Function In Chronic Heart Failure Patients Research Articles

Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure.

The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this exploratory cross-sectional study, we aimed to investigate relationships between gut microbiota diversity, markers of gut barrier dysfunction, inflammatory markers, and cardiac function in chronic HF patients. In total, 151 adult patients with stable HF and left ventricular ejection fraction (LVEF) < 40% were enrolled. We measured lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and soluble cluster of differentiation 14 (sCD14) as markers of gut barrier dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) level above median was used as a marker of severe HF. LVEF was measured by 2D-echocardiography. Stool samples were sequenced using 16S ribosomal RNA gene amplification. Shannon diversity index was used as a measure of microbiota diversity. Patients with severe HF (NT-proBNP > 895 pg/ml) had increased I-FABP (p < 0.001) and LBP (p = 0.03) levels. ROC analysis for I-FABP yielded an AUC of 0.70 (95% CI 0.61-0.79, p < 0.001) for predicting severe HF. A multivariate logistic regression model showed increasing I-FABP levels across quartiles of NT-proBNP (OR 2.09, 95% CI 1.28-3.41, p = 0.003). I-FABP was negatively correlated with Shannon diversity index (rho = -0.30, p = <0.001), and the bacterial genera Ruminococcus gauvreauii group, Bifidobacterium, Clostridium sensu stricto, and Parasutterella, which were depleted in patients with severe HF. In patients with HF, I-FABP, a marker of enterocyte damage, is associated with HF severity and low microbial diversity as part of an altered gut microbiota composition. I-FABP may reflect dysbiosis and may be a marker of gut involvement in patients with HF.

Renal Dynamic Imaging Information Data in the Evaluation of Renal Function in Patients with Chronic Heart Failure under the Guidance of Intelligent Region of Interest Detection Algorithm

This work aimed to explore the application value of intelligent region of interest (ROI) detection algorithm in evaluating renal dynamic imaging information data of renal function in patients with chronic heart failure (CHF). 52 patients with CHF were selected as the research objects and grouped according to the level of renal function into an experimental group (14 cases) and an observation group (38 cases). In addition, 10 healthy people were selected as the research objects, as the control group. Different calculation methods of glomerular filtration rate (GFR) were used to evaluate the renal function of patients, and the ROI detection algorithm-assisted delineation was compared with traditional manual delineation. It was found that the GFR of the experimental group calculated by different methods was 52.58 mL/min/1.73m2 and 43.77 mL/min/1.73m2, respectively, which was significantly lower than that of the observation group ( P &lt; 0.05 ), and that in both groups was lower than that of the control group ( P &lt; 0.05 ). In addition, the unilateral renal function values of the two auxiliary delineations were both 13.61 mL/min/1.73 m2, while the results of the two manual delineations were significantly different ( P &lt; 0.05 ). Therefore, renal dynamic imaging based on the ROI detection algorithm to evaluate the renal function of CHF patients showed a great improvement in effectiveness, sensitivity, stability, and efficiency compared with the traditional manual delineation, which was worthy of clinical promotion.

The Circular RNA CDR1as Regulates the Proliferation and Apoptosis of Human Cardiomyocytes Through the miR-135a/HMOX1 and miR-135b/HMOX1 Axes.

Background: Chronic heart failure (CHF) is a major health burden worldwide, but there are a lack of effective methods for its early diagnosis and prognostic evaluation. Circular RNAs (circRNA), as a class, have been found to regulate gene expression and are implicated in multiple types of diseases. The circRNA, CDR1as, is reported to regulate gene transcription by acting as a microRNA inhibitor. However, the role of CDR1as in CHF remains to be elucidated. The aim of this study was to investigate the role and mechanism of action of the circRNA, CDR1as, in CHF. Methods: A total of 30 patients with CHF and 30 healthy persons were included in the study. The levels of CDR1as, miR-135a, and miR-135b in the plasma of all subjects were quantified by qRT-PCR. ELISA was used to detect the level of HMOX1 in plasma. The effect of CDR1as was investigated in human cardiomyocytes, including HCMs and AC16 cells. Results: CDR1as was upregulated in the plasma of patients with CHF and is a potential diagnostic marker of CHF. The levels of miR-135a and miR-135b were downregulated in the plasma of patients with CHF. The plasma level of HMOX1 in patients with CHF was significantly higher compared with the control group and was highly correlated with cardiac function in CHF patients. CDR1as was shown to act as a sponge for miR-135a and miR-135b and regulated the proliferation and apoptosis of human cardiomyocytes through the miR-135a/HMOX1 and miR-135b/HMOX1 signaling axes. Conclusion: CDR1as is a potential biomarker of CHF that is mechanistically involved in the disease pathogenesis and participates in regulating the occurrence and development of CHF through the miR-135a/HMOX1 and miR-135b/HMOX1 signaling axes.

