Documento de consenso y recomendaciones sobre cuidados paliativos en insuficiencia cardiaca de las Secciones de Insuficiencia Cardiaca y Cardiología Geriátrica de la Sociedad Española de Cardiología

Review[Abstract] Heart failure is a complex entity, with high morbidity and mortality. The clinical course and outcome are uncertain and difficult to predict. This document, instigated by the Heart Failure and Geriatric Cardiology Working Groups of the Spanish Society of Cardiology, addresses various aspects related to palliative care, where most cardiovascular disease will eventually converge. The document also establishes a consensus and a series of recommendations with the aim of recognizing and understanding the need to implement and progressively apply palliative care throughout the course of the disease, not only in the advanced stages, thus improving the care provided and quality of life. The purpose is to improve and adapt treatment to the needs and wishes of each patient, who must have adequate information and participate in decision-making.[Resumen] La insuficiencia cardiaca es una entidad compleja, que conlleva elevada morbilidad y mortalidad y cuyo curso y evolución son inciertos y difíciles de predecir. Este trabajo, impulsado por las Secciones de Insuficiencia Cardiaca y Cardiología Geriátrica de la Sociedad Española de Cardiología, aborda los diferentes aspectos relacionados con los cuidados paliativos en el campo de la insuficiencia cardiaca, vía final común de la mayoría de las enfermedades cardiovasculares. También establece un consenso y una serie de recomendaciones con el objetivo de reconocer y comprender la necesidad de implementar y aplicar, de modo progresivo, este tipo de cuidados a lo largo del curso de la enfermedad, y no únicamente en sus estadios avanzados, para mejorar la atención que reciben los pacientes y su calidad de vida. La finalidad es mejorar y adecuar los tratamientos a las necesidades y los deseos de cada paciente, que debe contar con información adecuada y ser partícipe de la toma de decisiones

Gender Differences in Health-Related Quality of Life in Patients with Systolic Heart Failure: Results of the VIDA Multicenter Study

Previous studies have shown that heart failure is associated with worse health-related quality of life (HRQoL). The existence of differences according to gender remains controversial. We studied 1028 consecutive outpatients with heart failure and reduced ejection fraction (HFrEF) from a multicentre cross-sectional descriptive study across Spain that assessed HRQoL using two questionnaires (KCCQ, Kansas City Cardiomyopathy Questionnaire; and EQ-5D, EuroQoL 5 dimensions). The primary objective of the study was to describe differences in HRQoL between men and women in global scores and domains of health status of patients and explore gender differences and its interactions with heart failure related factors. In adjusted analysis women had lower scores in KCCQ overall summary scores when compared to men denoting worse HRQoL (54.7 +/- 1.3 vs. 62.7 +/- 0.8,p< 0.0001), and specifically got lower score in domains of symptom frequency, symptoms burden, physical limitation, quality of life and social limitation. No differences were found in domains of symptom stability and self-efficacy. Women also had lower scores on all items of EQ-5D (EQ-5D index 0.58 +/- 0.01 vs. 0.67 +/- 0.01,p< 0.0001). Finally, we analyzed interaction between gender and different clinical determinants regarding the presence of limitations in the 5Q-5D and overall summary score of KCCQ. Interestingly, there was no statistical significance for interaction for any variable. In conclusion, women with HFrEF have worse HRQoL compared to men. These differences do not appear to be mediated by clinical or biological factors classically associated with HRQoL nor with heart failure severity

Soluble Transferrin Receptor as Iron Deficiency Biomarker: Impact on Exercise Capacity in Heart Failure Patients

