Function In Chronic Heart Failure Research Articles

Unlocking Pathways That Improve Cardiac Function in Chronic Heart Failure: Are Ketones the Key?

Unlocking Pathways That Improve Cardiac Function in Chronic Heart Failure: Are Ketones the Key?

Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis

PurposeNumerous clinical studies have explored sodium–glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients.MethodsA comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials (http://www.clinicaltrials.gov) were also searched.ResultsA total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: −253.36, − 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline.ConclusionsThe SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.

Prognostic significance of right ventricular dysfunction in patients presenting with acute left-sided heart failure.

The prognostic value of right ventricular (RV) function in chronic heart failure (HF) has lately been well established. However, research on its role in acute heart failure (AHF) is sparse. This study comprised 195 patients, aged between 18 and 80years, with acute left-sided heart failure (HF) and a left ventricular ejection fraction (LVEF) < 50%. Patients with LVEF ≥ 50%, mechanical ventilatory or circulatory support, poor echocardiographic windows, prosthetic valves, congenital heart diseases, infective endocarditis, and/or life expectancy < 1year due to non-cardiac causes were excluded. The study participants' mean age was 57.7 ± 10.9years, and 74.9% were males. Coronary artery disease was present in 80.5% of patients. The mean LVEF was 31% ± 8.7. RV dysfunction (RVD), defined as tricuspid annular plane systolic excursion (TAPSE) < 17mm, RV S' < 9.5cm/s and/or RV fractional area change (FAC) < 35%, was identified in 48.7% of patients. The RV was dilated in 67.7% of the patients. RVD was significantly associated with a longer HF duration, atrial fibrillation, and idiopathic dilated cardiomyopathy. The primary outcome, a 6-month composite of cardiovascular death or hospitalization for worsening HF (HHF), occurred in 42% of the participants. Cardiovascular mortality and HHF occurred in 30.5% and 23.9% of the patients, respectively. The primary endpoint and longer CCU stays were significantly more common in patients with RVD than in those with normal RV function. RV dilatation was significantly associated with the primary outcome, whether alone or in combination with RVD. Multivariate regression analysis showed that only RV global longitudinal strain (GLS) independently predicted poor outcomes. RVD and RV dilatation strongly predict CV death and HHF in patients with AHF and LVEF < 50%. Multivariate analysis showed that RV GLS was the only predictor of a composite of CV death and HHF.

Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1β, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1β, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1β and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

Acute vasopressin neutralization improves cardiac function in rats with chronic heart failure

Vasopressin is one of the leading pathophysiological drivers of chronic heart failure (CHF) acting via V1a-, V1b- and V2 receptors. Selective V2 and dual V1a-V2 receptor antagonists increases plasma sodium levels, but failed to reduce mortality in clinical studies. Vasopressin neutralization is an original alternative to receptor blockers but its effect in CHF is unknown. For this purpose, we investigated the short-term cardiac and vascular effects of the vasopressin neutralizing aptamer NOX-F37. Left ventricular (LV) function (hemodynamic by LV catheterization) and LV tissue perfusion (MRI) as well as mesenteric artery endothelial function (flow-mediated dilation by arteriography) were determined 2 hours after NOX-F37 administration (80 nM/kg; IP) to rats with CHF induced by left coronary artery ligation. Two hours after administration, NOX-F37 improved LV systolic function, illustrated by the increase in LV end-systolic pressure volume relationship (CHF: 20.2 ± 0.0.7; CHF + NOX: 23.3 ± 1.0 mmHg/RVU; P < 0.05) and diastolic function, illustrated by the decrease in LV end-diastolic pressure volume relationship (CHF: 4.03 ± 0.48; CHF + NOX: 2.06 ± 0.21 mmHg/RVU; P < 0.01), together with an increase in LV tissue perfusion (CHF: 6.12 ± 0.24; CHF + NOX: 10.10 ± 0.26 ml/min/g LV tissue; P < 0.001). However, mesenteric artery flow-induced dilatation was not improved (% dilatation at 150 μL/min; CHF: 10 ± 7; CHF + NOX: 9 ± 8). These results illustrate the immediate beneficial effects of vasopressin neutralization on cardiac function in CHF, confirming the existence of a deleterious vasopressinergic tone in this pathophysiological context. Investigations still needed to evaluate the persistence of effects of vasopressin neutralization over time during chronic and could contribute to the resolution of acute heart failure.

