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Resumen Introduccion El objetivo general del estudio fue realizar una reflexion sobre los factores clave para avanzar en modelos optimos de atencion a la Insuficiencia Cardiaca (IC) y, en concreto, sobre los elementos de macrogestion mas necesarios para el desarrollo de modelos integrales de gestion de la IC. Material y Metodos Se designo un Comite Asesor integrado por 15 expertos y un grupo multidisciplinar de 31 expertos adicional, conformando un panel Delphi de 46 expertos. A partir de una revision bibliografica narrativa y del analisis del recorrido asistencial del paciente con IC se identifico por el Comite Asesor una bateria inicial de factores clave para el desarrollo de Modelos Asistenciales de IC. Esta propuesta fue ajustada y priorizada por el panel Delphi aplicando metodologia Delphi Rand/UCLA. Resultados Tras dos rondas Delphi, se definieron 75 factores clave agrupados en 7 retos. En el primero de los retos, relacionado con el desarrollo de Modelos de Gestion de la IC, se identificaron 16 factores clave, 7 de los cuales fueron valorados como altamente prioritarios relacionados con el planteamiento de objetivos comunes, recursos para la continuidad asistencial y mejorar la medicion de resultados en salud. Conclusiones El comite de expertos de este estudio, a traves de metodologia Delphi, consensuo que el establecimiento de elementos de macrogestion es un elemento clave para poder avanzar en el desarrollo de modelos optimos de asistencia a la IC.

Background Low socioeconomic status (SES) has a negative impact in terms of outcomes and medical resource use despite open access to care in universal health-care systems in patients with heart failure (HF). Whether the breach in outcomes determined by SES inequalities can be mitigated by intensive HF management in integrate care programs is not known. Purpose To analyse the effect of SES status on health outcomes before and after a pragmatic implementation of an intensive transitional care nurse-based HF management program integrating hospital and primary care and resources for patients with HF at a high risk of events in a health-care area of 209,255 inhabitants. Methods For the purposes of this study, we included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January, the 1st, 2015 and December, the 31st of 2019. We considered 3 distinct periods of implementation of the HF programme: pre-implementation (2015–2016), transition (2017 start of implementation) and consolidation (2018–2019). To evaluate the efficacy of the programme according to SES strata, we compared outcomes between HF patients of the implementation area and HF patients of the remaining healthcare areas of Catalonia across implementation periods and stratified according to levels of SES. SES was defined based on individual annual income. Results We included 77,554 patients in the study: 3,396 in the implementation area and 74, 158 in the rest of Catalonia. Distribution of patients according to SES was: 12,018 (15.5%) high or medium SES, 61,967 (79.9%) low SES and 3,535 (4.5%) very low SES. During the period of the study death occurred in 37,469 (48.3%), clinically related hospitalisation in 41,709 (53.8%) and HF readmission in 29,755 (38.4%). Multivariate Cox proportional hazards models (Table 1) showed that low or very low SES was associated with worse outcomes compared to patients with high or medium SES. Implementation of HF programme significantly improved outcomes in patients with HF (Figure 1, left column). As shown in Figure 1 central and right columns, improvement in clinical outcomes was observed across all SES strata in patients exposed to the HF programme. The size effect for hospitalisation was more prominent among patients with medium of high SES (47% relative change) compared to patients with low or very low SES (32% relative change). Size effect for mortality did not differ between both strata (10% relative improvement in both groups). Conclusions The SES is an independent predictor of mortality, clinically related hospitalisation, and HF hospitalisation in vulnerable patients with HF. The implementation of an intensive transitional care nurse-based HF management program improve clinical outcomes across SES strata. However, the size effect in the prevention of hospitalisation is more pronounced among patients with medium or high SES. Funding Acknowledgement Type of funding sources: None.

Background In chronic cardiovascular diseases, the renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment and have revealed improvements in clinical outcomes in many clinical trials. In contrast, is well defined as non-desirable effect of RAASI the development of hyperkalemia, which could force to interrupt these treatments. Hyperkalemia has been associated with worse outcomes in observational studies. Though, it is controversial if those negative outcomes in hyperkalemic patients could be because the potassium derangement itself or the circumstance that in these individuals could be enforced to discontinue RAASI medications with prognostic consequences at mid- to long-term. Purpose Assess associations between management of RAASI and clinical outcomes among individuals with chronic cardiovascular conditions and hyperkalemia. Methods Data from more than 375,000 individuals 55 years of age or older were analyzed, in a population-based healthcare database of a public Institute of Health between 2015 and 2017. We conducted a longitudinal analysis, in which participants with at least one relevant condition were included: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalemia (serum potassium >5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. Subsequently, all-cause death and hospitalization has been assessed in the follow-up period as clinical outcomes. For the statistical analysis, we calculated unadjusted incidence rate ratios and Cox Proportional Hazards Regression models to calculate the multivariable-adjusted risk ratios for the clinical endpoints comparing both groups. Results There was found an association with mortality and hospitalization for the RAASI treatment interruption/down-titration group when compared unadjusted incidence rate ratios of each clinical endpoints to RAASI treatment unchanged patients (reference group). We presented these results in a Kaplan-Meier survivor curves for endpoint mortality (Figure 1). In the multivariable-adjusted model, the risk of mortality and hospitalization was associated mainly with older age, hypokalemia and down-titration of RAASI treatments, achieving statistical significance (Table 1). The risk ratio for mortality associated with down-titration and with hyperkalemia compared with the reference group was 1.676 (95% CI 1.54–1.82) and 1.161 (95% CI 1.07–1.26) respectively. Conclusion These results suggest that the worse outcomes in hyperkalemia individuals could be influenced more for the discontinuation of RAASI prognostic drugs then for the hyperkalemia itself. It is necessary clinical randomized trials to confirm this observational hypothesis. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma

