Prognosis In Chronic Heart Failure Research Articles

Biventricular pacemaker and defibrillator implantation in patients with chronic heart failure in China.

AimsThis study aims to investigate the current status of biventricular pacemaker and defibrillator implantation in chronic heart failure (CHF) patients with indications for primary prevention of sudden cardiac death (SCD) in China and the effects of cardiac resynchronization therapy (CRT)‐pacemaker (P) and CRT‐defibrillator (D) implantation on the clinical prognosis of CHF among patients undergoing CRT.Methods and resultsOverall, 798 consecutive patients who had devices implanted (implantable cardioverter defibrillator: 199, CRT‐D: 362, and CRT‐P: 237) from May 2012 to July 2013 in POSCD‐China, a multicentric prospective cohort study, were enrolled. The primary endpoint was all‐cause death, and the secondary endpoint was SCD. In total, 71.3% of patients had non‐ischaemic CHF. The mean follow‐up time was 27.7 ± 12.0 months, and death occurred in 158 cases, with 35 cases of SCD. CHF was the main cause of death (68.4%), followed by sudden death (22.2%). In the CRT‐P group, the SCD rate was 8.0%, which was much higher than that in the CRT‐D (3.3%) and implantable cardioverter defibrillator (2.0%) groups. No significant differences were identified in the all‐cause death rate between the CRT‐D and CRT‐P groups (CRT‐D vs. CRT‐P, 20.4% vs. 19.4%, P = 0.840).ConclusionsIn China, among CHF patients with indications for primary prevention of SCD who received device implantation, non‐ischaemic CHF was the main aetiology, and the most important cause of death was heart failure. No differences in all‐cause death were observed between the CRT‐D and CRT‐P groups, but the CRT‐D group had a lower SCD rate than the CRT‐P group.

Preserved Skeletal Muscle Mitochondrial Function, Redox State, Inflammation and Mass in Obese Mice with Chronic Heart Failure.

Background: Skeletal muscle (SM) mitochondrial dysfunction, oxidative stress, inflammation and muscle mass loss may worsen prognosis in chronic heart failure (CHF). Diet-induced obesity may also cause SM mitochondrial dysfunction as well as oxidative stress and inflammation, but obesity per se may be paradoxically associated with high SM mass and mitochondrial adenosine triphosphate (ATP) production, as well as with enhanced survival in CHF. Methods: We investigated interactions between myocardial infarction(MI)-induced CHF and diet-induced obesity (12-wk 60% vs. standard 10% fat) in modulating gastrocnemius muscle (GM) mitochondrial ATP and tissue superoxide generation, oxidized glutathione (GSSG), cytokines and insulin signalling activation in 10-wk-old mice in the following groups: lean sham-operated, lean CHF (LCHF), obese CHF (ObCHF; all n = 8). The metabolic impact of obesity per se was investigated by pair-feeding ObCHF to standard diet with stabilized excess body weight until sacrifice at wk 8 post-MI. Results: Compared to sham, LCHF had low GM mass, paralleled by low mitochondrial ATP production and high mitochondrial reative oxygen species (ROS) production, pro-oxidative redox state, pro-inflammatory cytokine changes and low insulin signaling (p < 0.05). In contrast, excess body weight in pair-fed ObCHF was associated with high GM mass, preserved mitochondrial ATP and mitochondrial ROS production, unaltered redox state, tissue cytokines and insulin signaling (p = non significant vs. Sham, p < 0.05 vs. LCHF) despite higher superoxide generation from non-mitochondrial sources. Conclusions: CHF disrupts skeletal muscle mitochondrial function in lean rodents with low ATP and high mitochondrial ROS production, associated with tissue pro-inflammatory cytokine profile, low insulin signaling and muscle mass loss. Following CHF onset, obesity per se is associated with high skeletal muscle mass and preserved tissue ATP production, mitochondrial ROS production, redox state, cytokines and insulin signaling. These paradoxical and potentially favorable obesity-associated metabolic patterns could contribute to reported obesity-induced survival advantage in CHF.

