Prognosis Of Chronic Heart Failure Patients Research Articles

The impact of renal tubulointerstitial dysfunction on the early and long-term prognosis in chronic heart failure patients with preserved left ventricular ejection fraction

Aim. To study the dependence of the early-term (1 year) and long-term (5 years) prognosis in patients with chronic heart failure (CHF) of ischemic origin with preserved left ventricular ejection fraction (LVEF) depending on renal tubulointerstitial functional disorders. Materials and methods. The study involved 88 patients (men – 46.6 % (n = 41); women – 53.4 % (n = 47)) with CHF of ischemic origin, stage II A–B, stage II–IV according to NYHA, 67 % (n = 59) with sinus rhythm, and 33 % (n = 29) with atrial fibrillation. Patients with sinus rhythm and atrial fibrillation were matched in age (p = 0.483), height (p = 0.345), weight (p = 0.317), body surface area (p = 0.153). NGAL levels were analyzed using an ELISA kit (E-EL-H0096, Elabscience, USA). NAG levels were analyzed using an ELISA kit (SEA 069 Hu, Cloud-Clone Corp., USA). KIM-1 levels were analyzed using an ELISA kit (SEA 785 Hu, Cloud-Clone Corp., USA). Kaplan–Meier curves and Cox proportional hazards regression analysis were performed. Results. No significant difference was found in the frequency of the cumulative endpoint during the first-year follow-up from the initial level of two markers of tubulointerstitial injury – KIM-1 (Log-Rank Test: p = 0.57529) and NAG (Log-Rank Test: p = 0.86001). According to the results of analysis of the Cox proportional hazards, only a tendency to increase in the risk factors of adverse events were observed in case of elevated KIM-1 (HR = 1.66; p = 0.5795) and NAG levels (HR = 1.1712; p = 0.8626) in this CHF patients’ cohort. Kaplan–Meier analysis revealed a probable (Log-Rank Test; p = 0.00141) increase in the frequency of the cumulative endpoint during the first year of follow-up in CHF patients with preserved LVEF due to increased serum NGAL level more than 168 ng/ml. According to the univariate model, an elevated serum NGAL level is associated with an increase in the relative risk by 4.2 times (95 % CI 1.78–16.89; p = 0.014). A reduced sodium level less than 142.5 mmol/l was associated with an increase in number of adverse cardiovascular events during the first-year follow- ups by 22 % (HR = 1.22, p = 0.029). After 5 years of follow-up, a decrease in sodium level less than 142.3 mmol/l is also characterized by a probable difference of the cumulative Kaplan–Meier’s curves (Cox–Mantel F-Test, p = 0.00287). According to the univariate model of Cox proportional hazards, the relative risk of adverse cardiovascular events in patients with CHF during the 5-year follow-up has a tendency to increase by 1.04 times (95 % CI 0.85–1.27; p = 0.72). Serum NGAL, a marker of renal tubulo-interstitial injury, doesn’t lose its properties as a powerful marker of an unfavorable long-term prognosis in patients with CHF with preserved LVEF (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032). Conclusions. The most powerful factors of the early (1-year) prognosis of adverse cardiovascular events in CHF patients with preserved left ventricular ejection fraction are the marker of tubulointerstitial injury, serum NGAL over 168 ng/ml, as well as the marker of tubulointerstitial dysfunction – the serum sodium level less than 142.5 mmol/l. The electrolyte imbalance, decreased sodium level less than 142.3 mmol/l, remains a powerful marker of an unfavorable long-term 5-year prognosis in CHF patients with preserved left ventricular ejection fraction, meanwhile serum NGAL, a marker of renal tubulointerstitial injury, besides doesn’t lose its prognostic value (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032), but also is independent from the parameters of the age (p = 0.409) and gender (p = 0.397) in such patients.

Correlation between SUA and prognosis in CHF patients after revascularization.

