Left Ventricular End-systolic Volume Research Articles

A cross-sectional study of non-suicidal self-injury in adults with depressive disorder: Associations with inflammation and cardiac structure and function

ObjectiveNon-suicidal self-injury (NSSI) is associated with cardiovascular disease (CVD), whereas inflammation is associated with both CVD and NSSI. However, few studies have investigated the correlation among NSSI, inflammation, and cardiac structure and function in CVD-free adult patients with depressive disorders. MethodsWe recruited 88 CVD-free adult patients with depressive disorders and 37 healthy individuals. Patients were divided into NSSI (n = 21) and non-NSSI (n = 67) groups based on the presence or absence of NSSI. Healthy individuals comprised the controls (n = 37). Echocardiography was applied to assess cardiac structure and function, and C-reactive protein (CRP) levels were measured to indicate inflammation. ResultsCompared with controls, the NSSI group exhibited a larger left ventricular end-systolic diameter (LVESD) and smaller left ventricular ejection fraction (LVEF). Left ventricular end-systolic volume (LVESV) was larger in the NSSI group than in the non-NSSI group. The CRP levels were higher in the NSSI group than in the non-NSSI group; however, this difference was not statistically significant. NSSI was positively associated with LVESD (β = 1.928, p = 0.006) and LVESV (β = 5.368, p = 0.003), negatively correlated with LVEF (β = −2.600, p = 0.029), and positively correlated with CRP levels (β = 0.116, p = 0.004). CRP levels did not mediate the association between NSSI and cardiac structure and function. ConclusionsThis study indicated that NSSI was associated with left ventricular structure, systolic function, and inflammation, but CRP did not mediate the relationship between NSSI and echocardiogram parameters.

Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[<7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[>38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling ( Table ). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m 2 ; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m 2 ; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors ( Table ). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m 2 ; P = 0.01), LV indexed mass (β 1.17 g/m 2 ; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 ( Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction ( Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Abstract 4125026: Effect Of Pressure-Controlled Intermittent Coronary Sinus Occlusion On Echocardiographic Features In Patients With STEMI: A Systematic Review And Meta-Analysis With Trial Squential Analysis

Introduction: Primary percutaneous coronary intervention (pPCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, pPCI is still associated with poorer outcomes particularly left ventricular dysfunction. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) is a novel therapeutic approach proposed to improve myocardial perfusion and its function in patients with STEMI. Therefore, we performed this meta-analysis to evaluate the effects of PiCSO on left ventricular function in STEMI patients. Methods: We performed a comprehensive search on PubMed, Scopus, and Web of Science. Our primary endpoints were left ventricular ejection fraction (LVEF%), left ventricular end diastolic volume (LVEDV), and left ventricular end systolic volume (LVESV). The secondary endpoint was infarct size. We performed Trial Squential Analysis (TSA), and we pooled our continuous data as mean difference (MD) and 95% confidence interval (CI) in the fixed effects model. Results: A total of four studies, with 335 patients, were included in the analysis. Our pooled analysis showed that PiCSO significantly increased LVEF% compared to pPCI (MD = 3.52, 95% CI [1.05, 6.00], P= 0.005). However, there was no significant difference between the two groups in terms of LVESV and LVEDV (MD = -1.1, 95% CI [-9.28, 7.08], P= 0.79; MD = -1.69, 95% CI [-9.14, 5.76], P= 0.66, respectively). With regard to infarct size, a significant reduction was observed in PiCSO group compared to pPCI (MD = -4.26, 95% CI [-7.39, -1.14], P= 0.007). The TSA curve crossed the conventional boundary for statistical significance, indicating that the available evidence reach the predetermined threshold. Conclusions: Our meta-analysis revealed that PiCSO could mitigate left ventricular dysfunction in STEMI patients by improving LVEF% and reducing infarct size. Nevertheless, PiCSO failed to show a positive impact on LVESV and LVEDV. Further large-scale studies are warranted to draw a definitive conclusion.