Donepezil markedly prevents the progression of chronic heart failure and renal dysfunction in renal artery stenosis-induced hypertensive rats

Abstract Introduction Parasympathetic activation by donepezil has been shown to improve prognosis in chronic heart failure (CHF) rats following myocardial infarction. We examined whether donepezil is effective in the treatment of another CHF model complicated with renal artery stenosis (RAS)-induced hypertension. Methods RAS was created by ligating the left renal artery up to 50% in SD rats, at the same time, we implanted a blood pressure (BP) transmitter for confirming RAS-induced hypertension (7-week post-RAS: systolic BP = 154±7 mmHg; diastolic BP = 115±8 mmHg). In the 11th week after induction of RAS, surviving animals were randomly assigned to untreated (UT, n=10) or donepezil treated [DT, n=10, dissolved in drinking water (3mg/kg/day)] group. After a 6-week treatment, the effects of donepezil were evaluated by hemodynamics, blood levels of neurohumoral markers, and morphology. Results Compared with UT, DT significantly prevented the progression of the left kidney atrophy (2.38±0.13 vs. 1.51±0.34 g/kg, P&amp;lt;0.05) and kidney fibrosis (left: −64%, P&amp;lt;0.001; right: −55%, P&amp;lt;0.01). DT also significantly prevented the progression of CHF, through suppressing cardiac hypertrophy (2.30±0.06 vs. 2.57±0.08 g/kg, P&amp;lt;0.01), cardiac fibrosis (−70%, P&amp;lt;0.01), and cardiac dysfunction [cardiac index: 102±3 vs. 86±3 ml/min/kg, P&amp;lt;0.05; left ventricular (LV) end-diastolic pressure: 12±2 vs. 20±2 mmHg, P&amp;lt;0.05; LV dp/dtmin: 5856±259 vs. 4924±227 mmHg/sec, P&amp;lt;0.05]. DT not only decreased serum levels of creatinine (0.54±0.02 vs. 0.63±0.03 mg/dl, P&amp;lt;0.05) and uric acid (1.4±0.2 vs. 1.9±0.2 mg/dl, P&amp;lt;0.05); but also decreased plasma levels of norepinephrine (273±38 vs. 846±242, P&amp;lt;0.01), AVP (2729±347 vs. 4783±695 pg/ml, P&amp;lt;0.05), BNP (360±13 vs. 460±39 pg/ml, P&amp;lt;0.05), angiotensin II and aldosteron, and suppressed the systemic inflammation. Conclusions Donepezil treatment markedly prevented the progression of CHF and renal dysfunction, and improved the neurohumoral markers in the CHF rat model complicated with RAS-induced hypertension, suggesting that donepezil may be used as a new pharmacotherapy for CHF patients complicated with RAS-induced hypertension. Funding Acknowledgement Type of funding source: None

Clinical determinants and prognostic impact of osteoporosis in patients with chronic heart failure

Abstract Background Despite accumulating evidence of a close association between orthopedic fractures and chronic heart failure (CHF), the clinical risk factors of osteoporosis, defined as reduction in bone mineral densities (BMDs), in CHF patients have not been systematically analyzed. In addition, the impact of osteoporosis on prognosis of CHF remains unclear. Aims We aimed to clarify the prevalence, clinical risk factors, and prognostic impact of osteoporosis in CHF patients. Methods We retrospectively examined 303 CHF patients (75 years, [interquartile range (IQR), 66–82 years]; 41% female). BMDs at the lumber spine, femoral neck, and total femur were measured by dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when BMD at any of the three sites was less than 70% of Young Adult Mean. Results The prevalence of osteoporosis in the CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74–86] vs. 72 [IQR, 62–80] years), included a large percentage of females, had slower gait speed and had lower body mass index (BMI). Loop diuretics and warfarin were used more frequently and direct oral anticoagulants (DOACs) were used less frequently in patients with osteoporosis than in patients without osteoporosis. Multivariate logistic regression analysis indicated that sex (odds ratio [OR] 5.07, 95% Confidence Interval [CI] 2.68–9.61, p&amp;lt;0.01), BMI (OR, 0.83; 95% CI, 0.75–0.91; p&amp;lt;0.01), gait speed (OR, 0.80; 95% CI, 0.70–0.92; p&amp;lt;0.01), loop diuretics use (OR, 2.52; 95% CI, 1.20–5.27; p=0.01) and no DOACs use (OR, 0.43; 95% CI, 0.19–0.96; p=0.04) were independently associated with osteoporosis. During the mean follow-up period of 290±254 days, 92 patients (30.4%) had adverse events. When patients with osteoporosis were divided into subgroups according to the number of sites with BMD of an osteoporosis level, Kaplan-Meier survival curves showed that the rate of adverse events (death and cardiovascular events) was higher in patients with osteoporotic BMD at two or more sites than in patients without osteoporosis (51% vs. 23%, p=0.03) (Figure). In multivariate Cox regression analyses, osteoporotic BMD at two or more sites was an independent predictor of adverse events after adjustment for age, sex, and NT-proBNP level (Hazard ratio, 1.74; 95% CI, 1.01–2.99; p=0.04). Conclusion The risk of osteoporosis may be increased in users of loop diuretics and may be decreased in users of DOACs in CHF patients. Extent of osteoporosis is a novel predictor of adverse events in CHF patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Japan Society for the Promotion of Science KAKENHI

