Prognostic Role of Tissue Iron Deficiency Measured by sTfR Levels in Heart Failure Patients without Systemic Iron Deficiency or Anemia.

Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

Developing Cardio-Oncology Programs in the New Era: Beyond Ventricular Dysfunction Due to Cancer Treatments.

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

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 ß = -0.249, p < 0.001) and a higher MLHFQ OSS (standardized ß = 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.

Blood Differential Gene Expression in Patients with Chronic Heart Failure and Systemic Iron Deficiency: Pathways Involved in Pathophysiology and Impact on Clinical Outcomes.

BACKGROUND: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in this crosstalk are yet to be unfolded. METHODS: The present research attempts to investigate the intrinsic biological mechanisms between heart failure and iron deficiency and to identify potential prognostic biomarkers by determining the gene expression pattern in the blood of heart failure patients, using whole transcriptome and targeted TaqMan® low-density array analyses. RESULTS: We performed a stepwise cross-sectional longitudinal study in a cohort of chronic heart failure patients with and without systemic iron deficiency. First, the full transcriptome was performed in a nested case-control exploratory cohort of 7 paired patients and underscored 1128 differentially expressed transcripts according to iron status (cohort1#). Later, we analyzed the messenger RNA levels of 22 genes selected by their statistical significance and pathophysiological relevance, in a validation cohort of 71 patients (cohort 2#). Patients with systemic iron deficiency presented lower mRNA levels of mitochondrial ferritin, sirtuin-7, small integral membrane protein 20, adrenomedullin and endothelin converting enzyme-1. An intermediate mitochondrial ferritin gene expression and an intermediate or low sirtuin7 and small integral membrane protein 20 mRNA levels were associated with an increased risk of all-cause mortality and heart failure admission ((HR 2.40, 95% CI 1.04-5.50, p-value = 0.039), (HR 5.49, 95% CI 1.78-16.92, p-value = 0.003), (HR 9.51, 95% CI 2.69-33.53, p-value < 0.001), respectively). CONCLUSIONS: Patients with chronic heart failure present different patterns of blood gene expression depending on systemic iron status that affect pivotal genes involved in iron regulation, mitochondrial metabolism, endothelial function and cardiovascular physiology, and correlate with adverse clinical outcomes.

Consensus document and recommendations on palliative care in heart failure of the Heart Failure and Geriatric Cardiology Working Groups of the Spanish Society of Cardiology.

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.

A Cost-effectiveness Analysis of Ferric Carboxymaltose in Patients With Iron Deficiency and Chronic Heart Failure in Spain.

INTRODUCTION AND OBJECTIVES: Treatment with ferric carboxymaltose improves symptoms, functional capacity, and quality of life in patients with chronic heart failure and iron deficiency. The aim of this study was to assess the cost-effectiveness of ferric carboxymaltose treatment vs no treatment in these patients. METHODS: We used an economic model based on the Spanish National Health System, with a time horizon of 24 weeks. Patient characteristics and ferric carboxymaltose effectiveness (quality-adjusted life years) were taken from the Ferinject® Assessment in patients with IRon deficiency and chronic Heart Failure trial. Health care resource use and unit costs were taken either from Spanish sources, or from the above mentioned trial. RESULTS: In the base case analysis, patients treated with and without ferric carboxymaltose treatment acquired 0.335 and 0.298 quality-adjusted life years, respectively, representing a gain of 0.037 quality-adjusted life years for each treated patient. The cost per patient was €824.17 and €597.59, respectively, resulting in an additional cost of €226.58 for each treated patient. The cost of gaining 1 quality adjusted life year with ferric carboxymaltose was €6123.78. Sensitivity analyses confirmed the robustness of the model. The probability of ferric carboxymaltose being cost-effective (< €30 000 per quality-adjusted life year) and dominant (more effective and lower cost than no treatment) was 93.0% and 6.6%, respectively. CONCLUSIONS: Treatment with ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, is cost-effective in Spain.