Physiological ischemic training improves cardiac function through the attenuation of cardiomyocyte apoptosis and the activation of the vagus nerve in chronic heart failure.

This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT protocol, evaluated its cardioprotective effects and explored the underlying neural mechanisms. Patients with CHF were randomly divided into experimental group (n = 25, PIT intervention + regular treatment) and control group (n = 25, regular treatment). The outcomes included the left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) and cardiopulmonary parameters. LVEF and cardiac biomarkers in CHF rats after various PIT treatments (different in intensity, frequency, and course of treatment) were measured to identify the optimal PIT protocol. The effect of PIT on cardiomyocyte programmed cell death was investigated by western blot, flow cytometry and fluorescent staining. The neural mechanism involved in PIT-induced cardioprotective effect was assessed by stimulation of the vagus nerve and muscarinic M2 receptor in CHF rats. LVEF and VO2max increased while BNP decreased in patients subjected to PIT. The optimal PIT protocol in CHF rats was composed of five cycles of 5 min ischemia followed by 5 min reperfusion on remote limbs for 8 weeks. LVEF and cardiac biomarker levels were significantly improved, and cardiomyocyte apoptosis was inhibited. However, these cardioprotective effects disappeared after subjecting CHF rats to vagotomy or muscarinic M2 receptor inhibition. PIT improved functional outcomes in CHF patients. The optimal PIT protocol required appropriate intensity, reasonable frequency, and adequate treatment course. Under these conditions, improvement of cardiac function in CHF was confirmed through cardiomyocyte apoptosis reduction and vagus nerve activation.

Peripheral chemoreflex modulation of renal hemodynamics and renal tissue PO2 in chronic heart failure with reduced ejection fraction.

Aberrant carotid body chemoreceptor (CBC) function contributes to increased sympathetic nerve activity (SNA) and reduced renal blood flow (RBF) in chronic heart failure (CHF). Intermittent asphyxia (IA) mimicking sleep apnea is associated with additional increases in SNA and may worsen reductions in RBF and renal PO2 (RPO2) in CHF. The combined effects of decreased RBF and RPO2 may contribute to biochemical changes precipitating renal injury. This study sought to determine the role of CBC activity on glomerular filtration rate (GFR), RBF and RPO2 in CHF, and to assess the additive effects of IA. Furthermore, we sought to identify changes in gene expression that might contribute to renal injury. We hypothesized that GFR, RBF, and RPO2 would be reduced in CHF, that decreases in RBF and RPO2 would be worsened by IA, and that these changes would be ameliorated by CBC ablation (CBD). Finally, we hypothesized that CHF would be associated with pro-oxidative pro-fibrotic changes in renal gene expression that would be ameliorated by CBD. CHF was induced in adult male Sprague Dawley rats using coronary artery ligation (CAL). Carotid body denervation was performed by cryogenic ablation. GFR was assessed in conscious animals at the beginning and end of the experimental period. At 8-weeks post-CAL, cardiac function was assessed via echocardiography, and GFR, baseline and IA RBF and RPO2 were measured. Renal gene expression was measured using qRT-PCR. GFR was lower in CHF compared to sham (p < 0.05) but CBD had no salutary effect. RBF and RPO2 were decreased in CHF compared to sham (p < 0.05), and this effect was attenuated by CBD (p < 0.05). RBF and RPO2 were reduced to a greater extent in CHF vs. sham during exposure to IA (p < 0.05), and this effect was attenuated by CBD for RBF (p < 0.05). Downregulation of antioxidant defense and fibrosis-suppressing genes was observed in CHF vs. sham however CBD had no salutary effect. These results suggest that aberrant CBC function in CHF has a clear modulatory effect on RBF during normoxia and during IA simulating central sleep apnea.