Application of self-care based on full-course individualized health education in patients with chronic heart failure and its influencing factors.

BACKGROUNDThe treatment of heart failure not only needs to relieve the clinical symptoms and improve the quality of life for patients but also needs to select scientific and reasonable ways to prevent or delay the progression of the disease, thus reducing the mortality and hospitalization rate. Although the previous regimen can effectively relieve symptoms in the early stage of treatment, long-term use may cause adverse events, such as arrhythmia, and even increase mortality. Therefore, conventional treatment cannot meet the actual health needs of patients, and scientific nursing intervention is very necessary.AIMTo investigate the application of self-care based on full-course individualized health education (FCIHE) and its influencing factors in patients with chronic heart failure (CHF).METHODSWe enrolled CHF patients who were admitted to our center between September 2015 and June 2016 and divided them into an intervention group (n = 50) and control group (n = 50) using a random number table. Routine nursing care was applied to the control group, and FCIHE was offered to the intervention group. The self-care behavior, 6-min walking distance (6MWD), and 36-item short form health survey (SF-36) scores were compared between the two groups. The influencing factors of the self-care were also analyzed.RESULTSThe 6MWD was not significantly different between the two groups at admission (P > 0.05); however, at 3 and 6 mo after discharge, 6MWD was significantly increased, and it was significantly longer in the intervention group (P < 0.05). The scores for self-care behavior showed no significant difference at admission between the two groups (P > 0.05); however, at 3 and 6 mo after discharge, the total scores for self-care maintenance, management, confidence, and behavior of the intervention group were significantly higher than those of the control group (P < 0.05). There were no significant differences in the SF-36 scores at admission (P > 0.05); however, at 3 mo and 6 mo after discharge, the scores for all eight subscales, including physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health, were significantly higher in the intervention group (P < 0.05). As shown by logistic regression analysis, the influencing factors of self-care mainly included age, cardiac function class, and education background (odds ratio > 1; all P < 0.05).CONCLUSIONFCIHE improved self-care behavior and cardiac function in CHF patients. Age, cardiac function, and education level affected the implementation of self-care among CHF patients.

Qishenyiqi dripping pill improves ventricular remodeling and function in patients with chronic heart failure: A pooled analysis.

Qishenyiqi dripping pill for chronic heart failure (CHF) remains controversial due to lack of high-quality trials. Therefore, we conduct this pooled-analysis to evaluate the efficacy and safety of Qishenyiqi in CHF patients. We searched for randomized clinical trials for Qishenyiqi dripping pill in treating CHF up to August 2018 through China National Knowledge Infrastructure (CNKI), the PubMed Database, the Wanfang Database, the China Scientific Journal Database (VIP), and the Chinese Biomedicine Literature Service System. RevMan 5.3 was used for pooled analyses. Based on the New York Heart Association (NYHA) classification, the clinical therapeutic effect was collected as the primary endpoint. The efficacy and safety of Qishenyiqi combined with routine treatment significantly increased NYHA functional classification, left ventricular ejection fraction, cardiac index, and 6-minute walking test and decreased brain natriuretic peptide, left ventricular end-diastolic, and end-systolic dimensions with no obvious side effects in comparison with routine therapy alone. Together these results provide important insights into Qishenyiqi is effective and safe in improving ventricular remodeling and function of CHF patients. PROSPERO106695.