To explore the correlation between serum uric acid (SUA) and prognosis in patients with chronic heart failure (CHF) after revascularization. A total of 126 patients with CHF undergoing revascularization [coronary artery intervention (PCI) or coronary artery bypass grafting (CABG)] in the hospital were enrolled as CHF group between December 2021 and October 2022, while 126 healthy controls during the same period were enrolled as healthy control group. The levels of SUA, inflammatory factors and cardiac function in the two groups were detected. The correlation between SUA level and inflammatory factors, cardiac function levels was analyzed. All patients in CHF group were followed up for 6 months to observe prognosis. The differences in the above indexes among patients with different prognosis were compared. The risk factors of prognosis were analyzed by multivariate Logistic regression analysis, and their predictive value for prognosis was evaluated by ROC curves analysis.

Association Between Serum 3-Hydroxyisobutyric Acid and Prognosis in Patients With Chronic Heart Failure - An Analysis of the KUNIUMI Registry Chronic Cohort.

Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.Methods and Results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 μmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.

Obesity paradox in chronic heart failure with moderately reduced or preserved left ventricular ejection fraction: impact on a prognosis for patients according to a five-year follow-up

Aim. To investigate the obesity paradox by studying the impact of overweight and abdominal obesity on the prognosis in chronic heart failure (CHF) patients with moderately reduced or preserved left ventricular ejection fraction (LVEF) by five-year follow-up results. Materials and methods. A prospective, open, parallel-group study included 314 CHF patients with moderately reduced or preserved LVEF, average age was 65.3 ± 11.2 years. Group 1 – 66 patients with normal weight; Group 2 – 67 overweight patients; Group 3 – 90 patients with I degree abdominal obesity; Group 4 – 91 subjects with II–III degrees of obesity. Adverse cardiovascular events (CVEs) were studied as a cumulative endpoint, cardiovascular death, and rehospitalization due to decompensated CHF. Results. It has been found that excess body weight (overweight and I–III degrees of abdominal obesity) did not affect the prevalence and spectrum of adverse CVEs in CHF patients with moderately reduced and preserved LVEF. In overweight patients, compared to I degree obesity group, the incidence of cumulative end point (by 15.4 %; χ2 = 3.95, p < 0.05) and cases of re-hospitalization (by 19.0 %; χ2 = 5.6, p < 0.05) were more often observed. Concomitant overweight was associated with an increased risk for faster onset of the cumulative end point (HR 1.46, 95 % CI 1.1–2.2, p < 0.05) and re-hospitalization (HR 1.53, 95 % CI 1.1–2.4, p < 0.05). Conclusions. The presence of excess body weight (overweight and I–III degrees of abdominal obesity) did not affect the prevalence and spectrum of adverse CVEs in CHF patients with moderately reduced and preserved LVEF during the five-year follow-up. In the presence of overweight, in comparison with I degree abdominal obesity, the incidence of cumulative end point and re-hospitalization due to the disease decompensation were more often observed, which could be evidence for the existence of the obesity paradox. The most adverse effect on the prognosis in CHF patients with moderately reduced and preserved LVEF caused by concomitant overweight, in the presence of which, there was a significant increase in the risk for more faster onset of cumulative end point and re-hospitalization due to decompensation of the disease.

Cardiac cycle time-corrected electromechanical activation time greater than 15% is an independent risk factor for major adverse cardiovascular events in chronic heart failure outpatients.

Objectives:This study aimed to investigate the predictive value of cardiac cycle time-corrected electromechanical activation time (EMATc) for major adverse cardiovascular events (MACEs) in outpatients with chronic heart failure (CHF) in comparison with other clinic indexes.Methods:This prospective observational study at Beijing Anzhen Hospital from January 01, 2015 to January 01 2018 enrolled 120 CHF patients who were admitted for acute onset of CHF and followed up after discharge for 616.5 days (range: 202.75–875.25 days). Based on the different endpoints, cardiogenic death, all-cause death, and HF-related readmission, patients were assigned to the following groups: cardiogenic death and non-cardiogenic death groups, all-cause death and survival groups, and HF readmission and non-readmission groups. EMATc and other clinic indexes were measured and compared between these groups. Cox regression analysis was used to identify independent risk factors for MACEs.Results:The hazard ratio for EMATc>15% for cardiogenic death was 3.493 (P=0.046), suggesting that an EMATc>15% was an independent risk factor for cardiogenic death in CHF patients. The hazard ratios for B-type natriuretic peptide (BNP) >400 ng/L for all-cause death and CHF readmission were 3.810 (P=0.008) and 2.764 (P=0.031), respectively. Thus, BNP >400 ng/L was an independent risk factor for all-cause death and readmission for CHF. EF<40% was not found to be a significant risk factor for MACEs.Conclusions:BNP level can predict the risk for poor prognosis in CHF patients. EMATc>15% is an independent risk factor for cardiogenic death and should be considered as a supplement to serum BNP level and other clinical indexes for predicting cardiogenic death in CHF outpatients.

