Stable Chronic Heart Failure Research Articles

Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study

Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

The impact of left venticular filling pressure indexed to cardiac output on exercise capacity in heart failure subjects

Abstract Background/Introduction Exercise intolerance is the most common symptom of patients with heart failure (HF), regardless of the phenotypes. We aim to investigate the determinants of exercise capacity in chronic stable HF with reduced, mildly reduced, preserved, and recovered ejection fraction (EF). Methods Ambulatory HF subjects were recruited for a combined cardiopulmonary exercise test and exercise stress echocardiography. Peak oxygen consumption (peak VO2) and minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) were obtained. Impaired exercise capacity was referred to a peak VO2 of <14 ml/kg/min, and a VE/VCO2 slope of >34 was defined as ventilatory inefficiency. Results Among a total of 66 participants, there were 16 HF with reduced EF, 18 HF with mildly reduced EF, 12 HF preserved EF, and 20 HF recovered EF. While both LVEF, global longitudinal strain (GLS), E/e’ ratio and diastolic dysfunction indices were crudely associated with peak VO2 and VE/VCO2 slope, only diastolic dysfunction indices were independently predictive of impaired exercise capacity (odds ratio and 95% confidence intervals: 3.847, 1.369-10.810). GLS at rest was independently correlated with ventilatory inefficiency (1.404, 1.050-1.877). Among the exercise indices, the peak medial E/e' to cardiac output ratio was independently associated with impaired exercise capacity (3.478, 1.313-9.214) and peak GLS was best related to ventilatory inefficiency (1.403, 1.076-1.828). Conclusions Among resting and exertional echocardiographic variables, the peak medial E/e' to cardiac output ratio, a non-invasive assessment of exertional left ventricular filling pressure indexed to cardiac output, was the major determinant of exercise capacity in patients with different HF phenotypes.

Phosphorylated tau protein serum levels increase over time in patients with chronic heart failure

Abstract Background/Introduction Amongst various potential biomarkers associated with cognitive deficits, phosphorylated Tau (pTau) appears to link brain and cardiac abnormalities through a systemic tauopathy pathway. Purpose A recent report on the potential importance of myocardial pTau in chronic heart failure (HF) prompted the here described longitudinal quantification of circulating pTau serum levels in patients with HF. We hypothesized that serum pTau accumulates in HF and is associated with markers of myocardial dysfunction. Methods Eligible patients within the prospective, investigator-initiated, monocentric follow-up study Cognition.Matters-HF were older than 18 years, suffered from stable chronic HF and were free from major neurological or psychiatric disorders. Beyond the cardiological assessment including transthoracic echocardiography and six minute walking distance (6-MWD), investigations at baseline, 1 year and 3 years comprised extensive, domain-specific psychological testing and volumetric brain magnetic resonance imaging. Serum pTau was measured using the pTau181 advantage kit. Results Serum samples were available from 78 patients. Mean age was 63±10 years and 87% were men. Serum pTau longitudinally increased from a median of 1.05 (quartiles 0.26, 1.21) pg/ml at baseline to 1.84 (1.36, 3.60) pg/ml after 3 years (p<0.001). During that time period, LVEF, NT-proBNP, 6-MWD and the hippocampal volume remained unaltered, whereas global brain volume and cortical thickness shrank age-appropriately. Cognitive testing revealed that domain-specific T-scores within 36 months remained stable for attentional intensity and executive functioning, and even improved for memory. When we entered baseline values of age and above-mentioned cardiac, brain-volumetric, and cognitive parameters into a multivariable regression model predicting log-transformed pTau, only age (β=0.34), NT-proBNP (β=0.24) and GBV (β=0.26) were independently associated with pTau serum levels (R2=0.18). Consistently, at 36 months, the same predictors were selected by the model (R2=0.29): age (β=0.41), NT-proBNP (β=0.43), and global brain volume (β=0.26). Moreover, higher baseline pTau (β=0.23) and lower 6-MWD (β=-0.39) independently predicted ΔpTau with an explained variance (R2) of 0.24. Conclusions We observed a prominent increase of serum pTau over time, which was predicted by prevalent myocardial dysfunction. Moreover, absolute NT-proBNP levels were independently associated with absolute pTau serum levels, along with age and global brain volume. Mechanistically, phosphorylation of cardiac tau is thought to destabilize its interaction with microtubules causing microtubule detyronisation and increased myocardial stiffness through enhancing the mechanical resistance of contracting cardiomyocytes. The etiological role of pTau in the development of HF and the potential of serum pTau as a novel biomarker of chronic HF warrants further studies.