Clinical Efficacy and Safety of Xinmailong Injection for the Treatment of Chronic Heart Failure: A Meta-Analysis.

Background: Chronic heart failure (CHF) is one of the most stubborn cardiovascular disease. Xinmailong (XML), a bioactive fraction extracted from Periplaneta americana L., has been commonly used for CHF treatment in China. However, there is few comprehensive evaluation for the clinical efficacy and safety of XML for CHF.Objectives: We aimed to evaluate the beneficial and adverse effects of Xinmailong Injection (XMLI) on CHF treatment with the use of meta-analysis.Methods: In accordance with the Cochrane Handbook and transparent reporting of systematic reviews and meta-analysis protocol (CRD42018087091), seven English and Chinese electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP medicine information system and China Biomedical Literature Database (CBM), were searched to retrieve potential randomized controlled trials (RCTs) before November 2017. The eligible trials were evaluated for methodological quality. The main outcome measures were analyzed with RevMan 5.3 software.Results: 26 RCTs involving 3447 participants were subjected to meta-analysis. The total effective rate was improved by XMLI plus conventional therapy (OR 3.10, 95% CI 2.47–3.90, P < 0.00001). When compared to the conventional treatment alone, the combination of XMLI and conventional treatment increased left ventricular ejection fraction (LVEF, MD 4.93, 95% CI 3.96–5.89, P < 0.00001) and 6-min walking distance (6-MWD, MD 46.76, 95% CI 32.51 to 61.01, P < 0.00001), and decreased left ventricular end-diastolic diameter (LVEDD, MD −4.73, 95% CI−5.64 to−3.83, P < 0.00001), serum brain natriuretic peptide (BNP, MD −149.59, 95% CI −211.31 to −87.88, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP, MD −322.35, 95% CI −517.87 to −126.83, P = 0.001). However, the frequency and severity of adverse effects was similar between these two different medications. Poor methodological quality and the limitations also existed in this study.Conclusions: The combinational use of XMLI on conventional treatment may exert better therapeutic effects on improving cardiac function in CHF patients, indicating that XMLI was suggested to be considered during the conventional treatment of CHF. High-quality and large scale RCTs are still required to confirm the impacts of XMLI.

Eight weeks of slow deep breathing training alters cardiorespiratory function and improves functional exercise capacity in chronic heart failure patients

Patients with chronic heart failure (CHF) display autonomic imbalance characterized by excessive sympathoexcitation and reduced vagal outflow. Respiratory sinus arrhythmia (RSA) and baroreflex sensitivity (BRS) are often used as non‐invasive indices of autonomic function. Slow deep breathing (SDB) has been shown to modulate RSA and BRS. In this preliminary study, we examined the effects of SDB in CHF patients (n=4) during a baseline condition of spontaneous breathing (5 minutes), during SDB (5 minutes) controlled at 6 breaths/minute, and during a post‐SDB condition of spontaneous breathing (5 minutes). The patients then underwent an SDB training protocol, in which SDB was practiced at least 5 days/week and with the duration of practice incrementally increasing from 10 min/day at week 0 up to 30 minutes/day by week 8. Comparisons in cardiorespiratory function were made between each of the conditions (i.e., baseline, SDB, and post‐SDB) and between each time point (i.e., week 0 and week 8). We hypothesized that acute SDB would transiently decrease blood pressure, increase BRS, and increase RSA compared to the baseline and post‐SDB conditions. We also predicted that 8 wks of SDB training would decrease baseline blood pressure, increase BRS, and increase RSA compared to week 0. SDB produced a statistically significant (p=0.01) reduction in systolic pressure after 8 wks (114 ± 5.4 mmHg) compared to week 0 (132 ± 12 mmHg). Further, 8 wks of SDB training appears to have altered acute blood pressure responses to SDB. During SDB at week 0, systolic pressure did not differ from baseline spontaneous breathing. However, after 8 wks of SDB training, patients showed a 5.4% reduction in systolic pressure to acute SDB compared to baseline spontaneous breathing (p=0.02). The decrease in systolic pressure was not correlated with the type or dose of antihypertensive drugs. Acute SDB also produced a transient increase in BRS of ~25% from the baseline condition with no differences between week 0 and week 8. RSA increased during acute SDB compared to baseline (p=0.001) but did not change after 8 weeks of SDB training. Further, a six‐minute walk test was performed to assess functional exercise capacity, and the patients with the greatest impairment at baseline showed improvements in the six‐minute walk test after 8wks of SDB. While the data are preliminary, the results suggest that SDB training improves exercise capacity and produces a stable reduction in systolic pressure and transient change in non‐invasive measures of autonomic function in CHF patients.Support or Funding InformationNIH PO1‐HL062222‐17This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cognitive performance of patients with chronic heart failure on sacubitril/valsartan : Aretrospective cohort study.

