Clinical impact and immunological alterations in asthmatic patients allergic to grass pollen subjected to high urban pollution in Madrid.

BACKGROUND: The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic. OBJECTIVE: Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients. METHODS: During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after "in vitro" stimulation with pollen from both cities. RESULTS: The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T-CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin. CONCLUSION: Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T-CD8+ and NK cells.

Cultivating awareness of sexual and gender diversity in a midwifery curriculum.

OBJECTIVE: To explore the perspectives of student midwives, midwifery educationalists and midwifery clinicians from and connected to one University in order to identify strategies to enhance awareness of sexual and gender diversity in a pre- registration midwifery curriculum. DESIGN: A mixed method study including an online survey and a series of focus groups Setting: One University in London Participants: 47 survey respondents and 16 focus group participants Findings: Two Inductive themes were developed from the data analysis: Practising Open Mindedness and Cultivating Openness and four sub themes; Making Assumptions, Developing self- awareness, Challenge and Discomfort and Safe spaces. Participants proposed learning strategies that they thought would facilitate cultivating openness and open mindedness.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

'The rollercoaster': A qualitative study of midwifery students' experiences affecting their mental wellbeing.

OBJECTIVE: Midwifery student mental wellbeing is an important consideration for the sustainability of the profession, however it has seldom been the subject of empirical research. Previous studies of the lived experience of midwifery students have focused on the impact of transition experiences and student satisfaction, rather than specifically on mental health and students' views on support for their mental wellbeing. DESIGN: A qualitative descriptive study using semi-structured interviews. SETTING: A midwifery undergraduate programme in one university in the South of England. PARTICIPANTS: 20 BSc midwifery students. FINDINGS: Two inductive themes were developed from our analysis. The theme of 'the rollercoaster' encapsulated students' experience over the length of the course, characterised by multiple culture shocks of being in different worlds, from one clinical placement to the next, from university to clinical placement. This experience was emotionally taxing. The theme of 'being noticed, feeling connected' encapsulated midwifery students' views on what could help them enjoy their training. They wanted to be seen as individuals by at least one educator, they wanted opportunities to connect with their peers and they wanted the support available to them to be consistent. CONCLUSIONS: Listening to students' insights into the lived experience of being a midwifery student can enable midwifery educators to improve the way courses are designed and support structures are put in place. The importance of having consistent contact with peers and educators cannot be underestimated. IMPLICATIONS FOR PRACTICE: The emotional demands of midwifery training must be acknowledged. Educators should identify ways in which they can provide students with consistent individualised support and regular opportunities to meet with their peers.

Metabolic Reprogramming in the Heart and Lung in a Murine Model of Pulmonary Arterial Hypertension.

A significant glycolytic shift in the cells of the pulmonary vasculature and right ventricle during pulmonary arterial hypertension (PAH) has been recently described. Due to the late complications and devastating course of any variant of this disease, there is a great need for animal models that reproduce potential metabolic reprograming of PAH. Our objective is to study, in situ, the metabolic reprogramming in the lung and the right ventricle of a mouse model of PAH by metabolomic profiling and molecular imaging. PAH was induced by chronic hypoxia exposure plus treatment with SU5416, a vascular endothelial growth factor receptor inhibitor. Lung and right ventricle samples were analyzed by magnetic resonance spectroscopy. In vivo energy metabolism was studied by positron emission tomography. Our results show that metabolomic profiling of lung samples clearly identifies significant alterations in glycolytic pathways. We also confirmed an upregulation of glutamine metabolism and alterations in lipid metabolism. Furthermore, we identified alterations in glycine and choline metabolism in lung tissues. Metabolic reprograming was also confirmed in right ventricle samples. Lactate and alanine, endpoints of glycolytic oxidation, were found to have increased concentrations in mice with PAH. Glutamine and taurine concentrations were correlated to specific ventricle hypertrophy features. We demonstrated that most of the metabolic features that characterize human PAH were detected in a hypoxia plus SU5416 mouse model and it may become a valuable tool to test new targeting treatments of this severe disease.

