Orientador: Fernanda Aparecida Cintra, Maria Cecilia Jayme Bueno Gallani / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T18:54:11Z (GMT). No. of bitstreams: 1 Saccomann_IzabelCristinaRibeirodaSilva_M.pdf: 1268829 bytes, checksum: f4a044fe5f528f3bc98a4da6155b095b (MD5) Previous issue date: 2005 / Resumo: A Insuficiência Cardíaca (IC) traz implicações na qualidade de vida (QV); nos idosos, a sua incidência e prevalência mostram-se elevadas. Recentes estudos têm sido desenvolvidos para identificar os determinantes de QV, buscando avaliar as mudanças no estilo de vida imposto pela própria doença. Dentre os instrumentos genéricos, o mais utilizado em nosso país é o The Medical Study 36-item Short-Form Health Survey (SF-36). Com respeito aos específicos, o Minnesota Living with Heart Failure (LHFQ) corresponde ao instrumento mais reconhecido para a IC, entretanto ele não contempla as especificidades dos idosos. Este estudo teve como objetivo verificar se o instrumento LHFQ apresenta propriedades psicométricas satisfatórias, na sua aplicação em idosos com IC. Trata-se de uma investigação de natureza metodológica. Os dados foram coletados junto a 170 idosos portadores de IC, em seguimento ambulatorial, por meio da aplicação de três instrumentos: 1. questionário para a caracterização dos sujeitos; 2. LHFQ; e, 3. SF-36. Os dados foram submetidos à análise estatística descritiva, de confiabilidade por meio do alfa de Cronbach, de Análise de Variância (ANOVA nos Ranks) e de correlação por meio do coeficiente de correlação de Spearman. A consistência interna do LHFQ foi elevada, indicando confiabilidade satisfatória (a >0,80). O LHFQ discriminou entre os três grupos de classificação funcional da New York Heart Association (NYHA), Classe Funcional I, II e III/IV (p < 0,0001), exceto a dimensão emocional que discriminou entre as Classes Funcionais I e III/IV (p < 0,0034). A validade convergente demonstrou correlação de moderada a forte magnitude com o SF-36, especialmente nas dimensões relacionadas às limitações físicas (r > 0,50; p< 0,001), entretanto, demonstrou ausência de validade divergente. O LHFQ apresentou itens não respondidos nas questões referentes ao trabalho e à atividade sexual, e mostrou efeito teto em suas dimensões. Esse instrumento revelou ser uma medida confiável e válida para avaliar as dimensões que afetam a QV dos idosos, embora contemple alguns itens não respondidos pela amostra estudada. Recomenda-se considerar com cautela a aplicabilidade desse instrumento, com respeito às questões que não se aplicam à idade avançada, pelas características inerentes à essa faixa etária / Abstract: The Heart Failure (HF) brings consequences to the quality of life (QOL); in the elderly its incidence and prevalence are very high. Recent studies have been developed to identify the quality of life determinants, trying to evaluate the changes in the life style imposed by the disease itself. The instruments that evaluate the quality of life focus on subjective aspects in different domains, like the physical, the emotional and the cognitive functioning. Among the generic instruments, the most used in our country is The Medical Study 36-item Short Form Health Survey (SF-36). Among the specific ones, The Minnesota Living With Heart Failure (LHFQ) corresponds to the most recognized instrument for HF despite not analyzing the elderly specificities. This study¿s objective was to check if the LHFQ instrument presents satisfactory psychometric properties in the elderly with HF. It is a methodological investigation, with a sample of 170 elderly people bearing HF, clinic outpatients. Data were collected through three instruments: 1. a questionnaire to characterize the subjects; 2. LHFQ and 3. SF-36. In the analysis, central trends (mean, standard deviation and median), frequency distribution, Cronbach's alpha, ANOVA in the ranks and Spearman correlation coefficients calculus were carried out. The LHFQ internal consistency was high, indicating satisfactory reliability (a >0,80). The LHFQ discriminated among the New York Heart Association (NYHA) class I, II and III/IV (p < 0,0001), except the emotional dimension that discriminated among NYHA class I and III/IV (p < 0,0034). The convergent validity has demonstrated moderate to strong magnitude correlation with the SF-36, specially in the dimensions related to the physical limitations (r> 0,50; p < 0,001), however it has showed absence of discriminative validity. The LHFQ presented items which were not answered in questions referring to work and sexual activity as well as ceiling effect in its dimensions. The LHFQ has proved to be a valid and reliable measure to evaluate the dimensions that affect the elderly quality of life although it analyses some items that were not answered by the population in this study. It is recommended that this instrument applicability be carefully considered in relation to the questions that do not apply to advanced age due to specific characteristics, inherent to this age range / Mestrado / Enfermagem e Trabalho / Mestre em Enfermagem

