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

Iron deficiency in chronic heart failure: case-based practical guidance

In patients with chronic heart failure, iron deficiency, even in the absence of anaemia, can aggravate the underlying disease and have a negative impact on clinical outcomes and quality of life. The 2016 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure recognize iron deficiency as a co-morbidity in chronic heart failure and recommend iron status screening in all newly diagnosed patients with chronic heart failure. Furthermore, the guidelines specifically recommend considerations of intravenous iron therapy, ferric carboxymaltose, for the treatment of iron deficiency. However, in spite of these recommendations, iron deficiency remains often overlooked and undertreated. This may be due, in part, to the lack of clinical context and practical guidance accompanying the guidelines for the treating physician. Here, we provide practical guidance complemented by a case study to assist and improve the timely diagnosis, treatment, and routine management of iron deficiency in patients with chronic heart failure

Nous reptes en la insuficiència cardíaca crònica : comorbiditats emergents i objectius centrats en el pacient /

La insuficiència cardíaca crònica (ICC) s'ha convertit en un autèntic repte per al sistemes de salut degut a la seva alta prevalença, alta mortalitat i elevats costos econòmics associats. En els pacients amb ICC de base comunitària la comorbiditat és la norma i en molts d'ells, la millora de la qualitat de vida és un objectiu d' eficàcia equiparable als objectius clàssics dels assajos clínics. La recerca moderna en aquesta síndrome ha de donar resposta terapèutica a comorbiditats emergents en la ICC com l' anèmia així com cobrir la necessitat de disposar instruments de mesura de qualitat de vida validats en aquestes poblacions. Aquesta tesi es presenta com compendi de dues publicacions. En la primera de les publicacions (A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes. Comin-Colet J et al. Journal of Cardiac Failure 2009;15[9]:727-735), davant la manca d'informació sobre la eficàcia de la correcció de l'anèmia en pacients amb ICC i síndrome d' anèmia cardio-renal es va dur a terme un estudi pilot prospectiu, controlat, paral·lel i no aleatoritzat mitjançant l'ús combinat de ferro sacarosa endovenosa i eritropoietina subcutània beta respecte no tractament en 65 pacients amb ICC i síndrome d' anèmia cardio-renal que no tenien altres opcions terapèutiques. Després d'un seguiment mig de 15 mesos, en el grup que va rebre el tractament comparat amb el grup no tractat (control) es va observar que la correcció de l'anèmia amb el tractament combinat normalitza els nivells d'hemoglobina, millora els símptomes i redueix els nivells de pèptids natriurètics i el risc d' esdeveniments cardiovasculars adversos. Davant de la necessitat de disposar d' instruments de mesura de la qualitat de vida relacionada amb la salut en pacients amb ICC del nostre entorn geogràfic i cultural, la segona de les publicacions presenta els resultats de l' estudi dut terme per tal de validar la versió espanyola del qüestionari específic de qualitat de vida Kansas City Cardiomyopathy Questionnaire (KCCQ), com a instrument de valoració objectiva centrada en el pacient (Validación de la versión española del Kansas City Cardiomyopathy Questionnaire. Comín-Colet J et al. Revista Española de Cardiologia 2011;64[1]:51-58). La validació es va dur a terme mitjançant un estudi multicèntric dut a terme en 34 centres de l'estat espanyol. L'objectiu del estudi va consistir en avaluar les propietats mètriques del KCCQ en el nostre entorn en els aspectes de factibilitat, fiabilitat (reproductibilitat), validesa i sensibilitat al canvi de la versió espanyola del KCCQ en situació de la pràctica clínica habitual. En aquest estudi es demostra que el KCCQ és un qüestionari amb unes adequades propietats mètriques, paral·leles a la de la versió original de les quals destaquen una excel·lent factibilitat, validesa i fiabilitat del constructe amb una notable capacitat de detecció del canvi de qualitat de vida del pacient al llarg de la seva evolució. En conclusió, en aquesta tesi s' aborden dos dels nous reptes davant la ICC: el maneig de l'anèmia com a mostra de comorbiditat emergent i la mesura dels objectius d' eficàcia centrats en el pacient. Amb la recerca que aquí es presenta s' estableixen les bases del tractament de la síndrome d' anèmia cardio-renal amb la combinació de ferro intravenós i eritropoietina i es qualifica el KCCQ com a un qüestionari òptim per a la avaluació de la qualitat de vida en pacients amb ICC de la nostra pràctica diària.Chronic heart failure (CHF) has become a challenge for health systems because of its high prevalence, high mortality and high economic costs. In patients with CHF, the presence of co-morbidity is the rule and improvement of quality of life is seen as a goal of efficacy comparable to the classical end-points of clinical trials. Modern research in CHF must give answers to emerging co-morbidities such as anaemia and develop and validate instruments to measure health-related quality of life (HRQoL) in these populations. This thesis is presented as a compendium of two publications. Given the lack of information available on the efficacy of correction of anaemia in patients with CHF and cardio-renal anaemia syndrome (CRAS), the first publications (A pilot evaluation of the long-term effect of combined therapy with erythropoietin and intravenous iron sucrose in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes. Comin-Colet J et al. Journal of Cardiac Failure 2009; 15 [9] :727-735), presents de results of a pilot study that was conducted with a prospective, non-randomized, parallel design to compare the combined use of subcutaneous erythropoietin and intravenous iron sucrose versus no treatment in 65 patients with CHF and CRAS. After a follow up of 15 months, correction of anaemia with the combined treatment normalized the levels of haemoglobin, improved symptoms and reduced natriuretic peptide levels and the risk of adverse cardiovascular events. Given the need for instruments for measuring HRQoL to assess patient self-reported outcomes in patients with CHF in our geographical and cultural environment, the second publication presents the results of a study carried out to validate the Spanish version of the HRQoL instrument Kansas City Cardiomyopathy Questionnaire (KCCQ), (Validation of the Spanish version of the Kansas City Cardiomyopathy Questionnaire. Comín-Colet J et al. Journal of Cardiology 2011, 64 [1]:51-58). The validation was done in a multicenter study conducted in 34 centres in Spain. The aim of this study was to evaluate the metric properties of the KCCQ in our environment in the aspects of feasibility, reliability (reproducibility), validity and sensitivity to change of the Spanish version of the KCCQ in a setting of current clinical practice. This study demonstrates that the KCCQ is a questionnaire with optimal metric properties, similar to the original version of the instrument, with an excellent feasibility, reliability and validity of the construct with a remarkable ability to detect changes in quality of life of patients throughout their evolution. In conclusion, this thesis is addressing two new challenges in CHF: the management of anaemia as an emerging co-morbidity and patient reported outcomes as a measure of efficacy in management of CHF. In this work, we define the fundamentals of the treatment of the CRAS with the combination of erythropoietin and intravenous iron and the KCCQ is qualified as an optimal instrument for evaluating the quality of life in patients with CHF in our daily practice

