Exhaled Acetone as a New Biomarker of Heart Failure Severity

Background: Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. Methods: Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. Results: The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 mu g/L; interquartile range [IQR], 1.69-10.45 mu g/L) than in the control group (median, 0.39 mu g/L; IQR, 0.30-0.79 mu g/L; P < .001) and higher in the ADHF group (median, 7.8 mu g/L; IQR, 3.6-15.2 mu g/L) than in the chronic HF group (median, 1.22 mu g/L; IQR, 0.68-2.19 P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). Conclusions: EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity. CHEST 2012; 142(2):457-466

Evaluation of Surgical Treatment of Congenital Heart Disease in Patients Aged Above 16 Years

Background: The increasing number of children with evolving congenital heart diseases demands greater preparation of professionals and institutions that handle them. Objective: To describe the profile of patients aged over 16 years with congenital heart disease, who have undergone surgery, and analyze the risk factors that predict hospital mortality. Methods: One thousand five hundred twenty patients (mean age 27 +/- 13 years) were operated between January 1986 and December 2010. We performed a descriptive analysis of the epidemiological profile of the study population and analyzed risk factors for hospital mortality, considering the complexity score, the year in which surgery was performed, the procedure performed or not performed by the pediatric surgeon and reoperation. Results: There was a significant increase in the number of cases from the year 2000. The average complexity score was 5.4 and the septal defects represented 45% of cases. Overall mortality was 7.7% and most procedures (973 or 61.9%) with greater complexity were performed by pediatric surgeons. Complexity (OR 1.5), reoperation (OR 2.17) and pediatric surgeon (OR 0.28) were independent risk factors influencing mortality. Multivariate analysis showed that the year in which the surgery was performed (OR 1.03), the complexity (OR 1.44) and the pediatric surgeon (OR 0.28) influenced the result. Conclusion: There is an increasing number of patients aged 16 years which, despite the large number of simple cases, the most complex ones were referred to pediatric surgeons, who had lower mortality, especially in recent years. (Arq Bras Cardiol 2012;98(5):390-397)

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Identification of Drosophila heart-specific Cis-Regulatory Modules under Hox control

Cardiac morphogenesis is a complex process governed by evolutionarily conserved transcription factors and signaling molecules. The Drosophila cardiac tube is linear, made of 52 pairs of cardiomyocytes (CMs), which express specific transcription factor genes that have human homologues implicated in Congenital Heart Diseases (CHDs) (NKX2-5, GATA4 and TBX5). The Drosophila cardiac tube is linear and composed of a rostral portion named aorta and a caudal one called heart, distinguished by morphological and functional differences controlled by Hox genes, key regulators of axial patterning. Overexpression and inactivation of the Hox gene abdominal-A (abd-A), which is expressed exclusively in the heart, revealed that abd-A controls heart identity. The aim of our work is to isolate the heart-specific cisregulatory sequences of abd-A direct target genes, the realizator genes granting heart identity. In each segment of the heart, four pairs of cardiomyocytes (CMs) express tinman (tin), homologous to NKX2-5, and acquire strong contractile and automatic rhythmic activities. By tyramide amplified FISH, we found that seven genes, encoding ion channels, pumps or transporters, are specifically expressed in the Tin-CMs of the heart. We initially used online available tools to identify their heart-specific cisregutatory modules by looking for Conserved Non-coding Sequences containing clusters of binding sites for various cardiac transcription factors, including Hox proteins. Based on these data we generated several reporter gene constructs and transgenic embryos, but none of them showed reporter gene expression in the heart. In order to identify additional abd-A target genes, we performed microarray experiments comparing the transcriptomes of aorta versus heart and identified 144 genes overexpressed in the heart. In order to find the heart-specific cis-regulatory regions of these target genes we developed a new bioinformatic approach where prediction is based on pattern matching and ordered statistics. We first retrieved Conserved Noncoding Sequences from the alignment between the D.melanogaster and D.pseudobscura genomes. We scored for combinations of conserved occurrences of ABD-A, ABD-B, TIN, PNR, dMEF2, MADS box, T-box and E-box sites and we ranked these results based on two independent strategies. On one hand we ranked the putative cis-regulatory sequences according to best scored ABD-A biding sites, on the other hand we scored according to conservation of binding sites. We integrated and ranked again the two lists obtained independently to produce a final rank. We generated nGFP reporter construct flies for in vivo validation. We identified three 1kblong heart-specific enhancers. By in vivo and in vitro experiments we are determining whether they are direct abd-A targets, demonstrating the role of a Hox gene in the realization of heart identity. The identified abd-A direct target genes may be targets also of the NKX2-5, GATA4 and/or TBX5 homologues tin, pannier and Doc genes, respectively. The identification of sequences coregulated by a Hox protein and the homologues of transcription factors causing CHDs, will provide a mean to test whether these factors function as Hox cofactors granting cardiac specificity to Hox proteins, increasing our knowledge on the molecular mechanisms underlying CHDs. Finally, it may be investigated whether these Hox targets are involved in CHDs.

