CI, 0.75–0.95]).Conclusions.In patients with AS and reduced LV stroke volume the AT/ET ratio is highly sensitive and well reproducible in the diagnosis of severe AS. The AT index has a weak diagnostic ability of severe AS in that patients.The threshold value of AT/ET >0.32 can diagnose severe AS with a high degree of probability in patients with reduced LV stroke volume and reduced transaortic gradients with reduced LV EF.

The Use of Global Longitudinal Strain to Detect Subclinical Reduction in Left Ventricular Pump Function.

Left ventricular (LV) ejection fraction (LVEF) is not a sensitive marker of LV systolic function in a subset of patients with preserved EF. The relation between LV pump function and global longitudinal strain (GLS) has not been elucidated well in patients with objectively preserved EF and no apparent heart failure (HF). We aimed to detect whether LV GLS can discover impaired LV pump function [presented as low stroke volume index (SVI) and low cardiac output (COP)] in patients with objectively preserved EF and no apparent clinical HF and its practice utility. In total, 100 participants with LVEF of ≥50% were studied for demographic and echocardiographic data, including LVEF, stroke volume, SVI, COP, LV longitudinal strain assessments, apical 4-, 3-, and 2-chamber views averaged for GLS, and were classified into 2 groups: group 1: normal GLS (more negative than -18%) and group 2: low GLS (less negative than -18%). Reduced LV GLS was associated with lower SVI (35.6 ± 13.6 vs. 43.8 ± 12.7 mL/m 2 ; P = 0.01), lesser COP (5.4 ± 1.9 vs. 6.5 ± 2.1 l/min; P = 0.02), GLS had strong positive correlations with SVI ( r = 0.75; P < 0.001), and COP ( r = 0.66; P < 0.001). LV GLS at a cutoff value less negative than -15% is a strong predictor of SVI ≤35 mL/m 2 (76% sensitivity and 79% specificity) and at a cutoff value less negative than -13.5% it is a strong predictor of COP ≤4 L/min (76% sensitivity and 73% specificity). LV GLS was the best independent predictor of low SVI (<35 mL/m 2 ) and low COP (<4 L/min). Impaired LV strain is associated with lower LV pump function, presented as lower COP and lower SVI in patients with preserved EF even in the absence of clinical HF. It is of great importance to incorporate GLS in the routine evaluation of LV function hand-by-hand with the noninvasive assessment of LV stroke volume and COP that can replace GLS on evaluation of LV pump function in old machines with no GLS modalities, for early pick-up of patients with impaired LV pump function before apparent HF.

Effect of Glucagon-like Peptide-1 Receptor Agonist on Cardiac Structure and Function in Patients with Heart Failure: A Systematic Review and Meta-analysis

Article Effect of Glucagon-like Peptide-1 Receptor Agonist on Cardiac Structure and Function in Patients with Heart Failure: A Systematic Review and Meta-analysis Xinyu Zhang 1, and Hongyuan Zhang 2, * 1 Division of Bioscience, University College London, London, UK 2 Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK * Correspondence: hongyuan.zhang-3@postgrad.manchester.ac.uk Received: 23 May 2023 Accepted: 8 August 2023 Abstract: Recent clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) yield positive effects on composite cardiovascular endpoints, rendering them potentially promising therapeutic agents for heart failure (HF). This study analysed the effect of GLP-1RAs on cardiac structure and function in HF patients. MethodsA comprehensive search was conducted across PubMed, Cochrane Library, Ovid Embase, Ovid Medline, and Web of Science databases, spanning from inception to August 1, 2022, to identify randomised controlled trials (RCTs) comparing alterations in cardiac structure and function in HF patients receiving GLP-1RAs or placebo. Cardiac structures were assessed through left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular mass (LVM). Systolic function was evaluated using left ventricular ejection fraction (LVEF), stroke volume (SV), and global longitudinal strain (GLS). Diastolic function was assessed via the early to late diastolic filling velocity ratio (E/A ratio) and the early transmitral filling velocity to early diastolic mitral annular velocity ratio (E/e ratio). The I2 statistic was used to test heterogeneity. Pooled relative risks were calculated using random-effects models. Potential publication bias was assessed using the Cochrane Risk of Bias 2 tool. ResultsA total of 1,417 patients from 16 randomised placebo-controlled trials were enrolled in this meta-analysis. Among all HF patients, GLP-1RAs demonstrated improvement in diastolic function as indicated by E/A (MD = -0.15; 95% CI: -0.21 to -0.09; P &lt; 0.00001; I2 = 43%) and E/e’ (MD = -0.82; 95% CI: -1.53 to -0.11; P = 0.02; I2= 62%). However, GLP-1RAs did not exhibit any improvement in cardiac structure and systolic function parameters for HF patients. ConclusionGLP-1RAs demonstrated potential for improving diastolic function in HF patients, but did not show any impact on systolic function and cardiac structure. Therefore, the application of GLP-1RAs should be based on the specific HF type and accompanying comorbidities.

