The Role of Anxiety in Patients With Persistent Atrial Fibrillation Undergoing Elective Cardioversion: An Observational Study.

OBJECTIVE: Anxiety is often present among patients with atrial fibrillation (AF). This condition has been associated with greater symptom severity and worse quality of life in these patients. However, the influence of anxiety on the risk of AF recurrence is not well known. We aimed to define the level of anxiety in patients with persistent AF undergoing elective cardioversion (EC) and determine whether there is an association between anxiety and the risk of early AF recurrence after EC. METHODS: Anxiety was measured before EC using the State-Trait Anxiety Inventory. Early AF recurrence was assessed with a control electrocardiogram at 30-day follow-up. RESULTS: We included 107 patients undergoing effective EC. Early AF recurrence was diagnosed in 40 patients (37.4%). Compared with those who remained in sinus rhythm, individuals with early AF recurrence had significantly higher levels of trait anxiety (23.1 [10.4] versus 17.9 [9.5]; p = .013) and larger left atrial volume index (45.8 [12.3] versus 37.9 [13.3] ml/m; p = .004). Both variables remained independently associated with early AF recurrence after multivariate analysis. A predictive model including trait anxiety score >20 and left atrial volume index >41 ml/m showed acceptable accuracy for the diagnosis of early AF recurrence (area under the curve = 0.733; 95% confidence interval = 0.634-0.832; p < .001). CONCLUSIONS: Our study shows that trait anxiety is an independent risk factor for early AF recurrence after EC. Further studies are warranted to assess the beneficial role of anxiety-reducing strategies on the outcomes of patients with AF.

Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients.

The emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include maximizing response and the use of maintenance therapy. We used whole exome sequencing to study the genetics of paired samples taken at presentation and at relapse from 56 newly diagnosed patients, following induction therapy, randomized to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomization. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterized by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumor suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response, the evolutionary features were predominantly stable with a similar mutational and structural profile seen at both time points. There were no significant differences between patients relapsing after lenalidomide maintenance versus observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse. This trial is registered at clinicaltrials.gov identifier: 01554852.

Coexistent hyperdiploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH translocations.

The acquisition of the cytogenetic abnormalities hyperdiploidy or translocations into the immunoglobulin gene loci are considered as initiating events in the pathogenesis of myeloma and were often assumed to be mutually exclusive. These lesions have clinical significance; hyperdiploidy or the presence of the t(11;14) translocation is associated with a favorable outcome, whereas t(4;14), t(14;16), and t(14;20) are unfavorable. Poor outcomes are magnified when lesions occur in association with other high-risk features, del17p and +1q. Some patients have coexistence of both good and poor prognostic lesions, and there has been no consensus on their risk status. To address this, we have investigated their clinical impact using cases in the Myeloma IX study (ISRCTN68454111) and shown that the coexistence of hyperdiploidy or t(11;14) does not abrogate the poor prognosis associated with adverse molecular lesions, including translocations. We have also used single-cell analysis to study cases with coexistent translocations and hyperdiploidy to determine how these lesions cosegregate within the clonal substructure, and we have demonstrated that hyperdiploidy may precede IGH translocation in a proportion of patients. These findings have important clinical and biological implications, as we conclude patients with coexistence of adverse lesions and hyperdiploidy should be considered high risk and treated accordingly.

Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome.

Intraclonal heterogeneity was recently described in multiple myeloma (MM), but its full impact on disease progression and relapse has not been entirely explored. The immunoglobulin type produced by myeloma cells provides an excellent marker to follow changes in clonal substructure over time. We have prospectively evaluated serial paraprotein and serum free light chain (FLC) measurements and found that 258 of 520 and 54 of 520 patients who presented with a whole paraprotein relapsed with paraprotein only (PO) and "FLC escape," respectively. The median overall survival of PO patients was longer, when compared with patients whose relapse manifested as an increase in FLC both alone and with a whole paraprotein, as a result of a significantly shorter survival from relapse of the latter groups. These observations fit a model in which 1 clone is able to produce a complete antibody, whereas the other secretes only FLC; the type of relapse represents the outgrowth of different clones, some of which are more resistant to therapy. To our knowledge, this is the largest series describing patients who have relapsed with FLC escape and highlights the importance of monitoring FLC when there is a suspicion of clinical relapse. This study was registered at www.isrctn.org as ISRCTN68454111.

