Function In Heart Failure Patients Research Articles

Abstract 4136678: Detecting Myosteatosis-Related Low Physical Function in Heart Failure Patients Using Abdominal Computed Tomography and Plasma Amino Acid Profile

Background: Evaluation of sarcopenia requires quantifying appendicular skeletal muscle mass and functional capacity, but resource constraints often limit feasibility. Alterations in muscle quality, especially intramuscular lipid infiltration (i.e., myosteatosis), and systemic metabolic derangements are associated with disability. Hypothesis: Opportunistic CT imaging and plasma amino acid profiling could identify low physical function in patients with heart failure (HF). Methods: We retrospectively examined 220 HF patients (74 ± 13 years old; 59% male) who underwent plasma amino acid profiling, abdominal CT imaging, and dual-energy X-ray absorptiometry (DXA) scan within two months. Myosteatosis was evaluated using single-slice CT imaging at the L3/4 level and quantified as mean muscle attenuation (MMA). Physical function was assessed by the short physical performance battery (SPPB), with low physical function defined as SPPB ≤9. Results: CT-derived single-slice areas of skeletal muscle and adipose tissue were highly correlated with DXA-derived appendicular skeletal muscle mass and total fat mass. Logistic regression analyses revealed that higher age and lower MMA, but not skeletal muscle area, were significantly associated with low physical function independently of NT-proBNP. Subjects with MMA below the median value (32.0 HU for males and 23.7 HU for females) had higher odds of low physical function (adjusted OR 2.04, 95% CI 1.04-3.96). Ten amino acids and the Fischer ratio were significantly correlated with MMA levels. Multivariate regression analyses, adjusted for potential confounders including age, gender, and body mass index, demonstrated that serum albumin and Fischer ratio were independent determinants of MMA levels. When serum albumin and Fischer ratio were dichotomized by their median values (3.6 mg/dL and 3.23, respectively), the prevalence of low physical function was significantly higher in subjects with low albumin and low Fischer ratio, but not in those with low levels of only either parameter, compared to those with high albumin and high Fischer ratio (adjusted OR 2.36, 95% CI 1.02-5.49). Conclusions: Myosteatosis assessed by single-slice abdominal CT imaging is an independent determinant of low physical function in HF patients. Combined with an assessment of serum albumin and Fischer ratio, these simple biomarkers could facilitate the early detection of patients at risk for developing frailty.

The effects of SGLT2 inhibitors on right ventricle functions in heart failure patients: update meta-analysis of the current literature

Abstract Background There is some discrepancy in the present studies concerning the effect of sodium-glucose cotransporter type 2 (SGLT2) inhibitors on right ventricular (RV) functions in heart failure (HF) patients. The current meta-analysis was focused on determining the impact of SGLT2 inhibitors on RV functions in such individuals. Methods Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were utilized to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The Robin-I risk of bias algorithm was used to assess the bias risks of randomized studies. Results This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT-2 inhibitors had substantially lower systolic pulmonary artery pressure (sPAP) and higher TAPSE values (mean difference (MD) = 1.30 [0.78;1.82], p =0.002 and MD =-5.39 [-7.88; -2.89], p=0.003, respectively). There was no significant difference in RVS’ values between follow-up and baseline (MD=1.38 [-1.35;3.80], p=0.169). However, as compared to the baseline period, fractional area contraction (FAC) values were substantially larger at the end of the follow-up period (MD=5.40 [3.74;7.07], p=0.015). Conclusion To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2 inhibitors on RV function in HF patients. Our findings suggest that SGLT2 inhibitors may improve RV performance in HF patients.

The effect of empagliflozin on right ventricular function in heart failure patients with reduced ejection fraction: analysis from the randomized empire hf clinical trial