Prevalence, mechanisms, and prognostic impact of dynamic mitral regurgitation assessed by isometric handgrip exercise.

The extent of mitral regurgitation (MR) may vary depending on the haemodynamic situation; thus, exercise testing plays an important role in assessing the haemodynamic relevance of MR. We aim to assess prevalence, mechanisms, and prognostic impact of exercise-induced changes in MR in patients with degenerative MR (DegMR) and functional MR (FMR). We enrolled 367 patients with at least mild MR who underwent standardized echocardiography at rest and during handgrip exercise. Handgrip exercise led to an increase in MR by one grade or more in 19% of DegMR and 28% of FMR patients. In FMR, patients with exercise-induced increases in MR, handgrip exercise led to a reduction in left ventricular stroke volume index, being maintained in DegMR patients. Exercise-induced changes in systolic pulmonary artery pressure were linked to changes in effective regurgitant orifice area (DegMR: r = 0.456; P < 0.001; FMR: r = 0.326; P < 0.001). Thus, 26% of patients with DegMR and FMR developed pulmonary hypertension during exercise. In both cohorts, a significant proportion of patients with non-severe MR at rest and exercise-induced severe MR underwent mitral valve surgery/intervention during follow-up. In FMR patients (but not in DegMR patients), early mitral valve surgery/intervention was independently associated with lower event rates during follow-up [0.177 (0.027-0.643); P = 0.025]. Handgrip exercise echocardiography provides important information regarding the dynamic nature of MR, exercise-induced changes in left ventricular function, and pulmonary circulation with subsequent consequences for further therapeutic decision making. Thus, it should be considered as a diagnostic tool in symptomatic patients with non-severe MR at rest.

Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.

Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR). Sex-specific uncorrelated genome-wide significant (P<5×10-8 ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11528 female and 14356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47309 cases and 930014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [β per nmol/L=-0.11 (-0.19 to -0.03), P=0.006], lower LVESV [β=-0.09 (-0.17 to -0.01), P=0.022], lower LVSV [β=-0.11 (-0.18 to -0.03), P=0.005], lower cardiac output [β=-0.08 (-0.16 to 0.00), P=0.046], and lower cardiac index [β=-0.08 (-0.16 to -0.01), P=0.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P=0.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [β per nmol/L=0.17 (0.08-0.25), P=2×10-4 ], higher LVESV [β=0.13 (0.05-0.22), P=0.003], and higher LVSV [β=0.18 (0.08-0.28), P=2×10-4 ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [β=-0.07 (-0.12 to -0.02), P=0.007] and LVEF [β=-0.11 (-0.18 to -0.04), P=0.003], respectively. This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.

Mueller maneuver attenuates left atrial phasic volumes and myocardial strain in healthy younger adults.

The left atrium (LA) is a key, but incompletely understood, modulator of left ventricular (LV) filling. Inspiratory negative intrathoracic pressure swings alter cardiac loading conditions, which may impact LA function. We studied acute effects of static inspiratory efforts on LA chamber function, LA myocardial strain, and LV diastolic filling. We included healthy adults (10 males/9 females, 24 ± 4 yr) and used Mueller maneuvers to reduce intrathoracic pressure to -30 cmH2O for 15 s. Over six repeated trials, we used echocardiography to acquire LA- and LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LA and LV chamber volumes, tissue relaxation velocities, transmitral filling velocities, and speckle tracking-derived LA longitudinal strain. Repeated measures were made at baseline, early Mueller, late Mueller, then early release, and late release. In the late Mueller compared with baseline, LV stroke volume decreased by -10 ± 4 mL (P < 0.05) and then returned to baseline upon release; this occurred with a -11 ± 9 mL (P < 0.05) end-diastolic volume reduction. Early diastolic LV filling was attenuated, reflected by decreased tissue relaxation velocity (-2 ± 2 cm/s, P < 0.05), E-wave filling velocity (-13 ± 14 cm/s, P < 0.05), and LA passive emptying volume (-5 ± 5 mL, P < 0.05), each returning to baseline with release. LA maximal volume decreased (-5 ± 5 mL, P < 0.05) during the Mueller maneuver, but increased relative to baseline following release (+4 ± 5 mL, P < 0.05), whereas LA peak positive longitudinal strain decreased (-6 ± 6%, P < 0.05) and then returned to baseline. Attenuated LA and in turn, LV filling may contribute to acute stroke volume reductions experienced during forceful inspiratory efforts.NEW & NOTEWORTHY In healthy younger adults, the Mueller maneuver transiently reduces left atrial filling and passive emptying during the reservoir and conduit phases, respectively. Corresponding reductions are seen in left atrial reservoir and conduit phase longitudinal myocardial strain and strain rate. However, left atrial pump phase active function and mechanics are largely preserved compared with baseline. Rapid changes in LA chamber volumes and myocardial strain with recurrent forceful inspiratory efforts and relaxation may reflect acute LA stress.