Sacubitril, aneprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System. Aretrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients' clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15Marchto 31October 2017. Patients in the sacubitril/valsartan group had aclinical history of at least 3months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled. The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, asimilar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups. In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3months had similar mean MMSE scores to control subjects.

Association between omentin and echo parameters in patients with chronic heart failure.

Adipose-derived adipokines have been demonstrated to be associated with the development of experimental heart disease through chronic inflammation and cardiac cell apoptosis. Omentin is to be one of the novel adipokines. The aim of this study is to investigate the relationship between circulating omentin and cardiac dysfunction in patients with chronic heart failure (CHF). A total of 189 CHF patients were studied, determining serum omentin and echocardiographic parameters. All participants were divided into two experimental groups: the 111 patients who had a left ventricular ejection fraction (EF) ≥40% (EF-H) and the 78 patients exhibiting EF values <40% (EF-L). The EF-L group showed significantly higher circulating omentin levels compared to the EF-H group (210.8±67.2 vs. 155.3±45.3, P<0.001; Student's t-test). Overall, the data of the linear regression analysis revealed that serum omentin levels correlated positively with left atrial diameters (r=0.31, P=0.006), left ventricular end-systolic dimensions (r=0.42, P<0.001), and left ventricular end-diastolic dimensions (r=0.38, P=0.002) and negatively with left ventricular EF (r=-0.45, P=0.001; Spearmen's rank correlations coefficients for each). The multiple regression model included all variables at p<0.1 by the univariate analysis. A multiple logistic regression analysis demonstrated that high levels of patients' serum omentin were associated with cardiac dysfunction in patients with CHF (OR=1.22; 95% CI: 0.91-1.58; P=0.009). These findings suggested that elevated serum omentin levels were only very mildly related to the changes in cardiac volume and function in CHF patients. Further studies are then needed to assess the real clinical value of omentin in this setting.

Prognostic role of metabolic risk factors (hyperhomocysteinemia) in the development of chronic heart failure

The aim of the study was to assess the relationship of homocysteine levels in the blood serum with the severity and nature of chronic heart failure (CHF) in patients with coronary heart disease. 94 patients with CHF were examined. The control group included 32 patients without cardiovascular disorders. At baseline and after 12 months of observation the homocysteine levels in the blood serum were determined by enzyme-linked immunosorbent assay. Correlative relationship of hyperhomocysteinemia with ischemic myocardial remodeling and with reduced inotropic function in CHF patients was observed. The homocysteine level in the blood serum of CHF patients significantly exceeded that of the control group and moderately increased with the progression of the disease severity of functional class. In the group with an unfavorable course of CHF the baseline homocysteine level proved to have the greatest value as compared to that in the group with a favorable course. In patients with a favorable course of CHF the homocysteinemia level tended to decrease towards the end of prospective study, whereas in patients with an unfavorable course, on the contrary, hyperhomocysteinemia persisted (p&lt;0.01). In case the hyperhomocysteinemia baseline exceeds 18.5 mkmol/L (ROC-AreaSE = 0.860.04, sensitivity 71 %, specificity 90%), the severity and characteristics of the ischemic CHF could be most likely predicted. Thus, hyperhomocysteinemia is related with the severity and nature of CHF. Determining the level of homocysteine in the blood serum can be recommended for early prediction of the severity and nature of CHF.