Whole-exome DNA sequence analysis of Brca2- and Trp53-deficient mouse mammary gland tumours.

Germline mutations in the tumour suppressor BRCA2 predispose to breast, ovarian and a number of other human cancers. Brca2-deficient mouse models are used for preclinical studies but the pattern of genomic alterations in these tumours has not yet been described in detail. We have performed whole-exome DNA sequencing analysis of mouse mammary tumours from Blg-Cre Brca2(f/f) Trp53(f/f) animals, a model of BRCA2-deficient human cancer. We also used the sequencing data to estimate DNA copy number alterations in these tumours and identified a recurrent copy number gain in Met, which has been found amplified in other mouse mammary cancer models. Through a comparative genomic analysis, we identified several mouse Blg-Cre Brca2(f/f) Trp53(f/f) mammary tumour somatic mutations in genes that are also mutated in human cancer, but few of these genes have been found frequently mutated in human breast cancer. A more detailed analysis of these somatic mutations revealed a set of genes that are mutated in human BRCA2 mutant breast and ovarian tumours and that are also mutated in mouse Brca2-null, Trp53-null mammary tumours. Finally, a DNA deletion surrounded by microhomology signature found in human BRCA1/2-deficient cancers was not common in the genome of these mouse tumours. Although a useful model, there are some differences in the genomic landscape of tumours arising in Blg-Cre Brca2(f/f) Trp53(f/f) mice compared to human BRCA-mutated breast cancers. Therefore, this needs to be taken into account in the use of this model.

Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma.

Outcome in multiple myeloma is highly variable and a better understanding of the factors that influence disease biology is essential to understand and predict behavior in individual patients. In the present study, we analyzed combined genomewide DNA methylation and gene expression data of patients treated in the Medical Research Council Myeloma IX trial. We used these data to identify epigenetically repressed tumor suppressor genes with prognostic relevance in myeloma. We identified 195 genes with changes in methylation status that were significantly associated with prognosis. Combining DNA methylation and gene expression data led to the identification of the epigenetically regulated tumor modulating genes GPX3, RBP1, SPARC, and TGFBI. Hypermethylation of these genes was associated with significantly shorter overall survival, independent of age, International Staging System score, and adverse cytogenetics. The 4 differentially methylated and expressed genes are known to mediate important tumor suppressive functions including response to chemotherapy (TGFBI), interaction with the microenvironment (SPARC), retinoic acid signaling (RBP1), and the response to oxidative stress (GPX3), which could explain the prognostic impact of their differential methylation. Assessment of the DNA methylation status of the identified genes could contribute to the molecular characterization of myeloma, which is prerequisite for an individualized treatment approach.

Identification of cellular and genetic drivers of breast cancer heterogeneity in genetically engineered mouse tumour models.

The heterogeneous nature of mammary tumours may arise from different initiating genetic lesions occurring in distinct cells of origin. Here, we generated mice in which Brca2, Pten and p53 were depleted in either basal mammary epithelial cells or luminal oestrogen receptor (ER)-negative cells. Basal cell-origin tumours displayed similar histological phenotypes, regardless of the depleted gene. In contrast, luminal ER-negative cells gave rise to diverse phenotypes, depending on the initiating lesions, including both ER-negative and, strikingly, ER-positive invasive ductal carcinomas. Molecular profiling demonstrated that luminal ER-negative cell-origin tumours resembled a range of the molecular subtypes of human breast cancer, including basal-like, luminal B and 'normal-like'. Furthermore, a subset of these tumours resembled the 'claudin-low' tumour subtype. These findings demonstrate that not only do mammary tumour phenotypes depend on the interactions between cell of origin and driver genetic aberrations, but also multiple mammary tumour subtypes, including both ER-positive and -negative disease, can originate from a single epithelial cell type. This is a fundamental advance in our understanding of tumour aetiology.

The impact of intra-clonal heterogeneity on the treatment of multiple myeloma.