Exercise Oscillatory Ventilation is Independently Associated with Right Ventricular Systolic Dysfunction in Patients with Chronic Heart Failure

Background Exercise Oscillatory Ventilation (EOV) is a crucial marker for disease severity and prognosis in chronic heart failure (HF) patients. Although the presence of EOV in chronic HF patients has been demonstrated the association with worse left ventricular (LV) function, the evidence regarding with right ventricular (RV) function is still lacking. This study aim was to determine the association of EOV and RV systolic function in chronic heart failure patients. Method We retrospectively analyzed a cardiopulmonary exercise stress testing (CPET) database in 709 chronic HF patients at Cleveland Clinic, between April 2018 and June 2019. RV systolic dysfunction was determined by tricuspid annular plane systolic excursion (TAPSE) Results The prevalence of EOV in chronic HF patients with RV systolic dysfunction was significantly higher than those without RV systolic dysfunction (75.7% vs. 24.3%, p Conclusion In the large contemporary cohort, exercise oscillatory ventilation was independently associated with RV systolic dysfunction in chronic heart failure patients.

Impact of right ventricular stroke work index on predicting hospital readmission and functional status of patients with advanced heart failure

Introduction and AimsThe prognosis of chronic heart failure with reduced ejection fraction (HFrEF) has been studied extensively, but factors predicting cardiac decompensation are poorly defined. Right ventricular stroke work index (RVSWI), an invasive measure of right ventricular (RV) systolic function, is a well-known prognostic marker of RV failure after left ventricular assist device insertion and after lung transplantation. Thus, the aim of this study was to assess whether there is a relationship between RVSWI, HFrEF hospital readmission due to cardiac decompensation, and prognosis. MethodsWe prospectively enrolled 132 consecutive patients with HFrEF. Right heart catheterization was performed and RVSWI values were calculated in all patients. The relationship between RVSWI values and readmission and prognosis was analyzed. ResultsDuring a median follow-up of 20±7 months, 33 patients were readmitted due to cardiac decompensation in the survivor group, and 18 patients died due to cardiac causes. There was no difference between patients who died and survived in terms of RVSWI values. Among patients with decompensation, mean RVSWI was significantly lower than in patients with stable HFrEF (6.0±2.2 g/m2/beat vs. 8.8±3.5 g/m2/beat, p<0.001). On correlation analysis, RVSWI was negatively correlated with NYHA functional class. RVSWI was also identified as an independent risk factor for cardiac decompensation in Cox regression survival analysis. ConclusionsWe showed that RVSWI predicts cardiac decompensation and correlates with functional class in advanced stage HFrEF. Our data suggest the value of combining information on right heart hemodynamics with assessment of RV function when defining the risk of patients with advanced HFrEF.

Association of long-chain non-coding RNA MHRT gene single nucleotide polymorphism with risk and prognosis of chronic heart failure.