Effect of ticagrelor and clopidogrel dual antiplatelet therapy on MPVLR, MAADP, and AA inhibition rate in acute coronary syndrome patients after percutaneous coronary intervention.

To explore the effects of ticagrelor and clopidogrel dual antiplatelet therapy on the mean platelet volume-to-lymphocyte ratio (MPVLR), maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP), and arachidonic acid (AA) inhibition rates in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). A total of 120 patients with ACS undergoing elective PCI in our hospital between March 2020 and November 2021 were recruited. Patients were divided into 2 groups using the random number table method, with 60 patients in each group. The control group received clopidogrel + aspirin dual antiplatelet therapy, while the study group received ticagrelor + aspirin dual antiplatelet therapy. MPVLR, MAADP, and AA inhibition rates were compared between the 2 groups. Platelet activation indices, platelet micro PNA-223, and platelet gelsolin levels were measured before and 4 weeks after PCI. Changes in cardiac function indices, bleeding rates, and major adverse cardiovascular events (MACE) were compared between groups. The MAADP score of the study group was lower than that of the control group 3 days after surgery (P < .05). Compared with before surgery, CD62p, CD63, miR-223, PAC-1, platelet membrane glycoprotein IIb/IIIa complex, and gelsolin levels markedly decreased in both groups 4 weeks after surgery (P < .05). The platelet activation index and platelet miR-223 and gelsolin levels were significantly lower in the study group than in the control group 4 weeks after surgery (P < .05). The overall platelet inhibition effect was significantly better in the study group than in the control group (P < .05). Compared with before surgery, the left ventricular ejection fraction and stroke volume were significantly increased, and the left ventricular end-diastolic volume and left ventricular end-diastolic diameter significantly decreased in both groups 4 weeks after surgery (P < .05). No significant differences were found between the 2 groups in terms of the incidence of bleeding events or MACE (P > .05). Ticagrelor is more effective than clopidogrel for platelet inhibition after PCI in patients with ACS and is worthy of clinical recommendation.

The potential predictive value of cardiac mechanics for left ventricular reverse remodelling in dilated cardiomyopathy.

Left ventricular reverse remodelling (LVRR) is an important objective of optimal medical management for dilated cardiomyopathy (DCM) patients, as it is associated with favourable long-term outcomes. Cardiac magnetic resonance (CMR) can comprehensively assess cardiac structure and function. We aimed to assess the CMR parameters at baseline and investigate independent variables to predict LVRR in DCM patients. Nighty-eight initially diagnosed DCM patients who underwent CMR and echocardiography examinations at baseline were included. CMR parameters and feature tracking (FT) based left ventricular (LV) global strain (nStrain) and nStrain indexed to LV cardiac mass index (rStrain) were measured. The predictors of LVRR were determined by multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of CMR parameters and were compared by the DeLong test. At a median follow-up time of 9 [interquartile range, 7-12] months, 35 DCM patients (36%) achieved LVRR. The patients with LVRR had lower LV volume, mass, LGE extent and stroke volume index (LVSVi) and higher left ventricular remodelling index (LVRI), nStrains, rStrains, and peak systolic strain rate (PSSR) in the longitudinal direction and rStrains in the circumferential direction at baseline (all P<0.05). In the multivariate logistic regression analyses, LVRI [per SD, odds ratio (OR) 1.79; 95% confidence interval (CI) 1.08-2.98; P=0.024] and the ratio of global longitudinal peak strain (rGLPS) (per SD, OR 1.88; 95% CI 1.18-3.01; P=0.008) were independent predictors of LVRR. The combination of LVSVi, LVRI, and rGLPS had a greater area under the curve (AUC) than the combination of LVSVi and LVRI (0.75 vs. 0.68), but not significantly (P=0.09). Patients with LVRR had a lower LV volume index, lower LVSV index, lower LGE extent, higher LVRI, and preserved myocardial deformation in the longitudinal direction at baseline. LVRI and rGLPS at baseline were independent determinants of LVRR.