It is clear that cancers comprise a mixture of clones, a feature termed intra-clonal heterogeneity, that compete for spatial and nutritional resources in a fashion that leads to disease progression and therapy resistance. This process of competition resembles the schema proposed by Darwin to explain the origin of the species, and applying these evolutionary biology concepts to cancer has the potential to improve our treatment strategies. Multiple myeloma (MM) has a unique set of characteristics that makes it a perfect model in which to study the presence of intra-clonal heterogeneity and its impact on therapy. Novel therapies have improved the outcome of MM patients, increasing both progression-free and overall survival. Current therapy comprises an induction, consolidation and maintenance phases and it is important to consider how these components of MM therapy are affected by the presence of intra-clonal heterogeneity. In this evolutionary context therapy can be considered as a selective pressure differentially acting on the myeloma clones and impacting on their chances of survival. In this review current knowledge of intra-clonal heterogeneity, as well as its impact on the different components of MM treatment is discussed.

Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma.

We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111.

The complex genetic landscape of familial breast cancer.

Familial breast cancer represents a minor percentage of all human breast cancers. Mutations in two high susceptibility genes BRCA1 and BRCA2 explain around 25 % of familial breast cancers, while other high, moderate and low susceptibility genes explain up to 20 % more of breast cancer families. Thus, it is important to decipher the genetic architecture of families that show no mutations to improve genetic counselling. The comprehensive description of familial breast cancer using different techniques and platforms has shown to be very valuable for better patient diagnosis, tumour surveillance, and ultimately patient treatment. This review focuses on the complex landscape of pathological, protein, genetic and genomic features associated with BRCA1-, BRCA2-, and non-BRCA1/BRCA2-related cancers described up to date. Special emphasis deserves the coexistence of distinct molecular breast cancer subtypes, the development of tumour classifiers to predict BRCA1/2 mutations, and the last insights from recent whole genome sequencing studies and miRNA profiling.

Early approach to LDL-related risk after acute coronary syndrome: the OPTA project.

INTRODUCTION: Hyperlipidemia is the main underlying cause of atherosclerotic cardiovascular disease. Reducing low-density lipoprotein (LDL) cholesterol to recommended targets after an acute coronary syndrome (ACS) is of utmost importance as it is associated with a reduction of mortality and further cardiovascular events. Unfortunately, there are considerable gaps between guideline recommendations and clinical practice. In addition, the approach to treatment of this population is very heterogeneous, even in specialized cardiovascular units. Some easy-to-implement strategies may help to optimize the management of these patients. AREAS COVERED: The OPTA Project was developed to identify these gaps and to provide recommendations to improve and harmonize the management of patients with ACS, with a specific focus on lipids. EXPERT OPINION: Five areas of interest were defined: 1) evaluation of cardiovascular risk at admission, 2) development of a strategy to effectively and rapidly reduce LDL cholesterol levels, 3) determining LDL cholesterol goals (<55 mg/dL or stricter) and follow-up, 4) data collection during hospitalization, and 5) standardized discharge report. Specific recommendations are given to reduce inequalities, following the targets 'the lower, the better' and 'the earlier, the better.'

Optimal surgical timing after post-infarction ventricular septal rupture.

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a dangerous condition. Surgical VSR closure is the definitive therapy, but there is controversy regarding the surgical timing and the bridging therapy between diagnosis and intervention. The objective of this study is to analyze the ideal time of surgical repair and to establish the contribution of mechanical circulatory support (MCS) devices on the prognosis. METHODS: We designed an observational, retrospective, multicenter study, selecting all consecutive patients with post-AMI VSR between January 1, 2008 and December 31, 2018, with non-exclusion criteria. The main objective of this study was to analyze the optimal timing for surgical repair of post-AMI VSR. Secondary endpoints were to determine which factors could influence mortality in the patients of the surgical group. RESULTS: A total of 141 patients were included. We identified lower mortality rates with an odds ratio of 0.3 (0.1-0.9) in patients operated on from day 4 compared with the surgical mortality in the first 24 hours after VSR diagnosis. The use of MCS was more frequent in patients treated with surgery, particularly for intra-aortic balloon pump (IABP; 79.6% vs. 37.8%, p < 0.001), but also for veno-arterial extracorporeal membrane oxygenation (VA-ECMO; 18.2% vs. 6.4%, p = 0.134). Total mortality was 91.5% for conservative management and 52.3% with surgical repair (p < 0.001). CONCLUSIONS: In our study, we observed that the lowest mortality rates in patients with surgical repair of post-AMI VSR were observed in patients operated on from day 4 after diagnosis of VSR, compared to earlier interventions.

Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer.

The search for novel oncogenes is important because they could be the target of future specific anticancer therapies. In the present paper we report the identification of novel amplified genes in lung cancer by means of global gene expression analysis. To screen for amplicons, we aligned the gene expression data according to the position of transcripts in the human genome and searched for clusters of over-expressed genes. We found several clusters with gene over-expression, suggesting an underlying genomic amplification. FISH and microarray analysis for DNA copy number in two clusters, at chromosomes 11q12 and 13q34, confirmed the presence of amplifications spanning about 0.4 and 1 Mb for 11q12 and 13q34, respectively. Amplification at these regions each occurred at a frequency of 3%. Moreover, quantitative RT-PCR of each individual transcript within the amplicons allowed us to verify the increased in gene expression of several genes. The p120ctn and DP1 proteins, encoded by two candidate oncogenes, CTNND1 and TFDP1, at 11q12 and 13q amplicons, respectively, showed very strong immunostaining in lung tumours with gene amplification. We then focused on the 13q34 amplicon and in the TFDP1 candidate oncogene. To further determine the oncogenic properties of DP1, we searched for lung cancer cell lines carrying TFDP1 amplification. Depletion of TFDP1 expression by small interference RNA in a lung cancer cell line (HCC33) with TFDP1 amplification and protein over-expression reduced cell viability by 50%. In conclusion, we report the identification of two novel amplicons, at 13q34 and 11q12, each occurring at a frequency of 3% of non-small cell lung cancers. TFDP1, which encodes the E2F-associated transcription factor DP1 is a candidate oncogene at 13q34. The data discussed in this publication have been deposited in NCBIs Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series Accession No. GSE21168.

[#CienciaenelParlamento: the need for a parliamentary office of science and technology advice]. / #CienciaenelParlamento: la necesidad de una oficina parlamentaria de asesoramiento científico y tecnológico.

One of the aims of the citizen's initiative #CienciaenelParlamento is helping to establishing a parliamentary office of scientific and technological advice in the Spanish parliament. Said office would be in charge of fostering networking spaces between scientific knowledge and public policies and of triggering public debate between policy-makers, experts and the general public. In this article, we first review the main parliamentary mechanisms of scientific advice, with special attention to one in particular: parliamentary offices of scientific and technological advice. These offices exist in 22 parliaments worldwide, but there are none in Spain. Second, we describe the activity undertaken by #CienciaenelParlamento in its collaboration with the Congress of Deputies during the 12th Spanish Legislature. This collaboration reached its peak with a two-day networking event in November 2018 with over 200 scientists and almost 100 deputies, who all debated twelve topics of social interest and the most up-to-date scientific knowledge. Thanks to this collaboration, the Congress has taken the first steps towards officially establishing a parliamentary science advice office. Lastly, we enumerate some examples about how these parliamentary offices in other countries have contributed with other stakeholders to better public debate and processing of public policies in public health and other areas. To conclude, we at #CienciaenelParlamento believe that a parliamentary science advice office would help to enhance the science-policy ecosystem in Spain.

Reproductive history determines Erbb2 locus amplification, WNT signalling and tumour phenotype in a murine breast cancer model.