Background/Introduction The renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment in chronic cardiovascular disorders and have shown improvements in clinical outcomes in many clinical trials. Hyperkalaemia is a well-defined non-desirable effect of RAASI that occasionally forces to interrupt these medications. That enforced RAASI discontinuation or down-titration due to hyperkalaemia may have adverse prognostic consequences. Purpose Describe the demographical, clinical and pharmacological variables associated to a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia among individuals with chronic cardiovascular conditions. Methods We used data from more than 375,000 individuals 55 years of age or older, included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. We included participants with at least one relevant condition: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalaemia (serum potassium >5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. For the statistical analysis, we used logistic regression to calculate the multivariable-adjusted odds ratios of each study variable, comparing RAASI discontinuation or down-titration group to RAASI treatment unchanged or up-titrated controls (reference group). Results In the multivariable-adjusted model, the risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia was significantly associated with the use of RAASI, very high comorbidity index, potassium derangements (both hypokalaemia and hyperkalaemia), prior hospitalizations and prior emergency visits. Among RAASI treatments, the use of Angiotensin receptor blockers (OR 2.518, 95% CI 2.317–2.735) and Angiotensin-converting enzyme inhibitors (OR 2.341, 95% CI 2.149–2.549) were associated with a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia than Aldosterone inhibitors (1.428, 95% CI 1.285–1.584). Conclusion These results suggest that vulnerable populations such as those with very high comorbidity index, potassium derangements or prior emergency visits or hospitalizations have a higher risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia. A more careful and exhaustive management of RAASI should be advised in those patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma.

Background Poor self-care behaviour is associated with a higher risk of readmission and mortality in patients with heart failure (HF). Psychosocial factors are key determinants of patient-reported outcomes (PROMs) such as health-realted quality of life (QoL). Little is known about the interplay between self-care and psychosocial factors on PROMs in HF. Purpose To describe the interaction of self-care and psycho-social factors on QoL in a real-world cohort of HF patients. Methods We conducted an observational, prospective, cohort study of 1120 consecutive patients with chronic. We used the modified European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure self-care (inverted and standardised: higher scores indicate better self-care). To assess QoL, we used Minnesota Living with Heart Failure Questionnaire (MLHFQ) (higher scores indicate worse QoL). General linear models (GLM) were constructed to explore the interaction between psychosocial factors and poor self-care (defined as EHFSCBS-9 ≤lower tertile) on adjusted MLHFQ scores. To determine the impact of self-care, multivariate linear regressions models to predict QoL were constructed stratified according to selected psycho-social determinants. All models were adjusted by age, sex and psycho-social determinants of QoL including literacy, cognitive function (Pfeiffer test), dependency (Barthel and Lawton & Brody test), social support (Duke UNC and APGAR Familyfunction), depressive symptoms (15-item Geriatric Depression Scale) and fragility (Barber test scores ≥1). Results A total of 484 patients (43%) were women, mean age was 72±11 years, and mean LVEF was 45±17%. Mean MLHFQ scores were 45±24. Mean EHFSCBS-9 scores were 69±28. There was a significant inverse correlation between EHFScBS-9 and MLHFQ scores (r=−0.158; p-value Conclusions We have shown that self-care behaviour is an independent predictor of PROMs in HF regardless the presence of important psycho-social determinants of QoL only when fragility status is taken into account. Fragility modulates the influence of self-care and QoL, including each one of its dimensions. Funding Acknowledgement Type of funding sources: None.

Background Poor self-care behaviour is associated with a higher risk in heart failure (HF). Gender is a determinant of patient-reported outcomes (PROMs) such as health-realted quality of life (QoL) in HF. Female gender is consistently associated with worse QoL. Whether gender may influence the effect of self-care on PROMS is not known. Purpose Describe the effect of self-care on QoL according to gender in a real world cohort of HF patients. Methods 1120 patients with chronic HF were analysed. We used the modified European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure self-care (inverted and standardised: higher scores indicate better self-care). To assess QoL, we used Minnesota Living with Heart Failure Questionnaire (MLHFQ) (higher scores indicate worse QoL). General linear models (GLM) were constructed to explore the interaction between gender and poor self-care (defined as EHFSCBS-9 ≤lower tertile) on adjusted MLHFQ scores. To determine the impact of global self-care and its dimensions, multivariate linear regressions models to predict QoL were constructed stratified according to gender. All models were adjusted by determinants of HF severity. Results Mean age was 72±11 years, 43% were women and mean LVEF was 45±17%. There was a significant inverse correlation between EHFScBS-9 and MLHFQ scores (r=−0.158; p-value Conclusions Self-care is an independent predictor of health-related QoL in HF, regardless of the level of disease severity. Global self-care, autonomy-based adherence and consulting behaviour were particularly associated with global QoL and emotional and social dimensions of QoL in women and men. In both genders, the effect of self-care on QoL was driven by its effect on emotional and social dimensions. Provider-based adherence did not influence QoL. Funding Acknowledgement Type of funding sources: None.