Circulating metabolites in patients with chronic heart failure are related to increased lipid utilisation but not to gut microbiota alterations

Abstract Background The gut microbiota produces numerous metabolites that can enter the circulation and exert their effects outside the gut. Some have been implicated in the pathogenesis of chronic heart failure (HF). Several studies have reported altered gut microbiota composition and circulating metabolites in patients with chronic HF compared to healthy controls (HC). However, limited data is available on the potential interplay between the dysbiotic features of the gut microbiota and the altered circulating metabolome in these patients. Purpose To examine differences in circulating metabolites between patients with chronic HF and HC, and their association with cardiac function and gut dysbiosis. Methods We included 123 patients, aged 18-75 years, with stable chronic HF and left ventricular ejection fraction (LVEF) <40%, and 51 HC. We collected fasting blood samples for metabolomic and lipidomic analyses, which were performed using liquid chromatography tandem mass spectrometry. A web-based platform was utilised for data preprocessing, filtering, pathway analysis, and metabolite annotation. Principal component analysis and orthogonal partial least squares discriminant analysis were used to explore differences in plasma metabolic profiles. Over-representation analysis was performed to identify the pathways in which relevant metabolites were involved. Stool samples were sequenced using 16S ribosomal RNA gene amplification. We calculated a dysbiosis index for each sample based on different abundances of microbial taxa in patients vs. controls. Results After adjusting for age and sex, we identified 73 enriched metabolites and 27 enriched lipids (odds ratio≥2 and p<0.05), and 124 depleted metabolites and 6 depleted lipids (odds ratio≤0.5 and p<0.05) in HF patients compared to HC. The enriched metabolites were involved in pathways related to lipid metabolism (beta oxidation, glycerolipid, sex hormone, and fatty acid metabolism), pyrimidine metabolism, Warburg effect, citric acid cycle, and pentose phosphate pathway. The depleted metabolites were involved in pathways related to lipid biosynthesis (fatty acids, steroids, bile acids), amino acid metabolism (glycine, serine, taurine, hypotaurine, cysteine, selenoamino acids), polyamine biosynthesis (spermidine, spermine), sulphate/sulphite metabolism, propanoate and pyruvate metabolism, carbohydrate metabolism (galactose, amino sugars, glycolysis), transfer of acetyl groups into mitochondria, urea cycle, and beta oxidation of very long chain fatty acids (Figure 1). LVEF, N-terminal pro B-type natriuretic peptide, and the dysbiosis index were not significantly related to any metabolite. Conclusions In patients with chronic HF, energy metabolism is significantly altered compared to HC, with a notable shift towards lipid utilisation. However, the alterations in circulating metabolites were not related to markers of cardiac function and appear to be unrelated to gut dysbiosis.Figure 1

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

The prothrombotic state in patients with type 2 diabetes mellitus and ischemic heart failure: an association with endothelial dysfunction

Abstract Background Heart failure (HF) is associated with a substantial prothrombotic state and an increased risk of thromboembolism, regardless of the presence of atrial fibrillation (AF). Although oral anticoagulation in HF with known AF is recommended, there is no conclusive evidence supporting clinical benefits of chronic anticoagulation in HF subjects without AF. Other factors enhancing prothrombotic state, often concomitant with HF, are type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). T2D as well as CAD are independently associated with a hypercoaguability due to multiple mechanisms including endothelial dysfunction and oxidative stress. Dysfunction of endothelium was observed in patients with HF, however a little is known about its influence on prothrombotic state in a very high risk HF population. Purpose This study aimed to investigate whether the prothrombotic state in patients with T2D, CAD, and HF, depends on the left ventricular ejection fraction (LVEF) or endothelial function. Methods We assessed 54 patients with stable chronic HF, CAD, and T2D. Based on the echocardiography examination 28 of them were those with HF with reduced ejection fraction (HFrEF) and 26 of them were classified as HF with preserved ejection fraction (HFpEF) according to current guidelines. Fibrin clot density reflected by clot permeability (Ks) and thrombin generation were evaluated. Endothelial function was determined in flow-mediated (FMD) and nitroglycerin-mediated dilatation (NMD) tests of the brachial artery. Results Subjects in both groups were comparable in terms of cardiovascular risk factors except for lower glomerular filtration rate (GFR) by 18.1%. HFrEF patients had lower Ks by 20.3%, along with higher endogenous thrombin potential (ETP) by 18.9% and maximum thrombin level (Peak) by 24.1% as compared with HFpEF. While there were no differences in FMD and NMD between subjects, we found negative correlations of NMD with ETP and Peak (r=-0.448, P=0.001; r=-0.304, P=0.034, respectively). Moreover, the proportion of NMD and FMD along with GFR and LVEF were also significantly associated with both thrombogram parameters (<0.01 for all). By the multivariate analysis of the whole population, NMD, LVEF, low-density lipoprotein and GFR were independent predictors of ETP (R2=0.530, P<0.001) while NMD, LVEF, and GFR predicted Peak levels (R2=0.327, P=0.002). Conclusion We showed for the first time that patients with ischemic etiology of HFrEF and T2D presented altered fibrin clot properties and enhanced thrombin generation compared to HFpEF subjects. It might be hypothesized that endothelial dysfunction induced by T2D could intensify hypercoagulability in patients with HF.Figurę 1