Impact of Premature Ventricular Complex (PVC) Burden on the Left Ventricle in the Structurally Normal Heart: Hemodynamic Alterations of Idiopathic PVC on Echocardiography.

Premature ventricular complex (PVC) without structural heart disease is mostly viewed as a benign arrhythmia. However, the high burden of PVC causes cardiomyopathy due to intraventricular dyssynchrony. The effects of ectopic contraction on left ventricular (LV) hemodynamics in the structurally normal heart are unclear. To examine the effect of PVC burden on LV dimension, LV systolic function, and intraventricular blood flow, and to determine whether ectopic ventricular contraction affects LV hemodynamics. Patients aged ≥ 18 years with PVC ≥ 5% on Holter recording were enrolled and divided into groups G1 (5-10%), G2 (10-20%), and G3 (≥ 20%). We excluded patients with structural heart diseases, pacemakers, and LV systolic dysfunction [LV ejection fraction (LVEF) < 50%]. Clinical characteristics and routine transthoracic echocardiography parameters were compared. The end-systolic LV internal dimension increased according to the PVC burden from G1 to G3 (p = 0.001). LVEF was inversely associated with PVC burden from G1 to G3 (p = 0.002). The same pattern was seen for LV outflow tract (LVOT) maximal velocity (p = 0.005) and maximal pressure gradient (PG) (p = 0.005), LVOT velocity time integral (VTI) (p = 0.03) and LV stroke volume index (LVSI) (p = 0.008). Systolic function and LV end-systolic dimension were inversely associated with PVC burden. Decreased LVOT flow velocity and PG were related to increased PVC burden. LVOT VTI and LVSI were smaller when the PVC burden exceeded 20%. These negative hemodynamic manifestations of idiopathic PVC were considerable even in structure normal hearts, hence the early elimination of PVC is strongly advised.

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction.

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.

Cardiac Structure and Function in Patients With Obesity and Non-alcoholic Fatty Liver Disease.

Introduction Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide. The global prevalence of NAFLD is expected to increase dramatically with the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). The role of NAFLD as a cardiometabolic risk factor or component of metabolic syndrome on the heart remains unclear. Thus, the independent effect of NAFLD on structural and functional heart parameters warrants validation. Our goal was to study cardiac structure and function in subjects with obesity and NAFLD. Methods A total of 164 patients were examined in this cross-sectional study. Participants were grouped based on BMIand the presence or absence of abdominal obesity (AO) and/or NAFLD. The subjects were divided into four groups:group 1: normal BMI without AO and NAFLD; group 2: BMI ≥ 25 kg/m2or AO without NAFLD; group 3: BMI ≥ 25 kg/m2and AO without NAFLD;group 4: patients with BMI ≥ 25 kg/m2,AO, and NAFLD. We performed a thorough clinical examination, a biochemical blood analysis, and echocardiography. Indices of liver steatosis and fibrosis were calculated. A study of liver assessment of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) was conducted. Statistical analysis was performed using IBM SPSS Statistics version 26 (IBM Corp., Armonk, NY). Results The mean age of the participants was 35.0 (31.0-38.5) years. We found a higher frequency of multiple cardiometabolic risk factors in the general cohort. However, on comparing groups 3 and 4, we found a higher frequency of hyperinsulinemia, homeostatic model assessment of insulin resistance (HOMA-IR), and obesity (p < 0.05). To assess the role of NAFLD independent of obesity, we conducted further analyses after adjusting for BMI. Among patients with NAFLD, we observed a similar trend for parameters of carbohydrate metabolism (p < 0.005).In individuals with NAFLD, an increase in left atrial (LA) volume, interventricular septal (IVS) thickness, and left ventricular (LV) myocardial mass, and a decrease in LV ejection fraction and LV stroke volume index were found (p < 0.005). The hepatic steatosis index (HSI) correlated with LA volume, LV end-systolic volume (ESV) and LV end-diastolic volume (EDV), stroke volume, and LV myocardial mass. An association between an increase in CAP score and an increase in the LA volume, stroke volume index, IVS thickness, LV myocardial mass, and the values of LSM with an increase in the LA volume was established. Conclusion The presence of NAFLD without cardiovascular disease and diabetes mellitus revealed an association with the structural and functional parameters of the heart.The results of this study can also be used to improve the effectiveness of a comprehensive assessment of patients and to develop strategies for the primary and secondary prevention of heart failure with preserved ejection fraction in NAFLD.

