Congestive heart failure (CHF) is a major cause of morbidity and mortality and the identification of modifiable risk factors is crucial in order to diminish suffering of this common disease. The primary aim of this thesis was to investigate novel metabolic risk factors for CHF, with a focus on insulin resistance and inflammation. The secondary aim was to examine the validity of the CHF diagnosis in the Swedish hospital discharge register. This thesis was based on the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, a community-based prospective study started in 1970. The participants were examined at age 50 and 70 and the data was completed with annual updates on mortality and in-hospital morbidity using national registers. We showed that insulin resistance predicts CHF incidence independently of established risk factors in both middle-aged and elderly men. The previously described association between obesity and subsequent CHF may be mediated partly by insulin resistance. Moreover, it was established that inflammation, measured as erythrocyte sedimentation rate is a significant predictor of CHF, independent of established risk factors including an interim myocardial infarction. Furthermore, a low beta-carotene level, as well as an increased apolipoprotein B/A-I-ratio was found to predict CHF independently of established risk factors. We also showed that the validity of the CHF diagnosis in the Swedish hospital discharge register appears less precise than for other recently investigated cardiovascular diagnoses. However, when including only cases from selected clinics or cases with a primary diagnosis of CHF, the validity is comparable to the above diagnoses. In conclusion, insulin resistance and inflammation are strong independent risk factors for the development of CHF, and seem to be involved in the early process leading to CHF. If confirmed, our observations could have large clinical implications as they may offer new approaches in the prevention of CHF.

Thesis (M.Pharm. (Pharmacy Practice))---North-West University, Potchefstroom Campus, 2008.

No description available.

No description available.

Cardiac Resynchronization Therapy (CRT) is a treatment option for heart failure patients with ventricular dyssynchrony. CRT corrects for dyssynchrony by electrically stimulating the septal and lateral walls of the left ventricle (LV), forcing synchronous con- traction and improving cardiac output. Current selection criteria for CRT rely upon the QRS duration, measured from a surface electrocardiogram, as a marker of electrical dyssynchrony. Unfortunately, 30-40% of patients undergoing CRT fail to benefit from the treatment. A multitude of studies have shown that presence of mechanical dyssynchrony in the LV is an important factor in determining if a patient will benefit from CRT. Furthermore, recent evidence suggests that patient response can be improved by placing the LV pacing lead in the most dyssynchronous or latest contracting segment. The overall goal of this project was to develop methods that allow for accurate assessment and display of regional mechanical dyssynchrony throughout the LV and at the site of the LV pacing lead. To accomplish this goal, we developed a method for quantifying regional dyssynchrony from standard short-axis cine magnetic resonance (MR) images. To assess the effects of LV lead placement, we developed a registration method that allows us to project the LV lead location from dual-plane fluoroscopy onto MR measurements of cardiac function. By applying these techniques in patients undergoing CRT, we were able to investigate the relationship between regional dyssynchrony, LV pacing lead location, and CRT response.

<p>S. 1-96: sammanfattning, s. 97-134: 5 uppsatser</p> / digitalisering@umu

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Thesis (Ph.D.) -- McMaster University, 2005. / "Health Research Methodology". Includes bibliographical references. Also available via World Wide Web.