An experiential model of education introduced to improve the confidence of student midwives in undertaking second stage management of the perineum (SSMP).

BACKGROUND AND OBJECTIVE: the limited availability of high quality evidence related to second stage management of the perineum (SSMP) combined with a perceived shift in UK practice towards a 'hands off' the perineum/fetal head approach are likely to have impacted significantly on student midwives' understanding of SSMP. This paper presents a classroom based educational session using low fidelity simulation, which was designed in response to student feedback and aimed to improve confidence in this skill. DESIGN: reflective teaching practice, based on evaluation of SSMP teaching. SETTING: an undergraduate midwifery programme based at an inner city university in London UK. PARTICIPANTS: student midwives. FINDINGS: the education session based on Kolb's experiential approach to learning appeared to address gaps in the previous teaching which was identified by students. The Classroom setting offered students a supportive setting in which to experiment with different SSMP approaches with a view to personalising care and without compromising safety. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: although further longitudnal research is needed, the experiential model appears to offer a low resource approach to teaching SSMP and has potential application in other countries.

Tick-host conflict: immunoglobulin E antibodies to tick proteins in patients with anaphylaxis to tick bite.

Tick-borne infectious diseases and allergies are a growing problem worldwide. Tick bite allergy has been associated with the direct effect of immunoglobulin E (IgE) response to tick salivary antigens, or secondary to the induction of allergy to red meat consumption through IgE antibodies against the carbohydrate α-Gal (Gal α 1-3Gal ß 1-(3)4GlcNAc-R). However, despite the growing burden of this pathology, the proteins associated with anaphylaxis to tick bite have not been characterized. To address this question, a comparative proteomics approach was used to characterize tick proteins producing an IgE antibody response in a healthy individual with record of tick bites, which had not resulted in any allergic reactions, and two patients with anaphylactic reactions to Rhipicephalus bursa or Hyalomma marginatum tick bites. Both patients and the healthy individual were red meat tolerant. The results supported a patient-specific IgE antibody response to tick species responsible for the anaphylaxis to tick bite. Both patients and the healthy individual serologically recognized tick proteins with and without α-Gal modifications, with proteins differentially recognized by patients but not control sera. These proteins could be used as potential antigens for diagnostics, treatment and prevention of tick bite-induced allergies.

Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion.

BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts antiapoptotic properties. We hypothesized that sphingosine-1-phosphate receptor activation with fingolimod during acute myocardial infarction (MI) inhibits apoptosis, leading to increased myocardial salvage, reduced infarct size, and mitigated left ventricular (LV) remodeling in a porcine model of ischemia/reperfusion. METHODS AND RESULTS: Ischemia/reperfusion was induced in pigs by balloon occlusion of the left anterior descending artery, followed by reperfusion. Animals randomly received fingolimod or saline (control). In short-term experiments, fingolimod treatment activated the cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways in the infarct border zone 24 hours after MI, leading to decreased cardiomyocyte apoptosis and reduced myocardial oxidative stress. These effects were abolished by specific inhibitors of both pathways, demonstrating that fingolimod-induced cardioprotection was mediated by reperfusion injury salvage kinase and survivor activating factor enhancement pathways. In long-term experiments, fingolimod significantly improved myocardial salvage, reduced infarct size, and improved systolic LV function measured by cardiac magnetic resonance 1 week and 1 month after MI. Importantly, fingolimod mitigated the development of adverse post-MI LV remodeling 1 month after MI. Specifically, fingolimod treatment led to a significant reduction in LV mass, LV dilatation, and neurohormonal activation, and it preserved LV geometry. Furthermore, fingolimod decreased interstitial fibrosis, cardiomyocyte hypertrophy, and chronic activation of Akt and extracellular receptor kinase 1/2 in the remote noninfarcted myocardium. CONCLUSIONS: Sphingosine-1-phosphate receptor activation with fingolimod during acute MI reduced infarct size via the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, improved systolic LV function, and mitigated post-MI LV remodeling. Our data strongly support a cardioprotective role for sphingosine-1-phosphate receptor activation during MI.