Orientador: Kleber Gomes Franchini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T01:54:36Z (GMT). No. of bitstreams: 1 Ribeiro_GustavoCaladodeAguiar_D.pdf: 2448805 bytes, checksum: 884ae49c4ce46337410548bb393439fa (MD5) Previous issue date: 2006 / Resumo: A insuficiência cardíaca é um dos maiores problemas de saúde publica da atualidade. Esforços têm sido feitos para a obtenção do entendimento dos mecanismos que resultam no comprometimento funcional e estrutural do miocárdio, responsáveis, em última instância, pela síndrome clínica. A doença isquêmica resulta em infarto do miocárdio e hipertrofia excêntrica das câmaras ventriculares que têm papel central no estabelecimento e evolução das alterações estruturais que acompanham a deterioração funcional do miocárdio e, por conseguinte, a da função global das câmaras cardíacas. No presente estudo foram avaliados pacientes portadores de insuficiência cardíaca decorrente de infarto do miocárdio e apresentando acinesia na parede anterior com indicação clínica de tratamento cirúrgico, com o objetivo de avaliar alterações estruturais e funcionais do miocárdio. Os pacientes foram avaliados clinicamente, por ecocardiografia e ressonância magnética no período pré-operatório e clínica e ecocardiograficamente em seguimento de 2 anos após a cirurgia. Foram realizadas biópsias intra-operatórias do endocárdio ventricular para avaliação de área de fibrose. A percentagem da área de fibrose encontrada na biópsia foi comparada com a percentagem de fibrose encontrada na ressonância magnética e comparada com a evolução. Os pacientes foram divididos de acordo com os territórios vasculares do miocárdio infartados e comparados na evolução. Os pacientes apresentavam sintomas importantes de insuficiência cardíaca (CF III-IV) no pré-operatório de cirurgia para correção da geometria do ventrículo esquerdo. A média da fração de ejeção era de 35,6% e o volume sistólico final do ventrículo esquerdo era de 150,6 ml. Foram verificadas reduções dos sintomas de insuficiência cardíaca (NYHA) no período de seguimento pós-operatório ( de 3,7± 0,4 para 1,53± 0,6, p<0,001) e melhora da fração de ejeção (de 35,5± 5,4 para 47,3± 7,3, p<0,001). Houve também redução do remodelamento no período de seguimento pós-operatório (de 150,6 ± 52,8 ml para 91,92± 32,7 ml, p<0,001). Houve correlação inversa entre o volume sistólico final do ventrículo esquerdo e as frações de ejeções do pré (r= -0,6) e pós-operatório (r=-0,88). Houve uma correlação positiva entre o percentual da área de fibrose tanto com o volume sistólico final (r=0,67) e correlação inversa com a fração de ejeção do ventrículo esquerdo (r=-0,78). Pacientes com menor percentual da área de fibrose do ventrículo esquerdo evoluíram com menor número de eventos cardiovasculares (p<0,001), assim como pacientes com menor volumes sistólico (p=0,004). Houve correlação com área de fibrose analisada pela ressonância magnética e mensurada pela biópsia (r=0,89) Os achados deste estudo são que pacientes com múltiplas áreas acinéticas também apresentam benefício com este procedimento e o percentual de área de fibrose mensurada por ressonância magnética correlaciona-se com a biópsia, e com a evolução pós-operatória analisada pelo volume sistólico final do ventrículo esquerdo, com a fração de ejeção do pós-operatório e com menor número de eventos. Esses achados permitem concluir que a cirurgia de reconstrução geométrica do ventrículo esquerdo alivia sintomas, melhora a remodelamento do ventrículo esquerdo em pacientes com insuficiência cardíaca com sintomas avançados. Finalmente, que a análise do percentual de área de fibrose avaliada por ressonância nuclear magnética sugere ser um importante método não-invasivo para análise da evolução / Abstract: Heart failure is one of the biggest problems faced by public health. Efforts have been made in order to achieve full understanding of the mechanisms that result in the myocardium structural and functional deterioration, which is responsible for advanced symptoms. Coronary disease results in myocardium infarction and eccentric hypertrophy of the ventricular chambers, which play a central role in the setting up and evolution of the structural alterations that follow myocardium functional deterioration and, consequently, the global ventricular dysfunction. In the present study patients presenting heart failure due to myocardium infarction and akinesia in the anterior wall that underwent surgery were evaluated, aiming at analyzing structural and functional alterations of the myocardium. These patients were evaluated by clinical exams, echocardiography, and magnetic resonance in the pre-operative period and underwent clinical and echocardiograph exams for a period of two years after surgery. Endomyocardial biopsy were done intra-operatively in all patients for fibrosis analysis. The fibrosis area in endomyocardium tissue was correlated with percentage of fibrosis found in magnetic resonance. The patients were separated in two groups, according of the number of myocardium infarctions. The patients presented advanced symptoms of heart failure (CF III-IV) in the pre-operative for the reconstruction of the left ventricle. The average ejection fraction was 35,6% and the left ventricle end systolic volume was 150,6ml. Patients with multiterritory myocardial infarction were evaluated and correlated with the percentage of scar tissue was measured by magnetic resonance imaging and was correlated to the patient¿s evolution and biopsy. Significant reductions in number and intensity of symptoms in the