Abstract 4129182: Transendocardial Stem Cell Therapy Improves Cardiac Parameters in Chronic Ischemic Heart Failure: A Meta-analysis of Randomized Controlled Trials

Introduction: Despite recent advances in therapy, chronic ischemic heart failure remains a significant cause of morbidity and mortality worldwide. Stem cell (SC) therapy has recently emerged as a potential therapeutic approach, yet its efficacy remains debatable. We aimed to systematically review and meta-analyze the current evidence to evaluate its effectiveness. Methods: A comprehensive literature search was conducted across the following databases: PubMed, Embase, and Cochrane, from inspection to April 2024. We identified RCTs with a blinded study design, done on patients diagnosed with chronic ischemic HFrEF, and utilized mesenchymal stem cells as an intervention in comparison to placebo/sham intervention using percutaneous endomyocardial catheter systems. Meta-analysis was conducted using RevMan v5.4 to calculate the odds ratio (OR) at 95% confidence intervals (CI) and a p-value of 0.05. I 2 was indicated for the assessment of heterogeneity. Sensitivity analysis was done in case of heterogeneity between studies. Results: A total of twenty studies were included in our meta-analysis. The overall change in left ventricular end-systolic volume (LVESV) and stress SPECT significantly favored the stem cell group (pooled effect size -7.59, 95% CI [-12.28 to -2.89], P=0.002), and (pooled effect size -5.33, 95% CI [-6.73 to -3.93], P=0.00001), respectively. Initially, the change in left ventricular end-diastolic volume (LVEDV) did not favor either group. However, sensitivity analysis which excluded one study at a time, reduced heterogeneity (P=0.01, I 2 =54%) and showed a significant effect favoring the stem cell group (pooled effect size -3.87, 95% CI [-6.77 to -0.97], P=0.009). However, the overall changes in left ventricular ejection fraction (LVEF) did not favor either of the two groups (pooled effect size 0.08, 95% CI [-0.1 to 0.26], P=0.39). Similarly, the overall change in myocardial oxygen consumption (MVO2) did not favor either group (pooled effect size 0.66, 95% CI [-0.1 to 1.32], P=0.05). Conclusion: Transendocardial SC therapy demonstrates promising results by significantly improving specific cardiac parameters. While the therapy shows potential, particularly after sensitivity adjustments, its impact on other critical measures like LVEF and MVO2 remains inconclusive. These findings highlight the need for further investigation to fully understand and enhance the therapeutic potential of stem cell interventions in heart failure management.

Abstract 4138716: A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure

Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. However, UCN-2 has a short half-life and intravenous delivery limits its therapeutic use. COR-1167 was discovered as a stable UCN-2 analog with qd pharmacological effects when injected subcutaneously. Hypothesis: Whether COR-1167 exerts chronic cardiorenal protection in Acute Decompensated HF (ADHF) is unknown, and in particular on background of SGLT2 inhibition, therefore both treatments were tested in a rat model of ADHF. Methods: Rats had coronary artery ligation to induce MI and a reduced ejection fraction phenotype. Three months later, rats were treated with vehicle or Empagliflozin (Empa) at 10 mg/kg/day PO. One month after starting Empa, two acute decompensation events were induced by administrating NaCl solution (1.8 g/kg, PO) on Day 0 and Day 14. Empa treated ADHF rats received vehicle or COR-1167 (3 µg/kg/day) by SC injections starting at 12 hours after the first decompensation and all treatments continued for 14 days. The groups were ADHF, ADHF + Empa and ADHF + Empa + COR-1167 (n=7-10/group). Left ventricular (LV) hemodynamics (cardiac catheters), cardiac output (echocardiography) and LV tissue perfusion (magnetic resonance imaging), cardiac mitochondrial coupling and ATP production (Seahorse) were measured 1 day after the second decompensation, while urine volume (uVol) and urine Na + excretion (uNa + ) collected from metabolic cages were analyzed 7 days after the first decompensation. Results: Compared to ADHF control rats, Empa treatment had no effect on systolic blood pressure (SBP), cardiac output (CO), LV end systolic pressure volume relationship (LVESPVR), LV end diastolic pressure volume relationship (LVEDPR), mitochondrial coupling and ATP production, but it increased myocardial perfusion, uVol and uNa + excretion. Compared to ADHF + Empa rats, COR-1167 treatment increased SBP, CO, LVESPVR, myocardial perfusion, mitochondrial coupling and ATP production, uVol, uNa + , while decreasing LVEDPVR. Conclusion: In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor.