Abstract Background Reverse remodeling of the left ventricle (LV) has been proposed as a key mechanism to the cardio-protective effects of sodium-glucose-transporter-2 (SGLT2) inhibitors in patients with heart failure and reduced ejection fraction (HFrEF). Deterioration of the right ventricular (RV) function is associated with poor outcome, whereas improvement in RV dysfunction has been correlated with improved outcomes in HFrEF patients. The impact of SGLT2 inhibitors on the RV remains unclear. Purpose The aim of this post-hoc study of the Empire HF trial was to investigate the effect of Empagliflozin on RV function assessed by echocardiography in patients with HFrEF after 12 weeks of treatment compared to placebo. Methods The Empire HF trial was a double-blind, placebo-controlled, randomized clinical trial, in which 190 stable HFrEF patients with a LV ejection fraction (LVEF) ≤40% were randomized (1:1) to receive Empagliflozin 10 mg once daily or matching placebo for 12 weeks. Echocardiographic images were analysed blinded to treatment allocation. Exploratory outcomes were changes in right ventricular function. Statistical analyses were performed using mixed-effects linear models adjusted for age, sex and baseline variables. Results Baseline characteristics were well balanced between the two groups; mean age 64 (SD±11) years; males: 85%; mean LVEF 29 (SD±8) %, RV free wall strain (RVFWS): -16.7 (SD±6)%, NYHA-functional class II: 78% and ischemic HFrEF etiology: 51%. No significant between-group differences were detected in RV free wall strain (RVFWS), tricuspid annular plane systolic excursion (TAPSE) or S’ RV free wall (all P>0.05), Figure 1. When stratified into baseline tertiles of RVFWS, patients in the lowest tertile showed a significant improvement in the Empagliflozin group compared to placebo (treatment effect: -4.4 % [95% CI: -8.0 to -0.8]; P=0.018), Figure 2. There was no correlation between the effect of Empagliflozin on RVFWS in the lowest RVFWS tertile and other changes such as LVEF (P=0.845), plasma volume (P=0.710) or weight loss (P=0.639). Conclusion In this randomized, short-term trial, Empagliflozin did exert a significant effect on RV function in stable HFrEF patients in the overall study population, but notably improved RVFWS in patients in the lowest tertile of RVFWS at baseline after 12 weeks of treatment. Additional research is required to confirm these explorative findings, and to better understand the impact of SGLT2i on RV function and identify patients who could potentially experience therapeutic and prognostic benefits by RV improvement.

Dietary strategies and nutritional supplements in the management of heart failure: a systematic review.

Heart failure (HF) is a syndrome of increased intracardiac pressure or decreased cardiac output. There is a lack of conclusive evidence to recommend the regular use of any dietary supplement in patients with HF. However, certain studies have shown nutritional interventions to be beneficial for patients with HF. Therefore, the purpose of this systematic review was to understand and map the updates of dietary interventions and nutritional supplementation measures related to patients with HF over the past 5 years. A systematic review. The PubMed, Web of Science, Scopus, and Cochrane Library databases were searched for randomized clinical trials on the association between dietary interventions and nutritional supplements and HF published between 2018 and 2023. A total of 1755 documents were retrieved, of which 19 were finalized for inclusion. The findings suggest that individualized nutritional support reduces mortality and risk of major cardiovascular events in chronic heart failure inpatients at high nutritional risk. The Mediterranean diet improves functionality, quality of life, and cardiac function. Additionally, supplementation with thiamine, ubiquinol, D-ribose, and L-arginine enhances left ventricular ejection fraction. Probiotic yogurt may effectively improve the inflammatory and antioxidative status of chronic heart failure. Whey protein and melatonin have a positive effect on improving endothelial function in HF patients. Certain dietary interventions and nutritional supplements may provide some benefit to patients with HF. However, there is no relevant definitive evidence on the impact of nutritional interventions on the prognosis of HF, and more high-quality clinical trials are needed for further in-depth studies. Identifier, CRD42024510847.

Remote Ischemic Conditioning Improves Cardiovascular Function in Heart Failure Patients.

Recently, it has been shown that remote ischemic conditioning (RIC) can be used as a healthy regimen to reverse disease and aging. With this in mind, we are studying the consequences of RIC on cardiovascular function in heart failure patients. Forty patients with stable heart failure were prospectively enlisted and randomly divided into RIC (n = 20) and control (n = 20) groups. The RIC protocol consists of a 3-min inflation and then deflation of the blood pressure cuff attached to the upper arm to produce transient ischemia of the arm. RIC treatment was performed once daily for 1 year. NYHA class, left ventricular ejection fraction (LVEF), left atrial and ventricular dimensions were all assessed in two groups. RIC was well tolerated. After 1 year of treatment, New York Heart Association (NYHA) class improved and LVEF showed a significant increase from 37.11% to 52.44% (P < 0.0001). Additionally, the dimensions of the left atrium (from 50.55 to 43.25 mm) and ventricle (from 53.04 to 50.15 mm) were significantly reduced in the RIC group. This study suggests that 1 year of RIC treatment as a health strategy could improve cardiovascular function in heart failure patients, leading to its widespread use in these patients.