Long-chain non-coding RNA (lncRNA) Myosin Heavy Chain Associated RNA Transcripts (MHRT) are newly identified cardioprotective lncRNAs. In this study, we investigated the association of MHRT gene single nucleotide polymorphisms with risk and prognosis of chronic heart failure (CHF).Sanger sequencing was performed to detect the genotypes of rs3729830, rs7140721, rs76614781, rs3729829, rs3729828, rs3729825, and rs3729822 loci in the non-coding region of the MHRT gene from 240 patients with CHF and 240 control subjects. After 3 years of follow-up, progression-free survival was recorded in patients with CHF.The risk of CHF in subjects carrying A allele of the MHRT gene rs7140721 locus was 1.43 times higher than that of C allele carriers (95% CI: 1.23–1.62, P < .001). The risk of CHF in subjects carrying A allele of the rs3729829 locus was 1.41 times higher than that of G allele carriers (95% CI: 1.20–1.61, P < .01). The risk of CHF in the carriers of T allele of the rs3729825 locus was 1.89 times higher than that of C allele carriers (adjusted OR = 1.89, 95% CI: 1.66–2.04, P < .01). Further, the level of lncRNA MHRT in the plasma of subjects carrying CA/AA genotype of the rs7140721 locus was significantly higher than that of subjects carrying the CC genotype. The level of lncRNA MHRT in the plasma of subjects carrying GA/AA genotype of the rs3729829 locus was significantly higher than that of subjects carrying the GG genotype. In addition, the level of lncRNA MHRT in subjects with CT/TT genotype of the rs3729825 locus carriers was significantly higher than that in subjects with the CC genotype (P < .05). In addition, significant differences in the mortality of patients with CHF were observed between different genotypes of rs7140721, rs3729829, and rs3729825 loci (P < .001).The single nucleotide polymorphisms of MHRT gene rs7140721, rs3729829, and rs3729825 loci were associated with the risk of CHF and prognosis.

Combined use of high-sensitivity ST2 and NT-proBNP for predicting major adverse cardiovascular events in coronary heart failure.

Elevated serum soluble ST2 (sST2) level is marker of poor prognosis in chronic heart failure (HF). N-terminal pro-brain natriuretic peptide (NT-proBNP) is an important biomarker in cardiovascular diseases. This study aimed to address the incremental usefulness of the combined use of high-sensitivity sST2 and NT-proBNP for predicting the risk of major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD). We used patient data along with data established by our research group to compare the performance of a combination of biomarkers reflecting ventricular fibrosis, remodeling, stretch and deterioration of cardiac function (sST2 and NT-proBNP) with that of established mortality risk factors [age, diabetes, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction (LVEF), body mass index (BMI), creatinine (Cr), uric acid (UA), glucose (Glu)] in stratifying the risk of MACEs in CHD patients. The median follow-up period was 3.9 years, during which time there were 3,724 cases with CHD, 113 cases of cardiovascular death, 30 cases with myocardial infarction, 49 cases with stroke, 39 cases of non-cardiovascular death, 6 cases of peripheral arterial occlusion, 55 cases with HF, and 73 cases of revascularization. A total of 365 cases had MACEs. In the multivariate Cox proportional hazard model, both sST2 and NT-proBNP were significant predictors of MACEs. Both sST2 and NT-proBNP were separately incorporated into the model with established MACE risk factors, which significantly improved the C-statistics for predicting MACEs [0.758 (0.724-0.792)] and saw an estimated net improvement in reclassification of 1.03% (P<0.001) and an integrated discrimination improvement of 0.48% (P<0.001). The Hosmer-Lemeshow test showed that the models were well calibrated with and without the two biomarkers (P>0.344 for all comparisons). Moreover, the model incorporating the two biomarkers was shown to have a better global fit than the model with only the established MACE risk factors (P<0.001). A model incorporating sST2 and NT-proBNP was shown to outperform a model based on established MACE risk factors alone in stratifying risk of MACEs in a group of CHD patients.