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure

Background: Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis.Methods: A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to collect the qualified studies that analyzed the prognostic value of GDF-15 in CHF from the inception of these online databases to September 25, 2021. The hazard ratio (HR) calculated for logGDF-15 of all-cause death and the related 95% confidence interval (CI) in multivariate analysis were used to measure the effect size. Additionally, subgroup analyses stratified by characteristics of the study participants were conducted for incremental evidence of GDF-15 in CHF with different clinical status.Results: A total of ten eligible studies involving 6,244 CHF patients were finally taken into the quantitative analysis. Results in the random-effects model indicated that there was an increased risk of 6% in all-cause mortality with a per 1LnU increase in baseline GDF-15 concentration (HR: 1.06, 95% CI: 1.03–1.10, P < 0.001). In stratified analyses, the association of GDF-15 with risk of all-cause mortality was found among chronic ischemic HF patients (HR:1.75, 95%CI: 1.24–2.48, P = 0.002), while the association was not found among chronic nonischemic HF patients (HR:1.01, 95%CI: 1.00–1.02, P = 0.219).Conclusion: The elevated GDF-15 is associated with an increased risk of all-cause mortality in CHF, especially, among CHF patients with ischemic etiology. The circulating GDF-15 might be a prognostic indicator in CHF patients.Registration Number: https://www.crd.york.ac.uk/PROSPERO; CRD42020210796.

Decreased albumin is associated with elevated N-terminal pro-brain natriuretic peptide and poor long-term prognosis in patients with chronic heart failure.

At present, the association between albumin, N-terminal pro-brain natriuretic peptide (NT-proBNP) and long-term prognosis in patients with chronic heart failure (CHF) is unclear. Therefore, the purpose of this study is to explore the relationship between albumin, NT-proBNP and all-cause mortality in CHF patients.Three hundred fifty two CHF patients were recruited in our study, and patients were divided into 2 groups according to the mean (37.16 g/L) of albumin concentration [low group (albumin < 37.16 g/L) and high group (albumin≥37.16 g/L)]. Differences between groups was compared by odds ratio (OR) and 95% confidence interval (CI).NT-proBNP in the high group was significantly lower than that in the low group at baseline [1811.50 (698.75–4037.00) vs 3479.50 (1538.50–7824.25), P < .001]. Spearman correlation analysis showed that there was a negative correlation between albumin and NT-pro BNP log10 transform (ρ= −0.217, P < .001). Furthermore, curve fitting further confirmed that albumin was negatively correlated with NT-proBNP. After a median follow-up of 1726 days, 90 patients in the high group occur all-cause mortality, and 98 patients in the low group occur all-cause mortality (46.88% vs 61.25%, OR = 0.29, 95% CI: 0.08–0.50). After adjusting for the selected confounding covariates by multivariate regression analysis, decreased albumin was still associated with increased all-cause mortality (high group vs low group: OR = 0.62, 95% CI: 0.39–0.97).Decreased albumin is associated with elevated NT-ProBNP and poor long-term prognosis in CHF patients. Clinicians need to pay enough attention to the nutritional status of CHF patients.