Effects of febuxostat and allopurinol on the inflammation and cardiac function in chronic heart failure patients with hyperuricemia

BackgroundAn elevated uric acid (UA) level is associated with an increased risk of adverse outcomes in patients with chronic heart failure (CHF). Febuxostat and allopurinol lower the UA levels and attenuate the expression of an inflammatory marker, monocyte chemoattractant protein (MCP)-1. However, a direct comparison of the effects of febuxostat and allopurinol on the inflammation and cardiac function in CHF patients with hyperuricemia has not yet been performed. MethodsA total of 61 CHF patients with hyperuricemia who had a mean left ventricular ejection fraction (LVEF) of 37.1±6.7% were randomly assigned to receive febuxostat (n=31) or allopurinol (n=30). ResultsThe MCP-1 levels and LVEF at baseline were comparable between the groups. However, after 12months of treatment, the febuxostat group achieved significantly higher percent decreases in the UA and MCP-1 levels from baseline than those of the allopurinol group (p<0.001). The LVEF in both groups had improved after 12months; however, a greater percent increase in the LVEF from baseline was observed in the febuxostat group than that in the allopurinol group (p<0.001). The percent increase in the LVEF from baseline was found to be significantly associated with the percent decrease in MCP-1 (r=−0.634, p<0.001) in the febuxostat group. ConclusionsThese data indicate that febuxostat is more effective than allopurinol in reducing the UA level and inflammation and may improve the cardiac function in CHF patients with hyperuricemia due, at least in part, to reductions in inflammation.

Chronic heart failure and aging - effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study.

A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age. We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed. As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls. Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.

Effects of Physical Exercise on Cardiovascular Diseases: Biochemical, Cellular, and Organ Effects.

It is well recognised that regular exercise is cardioprotective. On the other hand, sedentariety is an established risk factor for cardiovascular diseases. Furthermore, several clues suggest that exercise capacity is a strong predictor of risk of death from any cause in both healthy subjects and in those with cardiovascular diseases. However, the exact mechanisms through which regular physical activity confers cardiovascular protection are not yet well understood. Exercise probably acts at multiple levels. One possibility is that regular exercise modifies genes expression, thereby changing the production of bioactive molecules such as proteins and enzymes; another potential site of action is on the mechanisms of cardiovascular regulation during effort, which are improved after periods of training; finally, exercise can affect endothelial and platelet functions, thus reducing the risks of atherosclerosis and consequently the risk of infarction and stroke. This special issue focuses on potential beneficial mechanisms by which exercise operates to confer protection against cardiovascular diseases. The interesting paper by S. Heber and I. Volf reviews the effects of inactivity and training on platelet functions. In their literature review, they conclude that regular physical activity diminishes or prevents platelet activation in response to acute exercise and that habitual physical activity also positively modulates platelet functions. They also conclude that these effects support the well-recognised relation between exercise and the risk for cardiovascular events, as a physically active lifestyle dramatically reduces cardiovascular mortality. In another intriguing review, C.-Y. Hsu et al. focus on the important topic of the effects of exercise training on autonomic function in chronic heart failure (CHF). Exercise intolerance is one of the major and disturbing symptoms in these patients. Increased sympathetic tone and decreased parasympathetic activity have been often reported in CHF and these phenomena are associated with a poor survival. Data from this review indicate that participation in exercise training programs induces beneficial effects on autonomic function in CHF patients. They also point out that further research could examine additional aspects of the effects of exercise training in this population, such as the impact on the responses to exercise training in different levels of CHF severity, the possibility that a threshold intensity may be needed to affect cardiac autonomic function, and the type of exercise that should be recommended to achieve the highest positive effects on sympathovagal balance. In a third review by A. Crisafulli et al., the complex issue of cardiovascular reflexes during exercise is addressed. During exercise, the neural mechanisms controlling the cardiovascular apparatus regulate cardiac output and arteriolar tone in order to counteract the exercise-induced vasodilation due to functional sympatholysis in the working muscle. These cardiovascular adjustments guarantee adequate perfusion to vital organs (the brain and the heart) and to the working muscles as well as adequate washout of exercise-induced by-products. Moreover, these mechanisms prevent excessive increments in blood pressure. In this review, authors summarise neural reflexes operating during dynamic exercise, particularly their interaction. They point out that cardiovascular regulation during exercise is achieved through the contemporary integration and interaction of input arising from motor cortex (central command), skeletal muscle receptors (exercise pressor reflex), and arterial baroreceptors. They also conclude that further research is warranted to better understand how these reflexes interact during effort. The last interesting review by R. B. Batacan Jr. et al. is about the effects of light intensity activity on cardiovascular risk factors. These authors claim that there is little support for the role of light intensity activity to reduce cardiovascular disease risk factors and that further studies are needed to establish the value of light intensity physical activity in reducing cardiovascular risk factors. Finally, the research paper by N. G. Rocha et al. aims at evaluating the acute effects of exercise on endothelial functions in early metabolic syndrome. They find that these subjects, despite being free of symptoms, present with an early impairment of endothelial function. Moreover, they put forward the hypothesis that the analysis of some biomarkers changes could be potentially useful to develop preventive measures before the onset of overt metabolic syndrome. Collectively, these manuscripts confirm that sedentariety is harmful for the cardiovascular system. Moreover, exercise not only exerts positive effect on cardiovascular functions and reduces the risks of cardiovascular diseases (primary prevention), but could also revert cardiovascular disease and play a preventive role in the progression of pathological conditions (secondary/tertiary prevention).