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

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

Abstract 4125300: Prognostic Value of NT-proBNP and the H 2 FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP < and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.

The mechanistic interaction between mechanical dyssynchrony and filling pressure in cardiac resynchronization therapy candidates.

Both left ventricular (LV) mechanical dyssynchrony and filling pressure have been shown to be associated with outcome in heart failure patient treated with cardiac resynchronization therapy (CRT). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure and to assess their combined prognostic value in CRT candidates. Left atrial pressure (LAP) estimation and quantification of mechanical dyssynchrony were retrospectively performed in 219 CRT patients using echocardiography. LAP was elevated (eLAP) in 49% of the population, normal (nLAP) in 40%, and indeterminate (iLAP) in 11%. CRT response was defined as %-decrease in LV end-systolic volume after 12±6 months CRT. Clinical endpoint was all-cause mortality during 4.8 years (interquartile range: 2.7-6.0 years). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure, the CircAdapt computer model was used to simulate cardiac mechanics and hemodynamics in virtual hearts with LBBB and various causes of increased filling pressure. Patients with nLAP had more significant mechanical dyssynchrony than those with eLAP. The combined assessment of both parameters before CRT was significantly associated with reverse LV remodeling and post-CRT survival. Simulations revealed that mechanical dyssynchrony is attenuated by increased LV operational chamber stiffness, regardless of whether it is caused by passive or active factors, explaining the link between mechanical dyssynchrony and filling pressure. Our combined clinical-computational data demonstrate that in patients with LBBB, the presence of mechanical dyssynchrony indicates relatively normal LV compliance and low filling pressure, which may explain their strong association with positive outcomes after CRT.

Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure.

The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while FN1 and PRKAA2 were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. In vivo experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.

The Impact of Different Revascularization Strategies Implemented in Acute Myocardial Infarction on the Recovery of Left Ventricular Functional and Deformational Parameters

Background: Despite well-established therapeutic techniques, such as direct revascularization through percutaneous coronary intervention (PCI), acute myocardial infarction (AMI) remains a leading cause of mortality and morbidity. Objectives: To determine if two-dimensional speckle tracking echocardiography (STE) deformation parameters and the early recovery of left ventricular (LV) functions are affected by the timing of PCI in AMI. Methods: A total of 200 cases with newly-onset acute myocardial infarction (AMI) who had a baseline left ventricular ejection fraction (LVEF) higher than 40% and received effective therapy with percutaneous coronary intervention (PCI) were included in this investigation. cases were categorized as either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). cases were grouped into four groups according to the time between presentation and PCI. Using standard echocardiography and two-dimensional (2D) ST-elevation STE, individuals were re-evaluated three months later to find out if remodeling had taken place or if the LV function had returned. Results: Of the 200 AMI patients, including 140 males (70%), improvement in global longitudinal strain (GLS) and harmed longitudinal strain (HLS) were better in STEMI and NSTEMI patients received urgent revascularization with PCI (groups I and III) versus patients with pharmacoinvasive strategy or routine invasive strategy (Groups II and IV) (P < 0.05) while there was an insignificant difference between group I and III (P = 0.79). Of the 200 patients, 47 patients (23.5%) presented signs of LV remodeling at 3 months follow up. Age, smoking history, hypertension, dyslipidemia, Killip class, peak creatine phosphokinase - MB level, baseline left ventricular end diastolic volume (LVEDV), HLS, and harmed longitudinal strain rate (HLSR) were all factors that were found to be significantly associated with left ventricular remodeling (P<0.05) in the univariate logistic regression analysis. The following factors were identified as independent predictors of left ventricular remodeling in multivariate logistic regression analysis: damaged left ventricular ejection fraction (EF) and end-systolic volume, peak troponin I, Killip class, culprit left anterior descending (LAD), 2 and 3-vessel coronary artery disease (CAD), and wall motion score index (WMSI). Conclusion: Earlier PCI in AMI helps earlier improvement in myocardial strain parameters. HLS and HLSR are excellent predictors for LV remodeling and may do better than global parameters.