Background The efficacy of heart failure programs has been demonstrated in clinical trials but their applicability in the real-world practice setting is more controversial. Purpose This study evaluates the efficacy of a comprehensive, transitional-care nurse-based HF programme integrating hospital and primary care resources in a healthcare area covering a population of 209,255 (implementation area). Methods We designed a pragmatic, population-based evaluation of the implementation of the program conducting a natural experiment. Study periods were: pre-implementation period (years 2015 and 2016), transition period (year 2017) and consolidation of implementation period (years 2018 and 2019). For the purposes of this study, we included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January, the 1st, 2015 and December, the 31st of 2019. Efficacy of the implementation of the program was measured at two levels: first, comparing the outcomes of patients exposed to the HF program between periods of implementation taking 2015–2016 as the reference period and, second, comparing outcomes between patients of the implementation area with patients of the remaining areas of the Catalonia at each predefined period. Results We included 77,554 patients in the study: 3,396 exposed to the implementation area and 74,158 exposed to the rest of healthcare areas in Catalonia. During the period of the study, 55,886 (72.1%) patients experienced at least one major adverse event. Death occurred in 37,469 (48.3%), clinically related hospitalisation in 41,709 (53.8%) and HF readmission in 29,755 (38.4%). As shown in Table 1, multivariate Cox proportional hazards models adjusted for age, gender, previous hospitalisation, co-morbidities, socioeconomic status, and time since HF diagnosis showed there was a significant (all p-values Conclusions The implementation of multidisciplinary transitional-care nurse-based heart failure programmes integrating hospital and primary care reduce mortality and hospitalisation in vulnerable patients with heart-failure. Funding Acknowledgement Type of funding sources: None.

Background/Introduction The potential positive effect of electronic health (eHealth)-based heart failure (HF) monitoring remains uncertain, largely due to the heterogeneity of the studies published to date. A subgroup of patients in which its key role is particularly uncertain is in the “low literacy” or “computer or digital illiterate” patients mainly due to telemedicine (TM)-based strategies have been often discouraged on the basis of a foreseeable limited benefit in them. Purpose The aim of this study was to determine the effectiveness of a 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 (traditional and computer literacy) encompassed in the definition of “eHealth literacy” to the HF-patients included in the “insuficiència Cardíaca Optimitzaciό 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 event rates of primary (the occurrence of non-fatal HF event) and secondary (all-cause hospitalization, all cause death and the composite endpoint combining of allcause death or non-fatal HF events) 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, and p-value was used to compare the different curves. Results 178 patients were analysed (81 TM vs 90 UC). As far as the “traditional literacy” analyses, 65% of patients had only elementary education and the 6% had no literacy qualifications, defining the low-educated subgroup as “lower literacy” (126 patients, 71%). All the other patients were classified in the “middle or higher literacy” (52 patients, 29%) subgroup. Moreover, concerning new technological management, 128 patients (72%) referred presenting moderate to high difficulties in its handling, constituting the “lower ICT skills” subgroup. The remaining 28% (50 patients) were allocated into the “middle or higher ICT skills” subgroup due to their minor handicap in their ICT use. The beneficial effect of TM compared to UC strategy was consistent across all literacy domains (pvalue 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) (Picture 1) and those allocated to the “lower ICT skills” (p-value=0.001) (Picture 2) 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”). Funding Acknowledgement Type of funding sources: None.