post-operative outcome were verified (from 3.7± 0.4 to 1.53± 0.6, p<0.001). There was correlation between the left ventricle final systolic volume (from 150.6 ± 52.8 ml to 91.92± 32.7 ml, p<0.001). and the ejection fractions in the pre and port-operative (from 35.5± 5.4 to 47.3± 7.3, p<0.001). There was also a correlation between the percentage of the scar tissue both in the final systolic volume (r=0.67) and in the ejection fraction (r=-0,88) of the left ventricle. Patients having a smaller percentage of the scar tissue area evolved with a smaller number of cardiovascular events (p<0.001) Patients with multiple ventricle territories presenting myocardium infarction evolved with larger left ventricle final systolic volume (p=0.004) The findings of this study are patients presenting akinetic multiple areas are benefited by this type of procedure and the percentage of scar tissue area measured by resonance magnetic correlates to the left ventricle final systolic volume in post-operative, with an ejection fraction of the post-operative and with a smaller number of events. These findings lead to the conclusion that geometric reconstruction surgery of the left ventricle relieves symptoms, improve left ventricle remodeling in patients with advanced symptoms of heart failure. Finally, the analysis of the percentage of scar tissue evaluated magnetic resonance is an important non-invasive method to analyze evolution / Doutorado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Doutor em Fisiopatologia Medica

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / à importante avaliar a prÃtica do autocuidado de pacientes com insuficiÃncia cardÃaca (IC), visto que o cuidado pessoal à indispensÃvel para diminuiÃÃo das complicaÃÃes e reinternaÃÃes e melhoria da qualidade de vida. Este estudo teve como objetivos elaborar uma escala para avaliaÃÃo do autocuidado de pacientes com insuficiÃncia cardÃaca e realizar a validaÃÃo de conteÃdo da escala de avaliaÃÃo do autocuidado de pacientes com insuficiÃncia cardÃaca. Trata-se de um estudo do tipo metodolÃgico, cujo referencial teÃrico foi o Modelo PsicomÃtrico para construÃÃo de instrumentos de medida composto por trÃs procedimentos (teÃrico, empÃrico e analÃtico), sendo realizado o pÃlo teÃrico e seus seis passos. A primeira etapa da pesquisa envolveu o levantamento dos elementos que englobam as mÃltiplas facetas do construto âautocuidado de pacientes com insuficiÃncia cardÃacaâ por meio de uma revisÃo de literatura. Para tanto, procedeu-se a busca de artigos cientÃficos em periÃdicos cientÃficos nacionais e internacionais em bases de dados e livros acadÃmicos sobre IC e autocuidado nas bibliotecas das universidades nos meses de abril e maio de 2011. Foram selecionados 63 artigos, que atenderam aos critÃrios de inclusÃo, nas bases de dados SCOPUS, PUBMED, CINAHL, COCHRANE e LILACS apÃs o cruzamento dos descritores controlados autocuidado e insuficiÃncia cardÃaca e suas traduÃÃes em inglÃs e espanhol. Em relaÃÃo aos livros, selecionaram-se oito livros que atenderam aos critÃrios de inclusÃo estabelecidos. A leitura e sÃntese dos artigos e livros apontaram 28 prÃticas de autocuidado de pacientes com IC e orientaram a operacionalizaÃÃo da construÃÃo da escala, originando a primeira versÃo da Escala de AvaliaÃÃo do Autocuidado de Pacientes com InsuficiÃncia CardÃaca (EAAPIC). A coleta de dados com os juÃzes aconteceu nos meses de agosto, setembro e outubro de 2011, sendo utilizado um formulÃrio contendo dados referentes aos juÃzes e dados avaliativos da escala. O estudo respeitou os preceitos Ãticos e recebeu aprovaÃÃo do comità de Ãtica em pesquisa da Universidade Federal do Cearà sob protocolo de nÃmero 114/2011. A primeira versÃo do instrumento foi composta por 29 itens distribuÃdos em sete domÃnios, quais sejam: nutriÃÃo, eliminaÃÃo, atividade e repouso, percepÃÃo e cogniÃÃo, promoÃÃo da saÃde, tolerÃncia ao estresse e papÃis e relacionamentos. Cada item possuÃa cinco respostas possÃveis dispostas em escala de Likert, variando de 1 a 5, sendo um considerado pior autocuidado e cinco melhor autocuidado. Procedeu-se a anÃlise teÃrica da escala, submetendo-se à avaliaÃÃo de oito juÃzes considerados experts em insuficiÃncia cardÃaca. ApÃs os testes estatÃsticos (Ãndice de Validade de ConteÃdo â IVC, v de Cramer e coeficiente de correlaÃÃo intraclasses - ICC) e as alteraÃÃes decorrentes das sugestÃes dos juÃzes, obteve-se a segunda versÃo da escala formada por vinte itens distribuÃdos em seis domÃnios. O ICC da EAAPIC foi de 0,827 (p=0,001) indicando boa consistÃncia interna. Conclui-se, portanto, que foi possÃvel construir uma escala de avaliaÃÃo do autocuidado de pacientes com insuficiÃncia cardÃaca e que a mesma envolve e representa o conteÃdo do construto que pretende medir devido seu bom valor do coeficiente de correlaÃÃo intraclasses. / It is important to evaluate the practice of self-care of patients with heart failure (HF), as the personal care is essential to decrease complications and readmissions and improve the quality of life. This study aimed to develop a scale for evaluate self-care of patients with heart failure and perform content validation of self-care scale for evaluation of patients with heart failure. It is a methodological study, whose theoretical reference was the Psychometric model