Disparities in quantification of mitral valve regurgitation between cardiovascular magnetic resonance imaging and trans-thoracic echocardiography: a systematic review.

Primary mitral regurgitation (MR) is a prevalent valvular heart disease. Therapy stratification for MR depends on accurate assessment of MR severity and left ventricular (LV) dimensions. While trans-thoracic echocardiography (TTE) has been the standard/preferred assessment method, cardiovascular magnetic resonance imaging (CMR) has gained recognition for its superior assessment of LV dimensions and MR severity. Both imaging modalities have their own advantages and limitation for therapy guidance. However, the differences between the two modalities for assessing/grade severity and clinical impact of MR remains unclear. This systematic review aims to evaluate the differences between TTE and CMR in quantifying MR severity and LV dimensions, providing insights for optimal clinical management. A literature search was performed from inception up to March 21st 2023. This resulted in 2,728 articles. After screening, 22 articles were deemed eligible for inclusion in the meta-analysis. The included study variables were, mitral valve regurgitation volume (MRVOL), regurgitation fraction (MRFRAC), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF). TTE showed a significant higher MRVOL (10.4ml, I2 = 88%, p = 0.002) and MRFRAC (6.3%, I2 = 51%, p = 0.05) compared to CMR, while CMR demonstrated a higher LVEDV (21.9ml, I2 = 66%, p = < 0.001) and LVESV (16.8ml, I2 = 0%, p = < 0.001) compared to TTE. Our findings demonstrate substantial disparities in TTE and CMR derived measurements for parameters that play a pivotal role in the clinical stratification guidelines. This discrepancy prompts a critical question regarding the prognostic value of both imaging modalities, which warrants future research.

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

Circulating microRNA-409-5p and USP7 are associated with left ventricular remodeling in patients with acute myocardial infarction

BackgroundOur previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI).MethodsSixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled. The clinical characteristics, echocardiographic/serum parameters of LVR, and circulating miR-409-5p and USP7 mRNA levels between the two groups and between admission and 6 weeks after discharge were compared. The correlations between circulating miR-409-5p/USP7 levels and serum/echocardiographic parameters were analyzed.ResultsThe demographic characteristics of the AMI group and CCS group were comparable. Patients with AMI admitted to the study displayed significantly higher levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), along with a greater left ventricular end-systolic volume (LVESV). Conversely, their left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global radial strain (GRS) were significantly lower compared to patients with CCS. These changes were normalized 6 weeks after discharge. Circulating miR-409-5p levels at admission were significantly decreased while circulating USP7 mRNA expression levels were significantly increased in patients with AMI compared with those with CCS (both P < 0.01). However, these changes were restored 6 weeks after discharge (both P < 0.01). Moreover, circulating miR-409-5p and USP7 mRNA levels showed varying correlations with GLS, GRS, LVESV, LVEF, and NT-proBNP in patients with AMI but not in those with CCS. Additionally, circulating miR-409-5p and USP7 levels predicted the incidence of LVR and major adverse cardiovascular events (MACE) after AMI.ConclusionSerum miR-409-5p and USP7 may influence the occurrence and evolution of LVR and left ventricular dysfunction after AMI.

The in-hospital administration of sacubitril/valsartan in acute myocardial infarction: A meta-analysis.