Hematopoiesis and biochemical profi les of dogs' blood by chronic heart failure

The present study was undertaken to evaluate if any signifi cant hematological and biochemical changes occur in dogs with chronic heart failure (CHF), that will help in the diagnosis and prognosis of CHF. According to the obtained data, neutrophil leukocytosis was found in 22.2% of the animals in the experimental group, and anemia was found in 50.0%. Among them the 77,8 % of animals had nonregenerative anemia, the 77,8 % – hypochromic anemia, 38,9 % of – microcytic anemia. Neutrophil leukocytosis was registered in dogs with regenerative shift of the nucleus to the left (13.8%) and to the right (5.6%), and without changes in the leukogram (2.8%). It should be noted that 55.6% of animals with signs of CHF were also diagnosed with changes in the ratio of segmented neutrophils (degenerative shift of the nucleus to the left) in the absence of leukocytosis. Hypoproteinemia was found in 8,3% of animals, hypoalbuminemia in 13,8%, urea and creatinine concentrations were increased in 16,7 % and 19,4%, respectively. Hypocalcaemia was observed in 5,6% of dogs, inorganic phosphorus content was higher in 13,9%, slight hyponatremia was observed in 19,4%. The activity of enzymes in the serum of dogs in the experimental group ranged widely and was higher in ALT (p &lt;0.001), AST (p &lt;0.05), ALP (p &lt;0.001), GGTP (p &lt;0.01) compared with the control group.In the experimental group of 36 animals in 22,2 % of dogs were diagnosed cholestasis, in 22,2 % – hepatopathy, in 11,1 % – chronic kidney disease, and 8,3% –enteropathy, 5,5 % – paraneoplastic syndrome. Biochemical analysis of blood in dogs with signs of CHF is relevant, because it allows to diagnose comorbidities that may worsen the prognosis in these animals, and their timely detection and correction will increase the eff ectiveness of treatment. Key words: chronic heart failure, dog, hematology analysis, anemia, leukocytosis, hypoalbuminemia, renal failure,cholestasis, hepatopathy.

Relationship between echocardiographic and functional parameters in patients with heart failure undergoing cardiopulmonary exercise test.

HF patients typically show effort intolerance due to a reduction in peak exercise oxygen (peak VO2) consumption, which is related to inability to adapt systolic function to increased demand. Left ventricular ejection fraction (EF) is a surrogate marker of cardiac contractility and a powerful predictor of adverse prognosis in chronic heart failure (HF). The aim of the study was to explore the relationship between EF and other echocardiographic findings with peak VO2 in a population of HF individuals undergoing cardiopulmonary exercise testing (CPX). We evaluated 101 patients (61% hypertensives, 74% with documented coronary artery disease) undergoing both resting echocardiography and symptom-limited CPX. Mean age was 58±13 years, 83% were males. Mean EF was 55±12%; 20% of the patients showed EF<40%. Mean test duration was 9.4±2.2 min. Average peak VO2 was 21±6 mL/kg/min. Peak VO2 showed a robust positive correlation with EF (R=0.42, P<0.001). Other independent predictors of peak VO2 were age, male sex, height and tricuspidal anular plane systolic excursion (TAPSE), this latter reflecting right ventricular dysfunction. When subjects were dichotomized according to predicted peak VO2values, those with higher-than-predicted peak VO2 showed significantly lower VE/VCO2 slope, and higher values of both oxygen pulse and VO2/WR slope. EF and TAPSE are associated with peak VO2 in HF patients independently from age, sex and height. The evaluation of potentially relevant mechanisms affecting exercise capacity in HF patients requires further investigation.

Energy Metabolism and Nutritional Status in Hospitalized Patients with Chronic Heart Failure

Introduction: Malnutrition is a factor that defines vital prognosis in chronic heart failure. Objective: This study investigated nutritional and metabolic disorders in patients with heart failure by examining the association of severity of heart failure with inflammatory cytokines, appetite-regulating hormones, and energy metabolism. Methods: Subjects were 50 patients with heart failure. On admission, nutritional status was assessed, and biochemical blood tests were performed, including for serum tumor necrosis factor-α, interleukin-6, ghrelin, and leptin levels. Resting energy expenditure (REE) was also measured by indirect calorimetry to examine its association with severity of heart failure and levels of inflammatory cytokines and appetite-regulating hormones. Results: There were significant associations between serum brain natriuretic peptide (BNP) level and nutrition indices, indicating that nutritional status was worse when heart failure was more severe. Inflammatory cytokine levels showed significant positive correlations with BNP level. Measured REE/bodyweight was not associated with severity of heart failure, but was negatively correlated with body fat percentage and leptin levels. Conclusions: Energy metabolism was not associated with serum BNP level among patients with heart failure with New York Heart Association functional class up to III. Body fat percentage and leptin levels may be a good predictor of energy metabolism in patients with heart failure.