The soluble transferrin receptor (sTfR) is a marker of tissue iron status, which could indicate an increased iron demand at the tissue level. The impact of sTfR levels on functional capacity and quality of life (QoL) in non-anemic heart failure (HF) patients with otherwise normal systemic iron status has not been evaluated. We conducted an observational, prospective, cohort study of 1236 patients with chronic HF. We selected patients with normal hemoglobin levels and normal systemic iron status. Tissue iron deficiency (ID) was defined as levels of sTfR > 75th percentile (1.63 mg per L). The primary endpoints were the distance walked in the 6 min walking test (6MWT) and the overall summary score (OSS) of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The final study cohort consisted of 215 patients. Overall QoL was significantly worse (51 +/- 27 vs. 39 +/- 20, p-value = 0.006, respectively), and the 6 MWT distance was significantly worse in patients with tissue ID when compared to patients without tissue ID (206 +/- 179 m vs. 314 +/- 155, p-value < 0.0001, respectively). Higher sTfR levels, indicating increased iron demand, were associated with a shorter distance in the 6 MWT (standardized beta = -0.249, p < 0.001) and a higher MLHFQ OSS (standardized fi = 0.183, p-value = 0.008). In this study, we show that in patients with normal systemic iron parameters, higher levels of sTfR are strongly associated with an impaired submaximal exercise capacity and with worse QoL

Impacto del déficit de hierro en los síntomas, capacidad funcional y calidad de vida relacionada con la salud en pacientes con insuficiencia cardiaca crónica: nuevas evidencias

A pesar de la mejoría en el tratamiento de la IC en los últimos años, muchos pacientes siguen presentando síntomas que repercuten negativamente en las actividades de la vida diaria. Las comorbilidades podrían estar jugando un papel determinante en este aspecto. La anemia es una comorbilidad frecuente en IC que se asocia con la severidad de la enfermedad y condiciona peor pronóstico. El estudio de los mecanismos por los cuales la anemia contribuye a estos resultados, nos ha guiado al descubrimiento del déficit de hierro como una comorbilidad emergente potencialmente relacionada con aspectos clínicos de la IC. En esta misma línea, la experiencia obtenida de los ensayos clínicos, nos muestra que el tratamiento con hierro endovenoso mejora síntomas, capacidad de ejercicio y calidad de vida en pacientes con IC lo que sugiere la existencia de una potencial relación entre el déficit de hierro y estos objetivos centrados en el paciente. La hipótesis de trabajo de esta tesis, se fundamenta en el impacto que ocasiona el déficit de hierro a nivel de disfunción energética en el músculo esquelético y cardiaco. Esta alteración condicionaría la intolerancia al esfuerzo y la presencia de disnea y fatiga y consecuentemente una alteración en la capacidad funcional con limitación para realizar las actividades de la vida diaria. Esta limitación funcional impacta a su vez en una peor calidad de vida relacionada con la salud. El primer trabajo, diseñado para evaluar el impacto del déficit de hierro en la calidad de vida, se realizó con pacientes de un único centro y mostró que el déficit de hierro juega un papel determinante en la calidad de vida de los pacientes con IC y que este empeoramiento es sobre todo debido a la alteración en la dimensión física. Estos hallazgos son independientes de la hemoglobina o la presencia de anemia, es decir, no son debidos al papel del hierro en la eritropoyesis. El segundo trabajo confirmó los hallazgos previos en pacientes de varios países con diferentes características culturales y ámbitos geográficos y en un amplio espectro de severidad o función ventricular desde una perspectiva multimarcador de diagnóstico del déficit de hierro. El tercer trabajo evalúa la relación entre el déficit de hierro y los síntomas que presenta el paciente, así como la capacidad de esfuerzo submáxima. Los pacientes con IC y alteración en el estado del hierro tienen una peor capacidad de ejercicio submáxima independientemente de la hemoglobina y el síntoma más frecuente referido a un nivel de ejercicio submáximo es la fatiga.Despite the improvement in the treatment of HF in recent years, many patients continue to present symptoms that have a negative impact on activities of daily living. Comorbidities may be playing a determining role in this regard. Anemia is a frequent comorbidity in HF that is associated with the severity of the disease and worse prognosis. The study of the mechanisms by which anemia contributes to these results has led us to the discovery of iron deficiency as an emerging comorbidity potentially related to clinical aspects of HF. In the same line, the experience obtained from clinical trials shows that treatment with intravenous iron improves symptoms, exercise capacity and quality of life in patients with HF, which suggests the existence of a potential relationship between iron deficiency and these patient-centered outcomes. The working hypothesis of this thesis is based on the impact of iron deficiency on the level of energy dysfunction in skeletal and cardiac muscle. This would determine the intolerance to the effort and the presence of dyspnea and fatigue and consequently would impair functional capacity with limitation to carry out the activities of the daily life. This functional limitation impacts on a poorer quality of life, The first study, designed to evaluate the impact of iron deficiency on quality of life, was performed with patients from a single center and showed that iron deficiency plays a determinant role in the quality of life of patients with HF and that this worsening is mainly due to the alteration in the physical dimension. These findings are independent of hemoglobin or the presence of anemia, wich means they are not due to the role of iron in erythropoiesis. The second study confirmed the previous findings in patients from several countries with different cultural characteristics and geographical areas and in a broad spectrum of severity or ventricular function from a multi-marker perspective of diagnosis of iron deficiency. The third paper evaluates the relationship between the iron deficiency and the symptoms presented by the patient, as well as the capacity of submaximal exercise capacity. Patients with HF and abnormal iron status had worse submaximal exercise capacity independently of hemoglobin and the most frequent symptom referred was fatigue