Os modelos experimentais de falência do ventrículo direito (VD) descritos são de difícil execução, por envolverem procedimentos cirúrgicos complexos e dispendiosos, com alta mortalidade e baixa reprodutividade. Também são raros aqueles que promovem falência ventricular exclusiva do ventrículo direito. Com o objetivo de simular a situação clínica de falência ventricular exclusiva do VD, desenvolvemos um modelo experimental de falência crônica isolada do VD, feito através da injeção de etanol intramiocárdico. A disfunção do VD foi induzida em treze cães adultos, através de múltiplas injeções de etanol a 96% (dose total 1ml/kg), na via de entrada e na porção trabecular do VD. Foram analisados parâmetros hemodinâmicos, metabólicos e ecocardiográficos, em condições basais e após indução da falência. Os animais foram mantidos vivos por um período de 14 dias, após o qual foram reoperados e mortos para análise morfológica dos corações. As pressões foram aferidas na artéria femoral, átrio esquerdo (AE), átrio direito (AD), tronco pulmonar (TP) e VD. O fluxo sanguíneo foi medido na aorta e no tronco pulmonar. Na primeira operação, os dados hemodinâmicos foram registrados antes e imediatamente após a indução da falência do VD. Estes parâmetros também foram coletados na reoperação (14 dias pós-indução da falência). Amostras de sangue arterial e venoso foram colhidas simultaneamente ao registro dos parâmetros hemodinâmicos para avaliação dos gases sanguíneos e dosagem de lactato. Foram feitas avaliações ecocardiográficas no pré-operatório, no sexto e no 130 dia pós-operatório (PO). Houve uma mortalidade de 15,4% (2/13). Observou-se uma queda significativa no débito cardíaco pulmonar após a indução da falência e na reoperação (14º PO), quando comparado aos valores medidos no momento basal (p=0,002). Esta queda do desempenho ventricular direito ocasionou um aumento nos valores do lactato venoso, quando comparados os valores basais contra aqueles do pós infusão de etanol (p=0,0001) e com os da reoperação (p=0,0003). Os dados ecocardiográficos revelaram um aumento no volume diastólico do VD, quando comparados os dados basais com aqueles da primeira semana de seguimento (p=0,0001) e com aqueles medidos duas semanas após a indução da falência (p=0,0084). Houve uma queda significativa da fração de ejeção do VD na primeira e segunda semanas em comparação aos valores basais (p=0,0001). A avaliação microscópica feita a partir de amostras retiradas do VD revelou infartos transmurais, com características histológicas compatíveis com infarto de duas semanas de evolução. A injeção de etanol intramiocárdio permitiu a criação de um modelo simples, econômico e reprodutível de falência crônica isolada do VD. A avaliação dos dados hemodinâmicos, ecocardiográficos e bioquímicos medidos nos diferentes momentos do experimento é compatível com a indução de falência grave do VD. Este modelo pode ser útil no estudo da fisiopatologia da falência isolada do VD, bem como na avaliação de assistência ventricular. / Isolated chronic right ventricle (RV) dysfunction is difficult to achieve in experimental models, and sometimes very expensive. Some models require complex surgical procedures, with a high mortality rate and low reproducibility. In order to simulate the clinical status of RV failure, we have developed an experimental model of chronic RV failure by injecting local intramyocardial ethanol 96%. A severe RV dysfunction was induced in 13 mongrel dogs by means of multiple intramyocardial injections of ethanol 96% (total dose of 1ml/kg), in the inlet and trabecular portions of the RV. The hemodynamics, metabolic and ecocardiografic parameters were evaluated at baseline condition and after RV failure. The animals were followed for a 14-day period. After that, they were reoperated for pressure measurements, taken from femoral artery, left atrium (LA), right atrium (RA), RV and main pulmonary artery (PA). Blood flow was measured in the aorta (AO) and PA. Metabolic parameters were assessed simultaneously to pressure measurements, with arterial and venous blood samples withdrawn for gas and lactate analysis, and then, they were killed for morphological evaluation of the heart. All the animals were submitted to echocardiographic evaluation before the first operation, on sixth and on de 13th postoperative day. The mortality rate was 15,4% (2/13). There was a significant decrease in the pulmonary blood flow after RV failure induction (p=0,0018), as well as in the reoperation (p=0,002), as compared to baseline. This decrease in RV performance caused an increase in the venous lactate level, when baseline values are compared with pos infarction values (p=0,001) and reoperation (p=0003). The echocardiografic findings revealed an increased RV diastolic volume on the 6th (p=0,0001) and 13th postoperative day (p=0,0084), as compared to baseline values. Conversely, there was a significant decrease in the RV ejection fraction on the 6th and 13th postoperative day, when compared with baseline values (p=0,0001). Microscopic evaluation of RV samples showed transmural infarctions with histological characteristics aged of two weeks. Intra myocardial ethanol injection has allowed the creation of a simple, inexpensive and reproducible model of chronic RV failure. The hemodynamic, metabolic and echocardiographic parameters assessed in different moments of the protocol are compatible with severe RV failure. It may be useful for RV physiology studies of isolated right sided heart failure, as well as in the assessment of ventricular assist devices.