Prognostic value of circulating glypican-4 in patients with chronic heart failure with reduced ejection fraction

Abstract Background Chronic heart failure is one of the leading causes of hospitalization and mortality worldwide, with an ever-increasing prevalence. Glypican-4 (GPC4) is a cell surface protein part of the endothelial glycocalyx which is actively released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. The current literature on the association between circulating GPC4 and heart failure is limited and its prognostic value on top of established risk markers in chronic heart failure is unknown. Purpose In the present study, we aim to investigate the prognostic value of circulating GPC4 on clinical outcomes in a contemporary cohort of patients with stable chronic heart failure with reduced ejection fraction (HFrEF). Methods Symptomatic outpatients with stable chronic HFrEF were consecutively enrolled in a prospective cohort study. Circulating serum GPC4 levels were assessed using an enzyme-linked immunosorbent at baseline. Patient outcomes were retrieved from medical and health insurance records. Results We enrolled 205 patients with a median (interquartile range) age of 66 (59-74) years, with 22% females. Median left ventricular ejection fraction (LVEF) was 37 (30-43)%, median estimated glomerular filtration rate (eGFR) was 64 (48-80) ml/min/1,73 m2, median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 964 (336-2173) pg/ml, median interleukin 6 (IL6) was 4.7 (3.2-7.9) pg/ml, and median GPC4 was 1553 (1034-1950) pg/ml. During a median follow-up of 4.7 (4.0-5.3) years, 46 patients (22%) were hospitalized due to worsening heart failure (WHF), 18 patients (9%) died of cardiovascular (CV) cause, and 58 patients (28%) died of any cause. In univariate Cox-regression, serum GPC4 levels predicted WHF (HR 1.57, 95%CI 1.29-1.92, p<0.001), CV death (HR 2.07, 95%CI 1.56-2.74, p<0.001), and all-cause mortality (HR 1.93, 95%CI 1.59-2.34, p<0.001). The association between serum GPC4 levels and both, CV death (HR 1.69, 95%CI 1.04-2.86, p=0.048) and all-cause mortality (HR 1.56, 95%CI 1.14-2.14, p=0.006) remained significant in a multivariable Cox-regression model adjusted for age, sex, eGFR, IL6, NT-proBNP, and LVEF. Conclusion In patients with stable chronic HFrEF, circulating GPC4 is significantly associated with cardiovascular outcome and is an independent predictor of all-cause mortality. The potential prognostic value in clinical routine of GPC4 should be addressed in prospective studies.

Efficacy of Inspiratory Muscle Training in Patients With Acute Decompensated Heart Failure.