Prognostic value of heart failure echocardiography index in HF patients with preserved, mid-ranged and reduced ejection fraction

BackgroundTo investigate the clinical value of heart failure echocardiography index (HFEI) in evaluating the cardiac function and predicting the prognosis of patients with different types of heart failure (HF).MethodsFour hundred eighty-nine consecutively admitted HF patients were divided into three groups: HF with reduced ejection (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The baseline characteristics and ultrasound indexes were compared between the three groups. The correlation between HFEI and one-year risk of adverse events was compared by multivariate logistic regression. The clinical value of HFEI and plasma level of NT-proBNP in assessing the prognosis of patients with chronic heart failure (CHF) was analyzed by the receiver operating characteristic (ROC) curve.ResultsHFEI in HFrEF was significantly higher than that in HFmrEF and HFpEF. Multivariate regression analysis indicated that HFEI and plasma level of NT-proBNP were independent risk factors for predicting the short-time prognosis of HF patients. The ROC curve indicated that the HFEI cutoff level of 3.5 and the plasma NT-proBNP level of 3000 pg/ml predicted a poor prognosis of CHF patients with a sensitivity of 64% and a specificity of 75% vs. 68 and 65%.ConclusionHFEI can comprehensively evaluate the overall cardiac function of patients with various types of HF, and may prove to be an important index of assessing the prognosis of HF patients.

Clinical and laboratory associations of liver fibrosis indexes in patients with decompensated Chronic Heart Failure II-IV Functional Classes

Aim To study clinical and laboratory associations of hepatic fibrosis indexes in patients with decompensated NYHA functional class II-IV chronic heart failure (CHF).Material and methods The study included 128 patients admitted to the cardiological or therapeutic department of the University Clinical Hospital #4 at the I. M. Sechenov First Moscow State Medical University (Sechenov University) with symptoms of CHF associated with ischemic heart disease (IHD) and/or arterial hypertension (AH). All patients had signs of liver disease (liver enlargement on physical examination ± diffuse changes in hepatic tissue according to ultrasound data). Mean age was 70.59±10.71 years. Along with general clinical examination, severity of hepatic fibrosis was evaluated by calculated indexes, FIB-4, APRI, MELD-XI, and BARD. All calculations were based on laboratory data obtained within the first two days of hospitalization for decompensated CHF, at the onset of active therapy with intravenous diuretics. Statistical analyses were performed with the R programming language (3.6.1).Results In patients with NYHA FC II-IV CHF, the FIB-4 index significantly increased with the increase in NYHA FC (р&lt;0.05). Also, the high liver density by most fibrosis indexes correlated with the probability of LV EF decrease to &lt;40 % (FIB-4: RR, 1.32 at 95 % CI from 0.53 to 3.28, р=0.079; MELD-XI: RR, 1.62 at 95 % CI from 1.19 to 2.20, р=0.004; BARD: median LV EF, 42.5 % vs. 56 %, р=0.019), and a tendency to heart rhythm disorders was observed (FIB-4: RR, 1.92 at 95 % CI from 0.75 to 4.90, р=0.218; BARD: RR, 1.09 at 95 % CI from 0.97 to 1.22, р=0.174; MELD-XI: RR, 1.34 at 95 % CI from 0.94 to 1.90, р=0.101). Increases in liver fibrosis indexes correlated with other multiorgan disorders in CHF patients evident as a decrease in platelet count (FIB-4: р&lt;0.01; APRI: р=0.045) and a tendency to a decrease in hemoglobin (FIB-4: 127 g/l vs. 137 g/l, p=0.249; APRI: 127 g/l vs. 136 g/l, p=0.749). Patients with a high liver density more frequently had cardiorenal syndrome diagnosed by reduced glomerular filtration rate (GFR) estimated by CKD-EPI to less than 60 ml/min / 1.73 m2 (FIB-4: р&lt;0.03; MELD-XI: p=0.0001; BARD: р=0.005). In comparing liver fibrosis indexes in subgroups of CHF patients with preserved and reduced left ventricular ejection fraction (LV EF), significant differences were found only for MELD-XI (12.08 vs. 9.32, р=0.001).Conclusions For all studied indexes, correlations were observed with LV EF, decreases in hemoglobin, and incidence of heart rhythm disorders. For the BARD, FIB-4, and MELD-XI indexes, high results of calculations correlated with the presence of other predictors for unfavorable prognosis and disease severity (LV EF, NYHA FC, presence of type 2 diabetes mellitus, chronic kidney disease, and lower GFR). Liver fibrosis indexes are a new and promising but understudied instrument for evaluation of prognosis in CHF patients, which requires further study to determine most appropriate prognostic formulas.