for construction of measuring instruments composed of three procedures (theoretical, empirical and analytical), beeing performed the theoretical pole and its six steps . The first stage of the research involved the investigation of the elements that comprise the multiple facets of the construct "self-care of patients with heart failure" through a literature review. For this, we proceeded to search for scientific articles in national journals and international databases and scholarly books about HF and self-care in the university libraries in the months of April and May 2011. We selected 63 articles that met criteria for inclusion in databases SCOPUS, PubMed, CINAHL, Cochrane Library and LILACS after the crossing of controlled descriptors self-care and heart failure and their translations into English and Spanish. Regarding the books, we selected eight books that met the inclusion criteria established. Reading and summaries of articles and books have been identified 28 practice of self-care of patients with HF guided the operationalization of the construction of the scale, resulting in the first version of the Scale of Evaluation of Self-Care of Patients with Heart Failure (EAAPIC). Data collection with the judges took place in August, September and October 2011, we used a form containing data regardings jugdes and evaluate data on the scale. The study complied with the ethical guidelines and was approved by research ethics committee of the Federal University of Cearà under protocol number 114/2011. The first version of the instrument comprised 29 items divided into seven areas, namely: nutrition, elimination, activity and rest, perception and cognition, health promotion, stress tolerance, and roles and relationships. And each item had five possible answers arranged in Likert scale ranging from 1 to 5, with 1 considered worse self- care and 5 the best self-care. There has been the theoretical analysis of the scale, submitting to the evaluation of eight judges considered experts in heart failure. After statistical tests (Index of Validity of Content - IVC and coefficient of intraclass correlation - ICC) and the changes resulting from the suggestions of the judges, we obtained the second version of the scale consisting of twenty items divided in six areas. ICC of EAAPIC was 0.827 (p= 0,001), indicating good internal consistency. We conclude, therefore, that it was possible to construct a evaluation scale of self-care of patients with heart failure and that it involves and represents the content of the construct to be measured due to its good value for coefficient of intraclass correlation.

Objetivos: Comparar as distribuições das medidas dos instrumentos DUFS, DEFS e Pictograma de Fadiga de acordo com a gravidade da insuficiência cardíaca (IC) avaliada pela Classe Funcional da New York Heart Association (CF-NYHA) e a avaliar sua relação com a fração de ejeção do ventrículo esquerdo (FEVE). Método: Estudo metodológico, de corte transversal, cuja amostra foi composta por adultos com IC atendidos em um hospital universitário do Estado de São Paulo, de setembro de 2014 a março de 2015. O DUFS avalia a fadiga relacionada à cardiopatia (8 itens, intervalo total de 8 a 40; quanto maior o valor, maior a intensidade da fadiga) e o DEFS avalia a fadiga relacionada às atividades físicas e aos esforços (9 itens, intervalo de nove a 45; maiores valores indicando maior intensidade da fadiga). O Pictograma de Fadiga avalia a intensidade (item A) e o impacto (item B) da fadiga relacionada às atividades da vida diária, quanto maior a pontuação em cada item, maior a sensação e o impacto da fadiga. Os dados foram coletados por entrevistas e consulta aos prontuários. Para testar se as médias dos grupos eram diferentes, fizemos uma Análise de Variância com o valor da escala como variável resposta e CF-NYHA grupo como variável explanatória. Quando o fator grupo era estatisticamente significante, fizemos o teste de comparação múltipla de médias (método post hoc de Bonferroni). Para verificar a correlação entre as medidas obtidas pelos instrumentos DUFS e DEFS e a FEVE, foi utilizado o teste de Correlação de Pearson. A associação entre as distribuições das respostas aos itens do Pictograma de Fadiga e a FEVE, categorizada em preservada (>= 55) ou reduzida (<55), foi analisada pelo teste Exato de Fisher. O nível de significância adotado foi de 0,05. Resultados: Participaram 118 pacientes, com média de idade de 63 (D.P.=13) anos, 62% do sexo masculino, 86% não desempenhavam atividades remuneradas, com média de 6 (D.P.