Background Poor self-care behaviour is associated with a higher risk of readmission and mortality in patients with heart failure (HF). The interplay between self-care and patient-reported outcomes such as health-related quality of life (QoL) has not been fully established. Purpose To describe the association between self-care and QoL in real-world cohort of HF patients. Methods We conducted an observational, prospective, cohort study of 1120 consecutive patients with chronic HF. We used the modified European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure self-care. Scores were inverted and standardized (higher scores indicate better selfcare). To assess QoL, we used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (higher scores indicate worse QoL). Written informed consent, complete clinical and psychosocial information of patients were obtained at baseline. To determine the impact of global self-care and its dimensions (autonomy-based adherence, consulting behaviour and provider-based adherence), multivariate linear regressions models (backwards stepwise methods) to predict QoL were constructed. The multivariate parametric and non-parametric associations between EHFSCBS-9 scoresand the β estimated risk of impairment of QoL (defined as MLHFQ scores ≥ median values) were explored using General Additive Models (GAM). All models were adjusted by age, sex and prognostic factors such as LVEF, NYHA, NT-proBNP levels and recent hospitalization among other well-known determinants of HF severity. Results A total of 484 patients (43%) were women, mean age was 72±11 years, and mean LVEF was 45±17%. Mean MLHFQ scores were 45±24. Mean EHFSCBS-9 scores were 69±28. There was a significant inverse correlation between EHFScBS-9 and MLHFQ scores (r=−0.158; p-value Conclusions We have shown that self-care behaviour is an independent predictor of health related QoL in HF regardless the level of disease severity. Global self-care and consulting behaviour were particularly and significantly associated with global QoL and emotional and social dimensions of QoL. Interestingly the relationship between self-care scores and the risk of impaired global QoL was non-linear showing a “U-shape” association pointing out that patients with extreme levels of self-care were more likely to experience impairments in QoL. Funding Acknowledgement Type of funding sources: None.

Background Poor self-care is associated with a poorer outcomes in patients with heart failure (HF). Psycho-social factors are determinants of patient-reported outcomes (PROMs) such as health-realted quality of life (QoL). However, little is known about the interplay between self-care and psychosocial factors such as cognitive function on PROMs in patients with HF. Purpose Describe the effect of self-care on QoL across cognitive function and explore whether the interaction between self-care and cognitive function may account for this effect. Methods 1120 patients with chronic HF from DAMOCLES study were analyzed. We used the modified European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure self-care (inverted and standardised: higher scores indicate better self-care). To assess QoL, we used Minnesota Living with Heart Failure Questionnaire (MLHFQ) (higher scores indicate worse QoL). Cognitive function was evaluated using Mini-Mental State Examination (MMSE) and Short Portable Mental State Questionnaire (SPMSQ) Tests. Cognitive impairment was defined as abnormal age-and-literacy-adjusted scores. General linear models (GLM) were constructed to explore the interaction between cognitive function and poor self-care (defined as EHFSCBS-9 ≤lower tertile) on adjusted MLHFQ scores. To determine the impact self-care, multivariate linear regressions models to predict QoL were constructed stratified according to cognitive function. All models were adjusted by determinants of HF severity. Results Mean age was 72±11 years, 43% were women and mean LVEF was 45±17%. Lower MMSE scores (β=−0,163; p-value 3 errors in the SPMSQ indicating cognitive impairment (β=0.071; p-value = 0.023) were associated with higher scores in the MLHFQ. These associations were confirmed in multivariare linear regression models (β=0.062; p-value = 0.038). In adjusted GLM, poor global self-care (F=4.8; p-value = 0.029) was an independent predictor of higher adjusted scores in the MLHFQ. Interaction term poor self-care by cognitive impairment was significantly associated with MLHFQ scores (F=6.0; p-value=0.014; Figure 1). Multivariate linear regresion models (Table 1) stratified according the absence (panel A) or the presence (panel B) of cognitive impairment showed that cognitive function modulates the association between self-care behaviour and QoL. This effect was only seen in patients without cognitive impairment. In patients with cognitive dysfunction, self-care behaviour did not longer influence self-perceived health status in patients with HF. Conclusions Self-care behaviour is an independent predictor of PROMs in HF regardless cognitive disfunction. Cognitive function modulates 1) influence of global self-care and each one of its dimensions on emotional QoL and 2) impact of global self-care and consulting behaviour on global and social QoL. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Aims To evaluate predictors of electrical storm (ES), including chronic total occlusion in an infarct-related coronary artery (infarct-related artery CTO, IRACTO), in a cohort of patients with prior myocardial infarction (MI) and implantable cardioverter-defibrillators (ICD). Methods Multicenter observational cohort study including 643 consecutive patients with prior MI and a first ICD implanted between 2005 and 2018 at three tertiary hospitals. All the patients included in the study had undergone a diagnostic coronary angiography before ICD implantation. The variable prior ventricular arrhythmias (VA+) was positive in patients with secondary prevention ICDs and in those with at least one appropriate ICD therapy after primary prevention implantation. Results During a median follow-up of 42 months 59 patients (9%) suffered ES. The presence of at least one IRACTO not revascularized (IRACTO-NR) was associated with a significantly higher cumulative incidence of ES (14.5% vs 4.8%, p Conclusion In a cohort of patients with prior MI and ICD, IRACTO-NR is an independent predictor of ES. A new risk-prediction model allowed the identification of three categories of risk, with potentially important clinical implications.