Shen Qi Li Xin formula improves chronic heart failure through balancing mitochondrial fission and fusion via upregulation of PGC-1α

BackgroundOur previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear.MethodsH&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress.ResultsIn vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress.ConclusionOverall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

Disorders of Kidney Function in Chronic Heart Failure

The formation of cardiorenal syndrome (CRS) in patients with chronic heart failure (CHF) is a naturalmanifestation of a functionally interrelated process at the organ level. Moreover, impaired renal function is acommon and independent factor in the progression of the disease, a high incidence of cardiovascular eventsand death in a population of patients with asymptomatic and / or clinically manifested CHF, which is dueto the pathogenetic features of the formation of cattle in patients with CHF of ischemic genesis. The articleprovides an overview of studies on the pathogenesis of kidney damage in CHF, the role of various markersin the early diagnosis of cattle. A decrease in glomerular filtration rate (GFR) and an increase in urinaryalbumin excretion are currently considered as “renal” markers of a poor prognosis within the cardiorenalcontinuum. In this regard, for stratification of patients by stages of chronic kidney disease (CKD) and,consequently, for assessing the risks of increased overall and cardiovascular mortality in patients with CHF,the accuracy of calculating GFR, as the main indicator reflecting the severity of formed kidney damage, is ofgreat importance. Microalbuminuria is one of the early signs of CKD, the main cause of which is glomerularcapillary endothelial dysfunction that occurs in most patients with CHF. The presence and persistence ofsubclinical renal dysfunction during treatment, even with the achievement of risk factors (RF) control andregression of organ lesions, can adversely affect the patient’s prognosis. Assessment of the functional stateof the kidneys is important for early diagnosis, selection of effective preventive measures and treatment. Thetherapeutic strategy in patients with CHF in combination with CKD should be based on the nephroprotectiveeffects of drugs.

Pitfalls in Using Estimated Glomerular Filtration Rate Slope as a Surrogate for the Effect of Drugs on the Risk of Serious Adverse Renal Outcomes in Clinical Trials of Patients With Heart Failure.

Pitfalls in Using Estimated Glomerular Filtration Rate Slope as a Surrogate for the Effect of Drugs on the Risk of Serious Adverse Renal Outcomes in Clinical Trials of Patients With Heart Failure.

Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection fraction: Meta-analysis of randomized controlled trials.

Elevated resting heart rate in chronic heart failure (HF) patients has been associated with higher mortality and poor prognosis. Ivabradine is a new pure bradycardic agent that has been used to treat angina or heart failure reduced ejection fraction (HFrEF) with sinus heart rate above 70 beats per minute. However, the effect of ivabradine for chronic HF patients on rehospitalization and cardiac function is still inconsistent. Thus, this meta‐analysis aimed to elucidate the effect of Ivabradine in chronic HFrEF patients. We systematically searched PubMed, Medline, Clinical Trials.gov, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) of ivabradine with search terms Ivabradine (MeSH Terms), chronic heart failure and beta‐blocker. The primary endpoints of the study include the impact of Ivabradine on heart rate, left ventricle ejection fraction (LVEF), left ventricular remodeling, exercise capacity, and quality of life (QoL) in patients with chronic HFrEF. Secondary endpoints were safety analysis of Ivabradine including cardiovascular mortality, worsening HF readmission, visual disturbances, and asymptomatic bradycardia. The analysis was done by Review Manager 5.4 Analyzer, to analyze the mean differences (MD) for continuous data and risks ratio (RR) for dichotomous data. A total of six RCTs and one subgroup analysis showed add of Ivabradine to standard HF therapy was associated with greater resting heart rate reduction (MD = −9.57; 95% CI ‐11.15, −8.00), improved LVEF (MD = 3.89; 95% CI 2.61, 5.17), left ventricular reverse remodeling improvement (MD = −3.73; 95% CI ‐4.25, −3.21, LVESV; MD = −17.00, 95%CI ‐29.65, −4.35, LVEDD; MD = −1.43, 95%CI ‐2.78, −0.08, LVEDV; MD = −14.75, 95%CI ‐34.36, 4.87), increased exercise capacity (exercise duration; MD = 8.52; 95%CI 0.09, 16.94), and significant reduction on rehospitalization due to worsening HF (RR = 0.76, 95%CI 0.69, 0.84). However, Ivabradine has no significant effect on the quality of life (MD = 0.65; 95%CI ‐10.52, 11.82), and cardiovascular mortality (RR = 0.92; 95%CI 0.82, 1.03). Moreover, there were some events of visual disturbances and asymptomatic bradycardia observed in the Ivabradine group compared to the placebo group (RR = 4.76; 95%CI 3.03, 7.48; RR = 3.78; 95%CI 2.77, 5.15, respectively). Addition of Ivabradine to standard HF therapy is associated with cardiac function improvement, reduction on worsening HF readmission, greater HR reduction, and better exercise capacity in chronic HFrEF patients, although it cannot reduce cardiovascular mortality or improve the quality of life.

