Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22-5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication.

MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.

Nursing knowledge of the principles of self-care of heart failure in primary care: a multicentre study.

INTRODUCTION: Nurses play an important part in the education of patients with HF. To prepare patients with HF for self-care maintenance behaviours, nurses must have knowledge of basic self-care maintenance principles. AIM STUDY: The aim of this study was to determine the degree of knowledge of primary care (PC) nurses on the principles of self-management of HF and variables associated with this. METHODOLOGY: This is an observational, cross-sectional descriptive study, carried out in 2014, in the city of Barcelona (Catalonia). Nurses' Knowledge of Heart Failure Education Principles questionnaire (NKHFEP) was used to assess the principles of HF self-care education. Instrument items assess knowledge of nurses on 5 themes: diet, liquids/weight, worsening signs or symptoms, medication and exercise. Factors related to adequate knowledge were evaluated. RESULTS: Of 216 PC nurses, who completed the questionnaire, the average score was 15.6 (SD: 2.2). Only 36 (16.7%) obtained an adequate level of knowledge and defined as a score ≥ 18 points. In multivariate logistic regression, nurse factors associated with an adequate knowledge of principles of self-care of HF were having achieved a PhD degree (OR: 36.4, 95% CI: 2.8-468.2, p = 0.006) and previous specific training in HF (OR: 19.8, 95% CI: 1.4-279.3, p = 0.026). CONCLUSIONS: The degree of knowledge of PC nurses in the principles of self-care in HF was higher among nurses who had completed the doctorate and in nurses who had received specific training in HF.

Challenges of evaluating chronic heart failure and acute heart failure events in research studies using large health care databases.

Epidemiological studies on heart failure (HF) using large health care databases are becoming increasingly frequent, as they represent an invaluable opportunity to characterize the importance and risk factors of HF from a population perspective. Nevertheless, because of its complex diagnosis and natural history, the heterogeneous use of the relevant terminology in routine clinical practice, and the limitations of some disease coding systems, HF can be a challenging condition to assess using large health care databases as the main source of information. In this narrative review, we discuss some of the challenges that researchers may face, with a special focus on the identification and validation of chronic HF cases and acute HF decompensations. For each of these challenges, we present some potential solutions inspired by the literature and/or based on our research experience, aimed at increasing the internal validity of research and at informing its interpretation. We also discuss future directions on the field, presenting constructive recommendations aimed at facilitating the conduct of valid epidemiological studies on HF in the coming years.

Importance of iron deficiency in patients with chronic heart failure as a predictor of mortality and hospitalizations: insights from an observational cohort study.

BACKGROUND: Iron deficiency (ID) in patients with chronic heart failure (CHF) is considered an adverse prognostic factor. We aimed to evaluate if ID in patients with CHF is associated with increased mortality and hospitalizations. METHODS: We evaluated ID in patients with CHF at 3 university hospitals. ID was defined as absolute (ferritin < 100 µg/L) or functional (transferrin Saturation index < 20% and ferritin between 100 and 299 µg/L). We excluded patients who received treatment with intravenous Iron or Erythropoietin during follow-up. We evaluated if ID was a predictor of death or hospitalization due to heart failure or any cause using univariate and multivariate cox regression analysis. RESULTS: We included 1684 patients, 65% males, 38% diabetics, median age of 72 years, 37% in functional class III-IV and 30% of patients with a left ventricular ejection fraction > 45%. Patients were well treated, with 87% and 88% of patients receiving renin-angiotensin inhibitors and beta-blockers, respectively. Median transferrin saturation index was 20%, median ferritin 155 ng/mL and median haemoglobin 13 g/dL. ID was present in 53% of patients; in 35% it was absolute and in 18% functional. Median follow-up was 20 months. ID was a predictor of death, hospitalization due to heart failure or to any cause in univariate analysis but not after multivariate analysis. No differences were found between absolute or functional ID regarding prognosis. CONCLUSION: In a real life population of patients with CHF and a high prevalence of heart failure with preserved ejection fraction, ID did not predict mortality or hospitalizations after adjustment for comorbidities, functional class and neurohormonal treatment.