Echocardiographic characteristics of dogs with pulmonary hypertension secondary to respiratory diseases.

Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure. To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs. Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated. Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m2 , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively). Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.

Elevated atrial blood stasis in paroxysmal atrial fibrillation during sinus rhythm: a patient-specific computational fluid dynamics study.

Atrial fibrillation (AF) is associated with an increased risk of stroke, often caused by thrombi that form in the left atrium (LA), and especially in the left atrial appendage (LAA). The underlying mechanism is not fully understood but is thought to be related to stagnant blood flow, which might be present despite sinus rhythm. However, measuring blood flow and stasis in the LAA is challenging due to its small size and low velocities. We aimed to compare the blood flow and stasis in the left atrium of paroxysmal AF patients with controls using computational fluid dynamics (CFD) simulations. The CFD simulations were based on time-resolved computed tomography including the patient-specific cardiac motion. The pipeline allowed for analysis of 21 patients with paroxysmal AF and 8 controls. Stasis was estimated by computing the blood residence time. Residence time was elevated in the AF group (p < 0.001). Linear regression analysis revealed that stasis was strongest associated with LA ejection ratio (p < 0.001, R2 = 0.68) and the ratio of LA volume and left ventricular stroke volume (p < 0.001, R2 = 0.81). Stroke risk due to LA thrombi could already be elevated in AF patients during sinus rhythm. In the future, patient specific CFD simulations may add to the assessment of this risk and support diagnosis and treatment.

Abstract P3206: Sex-specific Differences In Proteasome Activity And Mitochondrial Function In Mouse Hearts Lacking Natriuretic Peptide Receptor A

Objective: Atrial natriuretic peptide (ANP) is a cardiac hormone that plays an important role in cardiovascular function and energy metabolism by signaling through natriuretic peptide receptor A (NPRA). Genetic ablation of NPRA in mice resulted in hypertension, cardiac hypertrophy, and fibrosis. The cardiovascular phenotypes were reported to be more severe in male NPRA-knockout (KO) mice. It is known that reductions in proteasomal activities can lead to mitochondrial dysfunction. Similarly, an imbalance between mitochondrial fission and fusion events can impair mitochondrial function. We hypothesized that alterations in proteasomal function and mitochondrial dynamics might form the basis for phenotype differences reported for NPRA-KO mice. Method/Results: Non-invasive echocardiography, RT-QPCR, Western blotting, and proteasomal assays were performed to evaluate cardiac functions. Preliminary results revealed significant decreases in the activities of two proteasome subunits (β1 and β5) in male and female NPRA-KO hearts compared to sex-matched wild-type (WT) hearts. Notably, the percent-activity reductions were much higher in male NPRA-KO hearts. Western blotting analysis revealed that the expression levels of mitochondrial fusion proteins (Mfn1, Mfn2, and Opa1) were significantly increased in both male and female NPRA-KO hearts compared to WT controls. However, the expression of fission proteins (Drp1 &amp; MFF) was significantly increased only in male NPRA-KO hearts. Consistent with a more imbalance in mitochondrial dynamics in male NPRA-KO hearts, the expression levels of enzymes that promote fatty acid oxidation (ECHS1 and phospho-PDH) were unfavorably altered in male but not in female NPRA-KO hearts compared to controls. In addition, various echocardiographic and electrocardiographic parameters related to the cardiac function such as cardiac output, diastolic volume, left ventricular wall thickness, QRS duration, and stroke volume, were altered significantly more in male than in female NPRA-KO hearts. Conclusion: Our findings suggest that more pronounced sex-specific alterations in proteasome/mitochondrial functions in male NPRA-KO hearts can lead to changes in cardiac metabolism and a severe disease phenotype.

Abstract P3100: Mice Lacking S-nitrosoglutathione Reductase (gsnor -/- ), A Mouse Model Of Preeclampsia, Exhibit Increases In Oxidative And Nitrosative Stress And Deterioration Of Cardiovascular Structure And Function In The Mother Postpartum.