=5) anos de estudo. Observamos aumento nas médias das medidas obtidas por DUFS ou DEFS entre os pacientes de acordo com a progressão da doença medida pela CF-NYHA (p<0,001, para os dois instrumentos). Não constatamos diferenças entre a fadiga (avaliada pelo DUFS) dos pacientes da CF-NYHA III com os das II e IV. Ao analisarmos as diferenças da fadiga, avaliada pelo DEFS, não observamos diferenças entre as médias dos pacientes da CF-NYHA II com os das I e III, e os da III, com os pacientes da IV. As correlações entre a FEVE com as medidas de fadiga foram de positiva e fraca magnitude para o DEFS (r=0,18; p=0,05) e para o DUFS (r=0,16; p=0,08). Somente o item A do Pictograma de Fadiga teve associação com os grupos de CF-NYHA (p<0,001). Conclusão: Os três instrumentos demonstraram piora nos níveis de fadiga de acordo com a gravidade da doença avaliada pela CF-NYHA, entretanto, não houve discriminação entre os grupos de maior gravidade, pois houve grande variação dentro de cada grupo funcional / Objectives: Compare the distributions of the measures of the Dutch Fatigue Scale (DUFS), Dutch Exertion Fatigue Scale (DEFS) and Fatigue Pictogram according to the severity of heart failure (HF), assessed by the New York Heart Association Functional Class (NYHA-FC) and to assess its relationship with the left ventricle ejection fraction (LVEF). Method: Methodological, cross-sectional study with a sample composed of adults with HF cared for by a university hospital in the state of São Paulo, Brazil from September 2014 to March 2015. The DUFS assesses fatigue related to heart disease (8 items, total interval from 8 to 40; the higher the score, the more intense the fatigue) and the DEFS assesses fatigue related to physical exertion (9 items, interval from nine to 45; higher scores indicate more intense fatigue). The Fatigue Pictogram assesses the intensity (item A) and impact (item B) of fatigue related to daily living activities; the higher each item\"s score, the greater the intensity and impact of fatigue. Data were collected using interviews and by consulting medical files. To test whether the groups\" means were different, an analysis of variance was performed with the scale\"s score as the response variable and the group\"s FC-NYHA as the explanatory variable. When the group factor was statistically significant, a multiple comparison test (Bonferroni\"s post-hoc method) was used. Person\"s Correlation test was used to verify correlation between the measures obtained by the DUFS, DEFS and LVFE. Association between the distributions of responses to the Fatigue Pictogram\"s items and LVEF, categorized in preserved (>= 55) or reduced (<55), was analyzed by the Fisher\"s exact test. The level of significance adopted was 0.05. Results: A total of 118 patients aged 63 (SD=13) years old on average participated; 62% were males, 86% did not have a paid job, with 6 (SD=5) years of education, on average. The means of the measures obtained by the DUFS or DEFS increased among patients as the disease progressed, as measure by the NYHA-FC (p<0.001 for both instruments). No differences were found between the fatigue (assessed by the DUFS) of patients classified in NYHA-FC III with those classified in NYHA-FC II and IV. When analyzing means of fatigue, measured by the DEFS, no differences were found between the means of patients in NYHA-FC II with those in functional classes I or III, or between those in NYHA-FC III with patients in IV. Correlations between LVEF and fatigue measures were of a positive and weak magnitude for the DEFS (r=0.18; p=0.05) and for the DUFS (r=0.16; p=0.08). Only item A of the Fatigue Pictogram was associated with NYHA- FC groups (p<0.001). Conclusion: The three instruments showed worse levels of fatigue according to the severity of the disease assessed by NYHA-FC, however, there was no discrimination between the groups with greater severity, as there was a large variation within each functional group

INTRODUCTION: While transitions of care (TOC) programs are known to decrease readmissions for heart failure (HF), significant policy and resource challenges inhibit the implementation of hospital based TOC programs, thus novel models of TOC are urgently needed. The purpose of this study is to evaluate the need and readiness of a private practice based TOC program led by DNP-prepared nurse practitioners. METHODS: In this descriptive study, cardiology providers from a private practice in the Southwest (N=14) participated in a survey on HF TOC. The practice’s electronic medical records (EMR) database was queried for patient demographic data along with other HF measures (N=3175). RESULTS: There were 1,827 females (57.5%) and 1,348 males (42.5%) with the mean age being 75.1 years +/-11.1. The 70-79 year age bracket represented 41.0% of all HF patients. The most common ICD-10 code for HF was [I50.32] Chronic Diastolic Congestive Heart Failure (N=986), which translates into 31.0% of the total HF population. Almost 30% of the providers (N=4) acknowledge that they never document their HF readmissions in the practice’s EMR. Nearly 65% percent of respondents “strongly agree,” that HF patients discharged from the hospital require a specific plan of care, while 86% of providers (N=12) either “somewhat agree” to “strongly agree” in the need for a TOC program for HF patients within their cardiology practice. Over 71% (N=10) of the providers “strongly agree” with a DNP-led TOC program for HF. CONCLUSION: This study provides encouraging results for the future implementation of a cutting edge private cardiology practice based TOC program for HF in Tucson, AZ. The study results clearly indicate the need and readiness for the Tucson-based private practice TOC program for HF. The DNP prepared nurse practitioner is thoroughly prepared to take the lead in designing, implementing and evaluating such a program and this unique role was supported by the practice. Importantly, the results of this study may provide the foundation for future studies examining the effects of private practice based TOC programs for HF.