Labeling galectin-3 for the assessment of myocardial infarction in rats.

BACKGROUND: Galectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF). It is an established biomarker associated with extracellular matrix (ECM) turnover during myocardial remodeling. The aim of this study is to test the ability of (123)I-galectin-3 (IG3) to assess cardiac remodeling in a model of myocardial infarction (MI) using imaging techniques. METHODS: Recombinant galectin-3 was labeled with iodine-123 and in vitro binding assays were conducted to test (123)I-galectin-3 ability to bind to ECM targets. For in vivo studies, a rat model of induced-MI was used. Animals were subjected to magnetic resonance and micro-SPETC/micro-CT imaging two (2 W-MI) or four (4 W-MI) weeks after MI. Sham rats were used as controls. Pharmacokinetic, biodistribution, and histological studies were also performed after intravenous administration of IG3. RESULTS: In vitro studies revealed that IG3 shows higher binding affinity (measured as counts per minute, cpm) (p < 0.05) to laminin (2.45 ± 1.67 cpm), fibronectin (4.72 ± 1.95 cpm), and collagen type I (1.88 ± 0.53 cpm) compared to bovine serum albumin (BSA) (0.88 ± 0.31 cpm). Myocardial quantitative IG3 uptake (%ID/g) was higher (p < 0.01) in the infarct of 2 W-MI rats (0.15 ± 0.04%) compared to control (0.05 ± 0.03%). IG3 infarct uptake correlates with the extent of scar (r s = 1, p = 0.017). Total collagen deposition in the infarct (percentage area) was higher (p < 0.0001) at 2 W-MI (24.2 ± 5.1%) and 4 W-MI (30.4 ± 7.5%) compared to control (1.9 ± 1.1%). However, thick collagen content in the infarct (square micrometer stained) was higher at 4 W-MI (20.5 ± 11.2 µm(2)) compared to control (4.7 ± 2.0 µm(2), p < 0.001) and 2 W-MI (10.6 ± 5.1 µm(2), p < 0.05). CONCLUSIONS: This study shows, although preliminary, enough data to consider IG3 as a potential contrast agent for imaging of myocardial interstitial changes in rats after MI. Labeling strategies need to be sought to improve in vivo IG3 imaging, and if proven, galectin-3 might be used as an imaging tool for the assessment and treatment of MI patients.

Comparison of echocardiographic measurements of left ventricular volumes to full volume magnetic resonance imaging in normal and diseased rats.

BACKGROUND: Clinical two-dimensional (2D) and clinical three-dimensional echocardiography are validated against cardiac magnetic resonance imaging (CMR), the gold standard for left ventricular (LV) volume measurement. In rodents, there is no widely accepted echocardiographic measure of whole LV volumes, and CMR measurements vary among studies. The aim of this study was to compare LV volumes by 2D echocardiography (using a hemisphere-cylinder [HC] model) with HC and full-volume (FV) CMR in normal and diseased rats to measure the impact of geometric models and imaging modalities. METHODS: Rats (n = 27) underwent ascending aortic banding, myocardial infarction induction by either permanent left anterior descending coronary artery ligation or ischemia-reperfusion, and sham thoracotomy. Subsequently, end-diastolic volume, end-systolic volume, and ejection fraction were measured using an HC 2D echocardiographic model combining parasternal short-axis and long-axis measurements, and these were compared with HC and FV CMR. RESULTS: Diseased groups showed LV dilatation and dysfunction. HC echocardiographic and FV CMR measures of end-diastolic volume, end-systolic volume, and ejection fraction were correlated. On Bland-Altman plots, end-diastolic volumes were concordant between both methods, while HC echocardiography underestimated end-systolic volumes, resulting in a modest overestimation of ejection fractions compared with FV CMR. Other 2D echocardiographic geometric models offered less concordance with FV CMR than HC. HC CMR overestimated LV volumes compared with FV CMR, while HC echocardiography underestimated HC CMR volumes. Echocardiography underestimated corresponding LV dimensions by CMR, particularly short axis. CONCLUSIONS: Concordant measures of LV volume and function were obtained using (1) a relatively simple HC model of the left ventricle inclusive of two orthogonal 2D echocardiographic planes and (2) FV CMR in normal and diseased rats. The HC model appeared to compensate for the underestimation of LV dimensions by echocardiography.