Understanding the mechanisms underlying tumour heterogeneity is key to the development of treatments that can target specific tumour subtypes. We have previously targeted CRE recombinase-dependent conditional deletion of the tumour suppressor genes Brca1, Brca2, p53 (also known as Trp53) and/or Pten to basal or luminal oestrogen receptor-negative (ER-) cells of the mouse mammary epithelium. We demonstrated that both the cell-of-origin and the tumour-initiating genetic lesions cooperate to influence mammary tumour phenotype. Here, we use a CRE-activated HER2 orthologue to specifically target HER2/ERBB2 oncogenic activity to basal or luminal ER- mammary epithelial cells and perform a detailed analysis of the tumours that develop. We find that, in contrast to our previous studies, basal epithelial cells are less sensitive to transformation by the activated NeuKI allele, with mammary epithelial tumour formation largely confined to luminal ER- cells. Histologically, most tumours that developed were classified as either adenocarcinomas of no special type or as metaplastic adenosquamous tumours. The former were typically characterized by amplification of the NeuNT/Erbb2 locus; in contrast, tumours displaying squamous metaplasia were enriched in animals that had been through at least one pregnancy and typically had lower levels of NeuNT/Erbb2 locus amplification but had activated canonical WNT signalling. Squamous changes in these tumours were associated with activation of the epidermal differentiation cluster. Thus, in this model of HER2 breast cancer, cell-of-origin, reproductive history, NeuNT/Erbb2 locus amplification and the activation of specific branches of the WNT signalling pathway all interact to drive inter-tumour heterogeneity.

Temporal trends in postinfarction ventricular septal rupture: the CIVIAM Registry.

INTRODUCTION AND OBJECTIVES: Postinfarction ventricular septal rupture is a rare but severe complication of myocardial infarction with high mortality rates. Our goal was to analyze which factors could have an impact on mortality due to this entity over the past decade, including those related to mechanical circulatory support. METHODS: The CIVIAM registry is an observational, retrospective, multicenter study carried out in Spain. We designed a comparative analysis, focused on description of in-hospital management and in-hospital and 1-year total mortality as the primary endpoints, dividing the total observation time into 2 equal temporal periods (January 2008 to June2013 and July 2013 to December 2018). RESULTS: We included 120 consecutive patients. Total mortality during this period was 61.7% at 1-year follow-up. Patients in the second period were younger. One-year mortality was significantly reduced in the second period (75.6% vs 52.7%, P=.01), and this result was confirmed after adjustment by confounding factors (OR, 0.40; 95%CI, 0.17-0.98). Surgical repair was attempted in 58.7% vs 70.3%, (P=.194), and percutaneous closure in 8.7% and 6.8%, respectively (P=.476). Heart transplant was performed in 1 vs 5 patients (2.2% vs 6.8%, P=.405). The main difference in the clinical management between the 2 periods was the greater use of venoarterial extracorporeal membrane oxygenatiom in the second half of the study period (4.4% vs 27%; P=.001). CONCLUSIONS: Postinfarction ventricular septal rupture still carries a very high mortality risk. There has been a progressive trend to increased support with venoarterial extracorporeal membrane oxygenatiom and greater access to available corrective treatments, with higher survival rates.

Initial outcomes of a multidisciplinary network for the care of patients with cardiogenic shock.

INTRODUCTION AND OBJECTIVES: Mortality remains high in cardiogenic shock (CS), especially in refractory CS involving the use of mechanical circulatory support (MCS) devices. The aim of this study was to analyze the results of a care program for patients in CS after the creation of a multidisciplinary team in our center and a regional network of hospitals in our area. METHODS: Observational and retrospective study of patients attended in this program from September 2014 to January 2019. We included patients in refractory CS who required MCS and those who, because of their age and absence of comorbidities, were candidates for advanced therapies. The primary endpoint was survival to discharge. RESULTS: A total of 130 patients were included (69 local and 61 transferred patients). The mean age was 52±15 years (72% men). The most frequent causes of CS were acute decompensated heart failure (29%), acute myocardial infarction (26%), and postcardiotomy CS (25%). MCS was used in 105 patients (81%), mostly extracorporeal membrane oxygenation (58%). Survival to discharge was 57% (74 of 130 patients). The most frequent destinations were myocardial recovery and heart transplant. Independent predictors of in-hospital mortality were SAPS II score, lactate level, acute myocardial infarction etiology, and vasoactive-inotropic score. CONCLUSIONS: The creation of multidisciplinary teams for patients with mainly refractory CS and a regional network is feasible and allows survival to discharge in more than a half of attended patients with CS.

Comprehensive characterization of the DNA amplification at 13q34 in human breast cancer reveals TFDP1 and CUL4A as likely candidate target genes.