Downregulated long noncoding RNA LUCAT1 inhibited proliferation and promoted apoptosis of cardiomyocyte via miR-612/HOXA13 pathway in chronic heart failure.

Long non-coding RNAs (lncRNAs) have been reported to play important roles in numerous kinds of cardiovascular disease, including chronic heart failure (CHF). In this study, we mainly focused on investigating the potential roles of lncRNA LUCAT1 patients with CHF. RT-PCR was used to detect the expressions of LUCAT1 and miR-612 in serum samples of CHF patients (n=60) and healthy volunteers. Relationships between the expressions of LUCAT1 and miR-612, LUCAT1 and overall survival (OS) were analyzed using the Kaplan-Meier method. Si-LUCAT1 and miR-612 mimic were constructed and respectively transfected into AC16 cells to explore the functions of LUCAT1 and miR-612. Cell proliferation abilities were detected by CCK-8 assay AC16 cells. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect the protein levels of HOXA13, Bcl-2, Bax, Bad and Cleaved Caspase3. In addition, luciferase gene reporter assay was used to prove the relationships between LUCAT1 and miR-612, miR-612 and HOXA13. Firstly, we found that LUCAT1 was decreased for 1.7 folds in CHF patients, which was correlated with poor prognosis patients. LUCAT1 repression inhibited cell proliferation and promoted cell apoptosis in human cardiomyocyte cell line AC16 cells. Furthermore, we found that miR-612 was increased for 2.0 folds in CHF patients, which was negatively interacted with LUCAT1 expression. Luciferase gene reporter assay demonstrated that LUCAT1 could directly bind with miR-612 in AC16 cells. Moreover, miR-612 overexpression also inhibited cell proliferation and promoted cell apoptosis in AC16 cells. Luciferase reporter assay indicated that miR-612 could directly target at HOXA13 in AC16 cells, which was associated with cell proliferation and apoptosis. Finally, miR-612 inhibitor was transfected into AC16 cells with si-LUCAT1. The results showed that the inhibited cell proliferation and promoted cell apoptosis were reversed, which confirmed that LUCAT1 repression inhibited cell proliferation and promoted apoptosis via miR-612/HOXA13 axis in CHF patients. According to the above results, our study revealed that LUCAT1 was decreased in CHF patients, which was correlated with poor prognosis of CHF patients. Furthermore, the downregulation of LUCAT1 inhibited cell proliferation and promoted cell apoptosis via targeting miR-612/HOXA13 axis. Our results elucidated a potential mechanism underlying cardiomyocyte apoptosis, which might be used as a promising prognostic marker and a potential target for CHF patients.

Predictive value of serum myostatin for the severity and clinical outcome of heart failure

BackgroundThe exact relationship between serum myostatin and the severity and prognosis of chronic heart failure (CHF) is unclear. In this study, we investigated the association between serum myostatin and the severity and prognosis in patients with CHF. MethodsTwo hundred and eighty-eight CHF patients and 62 healthy controls were studied. Cardiac ultrasound and serum myostatin, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were detected. CHF patients were divided into 3 groups according to tertiles of NT-proBNP or myostatin levels respectively. ResultsSerum myostatin levels were higher in CHF patients than in controls. New York Heart Association (NYHA) class IV patients had the highest levels of serum myostatin among the four NYHA classes. Compared with the low tertile NT-proBNP group, serum myostatin levels were significantly higher in the moderate and high tertile groups (15.47 ± 4.25 vs. 14.18 ± 3.69 ng/mL, p = .026; 16.28 ± 5.34 vs. 14.18 ± 3.69 ng/mL, p = .002). During 51-months follow-up, of 173 patients there were 36 deaths. Compared to survivors, nonsurvivors had significantly higher serum myostatin (18.11 ± 4.52 vs. 14.85 ± 5.11 ng/mL, p < .01). Patients in the high tertile myostatin group had lower survival rate (73.95% vs. 93.75%; p < .05) and larger number of CHF rehospitalization than those in the low tertile group. Cox regression analysis showed that serum myostatin was an independent predictor of mortality. ConclusionsSerum myostatin levels can reflect the severity of CHF and be a predictor of adverse prognosis in CHF patients.