Ischemic aetiology, self-reported frailty, and gender with respect to cognitive impairment in chronic heart failure patients.

BACKGROUND: Decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores. METHODS: A cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment. RESULTS: Cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p < 0.001), ischemic etiology (OR: 1.99 (1.25-3.17) p = 0.004), frailty (OR: 1.58 (0.99 to 2.50, p =0.050), albumin > 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function. CONCLUSION: The observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.

Serum potassium abnormalities, renin-angiotensin-aldosterone system inhibitor discontinuation, and clinical outcomes in patients with chronic cardiovascular, metabolic, and renal conditions: A population-based analysis.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASIs) play a crucial role in the treatment of several chronic cardiovascular conditions. Nonetheless, hyperkalemia, a frequent side effect, often leads to the discontinuation of RAASIs. The implications of hyperkalemia-driven changes in RAASI medications are poorly understood. METHODS: Population-based, observational, retrospective cohort study. Two large healthcare databases were utilized to identify 77,089 individuals aged 55 years and older with chronic conditions who were prescribed RAASIs between 2015 and 2017 in Southern Barcelona, Spain. We assessed the interplay between serum potassium abnormalities, RAASI management, and their associations with clinical outcomes, adjusting for potential confounders including socioeconomic factors, medical conditions, and potassium levels. RESULTS: The one-year prevalence of hyperkalemia (defined as serum potassium, K+ >5.0 mmol/L) was 17.8 %. RAASI were down-titrated in 16.1 % of these 13,673 patients with K+ levels. Factors linked to a higher likelihood of reducing/discontinuing RAASI after developing hyperkalemia included older age, impaired kidney function, higher potassium levels, and previous hospitalizations. Dose reduction/discontinuation of RAASI after developing hyperkalemia was associated with an increased risk of hospitalization (adjusted hazard ratio [HR] 1.16, 95 % confidence interval [CI] 1.10-1.21) and with increased mortality (HR 1.60, 95 % CI 1.56-1.84). CONCLUSION: In this large, observational study, hyperkalemia was linked to a greater likelihood of discontinuing RAASIs. Down-titration of RAASI was independently associated with unfavorable clinical outcomes such as hospitalization and specially mortality. Although the observational nature of the study, these findings underscore the importance of preventing circumstances that may lead to RAASI down-titration, such as hyperkalemia, as well as preventing hospitalizations and mortality, to ensure RAASI benefits.

Iron deficiency in chronic heart failure: an international pooled analysis.

BACKGROUND: Iron deficiency (ID) is an emerging problem in patients with chronic heart failure (HF) and can be a potential therapeutic target. However, not much is known about the prevalence, predictors, and prognosis of ID in patients with chronic HF. METHODS: In an international pooled cohort comprising 1,506 patients with chronic HF, we studied the clinical associates of ID and its prognostic consequences. RESULTS: Iron deficiency (defined as a ferritin level <100 µg/L or ferritin 100-299 µg/L with a transferrin saturation <20%) was present in 753 patients (50%). Anemic patients were more often iron deficient than nonanemic patients (61.2% vs 45.6%, P < .001). Other independent predictors of ID were higher New York Heart Association class, higher N-terminal pro-brain-type natriuretic peptide levels, lower mean corpuscular volume levels, and female sex (all P < .05). During follow-up (median 1.92 years, interquartile range 1.18-3.26 years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as a strong predictor for mortality (log rank χ(2) 10.2, P = .001). In multivariable hazard models, ID (but not anemia) remained a strong and independent predictor of mortality (hazard ratio 1.42, 95% confidence interval 1.14-1.77, P = .002). Finally, the presence of ID significantly enhanced risk classification and integrated discrimination improvement when added to a prediction model with established risk factors. CONCLUSIONS: Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia.

Psychosocial factors partially explain gender differences in health-related quality of life in heart failure patients.