Decreased plasma ELABELA level as a novel screening indicator for heart failure: a cohort and observational study.

The predictive power of B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) is limited by its low specificity in patients with heart failure (HF). Discovery of more novel biomarkers for HF better diagnosis is necessary and urgent. ELABELA, an early endogenous ligand for the G protein-coupled receptor APJ (Apelin peptide jejunum, Apelin receptor), exhibits cardioprotective actions. However, the relationship between plasma ELABELA and cardiac function in HF patients is unclear. To evaluate plasma ELABELA level and its diagnostic value in HF patients, a total of 335 patients with or without HF were recruited for our monocentric observational study. Plasma ELABELA and Apelin levels were detected by immunoassay in all patients. Spearman correlation analysis was used to analyze the correlation between plasma ELABELA or Apelin levels and study variables. The receiver operating characteristic curves were used to access the predictive power of plasma ELABELA or Apelin levels. Plasma ELABELA levels were lower, while plasma Apelin levels were higher in HF patients than in non-HF patients. Plasma ELABELA levels were gradually decreased with increasing New York Heart Association grade or decreasing LVEF. Plasma ELABELA levels were negatively correlated with BNP, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular posterior wall thickness and positively correlated with LVEF in HF patients. In contrast, the correlation between plasma Apelin levels and these parameters is utterly opposite to ELABELA. The diagnostic value of ELABELA, Apelin, and LVEF for all HF patients was 0.835, 0.673, and 0.612; the sensitivity was 62.52, 66.20, and 32.97%; and the specificity was 95.92, 67.23, and 87.49%, respectively. All these parameters in HF patients with preserved ejection fraction were comparable to those in total HF patients. Overall, plasma ELABELA levels were significantly reduced and negatively correlated with cardiac function in HF patients. Decreased plasma ELABELA levels may function as a novel screening biomarker for HF. A combined assessment of BNP and ELABELA may be a good choice to increase the accuracy of the diagnosis of HF.

Evaluating the impact of Sacubitril/valsartan on diastolic function in patients with heart failure: A systematic review and meta-analysis.

Heart failure is a common and severe condition, often complicated by diastolic dysfunction. Current standard therapies such as ACEIs and ARBs have limited efficacy in managing diastolic function. Sacubitril/Valsartan, an emerging therapy, warrants rigorous investigation to elucidate its impact on diastolic function in heart failure patients. This systematic review and meta-analysis were conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and utilized the PICO schema. Searches were performed on 4 databases-PubMed, Embase, Web of Science, and Cochrane Library-without temporal restrictions. Inclusion and exclusion criteria were strictly defined, and quality assessments were conducted using the Cochrane Collaboration Risk of Bias tool. Both fixed-effects and random-effects models were used for statistical analysis, depending on inter-study heterogeneity assessed by I2 statistics and Chi-square tests. Out of 1129 identified publications, 8 studies met the criteria and were included in the meta-analysis. These studies consisted of both randomized controlled trials and cohort studies and featured diverse global populations. Significant reductions were found in the echocardiographic parameter E/e' ratio and LAVi upon treatment with Sacubitril/Valsartan compared to standard therapies, with mean differences of -1.38 and -4.62, respectively, both with P values < .01. This meta-analysis demonstrates that Sacubitril/Valsartan significantly improves diastolic function parameters in heart failure patients compared to standard treatments. These findings underscore the potential benefits of Sacubitril/Valsartan in the management of heart failure, particularly for patients with diastolic dysfunction.

Left Ventricular Longitudinal Myocardial Function of Heart Failure Patients With Transition From Reduced to Preserved Ejection Fraction and of Those With Preserved Ejection Fraction.