Normal cardiac function is dependent on a healthy conduction system to maintain coordinated and synchronised activity. In the presence of heart failure, dyssynchronous ventricular activation due to left bundle branch block or right ventricular pacing can result in worsening symptoms and increased mortality; cardiac resynchronisation therapy in the form of biventricular pacing has therefore become an established and effective treatment. However, it also appears that right ventricular pacing can be a cause of heart failure in some individuals, even when there is no evidence of associated pre-existing cardiac disease. A better understanding of the processes leading to dyssynchrony-induced cardiomyopathy will allow better identification and treatment of patients who are at risk, and will contribute to our knowledge about heart failure in general. This PhD adopted a translational approach to cardiac dyssynchrony, by developing a novel model of atrial-synchronous ventricular pacing in adult Welsh Mountain sheep. The right ventricle was paced from the apex continuously for 3 months at a rate that was determined by the intrinsic atrial rate; this allowed the ventricular activation pattern to be altered without changing the heart rate. In parallel, a previously-developed model of rapid ventricular pacing was studied. In this model, the heart was paced continuously at a fixed rate of 210 bpm, which led to the development of symptomatic heart failure. In vivo parameters were characterised using standard clinical techniques of electrocardiography and echocardiography. Autonomic nervous system activity was investigated by examining the heart rate responses to pharmacological blockade using atropine and propranolol, and to beta-adrenergic stimulation using dobutamine. Heart rate variability was analysed in the time and frequency domains. In vitro, patch clamping studies were performed on ventricular myocytes isolated through enzymatic digestion from the interventricular septum and left ventricular free wall. Using the perforated patch current clamp technique at 37 C, action potential duration was measured and the associated triggered calcium transient was analysed using the calcium-sensitive fluorescent indicator Fura-2AM.Heart failure was associated with in vivo evidence of autonomic dysfunction, including a 38 % increase in the resting heart rate, blunting of the heart rate response to dobutamine, and almost complete loss of vagal tonic heart rate control. This pattern was not present in dyssynchrony. At a cellular level, normal sheep had heterogeneity of action potential duration, which was longer in the septum than the free wall. Heart failure disrupted this pattern, and was also associated with approximately a 40 % reduction in the magnitude of the calcium transient in both the septum and the free wall. Dyssynchrony was associated with a similar reduction in the calcium transient, but this was isolated to the free wall. RV apical pacing therefore induced a phenotype that resembled a localised cardiomyopathy, but without the associated autonomic dysfunction of the heart failure model. However, it was possible to identify a subgroup within these subjects that displayed a pattern of autonomic changes similar to those seen in heart failure, and this appeared to be associated with the most profound cellular changes. This raises the possibility that early dyssynchrony-induced cardiomyopathy may manifest as changes in the autonomic profile, which may be detectable in clinical practice.

Class of 2016 Abstract and Report / Objectives: An estimated 5.7 million Americans had heart failure (HF) in 2012 with an economic cost of $30.7 billion. By 2030 the prevalence of the disease is expected to increase by 46%. Centers for Medicare and Medicaid Services penalizes hospitals for 30-day readmissions. This study evaluated the effect of our multidisciplinary HF intervention on readmissions. Methods: This is a retrospective cohort study. Patients were identified from electronic inpatient admission records from January 1 to December 31, 2014. Patients who received any component of intervention were compared to patients who did not receive any intervention. Intervention included student pharmacist medication counselling, HF education, and post-discharge phone calls with Modified Morisky questionnaire. Age, sex, admission/discharge dates, readmission diagnosis, smoking status, ejection fraction, medications, and Charlson Comorbidity Index (CCI) conditions were collected. Results: A total of 221 patients with 249 discrete admissions were identified. No difference in age (p=0.42), sex (p=0.48), smoking status (p=0.10) existed between the groups. No difference in readmissions was found between patients receiving complete intervention and control (p=0.41) or patients receiving 1 or 2 intervention components and control (p=0.41). Patients with CCI score≥ 8 had greater risk of readmission compared to CCI scores 0-2 (OR 7.7, 95% CI 1.6-36.3, p=0.01). Conclusions: This analysis did not identify an intervention impact on 30-day readmissions in patients with HF; high CCI scores were associated with increased readmission risk. The intervention may be best targeted towards patients with high CCI scores as they have the highest readmission rate.

Class of 2013 Abstract / Specific Aims: To examine the relationship between hospital readmission rates and responses to a medication adherence questionnaire (Morisky) in patients with congestive heart failure (CHF). Methods: The Morisky questionnaire, assessing medication adherence, was administered to all CHF patients admitted from September 15, 2012 to March 7, 2013. Information collected from the electronic medical record (EMR) for all patients with complete Morisky questionnaires included: age, sex, ethnicity, insurance, height, weight, marital status, tobacco use, alcohol use, number of home medications, all-cause and CHF admission in the previous 365 days from when the questionnaire was administered as well as the following events/disease states: myocardial infarction, hypertension, atrial fibrillation, stroke, diabetes mellitus, peripheral vascular disease, chronic obstructive pulmonary disease, congestive heart disease and chronic kidney disease. Main Results: Of the 120 patients enrolled, 52% scored 1-5 on the Morisky questionnaire indicating some problem with medication adherence while 48% scored 0 (no problems). There was no correlation between the Morisky score and age (95% CI: -3.3-5.7), number of medications (95% CI: -0.26, 2.85), or number of comorbidities (95% CI: -1.02,0.03). The Morisky questionnaire was not predictive of all cause readmissions (95% CI: 0.35, 2.01) p = 0.691). For CHF readmissions the Morisky score was not significant (95% CI: 0.6, 4.11, p=0.358) but the confidence interval suggests a trend. Conclusion: There is no correlation between Morisky scores, age, comorbidities, and medication number. Readmission rates were not predicted by Morisky scores; with more participants a trend may be detected for CHF readmissions.