There is a need to address the evidence gap regarding the in-hospital administration of sacubitril/valsartan in acute myocardial infarction patients. After searching MEDLINE, Google Scholars and Scopus, a random-effects meta-analysis of randomized controlled trials comparing the in-hospital administration of the angiotensin receptor-neprilysin inhibitors (ARNis) versus the standard therapy in patients with reduced heart failure due to myocardial infarction was performed. The primary outcome was major adverse cardiovascular events. All-cause mortality, cardiac death, rehospitalization for heart failure, non-fatal myocardial infarction (MI), changes in left ventricular ejection fraction, left ventricular volumes, N terminal pro brain natriuretic peptide and adverse events were the secondary endpoints. Nine studies (eight randomized controlled trials and one echo-substudy) with a total 6597 individuals (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: 3300 patients vs. ARNis: 3297 patients) were included for quantitative analysis. Median follow-up was 6months. Patients receiving an in-hospital coadministration of ARNi had a lower risk of major cardiovascular event [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.32-0.63, P<0.0001] and lower rate of repeat rehospitalization for heart failure (OR 0.40, 95% CI 0.26-0.62, P<0.0001), compared with a standard regimen. Additionally, left ventricle volumes were significantly lower in the ARNi group [left ventricular end-diastolic volume, mean difference (MD) 11.48mL, 95% CI 6.10-16.85, P<0.0001; left ventricular end-systolic volume, MD 7.09mL, 95% CI 2.89-11.29, P=0.0009] with a significant change in left ventricular ejection fraction (MD 3.07, 95% CI 1.61-4.53, P<0.0001), compared with standard therapy. No significant differences were observed in terms of cardiac death, all cause of mortality, non-fatal myocardial infarction and N terminal pro brain natriuretic peptide. Higher rates of iatrogenic hypotensive events were observed in the ARNi group compared with the standard therapy (OR 1.42, 95% CI 1.26-1.60, P value<0.00001). In patients with acute myocardial infarction related heart failure, the in-hospital administration of ARNis was associated with a reduced risk of major cardiovascular events and re-hospitalization for heart failure, as well as cardiac remodelling, but higher rates of hypotensive events compared with standard therapy.

Mechanical dyssynchrony and response to cardiac resynchronization therapy in heart failure patients with right ventricular pacing: a pre-specified subgroup analysis of the BUDAPEST CRT Upgrade trial

Abstract Introduction The BUDAPEST CRT Upgrade trial has established the strong clinical benefit of upgrading heart failure patients with a reduced left ventricular (LV) ejection fraction (HFrEF) and a high right ventricular pacing (RVP) burden to cardiac resynchronization therapy with defibrillator (CRT-D). Importantly, however, the CRT upgrade response is not homogeneous regarding LV reverse remodeling and associated clinical outcomes. The presence of mechanical dyssynchrony (MD) assessed by echocardiography has been linked to more CRT benefits; still, its change in response to CRT and added prognostic value in HFrEF patients with high RVP are scarcely investigated. Purpose Accordingly, we aimed to assess the prevalence, clinical characteristics, CRT response rate, and prognostic value of RVP-induced MD in the BUDAPEST CRT Upgrade cohort. Methods The multicentre, randomized, controlled trial enrolled 360 HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD) and significant RVP (≥ 20%) who were randomly assigned to receive CRT-D upgrade or ICD in a 3:2 ratio. Protocol echocardiography was performed at baseline and at 12-month follow-up visits and was evaluated at a central core lab. Beyond LV end-diastolic (EDV) and end-systolic volumes (ESV), longitudinal strain-derived septal deformation patterns by speckle tracking were assessed to determine the presence of RVP-induced MD. The endpoints were volumetric non-response (defined by a relative decrease in LV ESV &amp;lt;15%) and the composite of volumetric non-response or HF hospitalization. Results The echocardiographic assessment was feasible in 325 patients at baseline; 133 (41%) patients presented with MD. Females were more likely to present with MD (female vs. male, 65% vs. 38%, p=0.003). MD patients had higher LV EDV (MD vs. no-MD, 248±78 vs. 219±78 mL, p=0.001) and LV ESV (190±67 vs. 165±64 mL, p&amp;lt;0.001) at baseline. In the CRT-D group, 126 (75%) patients were volumetric responders, and 41 (25%) were non-responders at 12 months. CRT patients with baseline MD were less likely to experience volumetric non-response (OR 0.35 [95% CI 0.15-0.82], p=0.015) or the composite endpoint (OR 0.37 [95% CI 0.17-0.77], p=0.008). Out of 57 CRT patients with baseline MD who had follow-up assessment available, 52 (91%) patients had a favorable change: the MD pattern disappeared. Patients with MD resolution at 12 months were less likely to experience volumetric non-response or the composite endpoint (OR 0.39 [95% CI 0.17-0.93], p=0.034; OR 0.38 [95% CI 0.16-0.86], p=0.021, respectively). CRT patients with resolved MD were less likely of ischemic etiology and had 100% posterior or lateral LV lead location. Conclusions The presence of RVP-induced MD and its resolution is associated with better clinical response in HFrEF patients undergoing CRT-D upgrade. MD assessment can refine patient selection algorithms of CRT.Figure 1