Stem cell factor gene transfer promotes cardiac repair after myocardial infarction via in situ recruitment and expansion of c-kit+ cells.

RATIONALE: There is growing evidence that the myocardium responds to injury by recruiting c-kit(+) cardiac progenitor cells to the damage tissue. Even though the ability of exogenously introducing c-kit(+) cells to injured myocardium has been established, the capability of recruiting these cells through modulation of local signaling pathways by gene transfer has not been tested. OBJECTIVE: To determine whether stem cell factor gene transfer mediates cardiac regeneration in a rat myocardial infarction model, through survival and recruitment of c-kit(+) progenitors and cell-cycle activation in cardiomyocytes, and explore the mechanisms involved. METHODS AND RESULTS: Infarct size, cardiac function, cardiac progenitor cells recruitment, fibrosis, and cardiomyocyte cell-cycle activation were measured at different time points in controls (n=10) and upon stem cell factor gene transfer (n=13) after myocardial infarction. We found a regenerative response because of stem cell factor overexpression characterized by an enhancement in cardiac hemodynamic function: an improvement in survival; a reduction in fibrosis, infarct size and apoptosis; an increase in cardiac c-kit(+) progenitor cells recruitment to the injured area; an increase in cardiomyocyte cell-cycle activation; and Wnt/ß-catenin pathway induction. CONCLUSIONS: Stem cell factor gene transfer induces c-kit(+) stem/progenitor cell expansion in situ and cardiomyocyte proliferation, which may represent a new therapeutic strategy to reverse adverse remodeling after myocardial infarction.

In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

OBJECTIVES: The goal of this study was to use noninvasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo. BACKGROUND: Collagen is an essential constituent of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help detect and better characterize AAAs and initiate intervention. METHODS: We used an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and transforming growth factor-ß neutralization results in AAA formation with incidence of aortic rupture. High-resolution, multisequence MRI was performed to characterize the temporal progression of an AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy. RESULTS: High-resolution, multisequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significantly higher magnetic resonance signal enhancement in the aneurysmal wall compared with nonspecific micelles. Histological studies revealed the presence of collagen in regions of magnetic resonance signal enhancement, and confocal microscopy proved the precise co-localization of CNA-35 micelles with type I collagen. In addition, in a proof-of-concept experiment, we reported the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress or rupture. CONCLUSIONS: High-resolution, multisequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.

Association of the peroxisome proliferator-activated receptor α gene L162V polymorphism with stage C heart failure.

OBJECTIVE: To analyze whether genetic variants of PPARA are associated with the development of stage C heart failure. METHODS: We analyzed the distribution of the rs1800206, rs4253778 and rs135551 polymorphisms in genomic DNA extracted from peripheral blood cells of 534 patients in different heart failure stages and 63 healthy individuals. The mRNA expression of the peroxisome proliferator-activated receptor (PPAR)α target genes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was measured in myocardial biopsies of a subgroup of stage B and C patients. Functional studies were performed in HL-1 cardiomyocytes. RESULTS: The V162 allele of the rs1800206 polymorphism was more frequent in stage C patients than in stage A and B patients and healthy individuals. Patients with the V162 allele exhibited decreased myocardial LCHAD and MCAD mRNA expression as compared to L162 homozygote patients. In addition, stage C patients exhibited lower myocardial LCHAD and MCAD mRNA expression than stage B patients. Cardiomyocytes transfected with the V162 allele presented decreased PPARα transcriptional activity, LCHAD mRNA expression and ATP production compared to cardiomyocytes transfected with the L162 variant. CONCLUSIONS: These findings suggest that the V162 allele of the human PPARA gene can be a new risk factor in the development of stage C heart failure, likely via depressed cardiac PPARα activity.

Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexin A5.