La stratification du risque des patients atteints d'insuffisance cardiaque (IC) systolique chronique est essentielle afin d'identifier ceux qui pourront bénéficier de stratégies invasives telle que la transplantation cardiaque. En dépit des avancées récentes, cette stratification nécessite d'être encore améliorée. En effet, certains patients caractérisés à faible risque vont décéder précocement ; et inversement, d'autres identifiés à haut risque auront une survie prolongée.Objectif - Notre objectif était d'investiguer la place d'une analyse protéomique du plasma dans la stratification du risque des patients IC et de découvrir des biomarqueurs circulants associés à la mortalité cardiovasculaire précoce de ces patients.Méthodes et résultats - Pour ce faire, nous avons d'abord désigné 2 populations : une population test et une de validation. Ces 2 populations étaient issues de la population INsuffisance CArdiaque (INCA) constituée de l'ensemble des patients référés à notre centre pour une évaluation pronostique extensive d'une IC systolique chronique (FEVG <45%) entre novembre 1998 et mai 2010. Pour la phase test (population cas/témoins), nous avons sélectionné 198 patients entre novembre 1998 et décembre 2005: 99 patients décédés de cause cardiovasculaire dans les 3 ans suivant l'inclusion (cas) ont été comparés à 99 survivants à 3 ans appariés sur l'âge, le sexe et la cause de l'IC (témoins). Pour la phase de validation, nous avons évalué une cohorte de 344 patients consécutifs inclus entre janvier 2006 et mai 2010. Les populations ont été parfaitement caractérisées. La mortalité cardiovasculaire était définie comme un décès de cause cardiovasculaire, une transplantation en urgence (critère United Network for Organ Sharing status 1) ou une assistance cardiaque en urgence.Une analyse protéomique utilisant la technique SELDI-TOF-MS a ensuite été réalisée dans la population test sur des échantillons de plasma prélevés à l'inclusion. Les échantillons ont été déplétés des protéines majoritaires et analysés après randomisation en duplicate en utilisant des puces CM10 (échangeur de cations) et H50 (hydrophobie). Au total, 42 pics m/z étaient différentiellement abondants entre les cas et les témoins et ont été utilisés pour développer des scores protéomiques prédicteurs de la mortalité cardiovasculaire à l'aide de 3 méthodes statistiques de régression : machine à vecteur de support, régression des moindres carrés partiels et régression logistique de Lasso. Les scores protéomiques ont ensuite été testés dans la population de validation et étaient significativement plus élevés chez les patients qui vont décéder dans les 3 ans avec les 3 méthodes. Ces scores protéomiques persistaient associés à la mortalité cardiovasculaire après ajustement sur les facteurs confondants. De plus, l'utilisation de ces scores permettait une amélioration significative de la discrimination des patients IC par rapport à une évaluation pronostique classique selon les index suivants : "integrated discrimination improvement" et "net reclassification improvement".L'étape suivante a été de procéder à la purification et à l'identification des protéines correspondant aux pics m/z différentiellement abondants dans les 2 populations (n=13). Actuellement, nous avons pu identifier plusieurs apolipoprotéines : 14511 CM10-BM (ApoA1), 29024 CM10-BM (ApoA1), 3267 H50-BM (ApoC1), 6416 H50-BM (ApoC1), 6616 H50-BM (ApoC1), 6825 H50-BM (ApoC1), 8764 H50-BM (ApoC3), 9421 H50-BM (ApoC3). ceci a conduit à la quantification de ces apolipoprotéines dans la population INCA par une technique de "mass reaction monitoring".Conclusion - Une analyse protéomique des protéines du plasma semble améliorer la stratification du risque de mortalité précoce chez les patients atteints d’une IC chronique.Perspectives - Des investigations complémentaires sont en cours afin de déterminer l'impact des apoplipoprotéines dans la stratification du risque de ces patients. / Risk stratification of patients with systolic chronic heart failure (HF) is critical to better identify those who may benefit the most from invasive therapeutic strategies such as cardiac transplantation. In spite of recent advances, risk stratification of HF patients needs to be further improved. Indeed, there remains variability in the prognosis with some patients who are categorized at low risk but experience early mortality; and conversely, patients categorized as severe but have an unexpectedly prolonged survival. Proteomics has been used to provide prognostic information in various diseases.Aim – Our aim was to investigate the potential value of plasma proteomic profiling for risk stratification in HF and to find new circulating biomarkers that are associated with early cardiovascular mortality of chronic HF patients.Methods and results – For that purpose, we first designed 2 populations: a discovery and a validation population. Both populations issued from the INsuffisance CArdiaque (INCA) cohort, which is constituted of all consecutive patients referred in our institution for extensive prognostic evaluation of systolic chronic HF (LVEF <45%) between November 1998 and May 2010. For the discovery phase (case/control population), we selected 198 patients included between November 1998 and December 2005: 99 patients who died from cardiovascular cause within 