Eccentric Left Ventricular Hypertrophy and Left and Right Cardiac Function in Chronic Heart Failure with or without Coexisting COPD: Impact on Exercise Performance.

AimOur aim was to assess: 1) the impact of the eccentric left ventricular hypertrophy (ELVH) on exercise performance in patients diagnosed with chronic heart failure (CHF) alone and in patients with co-existing CHF and chronic obstructive pulmonary disease (COPD) and 2) the relationship between left and right cardiac function measurements obtained by doppler echocardiography, clinical characteristics and primary measures of cardiorespiratory fitness.MethodsThe current study included 46 patients (CHF:23 and CHF+COPD:23) that performed advanced pulmonary function tests, echocardiography and symptom-limited, incremental cardiopulmonary exercise testing (CPET) on a cycle ergometer.ResultsPatients with CHF+COPD demonstrated a lower work rate, peak oxygen uptake (VO2), oxygen pulse, rate pressure product (RPP), circulatory power (CP) and ventilatory power (VP) compared to those only diagnosed with CHF. In addition, significant correlations were observed between VP and relative wall thickness (r: 0.45 p: 0.03),VE/VCO2 intercept and Mitral E/e’ ratio (r: 0.70 p: 0.003) in the CHF group. Significant correlations were found between indexed left ventricle mass and RPP (r: −0.47; p: 0.02) and relative VO2 and right ventricle diameter (r: −0.62; p: 0.001) in the CHF+COPD group.ConclusionCompared to a diagnosis of CHF alone, a combined diagnosis of CHF+COPD induced further impairments in cardiorespiratory fitness. Moreover, echocardiographic measures of cardiac function are related to cardiopulmonary exercise performance and therefore appear to be an important therapeutic target when attempting to improve exercise performance and functional capacity.

MiR-221-3p targets Hif-1α to inhibit angiogenesis in heart failure

AbstractAngiogenesis is involved in ischemic heart disease as well as the prognosis of heart failure (HF), and endothelial cells are the main participants in angiogenesis. In this study, we found that miR-221-3p is highly expressed in vascular tissue, especially in endothelial cells, and increased miR-221-3p was observed in heart tissue of HF patients and transverse aortic constriction (TAC)-induced HF mice. To explore the role of miR-221-3p in endothelial cells, microRNA (miRNA) mimics and inhibitors were employed in vitro. Overexpression of miR-221-3p inhibited endothelial cell proliferation, migration, and cord formation in vitro, while inhibition of miR-221-3p showed the opposite effect. Anti-argonaute 2 (Ago2) coimmunoprecipitation, dual-luciferase reporter assay, and western blotting were performed to verify the target of miR-221-3p. Hypoxia-inducible factor-1α (HIF-1α) was identified as a miR-221-3p target, and the adverse effects of miR-221-3p on endothelial cells were alleviated by HIF-1α re-expression. In vivo, a mouse model of hindlimb ischemia (HLI) was developed to demonstrate the effect of miR-221-3p on angiogenesis. AntagomiR-221-3p increased HIF-1α expression and promoted angiogenesis in mouse ischemic hindlimbs. Using the TAC model, we clarified that antagomiR-221-3p improved cardiac function in HF mice by promoting cardiac angiogenesis. Furthermore, serum miR-221-3p was detected to be negatively correlated with heart function in chronic heart failure (CHF) patients. Our results conclude that miR-221-3p inhibits angiogenesis of endothelial cells by targeting HIF-1α and that inhibition of miR-221-3p improves cardiac function of TAC-induced HF mice. Furthermore, miR-221-3p might be a potential prognostic marker of HF.This study describes how miR-221-3p in endothelial cells reduces angiogenesis by inhibiting hypoxia-inducible factor-1α. Because antagonism of miR-221-3p significantly improves the cardiac function of mice with heart failure it may be a new and effective molecular target for progressing and treatment of heart failure.