Systematic review of efficacy and safety of Shenmai injection for chronic heart failure

The paper is to evaluate the efficacy and safety of Shenmai injection for chronic heart failure, retrieving the Pubmed, CBM, CNKI, Wanfang database and VIP database to comprehensively collect all types research report of Shenmai injection for chronic heart failure (CHF). Particularly wishing to point out, randomized controlled trials are include for the evaluation of effectiveness, which are statistically analyzed and evaluated by Rev-Man 5. 2. The current studies show that the improvement rate of NYHA classification of cardiac function of CHF patients and their related indexes figure such as LVEF, SV, CO, BNP, 6 min walking test value are all improved by the combination of Shenmai injection and foundation treatment. However, HR is almost no improvement. Meanwhile, serious ADR/AE of Shenmai injection for CHF isn't appear.

The Metabolic Modulator Perhexiline Induces Calcium-Cycling Dysfunction and Apoptosis in Cardiomyocyte Syncytia

Major pathogenic adaptations in chronic heart failure (CHF) include the reversion to glycolytic metabolism and the persistence of an energy deficient state. The use of metabolic modulators to increase the efficiency of glycolytic ATP production has emerged as a new therapeutic approach in CHF. Perhexiline (PHX), an anti-anginal agent, improves myocardial function in CHF patients by a mechanism that is thought to involve the inhibition of carnitine palmitoyl transferase (CPT) which prevents mitochondrial free fatty acid uptake. In silico modelling and cell-based experimental data predict that such alterations to the metabolic steady state would drive other compensatory (mal)adaptations that could negatively impact on cellular phenotype. Here, we investigated the phenotypic consequences of PHX-mediated metabolic modulation on Ca2+ cycling and apoptotic susceptibility in HL-1 syncytia. HL-1 cardiomyocytes exhibit a metabolic profile similar to that observed in CHF myocardium (glycolysis >> fatty acid oxidation). Contrary to the expected enhancement of Ca2+ cycling, PHX profoundly deranged Ca2+ signalling in a time- and concentration-dependent manner. The spatio-temporal organization and intercellular synchronization of Ca2+ oscillations was progressively reduced at [PHX] between 0.1 and 2.5μM and contractility was abolished at [PHX] > 5μM. These concentrations are below the levels of drug reported to accumulate in heart tissue following therapeutic dosing. Metabolic activity was compromised in PHX-treated cells and we determined PHX concentration-dependent caspase-linked apoptosis (EC50 ≈ 25μM). Oxfenicine (a potent CPT1 inhibitor) did not recapitulate any of these effects at concentrations up to 100μM. Our data show that, in the context of glycolytic metabolism, PHX provoked dysfunctional Ca2+ handling and increased cardiomyocyte susceptibility to apoptosis. These effects appeared to be independent of CPT inhibition.