Inspiratory muscle training (IMT) is supported for outpatients with stable chronic heart failure, but its efficacy in hospitalized patients with acute decompensated heart failure (ADHF) remains unclear. The aim of the present study was to clarify IMT efficacy and safety in hospitalized ADHF patients. Patients with inspiratory muscle weakness who underwent cardiac rehabilitation (CR) were analyzed. The control group was historical control data of patients admitted to the same facility. IMT was performed at 30% maximal inspiratory mouth pressure (15 reps/set, 2 sets/day, 5 times/week) with usual CR. Associations between IMT and changes in the 2-min walking distance (2MWD) were assessed using a linear mixed model. In total, 31 and 29 patients in the IMT and control groups (median age 83 [71-88] vs. 86 [77-88] years), respectively, were analyzed. After adjustment for covariates and propensity scores, calculated on the basis of heart-failure severity, frailty, physical function, nutritional status, and inspiratory muscle strength, the 2MWD was significantly higher in the IMT group than in the control group (F=4.697; P=0.035; ∆2MWD; +31.9 vs. +16.3 m). Among 348 IMT sessions, no adverse cardiovascular events or absolute termination criteria were identified. Eleven (3.2%) IMT sessions met relative termination criteria. Adding IMT to usual CR improves the 2MWD, can be safely performed in hospitalized patients with ADHF, and may represent a novel CR approach in patients with ADHF.

The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis.

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2< 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14-2.73), with no difference in mortality (RR 0.64, 95% CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68-1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Diabetes mellitus in stable chronic heart failure and the combination with humoral activation, their association, and prediction of 2-year adverse outcomes. Data from the FAR NHL registry.

The study aims to describe the role of diabetes in patients with heart failure. In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis. The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

Elevated Cystatin C Predicts Higher Mortality in Chronic Heart Failure Independently of Renal Function.

Cystatin C (CysC) is a known prognostic marker in cardiovascular diseases and its role in acute heart failure (HF) has been documented. We prospectively recruited HF patients followed in a HF clinic. Inclusion criteria: HF diagnosed ≥6 months, optimized evidence-based therapy, and ejection fraction <40% (Heart Failure with reduced ejection fraction). Exclusion criteria: renal replacement therapy and hospitalizations or therapeutic adjustments in the previous 2 months. A venous blood sample and 24-hour urine were collected. Follow-up: 5 years; endpoint: all-cause mortality. CysC was measured and creatinine clearance (CrCl) was calculated using 24-hour urine creatinine excretion. A Receiver operating characteristic curve was used to assess association of CysC with 5-year mortality. The prognostic role of CysC was determined using Cox-regression analysis. The multivariate model included CrCl (24-hour urine). We evaluated 215 chronic stable Heart Failure with reduced ejection fraction patients. Mean age was 68 years, 72.1% were male. Median CysC = 1.15 mg/L, creatinine = 1.20 mg/dL, and CrCl = 63.6 mL/min. During follow-up, 103 (47.9%) patients died. The area under the curve for CysC in predicting mortality was 0.77 (0.70-0.83). Best cut-off value for death prediction = 1.00 mg/L with a sensitivity = 83.5%, specificity = 56.2%, positive predictive value = 63.7%, and negative predictive value = 78.7%. Multivariate-adjusted (age-, B-type natriuretic peptide-, evidence-based therapy, New York Heart Association class, and CrCl) 5-year mortality Hazard ratio = 2.40 (95% Confidence interval, 1.25-4.61), P value = 0.008 when CysC ≥1.00 mg/L. Patients with CysC <1.00 mg/L have almost 80% probability of being alive at 5 years; If CysC ≥1.00 mg/L, there is almost 2.5-fold higher death risk independently of B-type natriuretic peptide and CrCl.

Conventional and Novel Inflammatory Biomarkers in Chronic Heart Failure Patients with Atrial Fibrillation.

(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013-1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068-1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population.

Feasibility of Short-Term Use of Ivabradine in Critical Ill Patients Who Have Atrial Fibrillation and Tachycardia.

Ivabradine is approved for heart rate reduction in patients with stable symptomatic heart failure (HF). The United States Food and Drug Administration and Taiwan Central Health Insurance Agency approved the use of ivabradine for patients with chronic stable HF with sinus rhythm, but it has not yet been approved for patients with acute decompensated HF or with atrial fibrillation (AF). To investigate whether short-term ivabradine use is feasible in critically ill patients with AF and rapid ventricular response (RVR). This study retrospectively analyzed 23 patients admitted to an intensive care unit with acute HF and AF-RVR who received ivabradine. All patients initially received a slow IV of amiodarone. Other medications for HF were prescribed according to current HF guidelines. The time taken for ivabradine to reduce HR to 80 beats per minute, referred to as "Time to 80," was measured in each patient. Overall, 69.6 % (16/23) of the patients had New York Heart Association functional class IV HF. In addition, 60.9% (14/23) of the patients required endotracheal intubation and ventilatory support, with more than half receiving vasopressor treatment to manage hypotension. Five patients died during the study period. The surviving patients had a significantly shorter "Time to 80" compared to those who did not survive (p = 0.037). Adding ivabradine to standard treatment might be feasible for critically ill patients with AF and tachycardia. The finding that surviving patients had a shorter "Time to 80" duration than those who did not survive may have clinical implications. However, further investigations are needed to assess its clinical utility.