A2084 Serum Potassium Levels and Cardiovascular Events in Patients with Heart Failure (HF) with Preserved Left Ventricular (LV) Ejection Fraction (HFpEF)

Objectives: Although serum potassium (sK) is closely associated with the prognosis of chronic HF patients, the clinical significance of sK levels in cardiovascular outcomes of HFpEF patients is not fully understood. Methods: We enrolled 506 consecutive HFpEF patients admitted to Kumamoto University Hospital and divided them into four groups according to quartiles of the sK levels at discharge (Q1; sK < 4.1 mEq/L, Q2; 4.1 ≤ sK < 4.4 mEq/L, Q3; 4.4 ≤ sK < 4.7 mEq/L, Q4; 4.7 mEq/L ≤ sK). Results: No significant differences were observed in the use of all drugs (loop diuretics, mineralcorticoid receptor antagonists (MRA), renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, β-blockers and statins) among 4 groups (p < 0.01). Haemoglobin, eGFR and pulse wave velocity levels were lower, and serum sodium levels were higher in Q4 compared to those in Q2. Kaplan-Meier analysis revealed significantly higher probabilities of both total cardiovascular and HF-related events in Q1, Q3 and Q4 than those in Q2 (p < 0.05), and that Q4 had significantly higher probabilities of them compared to those in Q1 (p < 0.05). We also found that Q4 tended to have lower probability of cardiovascular events than Q2, independently from the presence of chronic kidney disease and the use of MRA. Multivariate Cox proportional hazard analysis revealed that Q1, Q3 and Q4 had significantly and independently higher probabilities of cardiovascular events compared with those in Q2 (hazard-ratio [HR] = 3.56, 95% confidence-interval [CI] = 1.69–7.51, p < 0.01; HR = 3.02, 95% CI = 1.45–6.29, p < 0.01; and HR = 4.04, 95% CI = 2.09–7.81, p < 0.01, respectively), indicating J-shaped association between sK and cardiovascular events (Figure). Conclusion: sK levels at discharge could provide important prognostic information in HFpEF.

Baduanjin exercise for patients with ischemic heart failure on phase-II cardiac rehabilitation (BEAR trial): study protocol for a prospective randomized controlled trial

BackgroundPreliminary evidence based on clinical observations suggests that meditative exercise may offer potential benefits for patients with chronic heart failure (CHF). Cardiac rehabilitation (CR), as a class-IA indication in clinical practice guidelines, has been established as an effective strategy to improve quality of life and prognosis of CHF patients. Baduanjin exercise is an important component of traditional Chinese Qigong exercises. However, its benefits for CHF have not been rigorously tested. We sought to investigate whether Baduanjin, as an adjunct to standard care, improves cardiopulmonary function, exercise tolerance, and quality of life in patients with CHF caused by coronary artery disease (CAD).Methods/designIn this randomized controlled trial, 120 patients will be randomly allocated in a 1:1 ratio to Baduanjin exercise combined with conventional exercise of CR (Baduanjin exercise group) or conventional exercise of CR alone (conventional exercise group). In addition to conventional physical activity, participants in the Baduanjin exercise group will participate in a 45-min Baduanjin exercise training session twice a week, for 12 weeks. The primary outcome is walking distance in the 6-min Walk Test (6MWT), and the secondary outcomes are peak oxygen uptake (VO2 peak), ventilatory anerobic threshold (VAT), The minute ventilation to carbon dioxide production relationship (VE/VCO2 slope), left ventricular end-diastolic volume index (LVEDVi), left ventricular ejection fraction (LVEF), quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), amino-terminal pro-brain natriuretic peptide (NT-proBNP), hs-CRP, heart rate variability (HRV), New York Heart Association (NYHA) classification, and major adverse cardiovascular events.DiscussionThis is the first trial to evaluate the effects of a Baduanjin exercise-based CR program on cardiopulmonary function and exercise tolerance in ischemic CHF patients. If successful, it will prove the value of Baduanjin exercise in improving cardiopulmonary function and exercise tolerance in patients with ischemic heart failure on phase-II CR, and may further develop a Chinese Qigong exercise-based CR framework.Trial registrationClinicalTrials.gov, ID: NCT03229681. Registered retrospectively on 23 July 2017.