Features of course and treatment of chronic heart failure in patients with diabetes mellitus type 2

The epidemiology of chronic heart failure in patients with diabetes mellitus type 2, their general pathophysiological mechanisms, the influence of diabetes mellitus type 2 on the course and prognosis of chronic heart failure are considered. The high prevalence of chronic heart failure of all phenotypes among patients with diabetes mellitus type 2 and the increased risk of developing diabetes mellitus type 2 in patients with chronic heart failure confirm the close relationship and the high degree of comorbidity between these pathological conditions. It is shown that the development and progression of chronic heart failure in patients with diabetes mellitus type 2 is the formation of diabetic cardiomyopathy, which is characterized by disorders of energy metabolism of cardiomyocytes, mitochondrial dysfunction with subsequent apoptosis and myocardial fibrosis. Important links in the pathogenesis of chronic heart failure in diabetes mellitus type 2 are also the accession of diabetic cardiovascular autonomic neuropathy, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, exposure to atherogenic factors, arterial hypertension, obesity. The features of treatment of chronic heart failure in patients with diabetes mellitus type 2, the results of randomized clinical studies, the choice of target glycemic levels, the effectiveness of different groups of antihyperglycemic agents, drugs for the treatment of chronic heart failure, as well as their impact on the course and prognosis of chronic heart failure. Keywords: chronic heart failure, diabetes mellitus type 2, course, prognosis, treatment.

Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study.

Thyroid disorders may have a negative impact on the prognosis of patients affected by chronic heart failure (CHF). The aim of the current study was to evaluate the prognostic role of all thyroid disorders over a long term follow-up in a single centre large sample of CHF outpatients. In all patients, the function of the thyroid was evaluated at the enrolment and during the follow- up. On the basis of free triiodothyronine (T3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) serum levels, patients were classified into one of the following four categories: euthyroid subjects, patients affected by hypothyroidism, low T3 (LT3) syndrome and hyperthyroidism. During the follow-up, death for all causes was assessed as primary end-point, whereas time to the first hospitalization for heart failure worsening was the secondary end-point analyzed. Among 762 patients, 190 patients were affected by hypothyroidism (Hypo). LT3 syndrome was diagnosed in 15 patients and 59 patients were affected by hyperthyroidism (Hyper). During a long term follow-up (5.1±3.7 years), 303 patients died. Patients with Hypo showed an increased risk of death as well as of hospitalization due to heart failure worsening at univariate regression analysis. At multivariate regression analysis, Hypo remained associated with hospitalization after correction for age >75 years, ischemic aetiology, diabetes, therapy with ACE-inhibitors or ARBs, therapy with betablockers and with aldosterone antagonists, NYHA class 3, systolic arterial pressure <95 mmHg, left ventricular ejection fraction <30%, estimated glomerular filtration rate <60 ml/min, hyponatremia and NTproBNP> 1000 pg/ml. At multivariate analysis, the independent association with death was significant only for the subgroup of patients with TSH >10 mIU/L. LT3 was independently associated with both heart failure hospitalization and death, whereas Hyper was not associated with any of the two considered end-points. Hypo is associated with a worse prognosis over a long-term follow-up. The association with heart failure hospitalization is not dependent on the baseline TSH levels, whereas the association with death is significant only when TSH >10 mIU/L. Finally, Hyper does not have any association with a worse prognosis.

Intestinal microbiota in the pathogenesis of chronic heart failure

In this review, we have considered and discussed the existing data to achieve a deeper understanding of the role of intestinal microbiota in the development and progression of chronic heart failure (CHF). The key moments of the CHF pathogenesis (an imbalance of neurohumoral systems, inflammatory theory and metabolic disorders) and the respective changes of the intestinal microflora composition were compared. Here, we also present the latest results of the positive influence of the microflora modulations on the course and prognosis of CHF with the prescribing antibiotics, probiotics and prebiotics.

Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults

CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults. We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49). Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.

Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han.