#2848 Persistent albuminuria is a marker of persistent congestion in patients with chronic heart failure

Abstract Background and Aims Albuminuria is prevalent in patients with heart failure (HF) and associated with poor prognosis. Initial reports indicate albuminuria as a congestion marker in HF. Frequency and associations of persistent albuminuria with kidney function, NT-proBNP and venous congestion in this population are not clearly understood. We aimed to evaluate the dynamics of albuminuria and its relationship with congestion and renal function in patients with chronic HF (CHF). Method The study included patients ≥18 years, observed in an outpatient HF center, who signed an informed consent. Patients receiving renal replacement therapy, with cancer or primary kidney diseases were excluded. The visits were carried out with an interval of 3 months. During each visit we performed routine physical examination, laboratory tests (NT-proBNP, urine albumin/creatinine ration (uACR), and serum creatinine) and pulse-wave Dopplerography to assess renal venous blood flow. Persistent albuminuria was defined as maintaining an uACR &amp;gt; 30 mg/g on two visits. Albuminuria level was assessed according to KDIGO guidelines 2012 (A1, A2, A3). The absence of venous congestion was defined as continuous renal blood flow, while venous congestion - as intermittent (biphasic or monophasic) blood flow. A P value &amp;lt;0.05 was considered statistically significant. We prospectively included 103 patients with CHF (46% male, mean age - 70 (61;75) Me (IQR) years, 53% with reduced ejection fraction (EF), mean EF 45(34;53)%, 92% hypertensive, 60% with atrial fibrillation, 34% with diabetes mellitus type 2, 51% with chronic kidney disease (CKD), 43% with coronary heart disease). Results Mean uACR values at the 1st visit was 18(8;56) mg/g, at the 2nd visit - 11(0;35) mg/g. The frequency of albuminuria levels at the 1st visit were A1-66%, A2-26%, A3-8%; at the 2nd visit – A1-73%, A2-23%, A3-4%. Persistent albuminuria was detected in 37 patients (36%). The mean values of albuminuria were higher in the persistent albuminuria group on the 1st visit (76(39;222) vs 10.5(0;19.5) for patients with and without persistent albuminuria, p&amp;lt;0.001) and on the 2nd visit (94(44;176) vs 7(0;13), p &amp;lt; 0.001). The patient groups were comparable in gender, age, frequency of comorbidities, EF. The administration of disease-modifying therapy was the same in the groups, however, the dose of loop diuretic was higher in the group of persistent albuminuria (20 (10;75) vs 10(5;20) mg respectively, p = 0.024 (doses in terms of furosemide)). Serum creatinine level was 95(79;121) mmol/l; GFR (CKD-EPI 2021)- 69(52;88) mL/min/ 1.73 m2 at the 1st visit. Kidney function did not statistically differ in the groups with and without persistent albuminuria (at the 1st visit eGFE - 63(52;87) vs 70 (50;90) mL/min/1.73 m2, p = 0.52 and the 2nd visit eGFR- 68(48;85) vs 66 (48;89) mL/min/1.73, p = 0.65 respectively). The level of NT-proBNP was higher in patients with persistent albuminuria during the 1st (926 (472;1820) vs 550(260;919), pg/ml p = 0.04) and the 2nd visit (1244(987;2000) vs 593(264;1405), pg/ml, p = 0.0008). Intermittent renal veins blood flow on the 2nd visit was observed in 26 patients (25%). In patients with persistent albuminuria persistence of intermittent venous renal blood flow was more frequently than in patients without it (43% vs 7%, p = 0.017, respectively). Figs. 1 and 2 demonstrate that renal venous congestion was more severe in group of persistent albuminuria on visit 1st and 2nd respectively. Conclusion Persistent albuminuria over 3 mounts in patients with stable chronic heart failure is associated with persisting congestion (higher NT-proBNP levels and higher incidence and severity of renal venous congestion). There was no association between changes in albuminuria and changes in renal function.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. The median age was 74years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300mg/g and 64 (7.4%) had a UACR >300mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2=57.6%), systolic blood pressure (R2=21.1%), previous furosemide equivalent dose (FED; R2=7.5%), antigen carbohydrate 125 (CA125; R2=6.1%), diabetes mellitus (R2=5.6%) and oedema (R2=1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