AIMS: There is little information about the influence of gender on quality of life (QoL) in heart failure. The purpose of this study was to evaluate whether the health-related QoL gap between men and women can be explained by the interaction between psychosocial factors and clinical determinants in a real-word cohort of patients with chronic heart failure. METHODS AND RESULTS: We conducted a single-centre, observational, prospective cohort study of 1236 consecutive patients diagnosed with chronic heart failure recruited between 2004 and 2014. To assess QoL, we used the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Female gender was associated with worse global QoL compared to male gender (MLHFQ overall summary score: 49 ± 23 vs. 43 ± 24; P value <0.001, respectively) and similarly had poorer scores in physical and emotional dimensions but scored better on social dimension. In univariate models and in models adjusted for clinical determinants, female gender behaved as a predictor of worse global, physical and emotional QoL, and better social QoL compared with men. In models only including psychosocial determinants and in comprehensive models including all psychosocial and clinical factors, these differences according to gender were no longer significant. CONCLUSIONS: In this study, we have shown that the gap in health-related QoL between men and women with chronic heart failure can be partially explained by the interaction between biological and psychosocial factors. Biological factors are the main drivers of QoL in HF patients. However, the contribution of psychosocial factors is essential to definitively understand the role of gender in this field.

Prognostic Value of Soluble AXL in Serum from Heart Failure Patients with Preserved and Reduced Left Ventricular Ejection Fraction.

Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. Two groups of HF patients with reduced (HFrEF; n = 134) and preserved ejection fraction (HFpEF; n = 134) were included in this prospective observational study, with measurements of candidate biomarkers and functional, clinical, and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events: cardiovascular mortality and all-cause mortality. sAXL circulating values predicted outcome in HF: for a 1.0 ng/mL increase in serum sAXL, the mortality hazard ratio (HR) was 1.019 for HFrEF (95% CI 1.000 to 1.038) and 1.032 for HFpEF (95% CI 1.013 to 1.052). In a multivariable Cox regression analysis, sAXL and NT-proBNP were independent markers for all-cause and cardiovascular mortality in HFpEF. In contrast, only NT-proBNP remained significant in the HFrEF group. When analyzing the event-free survival at a mean follow-up of 3.6 years, HFrEF and HFpEF patients in the higher quartile of sAXL had a reduced survival time. Interestingly, sAXL is a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort. The results suggest an important role for AXL in HFpEF, supporting sAXL evaluation in larger clinical studies and pointing to AXL as a potential target for HF therapy.

Breaking the 30-day barrier: Long-term effectiveness of a nurse-led 7-step transitional intervention program in heart failure.

BACKGROUND AND AIMS: Heart failure (HF) programs successfully reduce 30-day readmissions. However, conflicting data exist about its sustained effects afterwards and its impact on mortality. We evaluated whether the impact of a new nurse-led coordinated transitional HF program extends to longer periods of time, including 90 and 180 days after discharge. METHODS AND RESULTS: We designed a natural experiment to undertake a pragmatical evaluation of the implementation of the program. We compared outcomes between patients discharged with HF as primary diagnosis in Period #1 (pre-program; Jan 2017-Aug 2017) and those discharged during Period #2 (HF program; Sept 2017-Jan 2019). Primary endpoint was the composite of all-cause death or all-cause hospitalization 90 and 180 days after discharge. 440 patients were enrolled: 123 in Period #1 and 317 in Period #2. Mean age was 75±9 years. There were more females in Period #2 (p = 0.025), with no other significant differences between periods. The primary endpoint was significantly reduced in the HF program group, at 90 [adjusted OR 0.31 (0.18-0.53), p <0.001] and at 180 days [adjusted OR 0.18 (CI 0.11-0.32), p <0.001]. Such a decrease was due to a reduction in cardiovascular (CV) and HF hospitalization. All-cause death was reduced when a double check discharge planning was implanted compared to usual care [0 (0%) vs. 7 (3.8%), p = 0.022]. CONCLUSION: A new nurse-led coordinated transitional bundle of interventions model reduces the composite endpoint of all-cause death and all-cause hospitalization both at 90 and 180 days after a discharge for HF, also in high-risk populations. Such a decrease is driven by a reduction of CV and HF hospitalization. Reduction of all-cause mortality was also observed when the full model including a more exhaustive discharge planning process was implemented.