Chronic heart failure (CHF) has poor prognosis and polygenic heritability, and the genetic risk score (GRS) to predict CHF outcome has not yet been researched comprehensively. In this study, we sought to establish GRS to predict the outcomes of CHF. We re‐analysed the proteomics data of failing human heart and combined them to filter the data of high‐throughput sequencing in 1000 Chinese CHF cohort. Cox hazards models were used based on single nucleotide polymorphisms (SNPs) to estimate the association of GRS with the prognosis of CHF, and to analyse the difference between individual SNPs and tertiles of genetic risk. In the cohort study, GRS encompassing eight SNPs harboured in seven genes were significantly associated with the prognosis of CHF (P = 2.19 × 10−10 after adjustment). GRS was used in stratifying individuals into significantly different CHF risk, with those in the top tertiles of GRS distribution having HR of 3.68 (95% CI: 2.40‐5.65 P = 2.47 × 10−10) compared with those in the bottom. We developed GRS and demonstrated its association with first event of heart failure endpoint. GRS might be used to stratify individuals for CHF prognostic risk and to predict the outcomes of genomic screening as a complement to conventional risk and NT‐proBNP.

P3501Oral administration of donepezil markedly prevents the progression of chronic heart failure in renal artery stenosis-induced hypertensive rats

Abstract Introduction Parasympathetic activation by donepezil has been shown to improve prognosis in chronic heart failure (CHF) rats following myocardial infarction. We examined whether donepezil is effective in the treatment of another CHF model complicated with renal artery stenosis (RAS)-induced hypertension. Methods RAS was created by ligating the left renal artery up to 50% in SD rats, at the same time, we implanted a blood pressure (BP) transmitter for confirming RAS-induced hypertension (7-week post-RAS: systolic BP = 154±7 mmHg; diastolic BP = 115±8 mmHg). At the 11th week after induction of RAS, surviving animals were randomly assigned to untreated (UT, n=10) or donepezil treated [DT, n=10, dissolved in drinking water (3mg/kg/day)] group. After a 6-week treatment, the effects of donepezil were evaluated by hemodynamics, blood levels of neurohumoral markers, and morphology. Results Compared with UT, DT significantly prevented the progression of the left kidney atrophy (2.38±0.13 vs. 1.51±0.34 g/kg, P&lt;0.05). DT also significantly improved cardiac remodeling, through suppressing the progression of cardiac hypertrophy (2.30±0.06 vs. 2.57±0.08 g/kg, P&lt;0.01), cardiac dysfunction [cardiac index: 102±3 vs. 86±3ml/min/kg, P&lt;0.05; left ventricular (LV) end-diastolic pressure: 12±2 vs. 20±2 mmHg, P&lt;0.05; LV dp/dtmin: 5856±259 vs. 4924±227 mmHg/sec, P&lt;0.05]. DT not only decreased serum levels of creatinine (0.54±0.02 vs. 0.63±0.03 mg/dl, P&lt;0.05) and uric acid (1.4±0.2 vs. 1.9±0.2 mg/dl, P&lt;0.05); but also decreased plasma levels of norepinephrine (273±38 vs. 846±242, P&lt;0.01), angiotensin II (17±2 vs. 23±2 pg/ml, P&lt;0.05), AVP (2729±347 vs. 4783±695 pg/ml, P&lt;0.05) and BNP (360±13 vs. 460±39 pg/ml, P&lt;0.05), and suppressed the systemic inflammation (CRP: 190±12 vs. 382±58 mg/ml, P&lt;0.01). Conclusions Donepezil treatment markedly prevented the progression of cardiac remodeling and renal dysfunction, and improved the neurohumoral markers in the CHF rat model complicated with RAS-induced hypertension, suggesting that donepezil may be used as a new pharmacotherapy for CHF patients complicated with RAS-induced hypertension.