Intermittent Vagus Nerve Stimulation Reflexively Modulates Heart Rate Variability in Rats With Chronic Ischemic Heart Failure

Heart disease is the leading cause of death in the developed world. Despite major strides made in the past decade regarding the treatment and prevention of heart disease, cardiac injury due to acute myocardial infarct (MI) remains a difficult and complicated problem to solve. When enough tissue damage occurs in the myocardium, the ability of the heart to circulate blood is reduced and the organ changes shape in a maladaptive attempt to compensate for its lack of pumping capacity, ultimately leading to an even greater lack of circulatory output known as heart failure. Such tissue damage begins for a great number of patients the downward spiral termed ‘heart failure’ which culminates almost certainly at death. At rest, the heart rate of healthy individuals exhibits spontaneous variation as a result of respiratory-driven neural modulation of sinus node function (respiratory sinus arrhythmia, RSA). Heart rate variability (HRV) is defined as time-domain variations of the R-R intervals in the electrocardiogram. HRV driven primarily by RSA is strongly influenced by cholinergic nerve activity in and on the heart. Depressed parasympathetic activity within the autonomic nervous system resulting from cardiovascular disease has been linked to significantly diminished HRV in humans suffering with chronic heart failure (CHF). CHF is associated with autonomic dysregulation characterized by a sustained increase in sympathetic activity and decrease in parasympathetic activity [1]. Mainstream methods of nervous system modulation include beta-blockers, aldosterone agonists, and ACE inhibitors. Recently, modulation of parasympathetic activity through cardiac vagal nerve stimulation (VNS) has emerged as a potential therapy for CHF. VNS has been shown to prevent cardiac remodeling, eventually leading to an improved prognosis of HF rats after initial MI [2]. VNS also inhibited sudden cardiac death in dogs with MI [3] and markedly suppressed arrhythmias in conscious rats [4]. Chronic VNS may even improve quality of life and LV function in CHF patients with severe systolic dysfunction [5]. Recently, lowlevel VNS was implemented to reduce atrial tachyarrhythmia in ambulatory dogs [6]. Implantable VNS stimulators are currently undergoing human clinical trials for possible future use as a CHF therapy [8]. While human trials may be advancing, little is still known about the underlying antiarrhythmic mechanisms of VNS. VNS may indeed present a very promising future therapy for patients suffering from CHF, but further work is necessary to develop a reliable and efficacious treatment. Here we investigated changes induced in in-vivo MI heart rat model by means of chronic VNS. Specifically, we focused on changes in heart rate, and HRV. The objective of this paper was to investigate the changes induced in in-vivo MI heart rat model by means of chronic VNS. Specifically, we focused on changes in heart rate, and HRV that followed after chronic stimulation in 8-week animal study. Because VNS will soon be used for human CHF therapy, we must know how clinically relevant parameters such as HRV respond to VNS therapy and specifically, how they may change over time.

Short-term use of adaptive servo ventilation improves renal function in heart failure patients with sleep-disordered breathing

Sleep-disordered breathing (SDB) deteriorates the prognosis of patients with chronic heart failure (CHF). Adaptive servo ventilation (ASV) is a new therapeutic modality to treat SDB including Cheyne-Stokes respiration associated with central sleep apnea. Renal function plays critical roles in the progression of CHF and is a strong predictor of clinical outcomes. Cystatin C is a marker of renal function, and more sensitive than serum creatinine. The purpose of the present study was to examine whether ASV is effective for cardiac overload and renal dysfunction in CHF patients with SDB. Fifty patients with CHF and SDB (mean left ventricular ejection fraction 34.0%, estimated glomerular filtration rate (eGFR) 62.8ml/min/1.73cm(2)) were examined. We performed polysomnography for two consecutive days (baseline and on ASV), and measured levels of serum N terminal-pro B-type natriuretic peptide (NT-pro BNP), cystatin C, and estimated glomerular filtration rate based on cystatin C (eGFR Cyst C). ASV significantly improved the apnea hypopnea index, central apnea index, obstructive apnea index, arousal index, mean SPO2, and lowest SPO2 compared to baseline. ASV decreased NT-pro BNP (1,109.0 (2,173.2) to 912.8 (1,576.7) pg/ml, p<0.05), cystatin C (1.391±0.550-1.348±0.489mg/l, p<0.05), and increased eGFR Cyst C (61.9±30.8-65.7±33.8ml/min/1.73cm(2), p<0.01). ASV improved SDB, reduced cardiac overload, and ameliorated renal function in CHF patients with SDB. ASV has short-term beneficial effects on not only SDB but also cardio-renal function. ASV might be a promising useful tool for CHF as an important non-pharmacotherapy with cardio-renal protection.

Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure

Chemoreflex-mediated sympathetic activation contributes to both initiation and progression of chronic heart failure (CHF). To study the direct role of increased peripheral chemosensitivity in reducing sympathetic baroreflex function in CHF patients, we compared sympathetic baroreflex function, assessed by the slope of the relationship between muscle sympathetic nerve activity (MSNA) and DBP, in CHF patients with augmented (n = 18) and normal (n = 20) peripheral chemosensitivity. Using a double-blind, randomized, vehicle-controlled study, we examined the effect of chemoreflex deactivation (by breathing 100% oxygen for 15 min) on sympathetic baroreflex function in CHF patients with elevated and with normal chemosensitivity. Baseline MSNA was elevated (60.6 ± 3.2 vs. 48.9 ± 3.7 bursts/min, P < 0.05) and sympathetic baroreflex function impaired (3.06 ± 0.55 vs. 5.51 ± 0.69 % bursts/mmHg, P < 0.05) in CHF patients with augmented peripheral chemosensitivity compared with controls. Administration of 100% oxygen led to a significant decrease in MSNA (from 60.5 ± 3.2 to 52.6 ± 3.2 bursts/min, P < 0.001) and increase in sympathetic baroreflex (from 2.95 ± 0.56 to 6.18 ± 0.77, P < 0.001) in CHF patients with enhanced chemoreflex sensitivity. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamics or sympathetic baroreflex function in CHF patients with normal chemosensitivity. We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.

Incidence and Prevalence of Hypothyroidism in Patients Affected by Chronic Heart Failure: Role of Amiodarone

It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

Intrathoracic Impedance Changes Reflect Reverse Left Ventricular Remodeling in Response to Cardiac Resynchronization Therapy in Chronic Heart Failure Patients

Intrathoracic impedance monitoring has been reported to be useful for prediction of worsening chronic heart failure (CHF). However, it has not revealed the relation between changes in intrathoracic impedance and improvement of cardiac function in CHF patients with cardiac resynchronization therapy (CRT) implantation. Therefore, we investigated whether intrathoracic impedance change reflects reverse left ventricular (LV) remodeling in response to CRT in patients with CHF. The study subjects consisted of 29 CHF patients (23 males, mean age 64 ± 12 years) with CRT-defibrillator (CRT-D) implantation. The patients were divided into two groups based on whether the Opti-vol Fluid Index® reached over 60 ohms (group A, n = 7) or not (group B, n = 22) within 6 months of observation after CRT-D implantation. Levels of plasma B-type natriuretic peptide (BNP) were measured, and LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were evaluated before and 6 months after CRT-D implantation. In group B, BNP (556 ± 88 pg/mL versus 330 ± 70 pg/mL, P < 0.05), LVEDV (177 ± 18 mL versus 149 ± 14 mL, P < 0.01), and LVESV (128 ± 14 mL versus 100 ± 12 mL, P < 0.01) were significantly decreased 6 months after CRT-D implantation. LVEF (28 ± 2% versus 35 ± 2%, P < 0.01) was significantly increased after CRT-D implantation. On the other hand, no significant changes were detected in any parameters in group A. These data showed intrathoracic impedance changes reflected reverse LV remodeling in response to CRT in patients with CHF. Therefore, the monitoring of changes in intrathoracic impedance is useful for predicting CRT responders in patients with CHF.