Introduction: Preeclampsia (PE), a leading cause of maternal mortality, is linked to persistent pathological changes in the heart, predisposing the mother to increased risk of chronic cardiovascular (CV) disease later in life. PE is characterized by increased S-nitrosylated (SNO) proteins and nitrosative stress. We recently showed that mice lacking S-nitrosoglutathione reductase (GSNOR -/ - mice), a denitrosylase that regulates protein S-nitrosylation, exhibit the clinical features of PE including maternal hypertension, blunted increase in cardiac output, abnormal remodeling of left ventricular (LV) cardiac structure, dysregulation in nitrosylation and increased nitrosative stress. We hypothesize that the aberrant nitrosylation and nitrosative stress seen during pregnancy persist postpartum (PP), leading to increased maternal susceptibility to CV injury. Methods: Pregnant control (WT [C57Bl/6J]) and GSNOR -/- mice (N=5) were examined at baseline, late-stage pregnancy (17.5 dpc) and 6 weeks PP. LV structure, cardiac output and stroke volume were determined using echocardiography (Vevo 2100). Cardiomyocytes (CM) were isolated at 6 weeks PP and ROS and peroxynitrite levels determined using fluorescent dyes. Results: In WT mice, all normal maternal CV adaptions to pregnancy, reverted to pre-pregnant levels 6 weeks PP. In contrast, GSNOR -/- mice exhibited increased cardiac output (+21% vs. -19% in WT), stroke volume (+21% vs. -41% in WT), and LV chamber dimension (+13% vs. -4% in WT) at 6 weeks PP, indicating high cardiac output LV cardiomyopathy. CM isolated from GSNOR -/- hearts showed ~5-fold more ROS generation (9.9x10 -4 ±9x10 -5 vs. 2.1x10 -4 ±1.5 x10 -4 ΔF/F max .min -1 ) and elevated peroxynitrite levels (0.318±0.011 vs. 0.243±0.012 ΔF/F 0 ) compared to WT at 6 weeks PP, suggesting the presence of oxidative and nitrosative stress. All changes P&lt;0.05. Conclusion: Postpartum GSNOR -/- (preeclamptic) mothers exhibited cardiac dysfunction characterized by high cardiac output LV cardiomyopathy, which was accompanied by elevated levels of oxidative and nitrosative stress. These changes may predispose the mother to higher risk for future CV injury.

Cardiac Effects of Long-Duration Space Flight

BackgroundVentricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training. ObjectivesThe goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight. MethodsWe measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests. ResultsTotal cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112). ConclusionsThe current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.

Toward the Implementation of Optimal Cardiac Magnetic Resonance Risk Stratification in Pulmonary Arterial Hypertension

The 2022 European Society of Cardiology/European Respiratory Society pulmonary hypertension (PH) guidelines incorporate cardiac magnetic resonance (CMR) imaging metrics in the risk stratification of patients with pulmonary arterial hypertension (PAH). Thresholds to identify patients at estimated 1-year mortality risks of< 5%, 5%to 20%, and > 20%are introduced. However, these cutoff values are mostly single center-based and require external validation. What are the discriminative prognostic properties of the current CMR risk thresholds stratifying patients with PAH? We analyzed data from incident, treatment-naïve patients with PAH from the Amsterdam University Medical Centres, Vrije Universiteit, The Netherlands. The discriminative properties of the proposed CMR three risk strata were tested at baseline and first reassessment, using the following PH guideline variables: right ventricular ejection fraction, indexed right ventricular end-systolic volume, and indexed left ventricular stroke volume. A total of 258 patients with PAH diagnosed between 2001 and 2022 fulfilled the study criteria and were included in this study. Of these, 172 had follow-up CMR imaging after 3months to 1.5 years. According to the CMR three risk strata, most patients were classified at intermediate risk (n= 115 [45%]) upon diagnosis. Only 29(11%) of patients with PAH were classified at low risk, and 114 (44%) were classified at high risk. Poor survival discrimination was seen between risk groups. Appropriate survival discrimination was seen at first reassessment. Risk stratifying patients with PAH with the recent proposed CMR cutoffs from the European Society of Cardiology/European Respiratory Society 2022 PH guidelines requires adjustment because post-processing consensus is lacking and general applicability is limited. Risk assessment at follow-up yielded better survival discrimination, emphasizing the importance of the individual treatment response.

Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear. To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes. This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023. LTL. Cardiovascular imaging traits and HF. Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume. In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.