Impacto del déficit de hierro en los síntomas, capacidad funcional y calidad de vida relacionada con la salud en pacientes con insuficiencia cardiaca crónica : nuevas evidencias /

A pesar de la mejoría en el tratamiento de la IC en los últimos años, muchos pacientes siguen presentando síntomas que repercuten negativamente en las actividades de la vida diaria. Las comorbilidades podrían estar jugando un papel determinante en este aspecto. La anemia es una comorbilidad frecuente en IC que se asocia con la severidad de la enfermedad y condiciona peor pronóstico. El estudio de los mecanismos por los cuales la anemia contribuye a estos resultados, nos ha guiado al descubrimiento del déficit de hierro como una comorbilidad emergente potencialmente relacionada con aspectos clínicos de la IC. En esta misma línea, la experiencia obtenida de los ensayos clínicos, nos muestra que el tratamiento con hierro endovenoso mejora síntomas, capacidad de ejercicio y calidad de vida en pacientes con IC lo que sugiere la existencia de una potencial relación entre el déficit de hierro y estos objetivos centrados en el paciente. La hipótesis de trabajo de esta tesis, se fundamenta en el impacto que ocasiona el déficit de hierro a nivel de disfunción energética en el músculo esquelético y cardiaco. Esta alteración condicionaría la intolerancia al esfuerzo y la presencia de disnea y fatiga y consecuentemente una alteración en la capacidad funcional con limitación para realizar las actividades de la vida diaria. Esta limitación funcional impacta a su vez en una peor calidad de vida relacionada con la salud. El primer trabajo, diseñado para evaluar el impacto del déficit de hierro en la calidad de vida, se realizó con pacientes de un único centro y mostró que el déficit de hierro juega un papel determinante en la calidad de vida de los pacientes con IC y que este empeoramiento es sobre todo debido a la alteración en la dimensión física. Estos hallazgos son independientes de la hemoglobina o la presencia de anemia, es decir, no son debidos al papel del hierro en la eritropoyesis. El segundo trabajo confirmó los hallazgos previos en pacientes de varios países con diferentes características culturales y ámbitos geográficos y en un amplio espectro de severidad o función ventricular desde una perspectiva multimarcador de diagnóstico del déficit de hierro. El tercer trabajo evalúa la relación entre el déficit de hierro y los síntomas que presenta el paciente, así como la capacidad de esfuerzo submáxima. Los pacientes con IC y alteración en el estado del hierro tienen una peor capacidad de ejercicio submáxima independientemente de la hemoglobina y el síntoma más frecuente referido a un nivel de ejercicio submáximo es la fatiga.Despite the improvement in the treatment of HF in recent years, many patients continue to present symptoms that have a negative impact on activities of daily living. Comorbidities may be playing a determining role in this regard. Anemia is a frequent comorbidity in HF that is associated with the severity of the disease and worse prognosis. The study of the mechanisms by which anemia contributes to these results has led us to the discovery of iron deficiency as an emerging comorbidity potentially related to clinical aspects of HF. In the same line, the experience obtained from clinical trials shows that treatment with intravenous iron improves symptoms, exercise capacity and quality of life in patients with HF, which suggests the existence of a potential relationship between iron deficiency and these patient-centered outcomes. The working hypothesis of this thesis is based on the impact of iron deficiency on the level of energy dysfunction in skeletal and cardiac muscle. This would determine the intolerance to the effort and the presence of dyspnea and fatigue and consequently would impair functional capacity with limitation to carry out the activities of the daily life. This functional limitation impacts on a poorer quality of life, The first study, designed to evaluate the impact of iron deficiency on quality of life, was performed with patients from a single center and showed that iron deficiency plays a determinant role in the quality of life of patients with HF and that this worsening is mainly due to the alteration in the physical dimension. These findings are independent of hemoglobin or the presence of anemia, wich means they are not due to the role of iron in erythropoiesis. The second study confirmed the previous findings in patients from several countries with different cultural characteristics and geographical areas and in a broad spectrum of severity or ventricular function from a multi-marker perspective of diagnosis of iron deficiency. The third paper evaluates the relationship between the iron deficiency and the symptoms presented by the patient, as well as the capacity of submaximal exercise capacity. Patients with HF and abnormal iron status had worse submaximal exercise capacity independently of hemoglobin and the most frequent symptom referred was fatigue