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Worse self-care is associated with a higher risk of readmission and mortality in patients with heart failure (HF). Little is known about how the interplay between clinical and psycho-social factors may modulate self-care behaviours in these patients. The aim of our study was to identify clinical, and particularly psycho-social factors associated with worse self-care and assess their interaction inpatients with heart failure.We conducted an observational, prospective, cohort study of 1,123 consecutive patients with chronic heart failure. Self-care was assessed with the modified European Heart Failure Self-care Behavior Scale 9-item version (EHFSCBS-9), and both clinical and psycho-social profile of the patients included were also meticulously evaluated. A total of 484 patients (43%) were women, mean age was 72 years, and mean left ventricular ejection fraction was 44.5%. In multivariable analyses combining clinical and psycho-social factors, low social support (OR 3.53, 95% CI [2.13-5.86]; p-value0.001), absence of caregiver support (OR 2.16, 95% CI [1.34 -3.48]; p-value 0.001) and depressive symptoms (OR 2.40, 95% CI [1.53-3.77]; p-value0.001) were independent determinants of impaired global self-care. Advanced functional class was associated with better self-care (OR 0.43, 95%CI [0.26-0.70]; p-value 0.001). No other clinical factors remained significantly associated with self-care in these joint models. In discrimination analyses, models containing psycho-social determinants outperformed models only containing heart failure -related (clinical) variables (all p-values0.001).Impairment in self-care behaviour is strongly determined by psycho-social factors. Specifically, low social support, the lack of caregiver support and the presence of depressive symptoms are the main drivers of the risk of impairment of self-care in heart failure patients. Evaluation of self-care and self-care interventions should be complemented by a comprehensive psycho-social assessment in patients with heart failure.DAMOCLES, Definition of the neuro-hormonal Activation, Myocardial function, genOmic expressionand CLinical outcomes in hEart failure patients; NYHA, New York Heart Failure Association; GAM, Generalized Additive Model; BMI, Body Mass Index; GDS, GeriatricDepression Scale.

The general objective of the study was to reflect on the key factors to advance in optimal models of care for Heart Failure (HF) and specifically, on the macromanagement elements most necessary for the development of comprehensive HF management models.An Advisory Committee, composed of 15 experts and a multidisciplinary group of 31 additional experts, was appointed, together forming a Delphi panel of 46 experts. Based on a systematic bibliographic review and the analysis of the care course of the patient with HF, an initial battery of key factors for the development of HF care models was identified by the Advisory Committee. This proposal was adjusted and prioritized by the Delphi panel applying Delphi Rand/UCLA methodology.After two Delphi rounds, 75 key factors grouped into 7 challenges were defined. In the first of the challenges, related to the development of HF management models, 16 key factors were identified, 7 of which were valued as high priority and related to the establishment of common objectives, resources for the continuity of care and improving the measurement of health outcomes.The definition of management elements at the macro level was considered a priority to advance in the development of optimal models of assistance to HF.

Background Self-care is a crucial factor in the education of patients with heart failure (HF) and directly impacts in the progression of the disease. However, little is published about its major clinical implications as admission or mortality in patients with HF. Aims and methods The aim of the study was to analyze time to admission due to acute heart failure and mortality associated with poor self-care in patients with chronic HF. We prospectively recruited consecutive patients with stable chronic HF referred to a nurse-led HF programme. Selfcare was evaluated at baseline with the 9 item European Heart Failure Self-Care Behavior Scale. Scores were standardized and reversed from 0 (worst selfcare) to 100 (better self care). For the purpose of this study we analyzed the associations of worse self-care (defined as scores below the lower tertile of the scale) with demographic, disease-related (clinical) and psychosocial factors in all patients at baseline. Results We included 1123 patients, mean age 72±11, 639 (60%) were male, mean LVEF 45±17 and 454 (40,4%) were in NYHA class III or IV. Mean score of the 9-item ESCBE was 69±28. Score below 55 (lower tertile) defined impaired selfcare behaviour. Those patients with worse self-care had more ischaemic heart disease, more COPD, and they achieved less distance in the 6 minute walking test. Regarding psychosocial items patients in lower tertile of self-care needed a caregiver more frequently, they present more cognitive impairment, depressive symptoms and worse score in terms of health self-perception. Multivariate Cox Models showed that a score below 55 points in 9-item ESCBE was independently associated with higher readmission due to acute heart failure [HR 1.26 (1.02–1.57), p value=0.034] and with mortality [HR 1.24 CI95% (1.02–1.50), p value=0.028] Conclusion Poor self-care measured with the modified 9-item ESCBE was associated with higher risk of admission due to acute decompensation and higher risk of mortality in patients with chronic heart failure. These results highlight the importance of assessing self-care and provide measures to improve them. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Univesitario de Bellvitge

Background Reduction of readmissions in heart failure (HF) patients is a main goal of HF programmes. Establishing a discharge planning for the patient and coordinating it with primary care teams are key aspects for their success. Purpose Evaluate whether a double check discharge planning based on adding face-to-face joint weekly sessions with primary care managers to the conventional electronic communication of care plan reduces 6-month readmission and 6-month mortality. Methods We evaluated all patients discharged from hospital with HF as primary diagnosis between September 2017 and January 2019. We compared outcomes between patients discharged during Period #1 (single check; September 2017 - April 2018) and those discharged during Period #2 (double check; May 2018 - January 2019). Primary endpoint was the combined endpoint of all-cause death or all-cause hospitalization 6 months after discharge from the index hospitalization. Results The study enrolled 317 patients: 182 in Period #1 and 135 in Period #2. Mean age was 76±9 years. There was a higher proportion of patients with diabetes and COPD in Period #1, with no differences in other baseline characteristics. The combined endpoint of all cause-death and all-cause hospitalization at 6 months was significantly reduced in patients in the double check discharge planning group (27% vs. 16%, p 0.021). Conclusions In a HF programme, the addition of a double check discharge planning based on having joint weekly sessions with primary care managers on top of the conventional electronic communication of care plan reduces 6-month readmission and 6-month mortality. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Universitari de Bellvitge