Adherence to adjuvant chemotherapy and post-treatment surveillance in a large community-based cohort of patients with colon cancer

The objective of this dissertation was to determine the initiation and completion rates of adjuvant chemotherapy, its toxicity and the compliance rates of post-treatment surveillance for elderly patients with colon cancer using the linked Surveillance, Epidemiology, and End Results – Medicare database.^ The first study assessed the initiation and completion rate of 5-fluorouracil-based adjuvant chemotherapy and its relationship with patient characteristics. Of the 12,265 patients diagnosed with stage III colon adenocarcinoma in 1991-2005, 64.4% received adjuvant chemotherapy within 3-months after tumor resection and 40% of them completed the treatment. Age, marital status, and comorbidity score were significant predictors for chemotherapy initiation and completion.^ The second study estimated the incidence rate of toxicity-related endpoints among stage III colon adenocarcinoma patients treated with chemotherapy in 1991-2005. Of the 12,099 patients, 63.9% underwent chemotherapy and had volume depletion disorder (3-month cumulative incidence rate [CIR]=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Cox regression analysis confirmed such association (HR=2.76; 95% CI=2.42-3.15). The risk of ischemic heart diseases was slightly associated with chemotherapy (HR=1.08), but significantly among patients aged <75 with no comorbidity (HR=1.70). ^ The third study determined the adherence rate of follow-up cares among patients diagnosed with stage I-III colon adenocarcinoma in 2000 - June 2002. We identified 7,348 patients with a median follow-up of 59 months. The adherence rate was 83.9% for office visits, 29.4% for CEA tests, and 74.3% for colonoscopy. Overall, 25.2% met the recommended post-treatment care. Younger age at diagnosis, white race, married, advanced stage, fewer comorbidities, and chemotherapy use were significantly associated with guideline adherence.^ In conclusions, not all colon cancer patients received chemotherapy. Receiving chemotherapy was associated with increased risk of developing gastrointestinal, hematological and cardiac toxicities. Patients were more likely to comply with the schedule for office visits and colonoscopy but failed in CEA tests. ^

Nonmuscle myosin II-B is required for normal development of the mouse heart

We used targeted gene disruption in mice to ablate nonmuscle myosin heavy chain B (NMHC-B), one of the two isoforms of nonmuscle myosin II present in all vertebrate cells. Approximately 65% of the NMHC-B−/− embryos died prior to birth, and those that were born suffered from congestive heart failure and died during the first day. No abnormalities were detected in NMHC-B+/− mice. The absence of NMHC-B resulted in a significant increase in the transverse diameters of the cardiac myocytes from 7.8 ± 1.8 μm (right ventricle) and 7.8 ± 1.3 μm (left ventricle) in NMHC-B+/+ and B+/− mice to 14.7 ± 1.1 μm and 13.8 ± 2.3 μm, respectively, in NMHC-B−/− mice (in both cases, P < 0.001). The increase in size of the cardiac myocytes was seen as early as embryonic day 12.5 (4.5 ± 0.2 μm for NMHC-B+/+ and B+/− vs. 7.2 ± 0.6 μm for NMHC-B−/− mice (P < 0.01)). Six of seven NMHC-B−/− newborn mice analyzed by serial sectioning also showed structural cardiac defects, including a ventricular septal defect, an aortic root that either straddled the defect or originated from the right ventricle, and muscular obstruction to right ventricular outflow. Some of the hearts of NMHC-B−/− mice showed evidence for up-regulation of NMHC-A protein. These studies suggest that nonmuscle myosin II-B is required for normal cardiac myocyte development and that its absence results in structural defects resembling, in part, two common human congenital heart diseases, tetralogy of Fallot and double outlet right ventricle.

Trends in Socioeconomic Inequalities in Ischemic Heart Disease Mortality in Small Areas of Nine Spanish Cities from 1996 to 2007 Using Smoothed ANOVA

The aim of this study was to analyze the evolution of socioeconomic inequalities in mortality due to ischemic heart diseases (IHD) in the census tracts of nine Spanish cities between the periods 1996–2001 and 2002–2007. Among women, there are socioeconomic inequalities in IHD mortality in the first period which tended to remain stable or even increase in the second period in most of the cities. Among men, in general, no socioeconomic inequalities have been detected for this cause in either of the periods. These results highlight the importance of intra-urban inequalities in mortality due to IHD and their evolution over time.