AIMS: Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. METHODS AND RESULTS: AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) >10% and an increase in LV ejection fraction (LVEF) >10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non-responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. CONCLUSION: CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease.

Cardiovascular translational medicine (III). Genomics and proteomics in heart failure research.

Heart failure is a complex syndrome and is one of the main causes of morbidity and mortality in developed countries. Despite considerable research effort in recent years, heart failure prevention and treatment strategies still suffer significant limitations. New theoretical and technical approaches are, therefore, required. It is in this context that the "omic" sciences have a role to play in heart failure. The incorporation of "omic" methodologies into the study of human disease has substantially changed biological approaches to disease and has given an enormous impetus to the search for new disease mechanisms, as well as for novel biomarkers and therapeutic targets. The application of genomics, proteomics and metabonomics to heart failure research could increase our understanding of the origin and development of the different processes contributing to this syndrome, thereby enabling the establishment of specific diagnostic profiles and therapeutic templates that could help improve the poor prognosis associated with heart failure. This brief review contains a short description of the fundamental principles of the "omic" sciences and an evaluation of how these new techniques are currently contributing to research into human heart failure. The focus is mainly on the analysis of gene expression microarrays in the field of genomics and on studies using two-dimensional electrophoresis with mass spectrometry in the area of proteomics.

La genómica y la proteómica en la investigación de lainsuficiencia cardiaca / Genomics and Proteomics in Heart Failure Research

La insuficiencia cardiaca es un síndrome complejo yuna de las principales causas de morbilidad y mortalidaden los países occidentales. A pesar del enorme esfuerzorealizado en los últimos años, todavía existen importanteslimitaciones en la prevención y el tratamiento de la insuficienciacardiaca, por lo que se impone un nuevo enfoqueconceptual y práctico. En este contexto se inscribela aplicación de las ciencias ®ómicas» a la insuficienciacardiaca. La incorporación de la metodología ®ómica»al estudio de las enfermedades humanas ha modificadosustancialmente el enfoque biológico y ha estimuladoenormemente la investigación de nuevos mecanismos,así como de biomarcadores y dianas terapeúticas. Laaplicación de la genómica, la proteómica y la metabonómicaal estudio de la insuficiencia cardiaca puede facilitarla comprensión del origen y el desarrollo de las distintasentidades que configuran dicho síndrome, con lo que sepropiciaría el establecimiento de perfiles diagnósticos ypatrones terapéuticos diferenciales que pueden mejorarel mal pronóstico que la insuficiencia cardiaca conlleva.En esta breve revisión se definen brevemente aspectosbásicos sobre las ciencias ®ómicas» y se evalúa el estadoactual de la aplicación de estas nuevas tecnologías ala investigación de la insuficiencia cardiaca humana, centrándoseprincipalmente en los análisis de microarrays deexpresión génica en el campo de la genómica y los estudiosde electroforesis bidimensional acoplada a espectrometríade masas en el ámbito de la proteómica (AU)

Heart failure is a complex syndrome and is one of themain causes of morbidity and mortality in developedcountries. Despite considerable research effort in recentyears, heart failure prevention and treatment strategies stillsuffer significant limitations. New theoretical and technicalapproaches are, therefore, required. It is in this contextthat the ®omic» sciences have a role to play in heart failure.The incorporation of ®omic» methodologies into the studyof human disease has substantially changed biologicalapproaches to disease and has given an enormous impetusto the search for new disease mechanisms, as well as fornovel biomarkers and therapeutic targets. The applicationof genomics, proteomics and metabonomics to heart failureresearch could increase our understanding of the originand development of the different processes contributingto this syndrome, thereby enabling the establishment ofspecific diagnostic profiles and therapeutic templates thatcould help improve the poor prognosis associated withheart failure. This brief review contains a short descriptionof the fundamental principles of the ®omic» sciences andan evaluation of how these new techniques are currentlycontributing to research into human heart failure. The focusis mainly on the analysis of gene expression microarrays inthe field of genomics and on studies using two-dimensionalelectrophoresis with mass spectrometry in the area ofproteomics (AU)