A Insuficiência cardíaca (IC), síndrome clínica que afeta predominantemente os idosos, caracteriza-se por graus variados de comprometimento hemodinâmico e contínua estimulação neuro-hormonal, com conseqüente redução da capacidade funcional e elevação nas concentrações plasmáticas do peptídeo natriurético B (PNB). Diversos ensaios clínicos demonstraram os benefícios dos inibidores da ECA na atividade neuro-hormonal e na capacidade funcional de pacientes com IC, com a magnitude desses efeitos proporcional à dose desses agentes. Entretanto, a sistemática exclusão dos idosos, observada na grande maioria desses estudos, tem questionado a validação e incorporação de tais resultados na população geriátrica. O objetivo deste estudo foi avaliar os efeitos de diferentes doses de quinapril, um inibidor da ECA com meia-vida biológica >24 horas, nas concentrações plasmáticas do PNB, nas distâncias percorridas no teste da caminhada de 6 minutos (TC-6 min) e na incidência de reações adversas, em idosos com IC sistólica. Métodos: Ensaio clínico, aberto, não randomizado e prospectivo. Foram avaliados, segundo os critérios de inclusão e exclusão, 30 pacientes (76,1 ± 5,3 anos; 15 homens e 15 mulheres) com IC classe funcional II-III (NYHA), com fração de ejeção ventricular esquerda < 40% (33,5 ± 4,5%), em uso de diuréticos (30), digoxina (24) e nitratos (13). As avaliações foram realizadas no momento da inclusão (condição basal) e a cada dois meses, com a adição de 10, 20, 30 e 40 mg de quinapril, e incluíam avaliações clínicas, exames bioquímicos, análises das concentrações plasmáticas do PNB e TC-6 min. Resultados: Completados oito meses de terapêutica com inibidor da ECA, as concentrações plasmáticas do PNB foram 67,4% menores em relação à condição basal: redução de 33,3% com a dose de 10 mg em relação à condição basal, 27,1% com 20 mg em relação à dose de 10 mg, 23,6% com 30 mg em relação à dose de 20 mg e 12,5% com 40 mg em relação à dose de 30 mg de quinapril, com p<0,005 em todas as comparações. Do mesmo modo, as distâncias percorridas no TC-6 min foram, em média, 64,9% maiores no final do estudo em relação à condição basal: aumento de 22,8% com a dose de 10 mg em relação à condição basal, 13,3% com 20 mg em relação à dose de 10 mg, 12,2% com 30 mg em relação à dose de 20 mg e 5,6% com 40 mg em relação à dose de 30 mg de quinapril, com p<0,005 em todas as comparações. Reações adversas graves, como hipotensão arterial associada a sintomas de baixo débito cerebral e/ou disfunção renal, não foram observadas, o que possibilitou o emprego da dose máxima de quinapril (40 mg/dia) em todos os pacientes, incluindo-se dois octogenários e dois nonagenários. Conclusão: Os resultados deste estudo demonstraram os benefícios da terapêutica com inibidores da ECA no perfil neuro-hormonal e na capacidade funcional de idosos com insuficiência cardíaca sistólica, bem como a relação positiva entre a dose e o efeito dos inibidores da ECA. Ademais, os sucessivos aumentos nas doses de quinapril não foram associados a reações adversas, possibilitando o emprego da dose máxima em todos os pacientes, incluindo-se dois octogenários e dois nonagenários. / Heart Failure (HF), a clinical syndrome that affects specially the elderly, is characterized by varied degrees of hemodinamic compromise and continuous neuro-hormonal stimulation, with consequent reduction of the functional capacity and elevation in the plasmatic concentrations of the natriuretic peptide B (BNP). Several clinical attempts showed the benefits of the ACE inhibitors in the neuro-hormonal activity and in the functional capacity of patients with HF, with the magnitude of those effects being proportional to the dose of the agents. However, the observed systematic exclusion of the elderly in the most of studies, has questioned the validation and the incorporation of such results in the geriatric population. The objective of this paper was the evaluation of the effects caused by different doses of quinapril, an ACE inhibitor with biological half-life> 24 hours, in the plasmatic concentrations of BPN, in the distances in the walk test of 6 minutes and in the incidence of adverse reactions in elderly with sistolic HF. Methods: prospective and not randomized study. 30 patients (76,1 ± 5,3 years; 15 men and 15 women with HF - class II-III (NYHA) - were evaluated, following the criteria of enclosure and exclusion, with ejection fraction of left ventricular <40% (33,5 ± 4,5%), in use of diuretics (30), digoxina (24) and nitrates (13). The evaluations were carried out in the moment of the enclosure (basic condition) and every other month, with the addition of 10 mg, 20 mg, 30 mg and 40 mg of quinapril. It was included clinical evaluations, biochemical exams, analyses of the BNP plasmatic concentrations and walk test of 6 minutes. Results: After eight months of treatment with the ACE inhibitor, the plasmatic concentrations of BNP were 67,4% smaller than the ones in the basic condition: reduction of 33,3% with the dose of 10 mg regarding the basic condition, 27,1% with 20 mg regarding the dose of 10 mg, 23,6% with 30 mg regarding the dose of 20 mg and 12,5% with 40 mg regarding the dose of 30 mg of quinapril, with p<0,005 in all the comparisons. In the same way, the distances in the walk test of 6 minutes were, on average, 64,9% bigger in the end of the study regarding the basic condition; there was the increase of 22,8% with the dose of 10 mg regarding the basic condition; 13,3% with 20 mg regarding the dose of 10 mg; 12,2% with 30 mg regarding the dose of 20 mg and 5,6% with 40 mg regarding the dose of 30 mg of quinapril, with p<0,005 in all the comparisons. Serious adverse reactions, as arterial hypotension associated to syncope and/or kidney dysfunction, were not observed, which made possible the use of the maximum dose of quinapril (40 mg/day) in all patients, including two octogenarians and two nonagenarians. Conclusion: The results of the study showed the benefits of the treatment with ACE inhibitors in the neuro-hormonal profile and in the functional capacity of elderly with sistolic heart failure, as well as the positive relation between the dose and the effect of the ACE inhibitors. Moreover, the successive increases in the doses of quinapril were not associated to adverse reactions, making possible the use of the maximum dose in all of the patients, including two octogenarians and two nonagenarians.