Prevalence of systemic diseases in Brisbane general and periodontal practice patients

Background: Periodontitis has been associated with a number of systemic diseases such as atherosclerosis, coronary heart diseases, and respiratory diseases. This study aimed to determine whether there is a significant difference in the prevalence of systemic diseases (a) in patients referred for periodontal care compared to the general practice population, (b) in patients attending a public hospital and private practices, (c) in patients attending public and private periodontal practices, and (d) among patients with periodontitis of varying severity. Methods: Charts of 1000 adult patients were selected from four clinics (University of Queensland (UQ) School of Dentistry Admissions Clinic, UQ School of Dentistry Periodontics Clinic, Private Periodontal Practice, and Private General Dental Practice). The prevalence of medical conditions was evaluated using validated self-reported health questionnaires. The periodontal condition was assessed from the most recent relevant radiographs in the files. Results: Periodontal patients had a higher prevalence of systemic diseases compared to the general practice population. Public patients had a greater prevalence of systemic diseases compared to patients in private practice for both general practice and periodontal patients. In patients with advanced periodontitis, bronchitis, hepatitis and rheumatoid arthritis were most prevalent. Patients with periodontitis also took more medications and were more likely to suffer from multiple conditions compared to the general dental population. Conclusions: Patients attending public dental facilities have an increased prevalence of systemic disease compared to those attending private practices. Furthermore periodontal patients have a greater prevalence of disease compared to general practice patients. Patients with moderate or advanced periodontitis show an increase in the prevalence of some systemic diseases previously reported to be risk factors for periodontal disease.

A systematic review of trends and patterns of congenital heart disease in children in Nigeria from 1964-2015.

Background: Congenital heart diseases cause significant childhood morbidity and mortality. Several restricted studies have been conducted on the epidemiology in Nigeria. No truly nationwide data on patterns of congenital heart disease exists. Objectives: To determine the patterns of congenital heart disease in children in Nigeria and examine trends in the occurrence of individual defects across 5 decades. Method: We searched PubMed database, Google scholar, TRIP database, World Health Organisation libraries and reference lists of selected articles for studies on patterns of congenital heart disease among children in Nigeria between 1964 and 2015. Two researchers reviewed the papers independently and extracted the data. Seventeen studies were selected that included 2,953 children with congenital heart disease. Results: The commonest congenital heart diseases in Nigeria are ventricular septal defect (40.6%), patent ductus arteriosus (18.4%), atrial septal defect (11.3%) and tetralogy of Fallot (11.8%). There has been a 6% increase in the burden of VSD in every decade for the 5 decades studied and a decline in the occurrence of pulmonary stenosis. Studies conducted in Northern Nigeria demonstrated higher proportions of atrial septal defects than patent ductus arteriosus. Conclusions: Ventricular septal defects are the commonest congenital heart diseases in Nigeria with a rising burden.

Diagnóstico automático de patologías cardíacas de bloqueo

Los electrocardiogramas (ECG) registran la actividad eléctrica del corazón a través de doce señales principales denominadas derivaciones. Estas derivaciones son analizadas por expertos médicos observando aquellos segmentos de la señal eléctrica que determinan cada una de las patologías que pueden afectar al corazón. Este hecho en general, es un condicionante muy importante para el diseño de sistemas expertos de diagnóstico médico, ya que es preciso conocer, delimitar y extraer de la señal eléctrica aquellos segmentos que determinan la patología. Dar solución a estos problemas, sería fundamental para facilitar el diseño de sistemas expertos para el diagnóstico de enfermedades cardiacas. El objetivo de este trabajo es demostrar que es posible identificar patologías cardiacas analizando la señal completa de las diferentes derivaciones de los ECGs, y determinar puntos concretos que determinan la patología en lugar de segmentos de la señal. Para ello se ha utilizado una BBDD de electrocardiogramas y se ha determinado mediante un algoritmo, los puntos de la señal que determinan la patología. Se ha aplicado a la patología de bloqueos de rama y los puntos obtenidos con el algoritmo se han utilizado para el diseño de un clasificador automático basado en redes neuronales artificiales, obteniendo un coeficiente de sensibilidad del 100% y de especificad del 99.24%, demostrando su validez para el diseño de sistemas expertos de clasificación.

Protect your body, your temple : Heart Healthy Nutrition

These bookmarks state: poor diet can have bad effects on diabetes, high blood pressure and high cholesterol in African-Americans. What can you do? Eat more fruits and vegetables. Choose meat with less fat. Buy foods low in fat, salt and cholesterol. Have sugar-free drinks. Eat less. Choose less fried foods.

Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations

Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 x 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 x 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 x 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 x 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.