Morbidity and mortality of chronic heart failure (CHF) patients with sleep apnoea (SA) treated by adaptive servo-ventilation (ASV): Interim results of FACE cohort study_ UPDATE

Sleep disorder breathing is associated with a worse prognosis of CHF. The multicentre cohort study FACE is collecting real-world clinical data of CHF patients with reduced (HF-rEF), mid-range (HF-mrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) with predominant CSA or coexisting central and obstructive sleep apnea (CSA-OSA), eligible for ASV therapy. Morbidity and mortality, cardiac function, quality of life are assessed over a period of 2 years depending on whether the patient was compliant (≥ 3 h/night) with ASV therapy (ResMed, AutoSet CS) or not (control). Primary endpoint is all-cause death or unplanned hospitalization for worsening HF. Cumulative incidence will be estimated by Kaplan–Meier method and compared using log-rank test between ASV & control group. An update of the interim 2-year follow-up (FU) data is presented here. Three hundred and ninety-one CHF patients were included in the mITT analysis. Median FU for analysis was 21.6 months. Baseline characteristics were: age 70.7 ± 11.0 y, 87.5% male, body mass index 28.3 ± 5.2 kg/m 2 . Patients with HF-rEF, HF-mrEF and HFpEF were 38.7%, 22.1% and 39.2% respectively. Patients with an ischemic etiology were 55.2%. Sixty-nine percent had predominant CSA and 31% had CSA-OSA. Patients with severe sleep apnoea (AHI >30/h) were 76.2%. Sixty-six percent of patients were compliant to ASV therapy. In the global population, ASV therapy seemed to be beneficial in inpatients who had the highest level of nocturnal oxygen desaturation (T90, ODI) at baseline ( P = 0.013), in obese ( P = 0.009) & non-ischemic patientss ( P = 0.014) compared to control group. However, the subgroup analysis identified significant improvement of prognosis with ASV only in HFpEF but not in HF-rEF or HF-mrEF. ASV therapy is associated with a better prognosis in CHF patients with high level of oxygen desaturation during sleep, non-ischemic HF aetiology and with preserved LVEF. FACE study is a useful tool to better understand which CHF populations with CSA can benefit of ASV therapy.

Changes in brain natriuretic peptide in chronic heart failure patients treated with long-acting versus short-acting loop diuretics: J-MELODIC subanalysis.

We have previously reported that a long-acting loop diuretic, azosemide, reduces cardiovascular risks in patients with chronic heart failure (CHF) as compared with a short-acting one, furosemide, in Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure (J-MELODIC). However, the mechanisms of the difference have not been elucidated. This study aimed to examine whether there is a difference in the reduction in plasma brain natriuretic peptide (BNP) level and in left ventricular (LV) functional recovery between the CHF patients treated with the long-acting diuretic (the azosemide group) and the short-acting diuretic (the furosemide group). We reviewed changes in plasma BNP level and echo-assessed LV functional parameters from baseline to a year after the entry in 288 CHF patients with New York Heart Association class II or III symptoms that joined J-MELODIC. The decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group (p < 0.01). The changes in echocardiographic parameters were not more favorable in the azosemide group than in the furosemide group. In conclusion, the decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group. These findings may account for the better prognosis in CHF patients treated with azosemide than those with furosemide in J-MELODIC.

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure - Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Prognostic Impacts of Diuretics in Japanese Patients with Chronic Heart Failure

Although loop diuretics are widely used for the treatment of chronic heart failure (CHF), their impacts on outcomes in Japanese CHF patients remain unclear. Prognostic impacts of furosemide were examined in 3,746 consecutive patients with Stage C/D CHF registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). They were followed up for a median of 3.0 years. Propensity score analysis was performed to adjust for confounding factors. Among 3,746 patients, 1,662 received furosemide (furosemide group) and 2,084 did not (control group). After adjustment for potential co-variants, incidence of composite events (death, myocardial infarction, stroke and HF admission) in furosemide group (n=870) was significantly higher than in control group (n=870) (P<0.001). On multivariate Cox regression, furosemide was significantly associated with increased composite events (adjusted hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.15-1.67, P=0.001). Moreover, higher furosemide dose (> 40mg) was associated with incidence of composite events, especially in patients with reduced ejection fraction (<50%) (HR, 1.93; 95% CI, 1.37-2.71, P<0.001) and in patients with lower glomerular filtration rate (<60%) (HR, 1.68; 95% CI, 1.262.24, P<0.001). Use of higher dose of furosemide is associated with worsened prognosis in CHF patients.