Background Reduction of 30-day readmission in heart failure (HF) patients is a main goal of health-care systems. Programmes to decrease 30-day readmission have successfully reduced it but have failed to neither maintain benefit afterwards nor decrease mortality. Moreover, in many cases the price of reducing 30-day readmission is a mortality increase. Purpose Evaluate whether the impact of a fully nurse-led HF programme directed to reduce 30-day readmission and mortality extends to longer periods of time, including 90 days and 180 days after discharge. Methods We evaluated all patients discharged from hospital with HF as primary diagnosis between January 2017 and January 2019. We compared outcomes between patients discharged during Period #1 (pre-programme; Jan 2017 - Aug 2017) and those discharged during Period #2 (HF programme; Sept 2017 - Jan 2019). Primary endpoint was the combined endpoint of all-cause death or all-cause hospitalization 90 days and 180 days after discharge from the index hospitalization. Results The study enrolled 440 patients: 123 in Period #1 and 317 in Period #2. Mean age was 75±9 years. There was a higher proportion of female patients in Period #2 (38.2% vs 26.8%, p=0.025), with no differences in other baseline characteristics. The combined endpoint of all cause-death and all-cause hospitalization was significantly reduced in patients in the HF programme group, both at 90 days [OR 0.37 (0.22–0.63), p There were no differences between groups in mortality [OR 0.96 (0.18–5.00), p=0.293]. Conclusions A fully nurse-led HF programme reduces the combined endpoint of all-cause death and all-cause hospitalization both at 90 days and 180 days after an index discharge for HF. Such a decrease is driven by a reduction of CV and HF hospitalization, which are maintained over time. There were no differences between groups in mortality. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Universitari de Bellvitge

Background Efficacy of HF programmes in oldest old (octogenarians and nonagenarians) has not been fully explored. Methods We conducted a natural experiment evaluating all patients after hospitalization for heart failure as primary diagnosis between January 2017 and January 2019. We compared outcomes between patients discharged during Period #1, before the implementation of the program with patients discharged during Period #2, after the implementation of the 7-step bundle of interventions. We explored the interaction between age group ( Results The study enroled 440 patients. Mean age of the whole cohort was 75±9 years. In the oldest old subgroup (n=160), mean age was 84±3. No differences were found in baseline characteristics of patients between usual care and HF program. 30-day all-cause readmission was significantly reduced in patients in the HF programme group compared to patients in the usual care group in both age strata. In unadjusted Cox regression analyses in the oldest old group, management of patients in the HF programme was significanty associated with a reduction in the risk of the primary end-point (HR: 0.50; 95% CI [0.29–0.85]; p=0.011). Conclusions Management of patients in a nurse-led integrated care-based heart failure programme results in reduction of all-cause death or all-cause hospitalizations in oldest old patients. Event-free survival cumulative curves. Funding Acknowledgement Type of funding source: None

In recent years, several safety alerts have questioned or restricted the use of some pharmacological alternatives to allogeneic blood transfusion in established indications. In contrast, there seems to be a promotion of other alternatives, based on blood products and/or antifibrinolytic drugs, which lack a solid scientific basis. The Multidisciplinary Autotransfusion Study Group and the Anemia Working Group España convened a multidisciplinary panel of 23 experts belonging to different healthcare areas in a forum for debate to: 1) analyze the different safety alerts referred to certain transfusion alternatives; 2) study the background leading to such alternatives, the evidence supporting them, and their consequences for everyday clinical practice, and 3) issue a weighted statement on the safety of each questioned transfusion alternative, according to its clinical use. The members of the forum maintained telematics contact for the exchange of information and the distribution of tasks, and a joint meeting was held where the conclusions on each of the items examined were presented and discussed. A first version of the document was drafted, and subjected to 4 rounds of review and updating until consensus was reached (unanimously in most cases). We present the final version of the document, approved by all panel members, and hope it will be useful for our colleagues.

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711. © 2018 American Heart Association, Inc.