INTRODUCTION: Breast cancer subtypes exhibit different genomic aberration patterns with a tendency for high-level amplifications in distinct chromosomal regions. These genomic aberrations may drive carcinogenesis through the upregulation of proto-oncogenes. We have characterized DNA amplification at the human chromosomal region 13q34 in breast cancer. METHODS: A set of 414 familial and sporadic breast cancer cases was studied for amplification at region 13q34 by fluorescence in situ hybridization (FISH) analysis on tissue microarrays. Defining the minimal common region of amplification in those cases with amplification at 13q34 was carried out using an array-based comparative genomic hybridization platform. We performed a quantitative real-time - polymerase chain reaction (qRT-PCR) gene expression analysis of 11 candidate genes located within the minimal common region of amplification. Protein expression levels of two of these genes (TFDP1 and CUL4A) were assessed by immunohistochemical assays on the same tissue microarrays used for FISH studies, and correlated with the expression of a panel of 33 antibodies previously analyzed. RESULTS: We have found 13q34 amplification in 4.5% of breast cancer samples, but the frequency increased to 8.1% in BRCA1-associated tumors and to 20% in basal-like tumors. Tumors with 13q34 amplification were associated with high grade, estrogen receptor negativity, and expression of EGFR, CCNE, CK5, and P-Cadherin, among other basal cell markers. We have defined a 1.83 megabases minimal common region of genomic amplification and carried out mRNA expression analyses of candidate genes located therein, identifying CUL4A and TFDP1 as the most likely target genes. Moreover, we have confirmed that tumors with 13q34 amplification significantly overexpress CUL4A and TFDP1 proteins. Tumors overexpressing either CUL4A or TFDP1 were associated with tumor proliferation and cell cycle progression markers. CONCLUSIONS: We conclude that 13q34 amplification may be of relevance in tumor progression of basal-like breast cancers by inducing overexpression of CUL4A and TFDP1, which are both important in cell cycle regulation. Alternatively, as these genes were also overexpressed in non-basal-like tumor samples, they could play a wider role in cancer development by inducing tumor proliferation.

Trends and Bibliometric Impact of Research Grants of the Spanish Society of Cardiology/Spanish Heart Foundation (2007-2012).

INTRODUCTION AND OBJECTIVES: The Spanish Society of Cardiology/Spanish Heart Foundation (SEC/FEC) annually awards grants for cardiovascular research projects. Our objective was to analyze the trend in these investments and their resulting scientific production from 2007 to 2012. METHODS: A search of the publications funded by the SEC/FEC was carried out, according to the following inclusion criteria: publication in a journal indexed in MEDLINE or EMBASE, publication date after the grant, authorship by the principal investigator of the grant, and acknowledgment of SEC/FEC funding. The impact factor and subsequent citations of the articles were analyzed (Web of Science). RESULTS: A total of 235 grants were awarded (39/y) with an allocation of €3 854 300 (€642 383/y), 37% of them to women. In all, 122 publications resulted from 88 research projects (37%) funded by the SEC/FEC. Up to October 2017, these publications had received 2258 citations in subsequent studies in the Web of Science, with a mean of 18.5 and a median of 8 citations/study. CONCLUSIONS: Despite the economic crisis, the mean number and size of the grants awarded by the SEC/FEC increased in the period analyzed. Grants were awarded on an equal opportunity basis to men and women. The bibliometric impact of the funded projects is acceptable, although efforts should be made to improve it.

Cardiologists and the Cardiology of the Future. Vision and proposals of the Spanish Society of Cardiology for the Cardiology of the 21st Century.

The Cardiology of the Future is a project of the Spanish Society of Cardiology (SEC) whose objectives are as follows: to define the action policies of the SEC; to analyze the trends and changes in the environment that will influence the practice of cardiology in Spain; to define the profile of the cardiologists needed in the future; to propose policies to achieve the objectives resulting from the identified needs; and to identify the role of the SEC in the development and implementation of these policies. This article describes the methodology and the most relevant findings of the final report of this project and the strategic lines to be developed by the SEC in the immediate future, resulting from the analysis performed.