In vitro controlled release of extracellular vesicles for cardiac repair from poly(glycerol sebacate) acrylate-based polymers

Cell therapy to restore cardiac function in chronic heart failure has been extensively studied. However, its therapeutic value is limited due to poor cell engraftment and survival and the therapeutic outcomes have been attributed to paracrine secretions such as extracellular vesicles (EV). The direct use of EV is an attractive therapeutic strategy and it has been shown that the kinetics of delivery of the EV to the targeted tissue may impact the outcomes. However, there are currently no technologies to deliver EV to the heart in a controlled and tunable manner. The objective of this study was to design a controlled release system, based on a photocurable adhesive polymer, to locally deliver EV to the cardiac tissue. We have first demonstrated that the adhesive polymer, PGSA-g-EG, did not impact the EV bioactivity in vitro and was biocompatible in vivo when tested in a rat model. Importantly, the polymer remained attached to the heart surface for at least 1 month. We have then evaluated and optimized the in vitro release kinetics of the EV from the PGSA-g-EG polymer. Freeze-dried EV formulations were developed to tune the release kinetics and maximize the loading in the polymeric material. Moreover, despite the instability of the EV in aqueous medium at 37°C, the PGSA-g-EG polymer was able to release bioactive EV for at least 14 days. Overall, these results suggest that the PGSA-g-EG is a suitable material to promote the controlled delivery of bioactive EV over an extended period of time. Statement of SignificanceExtracellular vesicles (EV) are an investigational class of therapeutics that has shown promise to restore cardiac function following an ischemic event. Furthermore, its translation to the clinics is expected to pose less regulatory challenges than cell-based therapies. However, EV therapeutic outcomes are likely to be impacted by the route of administration and the kinetics of delivery to the target tissue. Therefore, there is a need for biomaterial-based technologies to deliver, in a controlled and tunable manner, EV to the heart. The present study describes the use of PGSA-g-EG polymer as an adhesive cardiac patch with potential to enable the controlled delivery of bioactive EV over an extended period of time to the cardiac tissue.

P1295OBSERVATION ON THE EFFECT OF DIGOXIN COMBINED WITH BENAZEPRIL HYDROCHLORIDE ON THE MAINTENANCE OF CHRONIC HEART FAILURE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims To observe the effect of digoxin combined with benazepril hydrochloride on the heart structure and function of chronic heart failure in patients with maintenance hemodialysis. Method Choose 36 patients with maintenance hemodialysis, chronic heart failure (NYHA II - III) from 2016 to 2017 in our department. The patients were randomly divided into three groups: control group 1: digoxin (0.125mg/ day), control group 2: benapril hydrochloride (20mg/ day), and observation group: digoxin (0.125mg/ day) + benapril hydrochloride (20mg/ day), with 12 people in each group. There was no statistical difference in the clinical baseline data of the three groups of patients. The experiment mainly observed left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDV), serum troponin T, I (TnT, TnI), and serum n-terminal brain natriuretic peptide precursor (NT-proBNP), human component bioelectrical impedance analysis (BCM), the blood pressure. No other RAAS inhibitors were allowed for all patients. The observation period was 1 year. Results 1. According to the findings of cardiac ultrasound, LVEF value increased significantly and LVEDV decreased significantly in the observation group. There was a statistical difference between the observation group and the control group (P&amp;lt;0.05), while there was no statistical difference between the two control groups. 2. Serum examination showed that TnT, TnI, nt-probnp were significantly decreased in the observation group, there was a statistical difference between the observation group and the two control groups (P&amp;lt;0.05), there was no statistical difference between the two control groups. 3. During the observation period, there was no significant difference in the incidence of hyperkalemia among the three groups (P &amp;gt;0.05). Conclusion A large dose of benazepril hydrochloride combined with a small dose of digoxin, had significant effect on the cardiac structure and function of chronic heart failure in patients with maintenance hemodialysis.