Antiplatelet drug resistance has been associated with thromboembolic complications in patients after coronary stent placement. It has not been well-studied in patients who have neurovascular stent-placement procedures. This study aimed to analyze the relationship between antiplatelet drug resistance and neurovascular stent-placement complications.A prospective data base of all patients treated at our institution was used to identify patients with neurovascular stent-placement procedures. During a 4.5-year period, all patients undergoing neurovascular stent placement were evaluated for aspirin and clopidogrel resistance by using the VerifyNow assay. During an observational phase, all patients received 75 mg of clopidogrel and aspirin (group A). During the intervention phase (group B), patients were given additional clopidogrel on the basis of the clopidogrel resistance assay. We assessed the development of thromboembolic complications within 30 days of the procedure in patients who were resistant-versus-nonresistant to clopidogrel.Of 96 patients who had neurovascular stent placement, 5.2% were resistant to aspirin and 36.5% were resistant to clopidogrel. Periprocedural thromboembolic complications were seen in 7 patients (7.3%). In a multivariate logistic regression model, clopidogrel resistance, higher diastolic blood pressure, and lack of statin use were significantly associated with periprocedural thromboembolic complication. There was a nonsignificant decrease in thromboembolic complications in patients whose clopidogrel dosage was tailored to the assay.In our series, clopidogrel resistance was associated with increased periprocedural thromboembolic complications from neurovascular stent-placement procedures. Targeting the clopidogrel dose to platelet inhibition assays may improve clinical outcomes and requires further study.

Las Rho GTPasas son una familia de proteínas clave en la transmisión de señales provenientes del exterior celular hacia efectores intracelulares tanto citoplasmáticos como nucleares. En los últimos año ha habido un desarrollo vertiginoso de múltiples herramientas genéticas y farmacológicas, lo que ha permitido establecer de manera mucho más precisa las funciones específicas de estas proteínas. El objetivo de la presente revisión es hacer foco en las múltiples funciones celulares reguladas por las Rho GTPasas, describiendo en detalle el mecanismo molecular involucrado. Se discute además la participación de estas proteínas en diversas enfermedades humanas haciendo énfasis en su vinculación con el cáncer. Por último, se hace una actualización detallada sobre las estrategias terapéuticas en experimentación que tienen a las Rho GTPasas como blancos moleculares.

Em conjunto com o crescente desenvolvimento da tecnologia para a produção de suínos ocorreu uma forte exploração e degradação do ambiente, razão pela qual a atividade se transformou em fonte poluidora das regiões produtoras. Buscam-se, então, alternativas que minimizem o potencial poluidor do atual sistema de produção. O trabalho proposto foi comparar o perfil de emissão de dióxido de carbono (CO2), metano (CH4) e gás sulfídrico (H2S) do manejo de dejetos suínos nas formas sólida (compostagem) e líquida (esterqueira), e avaliar a eficiência do processo de compostagem através dos parâmetros físico-químicos. O ensaio foi implantado no campo experimental da EMBRAPA Suínos e Aves, localizada no município de Concórdia, SC. Contatou-se, na compostagem, uma redução de 7 vezes na emissão de CH4, com relação à esterqueira; a emissão de CO2 representou 78,5% do carbono total mineralizado. Considerando-se que a emissão de H2S foi expressiva apenas no manejo dos dejetos na forma líquida, pode-se afirmar que o manejo dos resíduos na forma sólida é uma alternativa para a redução dos impactos ambientais pela mitigação do efeito estufa e pela redução de odores.In conjunction with the development of technologies for the production of swine meat, a strong exploration and degradation of the environment occurred and the activity became a source of pollution in the producing regions. Therefore, there is a need for alternative technologies that minimize the pollutant potential of the current system of production. The proposed work was to analyze and to compare the emission of carbon dioxide (CO2), methane (CH4) and hydrogen sulfide (H2S) between the management of swine manure in solid form (composting) and liquid manure (deep pit), and assess the efficiency of the process of composting through the physical and chemical parameters. The test was implemented in the experimental field of Embrapa Suínos e Aves, located in Concordia (SC). The results have showed that composting reduces 7 times the CH4 emission comparing to deep pit, and emission of CO2 represented 78.5% of total mineralized carbon. Considering that the emission of H2S was significant only in the management of waste in liquid form, then management of waste in solid form can reduce the environmental impacts, which tends to be beneficial in terms of mitigation of greenhouse effect and may contribute to the reduction of odors.

Synthetic diacylglycerol lactones (DAG lactones) are effective modulators of critical cellular signaling pathways downstream of the lipophilic second messenger diacylglycerol that activate a host of protein kinase C (PKC) isozymes as well as other non-kinase proteins that share with PKC similar C1 membrane-targeting domains. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study characterizes the membrane interactions and bilayer anchoring of a series of DAG lactones in which the hydrophobic moiety is a 'molecular rod', namely a rigid 4-[2-(R-phenyl)ethynyl]benzoate moiety in the acyl position. Use of assays employing chromatic biomimetic vesicles and biophysical techniques revealed that the mode of membrane anchoring of the DAG lactone derivatives was markedly affected by the presence of the hydrophobic diphenyl rod and by the size of the functional unit at the terminus of the rod. Two primary mechanisms of interaction were observed: surface binding of the DAG lactones at the lipid/water interface and deep insertion of the ligands into the alkyl core of the lipid bilayer. These membrane-insertion properties could explain the different patterns of the PKC translocation from the cytosol to membranes that is induced by the molecular-rod DAG lactones. This investigation emphasizes that the side residues of DAG lactones, rather than simply conferring hydrophobicity, profoundly influence membrane interactions, and thus may further contribute to the diversity of biological actions of these synthetic biomimetic ligands.