Usefulness of telemedicine-based heart failure monitoring according to 'eHealth literacy' domains: Insights from the iCOR randomized controlled trial.

BACKGROUND: The potential positive effect of electronic health (eHealth)-based heart failure (HF) monitoring remains uncertain mainly in the 'low literacy' or 'computer or digital illiterate' patients. The aim of this study was to determine the effectiveness of a telemedicine (TM)-based managed care solution across literacy levels and information and communications technology (ICT) skills. METHODS: We performed a sub-analysis on the basis of two literacy domains encompassed in the definition of 'eHealth literacy' to the HF-patients included in the 'insuficiència Cardíaca Optimització Remota' (iCOR) randomized study comparing TM vs. usual care (UC) in HF-patients. The primary study endpoint was the incidence of a non-fatal HF event after 6 months of inclusion. The event rates of primary and secondary study endpoints were calculated for each literacy domains and its combination. Cox proportional-hazards regression models were used to evaluate the effect of 'eHealth literacy' dimensions, treatment group and the interaction term 'eHealth literacy' domains by treatment group on study endpoints. RESULTS: The beneficial effect of TM compared to UC strategy was consistent across all literacy domains (p-value for interaction 0.207 and 0.117 respectively). The risk of experiencing a primary event was significantly lower in patients that underwent allocation to the TM arm compared to UC in both clustered in the 'lower literacy' (p-value=0.001) and those allocated to the 'lower ICT skills' (p-value=0.001) subgroup. CONCLUSIONS: Non-invasive eHealth-based HF monitoring tools are effective compared to UC in preventing HF events in the early post-discharge period, regardless of two 'eHealth literacy' domains ('traditional and computer literacy').

The relationship between self-care, long-term mortality, and heart failure hospitalization: insights from a real-world cohort study.

AIMS: The assumption that improved self-care in the setting of heart failure (HF) care necessarily translates into improvements in long-term mortality and/or hospitalization is not well established. We aimed to study the association between self-care and long-term mortality and other major adverse HF events (MAHFE). METHODS AND RESULTS: We conducted an observational, prospective, cohort study of 1123 consecutive patients with chronic HF. The primary endpoint was all-cause mortality. We used the European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure global self-care (overall score) and three specific dimensions of self-care including autonomy-based adherence, consulting behaviour and provider-based adherence. After a mean follow-up of 3.3 years, all-cause death occurred in 487 patients (43%). In adjusted analysis, higher EHFScBS-9 scores (better self-care) at baseline were associated with lower risk of all-cause death [hazard ratio (HR) 0.993, 95% confidence interval (CI) (0.988-0.997), P-value = 0.002], cardiovascular (CV) death [HR 0.989, 95% CI (0.981-0.996), P-value = 0.003], HF hospitalization [HR 0.993, 95% CI (0.988-0.998), P-value = 0.005], and the combination of MAHFE [HR 0.995, 95% CI (0.991-0.999), P-value = 0.018]. Similarly, impaired global self-care [HR 1.589, 95% CI (1.201-2.127), P-value = 0.001], impaired autonomy-based adherence [HR 1.464, 95% CI (1.114-1.923), P-value = 0.006], and impaired consulting behaviour dimensions [HR 1.510, 95% CI (1.140-1.923), P-value = 0.006] were all associated with higher risk of all-cause mortality. CONCLUSION: In this study, we have shown that worse self-care is an independent predictor of long-term mortality (both, all-cause and CV), HF hospitalization, and the combinations of these endpoints in patients with chronic HF. Important dimensions of self-care such as autonomy-based adherence and consulting behaviour also determine the risk of all these outcomes in the long term.