Background: Left ventricular (LV) longitudinal myocardial function is associated with the outcomes of heart failure (HF) patients. HF with improved ejection fraction (EF), known as HFimpEF, which is defined as current LVEF >40% but any previously documented LVEF ≤40%, has favorable outcomes compared with HF with preserved EF (HFpEF). However, LV longitudinal myocardial function in patients with previously reduced LVEF (<50%) but improved LVEF to within the normal range (≥50%) (HFnorEF) and its association with cardiovascular events remain unclear. Methods and Results: We studied 70 patients with HFpEF and 65 with HFnorEF. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The primary endpoint was defined as cardiovascular death or HF hospitalization during follow-up of 5.6±3.1 years. The GLS of HFpEF patients was significantly lower than that of HFnorEF patients (13.6±3.5% vs. 14.8±2.2%, P=0.02) even when the LVEF was similar. Multivariate Cox proportional hazards analysis showed that GLS was independently associated with cardiovascular events. Furthermore, of the entire study population, patients with GLS >15.0% had fewer cardiovascular events than those without (log-rank P=0.014) among all the patients. Conclusions: LV longitudinal myocardial dysfunction was more frequently observed in patients with HFpEF than in those with HFnorEF, even when LVEF was similar, and was independently associated with cardiovascular events for HF patients with current LVEF ≥50%.

Effects of SGLT2 inhibitors on right ventricular function in heart failure patients: Updated meta-analysis of the current literature.

There is some discrepancy in current studies concerning the effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on right ventricular (RV) functions in heart failure (HF) patients. Hence, this meta-analysis was focused on determining the impact of SGLT2i on RV functions in such individuals. Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were used to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The ROBINS-I risk of bias algorithm was used to assess bias risks of randomized studies. This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT2i had substantially lower systolic pulmonary artery pressure and higher tricuspid annular plane systolic excursion values (mean difference [MD] = -5.23 [-7.81; -2.66] and, MD = 1.47 [1.01; 1.93]; P <0.01, respectively). There was no significant difference in RVS' values between follow-up and baseline (MD = 1.54 [-0.19; 3.26]; P = 0.08). However, as compared to the baseline period, fractional area contraction values were substantially larger at the end of the follow-up (MD = 5.52 [4.23; 6.82]; P <0.01). To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2i on RV function in HF patients. Our findings suggest that SGLT2i may improve RV performance in HF patients.

Aldehyde Dehydrogenase 2 (ALDH2) rs671 Polymorphism is a Predictor of Pulmonary Hypertension Due to Left Heart Disease

Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD. A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression. The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness. Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD.

Does Speckle Tracking Transthoracic Echocardiography Indicate Subtle Changes in Left Ventricular Function in Heart Failure Patients with Reduced Ejection Fraction Treated by Sacubitril-valsartan?

In heart failure patients and reduced ejection fraction (HFrEF), assessing subtle changes in left ventricle (LV) function is crucial for monitoring treatment efficacy. This study aims to determine the effect of valsartan/sacubitril on LV ejection fraction (EF) assessed by two-dimensional (2D) transthoracic echocardiography (TTE) in comparison to that assessed by 2D TTE speckle tracking in patients with HFrEF ≤35% after 6 months of treatment. A prospective study will be conducted on 200 heart failure patients with reduced EF (HFrEF) undergoing sacubitril-valsartan treatment. Each participant underwent a comprehensive evaluation, including physical examination, history taking, serial 12-lead electrocardiogram, and 2D echo to evaluate cardiac parameters. In addition, 2D speckle tracking echocardiography (STE) assessments were conducted before and after 6 months of valsartan/sacubitril treatment. The enrolled patients had an average age of 48 years with 63% females. At the beginning of the study, 9 (4.5%) patients were classified as New York Heart Association (NYHA) FC I, 120 (60%) as NYHA FC II, 64 (32%) as NYHA FC III, and 7 (3.5%) as FC IV. Following treatment, 82 (41%) patients improved to NYHA FC I, and 118 (59%) were in NYHA FC II. Notably, 82 (41%) patients showed improved left ventricular EF (LVEF), detected either by traditional TTE or STE, whereas 118 (59%) showed no improvement in EF through traditional TTE. In addition, 74 (37%) patients demonstrated improvement detected by STE. In contrast, 44 (22%) patients demonstrated no improvement in EF detected by either TTE or STE. STE was a more reliable diagnostic method for seeing early LVEF improvement in patients with HFrEF receiving valsartan/sacubitril treatment not seen by conventional TTE.

Relationship between serum iron level and physical function in heart failure patients is lost by presence of diabetes.

