A cintilografia do miocárdio com radioisótopos e associada à administração de vasodilatadores coronários, é método estabelecido para o diagnóstico e estratificação de risco da coronariopatia aterosclerótica obstrutiva, utilizando a angiografia coronária como padrão. As capacidades diagnóstica e prognóstica ótimas são habitualmente obtidas na presença de lesões graves, sendo que para para graus menores de obstrução, de caracterização mais difícil pela própria angiografia coronária, observa-se menor acurácia da prova cintilográfica. Para testar a hipótese de que a cintilografia com adenosina correlaciona-se com os diâmetros e áreas da luz arterial, estabelecidos pela angiografia coronária quantitativa (ACQ) e o ultra-som intracoronário (UIC), avaliando a repercussão funcional das lesões, optamos por avaliar o método em portadores de doença arterial coronária caracterizada como de difícil manejo dentro do processo de decisão clínica. Desta forma, submetemos 70 pacientes (P) consecutivos à cintilografia do miocárdio com 99mTc-MIBI associada à injeção de adenosina, com média de idades de 60,6 anos, sendo 55,7% do sexo masculino, excluindo-se aqueles com angina instável, infarto do miocárdio de evolução recente, bloqueio do ramo esquerdo e outras condições inerentes à realização da prova farmacológica. Estabelecemos como objetivos: 1) a associação dos resultados da prova com as variáveis obtidas da ACQ e UIC; 2) a determinação da acurácia da prova, definida em relação a valores de estenose porcentual do diâmetro da luz, iguais a 50% e obtidos à análise visual da angiografia (%E) e ACQ (%Est); do diâmetro mínimo da luz (DML) e da área mínima da luz (AML) no local de maior estreitamento, iguais a 1,5 mm e 4 mm2 respectivamente, obtidos à ACQ e ao UIC; e da área porcentual de obstrução (AO%), igual a 70%, ao UIC; 3) avaliar a segurança do método pela análise das respostas clínicas, hemodinâmicas e eletrocardiográficas (ECG) ao estímulo farmacológico. A angiografia de admissão evidenciou 105 lesões obstrutivas nos 70 P, com doença em um, dois e três ou mais vasos em 43 P (61,4%), 20 P (28,6%) e 7 P (10%) respectivamente, e envolvimento predominante da artéria descendente anterior. As médias dos valores de %E foram de 49,94% (DP 12,69) e de %Est de 44,20% (DP 10,37), com boa correlação entre os dois métodos (r=0,79). Os resultados da cintilografia foram expressos como variáveis dicotômicas, definindo provas normais e alteradas ou normais e isquêmicas, sendo então associados às médias das variáveis da angiografia e do UIC. Os achados de qualquer alteração da captação às imagens cintilográficas, de hipocaptação sugestiva de isquemia e de alterações do espessamento correlacionaram-se à maior AO% ao UIC. Adicionalmente, as respostas clínicas, do ECG e o resultado das imagens de perfusão foram considerados em conjunto, criando-se uma variável dicotômica para, da mesma forma, traduzir provas normais e alteradas ou isquêmicas. A presença de isquemia, avaliada pela análise global da prova, associou-se a menores DML e AML à ACQ e ao UIC: DML isquêmico x normal pela ACQ= 1,49 mm (DP 0,34) x 1,71 mm, (DP 0,49), p < 0,05; DML isquêmico x normal pelo UIC= 1,63 mm (DP 0,38) x 1,97 mm (DP 0,50), p < 0,05; AML isquêmica x normal pela ACQ= 3,74 mm2 (DP 1,78) x 5,00 mm2 (DP 2,65), p<0,05; e AML isquêmica x normal pelo UIC= 2,74 mm2 (DP 1,38) x 4,01 mm2 (DP 1,79), p < 0,05). A acurácia da prova, expressa pela sensibilidade (S), especificidade (E), valores preditivos positivo (VPP) e negativo (VPN) foi calculada em relação aos valores de corte estabelecidos das variáveis quantitativas. As respostas do ECG, discriminantes em relação à E%, mostraram S=37% e E=77%. As alterações da captação consideradas isquêmicas e associadas à AO% ao UIC evidenciaram S=75%; E=64%; VPP=43% e VPN=88%. Os resultados globais da prova que se mostraram discriminantes, apresentaram os seguintes