3 years after the initial evaluation (cases) were individually matched for age, sex, and HF etiology with 99 patients who were still alive at 3 years (controls). For the validation phase, we evaluated a cohort of 344 consecutive patients included between January 2006 and May 2010. Study populations were carefully phenotyped. Cardiovascular death included cardiovascular-related death, urgent transplantations defined as United Network for Organ Sharing status 1 and urgent assist device implantation. A proteomic profiling using surface enhanced laser desorption ionization - time of flight - mass spectrometry was then performed in the case/control discovery population on plasma samples collected at inclusion. Plasma samples were depleted for major proteins and randomly analyzed in duplicate using CM10 (Weak Cation Exchanger) and H50 (Reverse Phase) proteinchip arrays. Forty two ion m/z peaks were found differentially abundant between cases and controls in the discovery population and were used to develop proteomic scores predicting cardiovascular death using 3 statistical regression methods: support vector machine, sparse partial least square discriminant analysis and lasso logistic regression. The proteomic scores were then tested in the validation population and score levels were significantly higher in patients who subsequently died within 3 years with the 3 methods. Proteomic scores remained significantly associated with cardiovascular mortality after adjustment on confounders. Furthermore, use of the proteomic scores allowed a significant improvement in discrimination of HF patients as determined by integrated discrimination improvement and net reclassification improvement indexes on top of “classic” prognostic evaluation. The next step was the purification and identification of the proteins related to the different m/z peaks (n=13) that were found significantly differentially abundant in both populations. We have currently identified several peaks as apolipoproteins: 14511 CM10-BM (ApoA1), 29024 CM10-BM (ApoA1), 3267 H50-BM (ApoC1), 6416 H50-BM (ApoC1), 6616 H50-BM (ApoC1), 6825 H50-BM (ApoC1), 8764 H50-BM (ApoC3), 9421 H50-BM (ApoC3). This has led to the quantification of these apolipoproteins in the INCA population using mass reaction monitoring technique.Conclusion – Proteomic analysis of plasma proteins may help to improve risk prediction of early mortality in HF patients.Perspectives – Further investigations are ongoing in order to determine the impact of the different apolipoproteins tested in risk stratification of chronic HF patients.

Advanced glycation end products (AGEs) are molecules formed through the nonenzymaticglycation of proteins and are central to the development of cardiovascularcomplications of diabetes including heart failure. AGEs influence cellular function throughthe cross-linking of cellular proteins as well as through actions on cell surface receptors,the most common of which is (RAGE). However, it is still unclear whether AGEs contributeto myocardial abnormalities observed in diabetes through direct myocardial actionsmediated through the RAGE receptor and if so, their underlying mechanisms of action. Wehave therefore investigated the effects of AGEs on calcium handling in isolated adultmouse cardiomyocytes and cultured neonatal rat cardiomyocytes (NRCM) andcharacterised their underlying mechanisms of action in NRCM.Standard molecular techniques were used. Western blot showed expression of RAGEreceptor in mouse whole heart tissue and in both NRCM and adult mouse cardiomyocytes. Incubation of NRCM for 24 hours with AGEs showed a dose dependant reduction ofcalcium transient amplitude with a maximum of 50% at 1 g/l (P<0.01) accompanied with32% reduction in SR calcium content with no detectable changes in calcium handlingproteins expression. We demonstrated a 24% increase (P<0.01) in the production ofreactive oxygen species (ROS) in AGE treated cardiomyocytes induced by enhancedNADPH oxidase activity (P<0.05) with subsequent activation and translocation of NF-kB, atranscriptional factor from the cytoplasm to the nucleus. Activation of NF-kB induced a56% increase in iNOS gene protein expression (P<0.01), a downstream target of NF-kBwhich was accompanied by a significant increase in NO production (P<0.05). Wedemonstrated nitrosylation of several key cellular proteins involved in excitationcontractioncoupling including the Ryanodine receptor and SERCA2a as detected byimmunofluorescence. In conclusion, our work provides insights into novel pathophysiological mechanisms thatunderlie the development of heart failure in diabetes. We demonstrate the presence andfunctionality of AGE receptors in myocardium and show that AGEs inhibit excitationcontractioncoupling through increased ROS production leading to activation andtranslocation of NF-kB from the cytoplasm to the nucleus resulting in increase in NOproduction. Concomitant increases in intracellular levels of ROS and NO favours theproduction of peroxynitrite with subsequent nitrosylation of key cellular proteins involved inthe process of excitation-contraction coupling such as the Ryanodine receptor andSERCA2a. This study provides novel insights into the role of AGEs in inducing myocardialdamage in diabetes mediated through RAGE receptor and independent from the vascular effects.