P2259Cognitive function and adherence to treatment in patients with chronic heart failure and reduced left ventricular ejection fraction: relation and prognostic meaning

Abstract Background Poor adherence to treatment increases risk of hospitalization and has negative impact on quality of life and clinical prognosis in chronic heart failure (CHF). Cognitive impairment (CI) is observed in more than half of patients (pts) with CHF and may affect their adherence to treatment. Nevertheless, association between cognitive function (CF) and adherence to treatment in CHF pts is studied insufficiently. Purpose To establish relationship between the state of CF and adherence to treatment in pts with CHF and reduced left ventricular ejection fraction (rLVEF). Methods 124 pts with stable CHF and rLVEF (&lt;40%) NYHA II-III non older than 75 years old were examined. Besides routine clinical examination, standard neuropsychological tests (MMSE, Schulte test, the HADS scale) were used. To assess adherence to treatment, Morisky-Green questionnaire (MGQ) was used. CI was defined as MMSE ≤26 points. Statistic methods included descriptive statistics, Mann-Whitney U-test, Spearman's rank correlation, Kaplan-Meier method. The difference was considered statistically significant at p&lt;0.05. Results CI was observed in 85 (68.5%) of pts. The presence of CI was associated with significantly lower survival rate (fig. 1). According MGQ poor adherence to treatment was observed in 37 (43.5%), moderate – in 30 (35.3%), good adherence – in 18 (21.2%) of pts. After distribution of pts to three groups depending on their adherence to treatment (0–2 poor, 3-moderate, 4-good adherence), it was found that they significantly differed in MMSE and Shulte test results (p=0.006 and p=0.038 respectively). At the same time, groups were comparable by HADS anxiety and depression scores. The number of MGQ points directly correlated with MMSE (r=0.186, p=0.038). Survival curves of CI vs non-CI pts Conclusion Insufficient adherence to treatment accessed by MGQ is observed in majority of CI pts with CHF and rLVEF. Adherence to treatment is reliably associated with cognitive status of pts, which, in turn, related to poor clinical outcome.

SST2 adds to the prognostic value of Gal-3 and BNP in chronic heart failure

Background: The soluble form of the IL-33 receptor (sST2) and Galectin-3 (Gal-3) are fibrosis biomarkers with prognostic value in heart failure (HF). We investigated the prognostic capacity of sST2 when combined with Gal-3, and determined if the prognostic utility of sST2 is affected by mineralocorticoid receptor antagonist (MRA) therapy.Methods: sST-2 and Gal-3 were measured in 101 stable chronic HF (CHF) patients receiving MRA therapy and compared to 97 BNP and cardiovascular risk factor matched patients not treated with MRA. sST2 and Gal-3 levels were measured to determine the relationship with all-cause mortality at 6-year follow-up.Results: ROC curve cut-off points were defined as sST2 = 36.3 ng/mL, Gal-3 = 17.8 ng/mL, and BNP = 500 pg/mL, and had 6-year mortality hazard ratios (HR) of 7.3, 6.6 and 5.4, respectively. The combination of an elevated sST2 and Gal-3 had a HR = 4.4 [95% CI 1.9–8.9]. Combining sST2 and Gal-3 to a clinical model relevant for CHF prognosis allowed a significant reclassification of 1-year adverse outcome risk, even when BNP was included. Finally, prognostic prediction by sST2 was unaffected by MRA treatment.Conclusion: Simultaneous sST2 and Gal-3 elevation is associated with poorer prognosis compared to either alone, regardless of BNP levels, and the prognostic capacity of sST2 is independent of MRA therapy.

Effects of 6-months of oral ferrous and ferric supplement therapy in patients who were hospitalized for decompensated chronic heart failure.

ObjectiveAnemia is common in patients with chronic heart failure (CHF). This study aimed to examine the frequency of iron deficiency anemia in patients with CHF. We investigated the effects of oral ferrous or ferric supplementation on prognosis of CHF and quality of life.MethodsA total of 201 patients with chronic decompensated heart failure were enrolled in a 6-month prospective study. Patients were randomly assigned to two groups. Patients in group I (n = 100) received ferrous fumarate and those in group II (n = 101) received ferric hydroxide polymaltose complex. Quality of life was measured by the 6-minute walking test (6MWT).ResultsA total of 49% of the patients had iron-dependent anemia in group I and 53.3% were anemic in group II. In group I, the number of anemic patients was significantly lower at 6 months after admission compared with at initial admission (49% versus 45%). Significant improvements were observed in hemoglobin values, the 6MWT distance, and New York Heart Association class after 6 months in both groups.ConclusionsIron deficiency is a significant comorbidity in CHF, even without anemia. Iron should be replaced orally or intravenously because it significantly improves the quality of life of patients.