Inferior Vena Cava Dilatation Predicts Mortality and Worsening Renal Function in Patients With Chronic Heart Failure

Although heart failure is thought to cause worsening renal function (WRF) through hypo perfusion secondary to a reduction in cardiac output, there is evidence to suggest that renal venous congestion may also be a contributing factor. Invasive studies have shown that central venous pressure predicts WRF in heart failure patients with a preserved cardiac output; however, non-invasive studies investigating this relationship are scarce. Potentially, assessment of inferior vena cava (IVC) diameter can be used to estimate venous congestion, as raised right arterial pressures dilate the IVC making it non-collapsible. We therefore aimed to investigate the association between IVC diameter and outcomes, including WRF, heart failure hospitalisations and all-cause mortality. We conducted a retrospective cohort study of 1,078 chronic heart failure (CHF) patients from the BIOSTAT-CHF Scotland study. All CHF patients were symptomatic, requiring the use of loop diuretics, and were optimally treated on recommended therapy for CHF. Venous congestion (VC) was defined as IVC diameter >2.1cm, identified from echocardiography at baseline review. Renal function was determined by estimated glomerular filtration rate (eGFR) using the abbreviated MDRD equation. Logistic regression models were used to examine the association between VC and eGFR. Cox proportional hazard models were applied to examine the influence of VC on all-cause mortality and CHF hospitalisations. Multivariate analysis showed that those with VC had significantly worse survival than those without VC after adjusting for age, sex, eGFR and furosemide daily dose (hazard ratio [HR]: 1.6, 95% CI: 1.2-2.1; p=0.01). Although time to first CHF hospitalisation was shorter for the VC group compared to those without VC, this was not a statistically significant difference. Logistic regression models showed that those with severe renal impairment (eGFR60 (Odds Ratio=7.7 (1.6-37.5), p=0.012)). IVC width as an indirect measurement of renal venous congestion predicts worse survival in CHF and is associated with severe renal impairment. As an easily obtainable non-invasive predictor of renal venous congestion, IVC diameter could therefore be a potentially useful marker for both renal function and overall prognosis in CHF patients.

Glycosylated haemoglobin is associated with neurohormonal activation and poor outcome in chronic heart failure patients with mild left ventricular systolic dysfunction.

We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF). Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles. Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.

0160 : Impact of elevated heart rate on clinical outcomes in patients with heart failure with reduced ejection fraction

Elevated heart rate (HR) is associated with higher mortality and morbidity in patients with heart failure (HF). This study is aimed to evaluate the clinical significance of heart rate in predicting the prognosis in patients with chronic heart failure (CHF). We enrolled 1581 consecutive CHF (mean age 68.1 years) registered in the Therapeutic Unit of Chronic Heart Failure. We divided the patients into 2 groups: group 1 with HR≤70 bpm, group 2 with HR >70 bpm. The relationships between HR and the prognosis of CHF patients were determined. Elevated HR was associated with male sex, hypertension, diabetes, strock attack and ischemic heart disease, but the association was modest with obesity. CHF patients with NYHA grade III/IV had higher HR than those with NYHA grade I/II with a good correlation. Hight HR correlated with increased cardiac decompensation and hospitalizations (p<0.0001), elevated filling pressure (p<0.0001). Also, there were statistical differences in atrial fibrillation between the group 1 and 2. Furthermore, ?-Blocker therapy and Ivabradine were associated with reduced HR (p<0.0001). We also observed negative correlations between HR and hemoglobin, glomerular filtration rate (GFR) were also found. Elevated HR was associated with increased cardiac decompensation and hospitalization. It may have good clinical predictive value in patients with CHF and should be a distinct therapeutic target.