Effectiveness of telemedicine in patients with heart failure according to frailty phenotypes: Insights from the iCOR randomised controlled trial.

BACKGROUND: The potential impact of telemedicine (TM) in the monitoring of patients with heart failure (HF) is still uncertain particularly in the frailest patients. The aim of this study was to define the efficacy of a TM-based managed care solution across different HF patient frailty phenotypes. METHODS: We performed a clustering analysis on the basis of 8 frailty-related dimensions to the HF-patients included in the 'insuficiència Cardíaca Optimització Remota' (iCOR) randomised study comparing TM vs. usual care (UC) in HF patients. The primary study endpoint was the incidence of a non-fatal HF event after 6 months of inclusion. The healthcare-related costs in each study group and cluster were also evaluated. The event rates of primary and secondary study endpoints were calculated for each cluster. Cox proportional-hazards regression models were used to evaluate the effect of cluster, treatment group and the interaction term cluster by treatment group on study endpoints. RESULTS: 5 different frailty phenotypes were identified. The positive effect of TM compared to UC strategy was consistent across all frailty phenotypes (p-value for interaction 0.711). The risk of experiencing a primary event was significantly lower in patients that underwent allocation to the TM arm compared to UC (p-value = 0.016). Ultimately, the healthcare costs were significantly reduced in patients allocated to the TM compared to UC in all 5 frailty phenotypes (all p-value < 0.05). CONCLUSIONS: Non-invasive TM-based follow-up tools are effective compared to UC follow-up in preventing HF events in the early post-discharge period, regardless of the 5 frailty phenotypes.

Impact on clinical outcomes and health costs of deranged potassium levels in patients with chronic cardiovascular, metabolic, and renal conditions.

INTRODUCTION AND OBJECTIVES: Potassium derangements are frequent among patients with chronic cardiovascular conditions. Studies on the associations between potassium derangements and clinical outcomes have yielded mixed findings, and the implications for health care expenditure are unknown. We assessed the population-based associations between hyperkalemia, hypokalemia and clinical outcomes and health care costs, in patients with chronic heart failure, chronic kidney disease, diabetes mellitus, hypertension, and ischemic heart disease. METHODS: Population-based, longitudinal study including up to 36 269 patients from a health care area with at least one of the above-mentioned conditions. We used administrative, hospital and primary care databases. Participants were followed up between 2015 and 2017, were aged ≥ 55 years and had at least 1 potassium measurement. Four analytic designs were used to evaluate prevalent and incident cases and the use of renin-angiotensin-aldosterone system inhibitors. RESULTS: Hyperkalemia was twice as frequent as hypokalemia. On multivariable-adjusted analyses, hyperkalemia was robustly and significantly associated with an increased risk of all-cause death (HR from Cox regression models ranging from 1.31-1.68) and with an increased odds of a yearly health care expenditure >85th percentile (OR, 1.21-1.29). Associations were even stronger in hypokalemic patients (HR for all-cause death, 1.92-2.60; OR for health care expenditure> percentile 85th, 1.81-1.85). CONCLUSIONS: Experimental studies are needed to confirm whether the prevention of potassium derangements reduces mortality and health care expenditure in these chronic conditions. Until then, our findings provide observational evidence on the potential importance of maintaining normal potassium levels.

Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Heart Failure: A Prospective Study.