Iron deficiency (ID) is common in patients with heart failure (HF) and is reportedly associated with exercise intolerance and impaired quality of life. Iron supplementation therapy in HF patients with ID improves exercise capacity. Conversely, protective roles of iron depletion in the development of diabetes mellitus (DM) and its complications have been proposed. This study aimed to determine the impact of ID on physical function in HF patients with and without DM. We enrolled consecutive patients who were admitted to our institute for HF diagnosis and management. The short physical performance battery (SPPB) was used to evaluate physical function, and low physical function was defined as an SPPB score of <10 points as individuals with SPPB scores of <10 points are most likely to be classified as frail and are at high risk for disability and future adverse events, including death. ID was defined as serum ferritin<100 or 100-299ng/mL when transferrin saturation (TSAT) was <20% according to the HF guidelines. Among the 562 HF patients (72±14years old; 56% male), 329 patients (58%) and 191 patients (34%) had ID and low physical function, respectively. Multivariate logistic regression analysis showed that TSAT as a continuous variable, but not ID, was a predictor of low physical function (odds ratio: 0.980, P=0.024). Subgroup analysis showed that a significant association between low TSAT and low physical function was lost in HF patients with DM (P for interaction<0.001). A spline dose-response curve for the relationship between TSAT and risk of low physical function with adjustments for covariates associated with low physical function in non-DM patients was almost linear with an increase in the risk of low physical function as the TSAT increased, but such a relationship was not found in the analyses of DM patients. A lack of close TSAT-SPPB relationship in HF patients with DM was confirmed also in a propensity-score-matched cohort. TSAT as a continuous variable, but not ID, was independently associated with physical function in HF patients, and a significant association was lost in patients with HF and DM, suggesting a limited impact of iron supplementation therapy in HF patients with DM.

Modulation of miR-29 influences myocardial compliance likely through coordinated regulation of calcium handling and extracellular matrix

MicroRNAs (miRNAs) control the expression of diverse subsets of target mRNAs, and studies have found miRNA dysregulation in failing hearts. Expression of miR-29 is abundant in heart, increases with aging, and is altered in cardiomyopathies. Prior studies demonstrate that miR-29 reduction via genetic knockout or pharmacologic blockade can blunt cardiac hypertrophy and fibrosis in mice. Surprisingly, this depended on specifically blunting miR-29 actions in cardiomyocytes versus fibroblasts. To begin developing more translationally relevant vectors, we generated a novel transgene-encoded miR-29 inhibitor (TuD-29) that can be incorporated into a viral-mediated gene therapy for cardioprotection. Here, we corroborate that miR-29 expression and activity is higher in cardiomyocytes versus fibroblasts and demonstrate that TuD-29 effectively blunts hypertrophic responses in cultured cardiomyocytes and mouse hearts. Furthermore, we found that adeno-associatedvirus (AAV)-mediated miR-29 overexpression in mouse hearts induces early diastolic dysfunction, whereas AAV:TuD-29 treatment improves cardiac output by increasing end-diastolic and stroke volumes. The integration of RNA sequencing and miRNA-target interactomes reveals that miR-29 regulates genes involved in calcium handling, cell stress and hypertrophy, metabolism, ion transport, and extracellular matrix remodeling. These investigations support a likely versatile role for miR-29 in influencing myocardial compliance and relaxation, potentially providing a unique therapeutic avenue to improve diastolic function in heart failure patients.

Left ventricular longitudinal myocardial function in heart failure patients with transition to preserved ejection fraction from reduced ejection fraction and those with preserved ejection fraction