Prognostic value of echocardiographic parameters in predicting major adverse cardiac events one year following st-segment elevation myocardial infarction

Abstract Approximately 50% of patients who survive an ST-segment elevation myocardial infarction (STEMI) experience irreversible damage to the heart muscle, which increases long-term risk of developing heart failure. Moreover, cardiovascular mortality constitutes half of all deaths. This research aimed to determine the best combination of patient data collected during a one-year follow-up period to enhance the accuracy of outcome predictions for patients with STEMI. Methods In this study, 246 patients who experienced STEMI and older than 18 were prospectively monitored. All participants received primary percutaneous coronary intervention treatment. The study's primary outcomes, observed over the year following hospital discharge, included cardiovascular death, recurrent myocardial infarction, newly diagnosed heart failure, and arrhythmias or conduction issues. Of the patients, 18% of patients reached the primary outcomes. Two-dimensional transthoracic echocardiography was conducted 3-5 days after the initial event to assess left ventricular global longitudinal strain (GLS) using 2D speckle-tracking echocardiography on the apical four-chamber, two-chamber, and long-axis views. Left ventricular mechanical dispersion was calculated as the standard deviation of the time from the Q/R wave onset to peak GLS across 17 segments of the left ventricle. Results The findings revealed that the overall GLS was -10.70 (-12.61 to -8.40), but in patients who met the study's primary outcomes, GLS was significantly lower at -7.83 (-8.70 to -6.90), compared to -12.02 (-13.11 to -10.17) in those who did not, with a significant difference (p=0.00001). Mechanical dispersion was 40.24±26.56 in the entire cohort but significantly higher at 65.62±22.57 in the outcome group compared to 25.79±14.81 in the non-outcome group (p=0.00001). The ejection fraction averaged 48.97±7.69% across all patients, 47.22±7.16% in those with outcomes, and 49.92±7.84% in those without, with a statistically significant difference (p=0.039). Cox regression analysis identified key predictors of major adverse cardiac events (MACE) within one year after STEMI, including global longitudinal strain (p=0.0006), left atrium volume index (p=0.0448), left ventricular end-diastolic diameter (p=0.045), and mechanical dispersion (p&amp;lt;0.0001). A multivariate logistic regression analysis demonstrated that a combination of GLS, left ventricular end-systolic volume (LVESV), mechanical dispersion, and ejection fraction could predict 1-year MACE with high accuracy (χ2 = 85.18; p&amp;lt;0.0001, AUC=0.961 [0.903-0.989]). In conclusion, this study identifies crucial metrics, such as global longitudinal strain, left ventricular end-systolic volume, mechanical dispersion, and ejection fraction, as predictive factors for MACE one year following STEMI. This predictive model is straightforward, reproducible, and can be easily implemented in cardiology practice.

Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction

Abstract Introduction Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown. Purpose To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction. Methods We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of &amp;lt;50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data. Results A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p &amp;lt;0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p &amp;lt;0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p &amp;lt;0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p &amp;lt;0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass. Conclusions The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.