Acute hyperglycemia has been associated with worse prognosis in patients hospitalized for heart failure (HF). Nevertheless, studies evaluating the impact of glycemic control on long-term prognosis have shown conflicting results. Our aim was to assess the relationship between acute-to-chronic (A/C) glycemic ratio and 4-year mortality in a cohort of subjects hospitalized for acute HF. A total of 1062 subjects were consecutively included. We measured glycaemia at admission and estimated average chronic glucose levels and the A/C glycemic ratio were calculated. Subjects were stratified into groups according to the A/C glycemic ratio tertiles. The primary endpoint was 4-year mortality. Subjects with diabetes had higher risk for mortality compared to those without (HR 1.35 [95% CI: 1.10-1.65]; p = 0.004). A U-shape curve association was found between glucose at admission and mortality, with a HR of 1.60 [95% CI: 1.22-2.11]; p = 0.001, and a HR of 1.29 [95% CI: 0.97-1.70]; p = 0.078 for the first and the third tertile, respectively, in subjects with diabetes. Additionally, the A/C glycemic ratio was negatively associated with mortality (HR 0.76 [95% CI: 0.58-0.99]; p = 0.046 and HR 0.68 [95% CI: 0.52-0.89]; p = 0.005 for the second and third tertile, respectively). In multivariable analysis, the A/C glycemic ratio remained an independent predictor. In conclusion, in subjects hospitalized for acute HF, the A/C glycemic ratio is significantly associated with mortality, improving the ability to predict mortality compared with glucose levels at admission or average chronic glucose concentrations, especially in subjects with diabetes.

Iron deficiency contributes to resistance to endogenous erythropoietin in anaemic heart failure patients.

AIMS: Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality. METHODS AND RESULTS: We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin <100 µg/L or 100-299 µg/L with transferrin saturation <20%. EPO-resistant patients (22%) had more advanced HF whereas those with EPO deficiency (57%) were more frequently females and had worse renal function. Lower serum ferritin (indicating depleted body iron stores) was related to higher EPO observed/predicted ratio when adjusted for significant clinical confounders, including C-reactive protein. One year all-cause mortality was 28% in patients with EPO resistance compared to 17% in patients with EPO deficiency and 10% in patients with adequate EPO (log-rank test for the comparison EPO resistance vs. adequate EPO: P = 0.02). When adjusted for other prognosticators, there was still a trend towards increased 12-month mortality in patients with higher EPO level. CONCLUSION: Anaemic HF patients with endogenous EPO deficiency vs. resistance have different clinical and laboratory characteristics. In such patients, ID contributes to EPO resistance independently of inflammation.

Quality of life and disease experience in patients with heart failure with reduced ejection fraction in Spain: a mixed-methods study.

OBJECTIVES: To gather insights on the disease experience of patients with heart failure (HF) with reduced ejection fraction (HFrEF), and assess how patients' experiences and narratives related to the disease complement data collected through standardised patient-reported outcome measures (PROMs). Also, to explore new ways of evaluating the burden experienced by patients and caregivers. DESIGN: Observational, descriptive, multicentre, cross-sectional, mixed-methods study. SETTING: Secondary care, patient's homes. PARTICIPANTS: Twenty patients with HFrEF (New York Heart Association (NYHA) classification I-III) aged 38-85 years. MEASURES: PROMs EuroQoL 5D-5L (EQ-5D-5L) and Kansas City Cardiomyopathy Questionnaire and patient interview and observation. RESULTS: A total of 20 patients with HFrEF participated in the study. The patients' mean (SD) age was 72.5 (11.4) years, 65% were male and were classified inNYHA functional classes I (n=4), II (n=7) and III (n=9). The study showed a strong impact of HF in the patients' quality of life (QoL) and disease experience, as revealed by the standardised PROMs (EQ-5D-5L global index=0.64 (0.36); Kansas City Cardiomyopathy Questionnaire total symptom score=71.56 (20.55)) and the in-depth interviews. Patients and caregivers often disagreed describing and evaluating perceived QoL, as patients downplayed their limitations and caregivers overemphasised the poor QoL of the patients. Patients related current QoL to distant life experiences or to critical moments in their disease, such as hospitalisations. Anxiety over the disease progression is apparent in both patients and caregivers, suggesting that caregiver-specific tools should be developed. CONCLUSIONS: PROMs are an effective way of assessing symptoms over the most recent time period. However, especially in chronic diseases such as HFrEF, PROM scores could be complemented with additional tools to gain a better understanding of the patient's status. New PROMs designed to evaluate and compare specific points in the life of the patient could be clinically more useful to assess changes in health status.