Abstract Background Left ventricular (LV) longitudinal myocardial dysfunction is considered the first marker of a preclinical form of heart failure (HF) with preserved ejection fraction (HFpEF), and is strongly associated with poor outcomes. LV ejection fraction (LVEF) may improve over time during treatment or follow-up in some patients with HF with reduced ejection fraction (HFrEF). Furthermore, it has been reported that patients with HF with improved EF, known as HFimpEF, which was defined as current LVEF &amp;gt; 40% but any previously documented LVEF ≤ 40%, had favorable outcomes compared to those with HFpEF. However, LV longitudinal myocardial function in patients with previously reduced LVEF who had improved LVEF to normal range (≥ 50%), and its association with cardiovascular events remains unclear. Purpose The purpose of this study was the comparison of LV longitudinal myocardial function in patients with HFpEF and those with previously reduced LVEF who had improved LVEF to normal range (reduced LVEF-HFpEF), and to investigate whether LV longitudinal myocardial function was associated with cardiovascular events. Methods We retrospectively studied 70 patients with HFpEF and 45 patients with reduced LVEF-HFpEF. Reduced LVEF-HFpEF was defined as current LVEF ≥ 50% but any previously documented reduced LVEF &amp;lt; 50% (mean: 34 ± 10%). HFpEF was defined as current and all previous LVEF reports ≥ 50%, and met the HFA-PEFF diagnostic algorithm criteria. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS) by means of two-dimensional speckle-tracking strain. The primary endpoint was defined as cardiovascular death over a median follow-up period of 5.0 (0.5-9.0) years. Results As expected, the Kaplan-Meier curve indicated that patients with reduced LVEF-HFpEF experienced fewer cardiovascular death than those with HFpEF (Figure A). GLS in patients with HFpEF was significantly lower than that in patients with reduced LVEF-HFpEF (13.6 ± 3.5% vs. 14.8 ± 2.2%, P = 0.03) regardless of similar LVEF (55.7 ± 3.3% vs 56.8 ± 5.0%, P = 0.15). An important finding of the multivariate Cox proportional hazards analysis showed that GLS was an independently associated with cardiovascular death (Figure B). Conclusion Impaired LV longitudinal myocardial function was observed in patients with HFpEF compared to those with reduced LVEF-HFpEF regardless of similar LVEF. Moreover, LV longitudinal myocardial function was independently associated with cardiovascular death HF patients with current LVEF ≥ 50%. Our findings may provide new insights for the management of HF patients.FigureAFigureB

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.

Mechanistic insights on age-related changes in heart-aorta-brain hemodynamic coupling using a pulse wave model of the entire circulatory system.

Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain.NEW & NOTEWORTHY We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.

PO-02-013 EFFICACY OF LEFT BUNDLE BRANCH PACING IN PATIENTS WITH DIFFERENT LEFT BUNDLE BRANCH BLOCK MORPHOLOGIES

Left bundle branch pacing (LBBP) is a novel technique to deliver cardiac resynchronization therapy (CRT) by correcting intrinsic LBBB to achieve electrical and mechanical resynchrony. Whether the efficacy of LBBP is different across different LBBB morphologies has not been reported. To explore the efficacy of LBBP in patients with different LBBB morphologies. Consecutive patients who received LBBP due to either heart failure (HF) with LBBB or atrioventricular block accompanied with a LBBB pattern escape rhythm were recruited. The changes of QRS duration (ΔQRSd) and left ventricular activation time (ΔLVAT) were compared before and after LBBP. Relationships of ΔQRSd and ΔLVAT with cardiac function in HF patients were also explored. HF patients were followed up for at least 6 months. Electrical resynchrony and cardiac function were compared based on 4 major LBBB morphological criteria. Comparison 1: LBBB meeting Strauss criteria vs not; Comparison 2: presence of q wave in lead I and aVL vs not; Comparison 3: presence of QS vs rS morphology of QRS in lead V1; and Comparison 4: presence of S wave in lead V6 vs not. A total of 82 patients were enrolled from January 2018 to August 2022. In Comparison 1, 59 patients had LBBB meeting Strauss criteria vs 23 not meeting criteria. Patients with LBBB meeting Strauss criteria had greater reduction in QRSd (56.95±24.10ms vs 36.83±32.16ms, P<0.05) and LVAT (56.47±14.90ms vs 41.52±17.13ms, P<0.001). Forty-two HF patients met the Strauss criteria had greater LVEF improvement (19.92±6.89% vs 12.41±13.10%, P<0.05) compared to those not meeting the criteria. Comparison 4 included 61 patients without S wave in lead V6 and these patients exhibited better electrical synchrony after LBBP (ΔQRSd: -55.18±24.79ms vs -40.05±33.67ms, P<0.05; ΔLVAT: -55.74±14.70ms vs -41.67±18.55ms, P<0.05) than patients with S wave in V6. Among them, 51 patients without S wave in V6 had HF and showed greater LVEF improvements than those with S wave in V6 (ΔLVEF: 18.65±10.13% vs 6.61±7.78%, P<0.05). Correlation analyses showed significant associations between both ΔQRSd (R=0.55, P <0.001) and ΔLVAT (R=0.39, P <0.01) with LVEF improvement. In multivariate analysis, ΔQRSd>53 ms is an independent predictor of cardiac super response (LVEF improvement>15%). LBBB pattern meeting the Strauss criteria and absence of S wave in lead V6 can predict better electrical resynchrony and LVEF improvement by LBBP.