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness

Healthcare resources and costs associated with nonvalvular atrial fibrillation in Spain: apixaban versus acenocoumarol

Aim: Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. Methods: This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. Results: 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of euro274/patient, from the perspective of society. Conclusion: Our results suggested that apixaban is a cost-effective alternative for patients with NVAF

Performance of comprehensive risk adjustment for the prediction of in-hospital events using administrative healthcare data: The queralt indices

Background: Accurate risk adjustment is crucial for healthcare management and benchmarking. Purpose: We aimed to compare the performance of classic comorbidity functions (Charlson's and Elixhauser's), of the All Patients Refined Diagnosis Related Groups (APR-DRG), and of the Queralt Indices, a family of novel, comprehensive comorbidity indices for the prediction of key clinical outcomes in hospitalized patients. Material and Methods: We conducted an observational, retrospective cohort study using administrative healthcare data from 156,459 hospital discharges in Catalonia (Spain) during 2018. Study outcomes were in-hospital death, long hospital stay, and intensive care unit (ICU) stay. We evaluated the performance of the following indices: Charlson's and Elixhauser's functions, Queralt's Index for secondary hospital discharge diagnoses (Queralt DxS), the overall Queralt's Index, which includes pre-existing comorbidities, in-hospital complications, and principal discharge diagnosis (Queralt Dx), and the APR-DRG. Discriminative ability was evaluated using the area under the curve (AUC), and measures of goodness of fit were also computed. Subgroup analyses were conducted by principal discharge diagnosis, by age, and type of admission. Results: Queralt DxS provided relevant risk adjustment information in a larger number of patients compared to Charlson's and Elixhauser's functions, and outperformed both for the prediction of the 3 study outcomes. Queralt Dx also outperformed Charlson's and Elixhauser's indices, and yielded superior predictive ability and goodness of fit compared to APR-DRG (AUC for in-hospital death 0.95 for Queralt Dx, 0.77- 0.93 for all other indices; for ICU stay 0.84 for Queralt Dx, 0.73- 0.83 for all other indices). The performance of Queralt DxS was at least as good as that of the APR-DRG in most principal discharge diagnosis subgroups. Conclusion: Our findings suggest that risk adjustment should go beyond pre-existing comorbidities and include principal discharge diagnoses and in-hospital complications. Validation of comprehensive risk adjustment tools such as the Queralt indices in other settings is needed

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

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  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

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period

Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks

Adaptación transcultural al español del cuestionario Patient empowerment in long-term conditions

Purpose To describe the process of translation and cultural adaptation of the Patient empowerment in long-term condition to the Spanish language. Design Translation, cross-cultural adaptation, and pilot testing (cognitive debriefing) Location Primary and Hospital care. Participants Ten patients admitted to a cardiology department of a University Hospital Main measurements 1) Direct translation, 2) conciliation and synthesis of the versions by expert panel, 3) back- translation, 4) agreement on the back-translated version with the author of the original version, 5) analysis of comprehensibility through cognitive interviews. Results There were no differences between the direct-translated versions. The expert panel introduced changes in 23 out of the 47 items of the questionnaire. The author of the original version agreed with the version of the back-translation. In the cognitive interviews, patients reported high difficulty in one item and low difficulty in 4. Conclusions The Spanish version of the Patient Empowerment in long-term conditions questionnaire is semantically and conceptually equivalent to the original tool. The assessment of the psychometric properties of the Spanish version of the questionnaire will be carried out at a later stage