Use of potassium-binder patiromer for up-titration of renin-angiotensin-aldosterone system inhibition therapy in a patient with chronic heart failure and reduced ejection fraction followed in a multidisciplinary integrated chronic care management programme: a case report.

BACKGROUND: Chronic heart failure (CHF) is a growing epidemic. The cornerstone of pharmacological therapy in CHF patients with reduced ejection fraction (HFrEF) is the inhibition of the renin-angiotensin-aldosterone system (RAAS). One of the adverse effects of RAAS blockade is the development of hyperkalaemia, which often limits the optimization of recommended, Class I treatments. In this context, potassium binders patiromer or sodium zirconium cyclosilicate (ZS-9) provide an opportunity to optimize the pharmacological management of these patients. CASE SUMMARY: We present a case report illustrating our real-life experience using the potassium-binder patiromer in a patient with HFrEF, in whom recurrent hyperkalaemia (up to 6.3 mmol/L with low doses of enalapril) was preventing titration of RAAS inhibition therapies. Use of patiromer allowed re-introducing ramipril (subsequently switched to sacubitril/valsartan) and eplerenone. Serum potassium levels remained normal with patiromer 16.8 g/24 h, and the patient's tolerance to patiromer was excellent. DISCUSSION: In patients with HFrEF and recurrent hyperkalaemia, optimal RAAS inhibition is often discontinued. In this context, novel potassium binders such as patiromer or ZS-9 have been shown to be effective in lowering potassium and maintaining normokalaemia, with a good safety profile and patient tolerance, all of which make them promising alternative options. Our preliminary experience suggests that patiromer may be a helpful and well-tolerated treatment option, which may aid in achieving optimal RAAS inhibition in HFrEF patients with recurrent hyperkalaemia. Registries of HFrEF patients will help better understand whether therapies such as patiromer have prognostic benefits through facilitating optimal RAAS blockade.

Real-World Epidemiology of Potassium Derangements Among Chronic Cardiovascular, Metabolic and Renal Conditions: A Population-Based Analysis.

BACKGROUND: The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin-angiotensin-aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K+) derangements among RAASI users. METHODS AND RESULTS: We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K+ levels >5.0 mEq/L and hypokalemia as K+ <3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2-77.3%). Among RAASI users, the frequency of K+ derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%). CONCLUSION: The high prevalence of K+ derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K+ derangements, and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk.

Use of intravenous iron in patients with iron deficiency and chronic heart failure: Real-world evidence.

INTRODUCTION AND OBJECTIVES: Treatment with intravenous iron in patients with heart failure (HF) and iron deficiency (ID) improves symptoms, however its impact on survival and safety is unknown. We aimed to evaluate the management of ID and anemia with intravenous iron in patients with HF and long-term safety of intravenous iron. METHODS: We evaluated anemia and ID in patients with chronic HF at 3 university hospitals. Anemia was defined using the World Health Organization definition and ID was defined as ferritin <100 ug/L or a Transferrin Saturation <20% if ferritin between 100 and 299 ug/L. We assessed treatment with intravenous iron during follow-up and its association with mortality and HF hospitalizations using multivariate cox regression analysis. RESULTS: We included 2,114 patients, median age 72 years and 57% had reduced left ventricular ejection fraction. ID was present in 55% and ID and anemia in 29%. Treatment with intravenous iron was used in 24% of patients with ID and 34% of patients with ID and anemia. In patients with ID, after multivariate adjustment, treatment with intravenous iron was associated with lower all-cause mortality: HR = 0.38 (0.28-0.56), lower cardiovascular mortality: HR = 0.34 (0.20-0.57) and no differences in HF hospitalizations: HR = 1.15 (0.88-1.50). Similar outcomes were found for patients with anemia and ID. CONCLUSIONS: In a real-world cohort of patients with HF, treatment with intravenous iron was used in one third of patients with ID and anemia and appears safe in mid-term follow-up.