Transitions of Care Between Acute and Chronic Heart Failure: Critical Steps in the Design of aMultidisciplinary Care Model to Prevent Recurrent Hospitalization

Pese a los avances en el tratamiento de la insuficiencia cardiaca, la mortalidad, el volumen de reingresos y sus costes sanitarios son muy elevados. Los modelos de atención a la insuficiencia cardiaca inspirados en el modelo de atención crónica, también denominados programas o unidades de insuficiencia cardiaca, han demostrado beneficios clínicos en pacientes de alto riesgo. Sin embargo, mientras que las unidades de insuficiencia cardiaca tradicionales se han centrado en los pacientes detectados en su fase ambulatoria, la presio´ n creciente de la hospitalización está desplazando el foco de interés hacia programas multidisciplinarios alrededor de las transiciones, especialmente entre las fases aguda y tras el alta. Estos nuevos modelos de atención sanitaria integrada para la insuficiencia cardiaca pivotan sus intervenciones en los momentos de transiciones, son de carácter multidisciplinario, centrados en el paciente, están diseñados para asegurar la continuidad asistencial y han demostrado una reducción de las hospitalizaciones potencialmente evitables. Componentes clave de estos modelos son la intervención precoz durante la hospitalización, planificación del alta, visita precoz y seguimiento estructurado tras el alta, planificación de transiciones avanzadas y la participación de médicos y enfermeras especializados en insuficiencia cardiaca. Es de esperar la progresiva implantación de estos modelos en nuestro entorn

Medical resource use and expenditure in patients with chronic heart failure: a population-based analysis of 88 195 patients.

AIMS: Heart failure (HF) is one of the diseases with greater healthcare expenditure. However, little is known about the cost of HF at a population level. Hence, our aim was to study the population-level distribution and predictors of healthcare expenditure in patients with HF. METHODS AND RESULTS: This was a population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on 31 December 2012 (n = 88 195). We evaluated 1-year healthcare resource use and expenditure using the Health Department (CatSalut) surveillance system that collects detailed information on healthcare usage for the entire population. Mean age was 77.4 (12) years; 55% were women. One-year mortality rate was 14%. All-cause emergency department visits and unplanned hospitalizations were required at least once in 53.4% and 30.8% of patients, respectively. During 2013, a total of €536.2 million were spent in the care of HF patients (7.1% of the total healthcare budget). The main source of expenditure was hospitalization (39% of the total) whereas outpatient care represented 20% of the total expenditure. In the general population, outpatient care and hospitalization were the main expenses. In multivariate analysis, younger age, higher presence of co-morbidities, and a recent HF or all-cause hospitalization were independently associated with higher healthcare expenditure. CONCLUSIONS: In Catalonia, a large portion of the annual healthcare budget is devoted to HF patients. Unplanned hospitalization represents the main source of healthcare-related expenditure. The knowledge of how expenditure is distributed in a non-selected HF population might allow health providers to plan the distribution of resources in patients with HF.Miguel Cainzos-Achirica was funded by a research grant frorn the Spanish Society of Cardiology

Unraveling the genetics of transformed splenic marginal zone lymphoma

The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event