The success rate of endovascular therapy for iliac occlusions is often limited by failure to traverse the lesion. A single institution's experience with the use of radiofrequency-assisted recanalization of occlusions in 10 iliac arteries is described. The median length of occlusion was 43 mm (range, 14–64 mm; mean, 42 mm). Revascularization was achieved in all cases. One case was complicated by vessel perforation with no adverse sequelae after stent insertion. All patients reported symptom resolution, and no target lesion reintervention or surgery was required. The median follow-up was 42 months (range, 11–63 mo; mean, 35 mo).

Aim The aim of this study was to evaluate the benefits and safety of long-term i.v. iron therapy in iron-deficient patients with heart failure (HF). Methods and results CONFIRM-HF was a multi-centre, double-blind, placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction

Resumen Estos ultimos anos han aparecido alertas de seguridad, no siempre bien sustentadas, que cuestionan el uso de algunas alternativas farmacologicas a la transfusion de sangre alogenica y/o lo restringen en indicaciones establecidas. Asistimos tambien a la preconizacion de otras alternativas, incluyendo productos hematicos y farmacos antifibrinoliticos, sin que haya una base cientifica solida que lo justifique. Por iniciativa del Grupo de Estudios Multidisciplinares sobre Autotransfusion y del Anemia Working Group Espana se reunio a un panel multidisciplinar de 23 expertos del area de cuidados de la salud en un foro de debate para: 1) analizar las diferentes alertas de seguridad en torno a ciertas alternativas a la transfusion; 2) estudiar los antecedentes que las han propiciado, la evidencia que las sustentan y las consecuencias que conllevan para la practica clinica, y 3) emitir una valoracion argumentada de la seguridad de cada alternativa a la transfusion cuestionada, segun el uso clinico de la misma. Los integrantes del foro mantuvieron contactos por via telematica y una reunion presencial en la que presentaron y discutieron las conclusiones sobre cada uno de los elementos examinados. Se elaboro un primer documento que fue sometido a 4 rondas de revision y actualizacion hasta alcanzar un consenso, unanime en la mayoria de los casos. Presentamos la version final del documento, aprobada por todos los miembros del panel, esperando sea de utilidad para nuestros colegas.

The herpes virus thymidine kinase (HSV-tk) is a critical enzyme for the activation of anti-HSV nucleosides. However, a successful therapeutic outcome depends not only on the activity of this enzyme but also on the ability of the compound(s) to interact effectively with cellular kinases and with the target viral or cellular DNA polymerases. Herein, we describe the synthesis and study of two nucleoside analogues built on a conformationally locked bicyclo[3.1.0]hexane template designed to investigate the conformational preferences of HSV-tk for the 2'-deoxyribose ring. Intimately associated with the conformation of the 2'-deoxyribose ring is the value of the C-N torsion angle chi, which positions the nucleobase into two different domains (syn or anti). The often-conflicting sugar and nucleobase conformational parameters were studied using North and South methanocarbadeoxythymidine analogues (6 and 7), which forced HSV-tk to make a clear choice in the conformation of the substrate. The results provide new insights into the mechanism of action of this enzyme, which cannot be gleaned from a static X-ray crystal structure.

Clopidogrel is an inhibitor of platelet aggregation, indicated for the prevention of ischemic stroke and in-stent thrombosis. However, it has a number of drawbacks, including an increased risk of hemorrhage; a clinical effect that is slow in onset and irreversible; a genetically determined variability in its clinical potency; and interactions with other commonly administered drugs.

Dabigatran (Pradaxa) is a member of the relatively new class of antithrombotic drugs known as direct thrombin inhibitors (DTIs). It may supplant warfarin (Coumadin) in a number of applications as it may produce a more predictable, potent, and immediate anticoagulant effect, with fewer significant side effects and interactions, and requires less monitoring.

A consecutive case series was conducted evaluating proximal splenic artery embolization (SAE) with the AMPLATZER Vascular Plug 4 (AVP4) (St. Jude Medical, Inc, St. Paul, Minnesota) in eight patients with high-grade splenic trauma. Three proximal and five combined proximal and distal subselective coiling procedures were successfully performed. Mean time from device deployment to splenic artery occlusion was 4.5 minutes (range, 2.1–10.0 min; standard deviation, 2.8 min). There were no immediate complications. One patient developed a perisplenic abscess requiring percutaneous drainage and antibiotics. Results of this initial study show the suitability of the AVP4, with its ease of deployment without a guiding sheath and accurate placement, as a viable adjunct to nonoperative management of blunt splenic injury.

Rho GTPases are a key protein family controlling the transduction of external signals to cytoplasmatic and nuclear effectors. In the last few years, the development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rho GTPases. The aim of this review is to describe the cellular functions regulated by these proteins with focus on the molecular mechanism involved. We also address the role of Rho GTPases in the development of different human diseases such as cancer. Finally, we describe different experimental therapeutic strategies with Rho GTPases as molecular targets.