Assessment of Diastolic Function of Heart Failure Patients Due to Systemic Hypertension

Introduction: Diastolic function as is the current conventional tradition, in order to gain deeper understanding it is more useful to view diastolic function as a problem to be solved! Once the basic problem of normal physiology of diastole has been mastered, it is nearly self-evident as to what the issues are in clinical heart failure and which physiologic mechanism and its hard-wired compensatory pathways one is confronted with. Objective: To evaluate diastolic function of heart failure patients with systemic hypertension. Methods: The present prospective observational study was undertaken in Cardiology Department, Dhaka Medical College hospital, Dhaka, Bangladesh from January to July, 2019. Fifty-four (54) patients with systemic hypertension who recently experienced heart failure with normal ejection fraction (≥50%) and no clinical history of ischaemic cardiomyopathy were studied. The patients were divided into two groups according to the degree of echocardiographic hypertrophy: Group-I (28 patients) with a ventricular mass/volume ratio &gt;1.8 and group-II (26 patients) with a ratio &lt;1.8. Results: Total 54 patients with diastolic dysfunction with hypertension were included in the study. Shows the age and sex distribution with highest frequency in the age group 61-70 years, comprising 31.5 percent and 51-60 years 25.9 percent, 41-50 year 24.1 percent, 71 + years 12.9 percent and 30-40 years 5.6 percent in descending order. Group I patients had a higher ejection fraction (67.62±3.14 vs 55.33 ±4.13, P&lt;0.001), smaller ventricular diameter (28.88±2.46 vs 34.38±4.37, P&lt;0.001), higher LV mass (154.42±6.80 vs 123.38±5.58, P&lt;0.001), lower ETT positivity (14%vs73%, P&lt;0.001). Clinically, group I had more frequent audible fourth heart sound (57% vs 21%, P&lt; 0.001), low incidence of audible third heart sound (17% vs 69%, P&lt;0.001), ECG evident LVH (96% vs 15%, P&lt;0.001), cardiomegaly (25% vs 73%, P&lt;0.001). Conclusion: There were no significant differences between groups ..........

Afterload reduction after non-invasive vagus nerve stimulation in acute heart failure.

While central blood pressure (BP) has been recognized as a major indicator of left ventricular (LV) afterload, the reduction of central pressure decreases LV afterload and may prevent heart failure (HF) decompensation. Non-invasive transcutaneous vagus nerve stimulation (tVNS) was shown to improve cardiac function in HF patients. In this study, the relationship between active tVNS and reduction of central BP was investigated in patients with acute HF (AHF). The 22 patients hospitalized for AHF after initial stabilization (median 80 yrs, males 60%) were randomly assigned to active or sham group. For 1 h daily over 5 days, low-level transcutaneous electrical stimulation (LLTS) (20 Hz, 1 mA) was performed after attaching an ear clip to the tragus (active group) or the earlobe (sham control group). Before and after stimulation, central aortic systolic pressure (CASP), brachial systolic BP (SBP), diastolic BP (DBP) as well as heart rate (HR) were noninvasively measured. No significant differences in baseline characteristics were observed between the active and sham groups. In the active group, CASP, SBP, DBP, and HR each decreased significantly after stimulation (all p < 0.05), whereas in the sham group, CASP, SBP, DBP, and HR each increased significantly after stimulation (all p < 0.05). All the changes in CASP, SBP, DBP and HR before and after stimulation were also significantly different between active and sham groups (all p < 0.01). There were no device-related side effects. In this study, the left tragus tVNS resulted in an acute afterload reduction in the elderly AHF patients. Non-invasive LLTS may be useful and safe for reducing afterload in AHF. ClinicalTrials.gov, identifier UMIN000044121.

Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism

BackgroundIncreased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction.Methods and resultsIncreased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation.ConclusionsOur findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.