How do Extracellular Vesicles Protect the Ischemic Myocardium?

Background & Aim Introduction Cell therapy for chronic heart failure has demonstrated that Cardiac Progenitor Cells (CPCs) delivered to the heart exert their beneficial effects through a paracrine mechanism harnessing endogenous repair pathways largely mediated by extracellular vesicles (EVs). We used a bi-transgenic fate-mapping MerCreMer/ZEG mouse model to assess whether the cardioprotection could be partly explained by de novo cardiogenesis. Methods, Results & Conclusion Methods Myocardial infarction (MI) was induced by permanent left anterior descending coronary artery ligation in MerCreMer/ZEG mice. Surviving animals (n=30) with a left ventricular ejection fraction (LVEF) ≤ 45% were treated 3 weeks after MI with either EV (from 1.4 × 106 human iPS-derived CPC; 10 × 109 particles; n=15) or PBS (n=15) delivered by echo-guided intra-myocardial injections targeted to the peri-infarcted area. To track a putative proliferation of endogenous cardiomyocytes, osmotic pumps delivering EdU were implanted for 10-13 days after EV or PBS treatnent. Cardiac function was assessed 4-6 weeks after injections by echocardiography (n=15 p/group) and MRI (n=6-7 p/group), blinded to treatment group. Hearts were harvested and subjected to histological and transcriptomic analyses by qRT-PCR and genome-wide microarrays (Affymetrix). Results In controls, echocardiographically assessed EF slightly decreased over time whereas in the EV-treated group, it increased so that at the end-study time point, the between-group difference in changes from baseline averaged 20.7 % ± 10.5 % (p=0.048). This improvement was confirmed by MRI (11%, p=0.05). EV-treated hearts did not show a different number of new cardiomyocytes (TnT+/EdU+/GFP+) compared to controls (32 analyzed sections/mouse). However, EV-treatment was associated with a reduction in infarct size (-11.9% ± 5.75%), and reduced expression of 4 pro-fibrotic genes (Col1a2, Col3a1, Lox, Col1a2) as assessed by qRT-PCR (n=5-6 p/group). Further, the EV-treatment group showed an over-expression of the anti-fibrotic miRNA 133a-1 (2.13 fold) as compared to controls (n=3 p/group; p=0.0015). Conclusions EV secreted by iPSC-CPC improve cardiac function in chronic heart failure by mechanisms which seem to be largely related to the modulation of fibrosis without participation of a de novo cardiogenesis. Funding Labex Revive, Fondation pour la Recherche Medicale, Fonds Marion Elizabeth BRANCHER

Renal tubular damage and worsening renal function in chronic heart failure: Clinical determinants and relation to prognosis (Bio-SHiFT study).

BackgroundIt is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.HypothesisChanges in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.MethodsDuring 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N‐acetyl‐β‐d‐glucosaminidase (NAG), and kidney‐injury‐molecule (KIM)‐1. The degree of tubular injury was ranked according to NAG and KIM‐1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF‐hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.ResultsHigher baseline NT‐proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT‐proBNP: 1.26 [1.07‐1.49]; per 10 mL/min/1.73 m2 eGFR decrease 1.16 [1.03‐1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08‐1.62]; spironolactone per 25 mg decrease: 1.76 [1.07‐2.89]; per 10 mL/min/1.73 m2 eGFR increase: 1.40 [1.20‐1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1‐3.4], tubular 8.4 [2.6‐27.9]; when combined risk was highest 15.0 [2.0‐111.0]).ConclusionSlopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.

Right Ventricular Function in Chronic Heart Failure: From the Diagnosis to the Therapeutic Approach.