Low irisin levels predict acutely decompensated heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements None. Background Acutely decompensated heart failure (ADHF) continues to be associated with unacceptably increasing in-hospital mortality rates and one-year mortality rates. Distinct scenarios of the natural course of ADHF relate to clinical heterogeneity among patients admitted to hospitals, cardiac dysfunction etiology, precipitating factors contributing to heart failure (HF) decompensation including type 2 diabetes mellitus (T2DM). The aim of this study was to determine the discriminative value of irisin for ADHF in T2DM patients with hemodynamically stable chronic HF. Methods A total of 738 patients with T2DM were prescreened using the local database of "Vita Center" (Ukraine). Using criteria of inclusion (male/female with age of ≥18 years, established T2DM with hemodynamically stable chronic HF, glycosylated hemoglobin &amp;lt; 6.9%, informed consent to participate in the study), we enrolled 489 patients with T2DM with concomitant chronic HF I-IV New York Heart Association (NYHA) functional classes. We enrolled 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. Results We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin &amp;lt; 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP &amp;gt; 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots (Figure) showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (&amp;lt;7.85 ng/mL versus ≥7.85 ng/mL). The intra-class correlation coefficient for inter-observer reproducibility of LV dimensions was 0.88 (95% CI = 0.83–0.92), of LVEF was 0.93 (95% CI = 0.90–0.97), of LAVI was 0.92 (95% CI = 0.89–0.94), and of E/e’ was 0.90 (95% CI = 0.87–0.94). Along with it, the intra-class correlation coefficient for the intra-observer reproducibility of LV dimensions was 0.91 (95% CI = 0.88–0.95), of LVEF was 0.94 (95% CI = 0.90–0.98), of LAVI was 0.95 (95% CI = 0.93–0.97), and of E/e’ was 0.92 (95% CI = 0.90–0.95). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.Flow chart of the study designThe Kaplan–Meier analysis of ADHF

The Prognostic Value of Right Ventricular Function in Patients with Chronic Heart Failure-A Prospective Study.

Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800-0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800-0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853-0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy.

Prevalence of Sarcopenia in Chronic Heart Failure and Modulating Role of Chronic Kidney Disease

Introduction: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD. Methods: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient’s medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected. Results: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73–0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69–0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047). Discussion/Conclusion: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Possible Correlations between Mean Platelet Volume and Biological, Electrocardiographic, and Echocardiographic Parameters in Patients with Heart Failure.

(1) Background: Despite advancements in medical research and discoveries, heart failure (HF) still represents a significant and prevalent public health challenge. It is characterized by persistently high mortality and morbidity rates, along with increased rates of readmissions, particularly among the elderly population. (2) Methods: This study was conducted retrospectively on 260 patients with stable or decompensated chronic HF. The parameter of interest in the study population was the mean platelet volume (MPV), and the main objective of the research was to identify a possible relationship between MPV and several variables-biological (NT-proBNP, presepsin, red cell distribution width (RDW)), electrocardiographic (atrial fibrillation (AFib) rhythm, sinus rhythm (SR)), and echocardiographic (left ventricle ejection fraction (LVEF), left atrial (LA) diameter, left ventricle (LV) diameter, pulmonary hypertension (PH)). (3) Results: By applying logistic and linear regression models, we assessed whether there is a correlation between MPV and biological, electrocardiographic, and echocardiographic variables in patients with HF. The results revealed linear relationships between MPV and NT pro-BNP values and between MPV and RDW values, and an increased probability for the patients to have an AFib rhythm, reduced LVEF, dilated LA, dilated LV, and PH as their MPV value increases. The results were deemed statistically relevant based on a p-value below 0.05. (4) Conclusions: Through regression model analyses, our research revealed that certain negative variables in HF patients such as increased levels of NT-proBNP, increased levels of RDW, AFib rhythm, reduced LVEF, dilated LA, dilated LV, and PH, could be predicted based on MPV values.