The impact of multimorbidity on cardiac remodelling in the UK Biobank

Abstract Background/Introduction Previous work has suggested that multimorbidity is associated with higher all-cause mortality and cardiovascular mortality in the UK Biobank (UKB). The impact of multimorbidity on cardiac remodelling as measured by cardiovascular magnetic resonance (CMR) has not been studied in large cohorts. Purpose To determine if CMR biomarkers act as surrogates for adverse cardiovascular outcomes in multimorbidity. Method We analysed 44957 UKB participants who had CMR. Self-reported cancer (UKB field ID 20001) and non-cancer illnesses (UKB field ID 20002) were used to calculate comorbidity count with multi-morbidity defined as 2 or more illnesses. The predictive value of comorbidity count (exposure counts measured in quintiles) on CMR traits (outcomes) was evaluated using a univariable and multivariable generalised linear model. Covariates included sex, age, BMI, smoking status, regular alcohol intake, and the Townsend deprivation index, a measure of socioeconomic deprivation. The first model utilised univariable regression without covariates with subsequent iterations including age and sex and then all covariates. An interaction term was included for age and sex and a quadratic term for age in the models. CMR outcome measures were indexed left ventricular mass (LVM), indexed left ventricular end diastolic volume (LVEDV), indexed left ventricular end systolic volume (LVESV), indexed left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and indexed maximal left atrial volume (LA). The absolute value of GLS was used in the regression models. Variance inflation factor testing was used to check for collinearity. Analyses were completed using R v4.1.1. Results Median comorbidity count was 2. The burden of long-term conditions in this population of European ancestry with largely healthy individuals is lower than in other large population cohorts. Table 1 summarises multivariable analyses for comorbidity count, LVM and GLS. Due to high collinearity relating to age in the model, we centred age around the mean. LVM was higher with multimorbidity (top quintile Beta 0.63 (95% CI 0.23 to 1.04), P = 2.21x10-03). GLS was lower with multimorbidity (top quintile Beta -0.29 (95%CI -0.42 to 0.16), P = 8.10x10-6). LA volume was lower with multimorbidity (top quintile Beta -0.63(95% CI -1.22 to 0.04), P = 3.53 x 10-2). LVEF and other volume measures were not associated with multimorbidity. Conclusion Multimorbidity in this large cohort was associated with adverse cardiac structural and functional remodelling on CMR. These include a lower global longitudinal strain and higher LV mass.

Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers

Abstract Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging. We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF. CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors. 14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM. By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study

Abstract Purpose Type 2 diabetes mellitus (T2DM) represents the most prevalent form of diabetes, exerting a significant influence on cardiovascular health. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to heightened cardiac dysfunction risk. Our study aimed to explore the additive effect of MAFLD on left ventricular (LV) deformation among T2DM patients, utilizing cardiac magnetic resonance (CMR) feature tracking technology. Methods This study retrospectively included 270 patients with T2DM, comprising 110 individuals with MAFLD and 160 without, alongside 80 age- and sex-matched healthy controls, all of whom underwent CMR examination. Parameters derived from CMR encompass those related to LV function and global strain metrics. LV global strain parameters include global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), measured across radial, circumferential, and longitudinal directions. Intergroup analysis, employing the Mann-Whitney U test, was utilized to compare LV function and global strain parameters. Results The LV function parameters, including LV end-diastolic volume (LVEDV), LVEDV index, LV end-systolic volume (LVESV), LVESVI, LV mass, and LV mass index, displayed a progressive augmentation from controls through T2DM patients without MAFLD, to those with MAFLD. In parallel, LVEF showed a declining trajectory across these groups. In contrast, LVSV and LVSVI were comparable among the three groups. In a similar vein, when examining global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. GRPS, GCPS and GLPS, along with PSSR and PDSR in radial, circumferential, and longitudinal directions, manifest a pronounced decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with T2DM and MAFLD (All p-values &amp;lt; 0.05). To assess the effect of MAFLD severity on global peak strain, patients with T2DM and MAFLD were stratified into two groups: a mild MAFLD group (N=77) and a moderate to severe MAFLD group (N=33). Although there was a noticeable decline in GRPS, GCPS and GLPS, as well as in PSSR and PDSR across the three groups—from those without MAFLD to those with mild and then moderate to severe MAFLD—the observed differences did not reach statistical significance. The absence of statistical significance is likely due to the small sample sizes of the groups categorized by severity of MAFLD. Conclusions This study revealed that MAFLD has additive worsening effects on LV function and LV global strains in T2DM patients evaluated by CMR. Besides, moderate to severe MAFLD, compared to mild MAFLD, exhibits worse global strain parameters. Early detection and intervention of MAFLD might improve the prognosis of T2DM patients.