There is growing attention for the study of the right ventricle in cardiovascular disease and in particular in heart failure. In this clinical setting, right ventricle dysfunction is a significant marker of poor prognosis, regardless of the degree of left ventricular dysfunction. Novel echocardiographic methods allow for obtaining a more complete evaluation of the right ventricle anatomy and function as well as of the related abnormalities in filling pressures. Specific and effective therapies for the right ventricle dysfunction are still not well defined and this represents the most difficult and important challenge. This article focuses on available diagnostic techniques for studying right ventricle dysfunction as well as on the therapies for right ventricle dysfunction.

Testosterone Supplementation in Patients With Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Background: The effect of testosterone supplementation in patients with chronic heart failure (CHF) remains uncertain.Methods: A meta-analysis of randomized controlled trials (RCTs) was performed. RCTs that evaluate the chronic effect of testosterone supplementation on exercise capacity and cardiac function in CHF were identified via searching of PubMed, Embase, and the Cochrane's Library databases. Heterogeneity was evaluated by the Cochrane's Q test and I2 statistics. A fixed-effect model was used if the heterogeneity was not significant (I2 < 50%); otherwise, a random-effect model was applied.Results: Eight studies including 170 patients in the testosterone supplementation group and 162 in the control group were included. Overall, testosterone supplementation was not associated with an improved exercise capacity (walking test: standardized mean difference [SMD] = 0.36, p = 0.07). Sensitivity analyses limited to male patients showed similar results (SMD = 0.21, p = 0.15), and subgroup analyses also showed similar results in male HF patients with baseline total testosterone (TT) ≥ or < 10 nmol/L. However, patients with TT at endpoint ≥ 25 nmol/L was associated with improved exercise capacity (SMD = 1.12, p = 0.02), but not for those with TT at endpoint < 25 nmol/L (SMD = 0.24, p = 0.12). In addition, VO2max (weight mean difference [WMD] = 0.85, p = 0.43), the functional classification (the New York Heart Association classification: WMD = −0.08, p = 0.16) and quality of life (Minnesota Living with Heart Failure [MLHF] questionnaire: WMD = −6.03, p = 0.12) were not significantly affected. Moreover, testosterone supplementation did not significantly affect left ventricular ejection fraction (WMD: −1.52%, p = 0.37), serum B-type natriuretic peptide (SMD: −0.19, p = 0.23), or a composite outcome of death or HF hospitalization (risk ratio [RR]: 1.02, p = 0.96). Although testosterone supplementation increased systolic blood pressure (BP) in CHF patients (WMD: 5.68 mmHg, p < 0.001), diastolic BP or heart rate was not significantly changed as compared to control.Conclusions: Testosterone supplementation within a physiological range is not associated with significantly improved exercise capacity, cardiac function, quality of life, or clinical outcome in CHF patients.

Evaluation of nine active components of Lu-Jiao Fang in normal and hypertrophic rat myocardia via LC-MS/MS.

Lu-Jiao Fang (LJF), a traditional Chinese medicine prescription, can improve the cardiac function of chronic heart failure (CHF) patients; however, knowledge about the cardiac distribution of LJF, especially in CHF animal models, is rather limited. This work aimed to explore the cardiac distribution of LJF in pressure overload-induced CHF rats at the last gavage administration of LJF after 30 weeks of treatment. LC-MS/MS methods for analyzing nine active components (i.e. loganin, hesperidin, epimedin C, icariin, psoralen, isopsoralen, baohuoside I, morroniside and specnuezhenide) of LJF in cardiac tissue samples were established, and the components were then analyzed in left ventricular wall (LVW) and right ventricular wall (RVW) in parallel at same time point postdose for three dose groups. The results showed that most analytical component levels in LVW (hypertrophic myocardium) were only 39-74% of those in RVW (normal myocardium); however, psoralen and isopsoralen levels in LVW were equal to or even greater than the levels in RVW, suggesting that the hypertrophic myocardium tissue affinity of psoralen and isopsoralen might overcome the negative effect of decreased blood flow on distribution. This study indicated that the pathological state may influence drug distribution, and the efficacy of psoralen and isopsoralen for improving CHF deserves further investigation.