índices: Método Variável S (%) E (%) VPP (%) VPN (%) ACQ DML 78 44 51 73 ACQ AML 71 43 65 50 UIC DML 93 39 50 90 UIC AML 83 56 86 50 Conclusões: Para a população estudada, a cintilografia com 99mTc-MIBI e injeção de adenosina correlaciona-se à AO% ao UIC, considerando-se as imagens de perfusão e de espessamento ventricular. Na avaliação dos resultados globais, caracterizados a partir da adição dos dados do ECG e das manifestações clínicas durante a injeção de adenosina às imagens, observa-se associação com os diâmetros e as áreas da luz nos locais de maior obstrução, obtidos à ACQ e ao UIC. Adicionalmente, pela análise das respostas clínicas, ECG e hemodinâmicas, o método mostrou-se seguro e factível / Radionuclide myocardial perfusion imaging (MPI) with 99mTechnetium - MIBI in combination with pharmacological vasodilation is used to detect ischemia and for the risk stratification of obstructive coronary artery disease (CAD), employing coronary angiography as gold standard. The best accuracy is found in presence of high-grade coronary stenosis, limited when less severity is seen. To test the hyphotesis that adenosine SPECT MPI correlates with coronary lesion lumen diameter and area dimensions by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), evaluating the functional significance of coronary stenosis, we intent to test the method in patients (P) with known coronary disease. Seventy consecutive P (55,7% male, mean age 60,6) were referred to adenosine SPECT 99mTc-MIBI. Were excluded those one with unstable angina, recent myocardial infarction, left bundle branch block, and any other conditions that makes the pharmacological stress impossible. The objectives were: 1) to establish the association between the clinical, EKG and scintigraphic findings with the QCA and IVUS variables; 2) to determine the accuracy of the test, based upon defined discriminant values of 50% luminal diameter narrowing by visual analysis of coronary angiography and QCA; minimum luminal diameter (MLD) and minimum luminal area (MLA) of 1,5 mm and 4 mm2 respectively, derived from QCA and IVUS and luminal percent area stenosis (AS%) of 70% by IVUS; 3) to determine the safety and feasibility of the method, throughout clinical, hemodinamic and electrocardiographic (EKG) responses to pharmacological vasodilation. The coronary angiography revealed 105 native artery lesions in 70 P, with one, two and multivessel disease in 43 p (61,4%), 20 p (28,6%) and 7 p (10%) respectively. Left anterior descending artery disease was present in 58%, 70% and 86% of the patients, respectively. Mean percent diameter stenosis values were 49,94% (SD 12,69) by visual analysis of angiography and 44,20% (SD 10,37) by QCA. Myocardial scintigraphy findings were defined as dicotomic variables categorized as normal x abnormal uptake or normal x reversible uptake; these findings were associated with visual, QCA and IVUS variables through mean comparison (t test). Chest pain during adenosine infusion was not related with greater stenosis severity, but ischemic EKG abnormalities were associated with different mean values when percent diameter stenosis derived from visual analysis was compared (p < 0,05). Therefore, any myocardial uptake abnormality, reversible uptake or any tickening abnormalities were correlated with AS% by IVUS (p< 0,05). Finally, the clinical, electrocardiographic and scintigraphic findings were considered together and categorized into global abnormal x normal response or global ischemic x normal response. Global ischemic response was associated to smaller mean values of MLD and MLA by QCA and IVUS: ischemic x normal MLD by QCA = 1,49 ± 0,34 mm x 1,71 ± 0,49 mm, p< 0,05; ischemic x normal MLD by IVUS = 1,63 ± 0,38 mm x 1,97 ± 0,50 mm, p<0,05; ischemic x normal MLA by QCA = 3,74 ± 1,78 mm2 x 5,00 ± 2,65 mm2, p<0,05; and ischemic x normal MLA by IVUS = 2,74 ± 1,38 mm2 x 4,01 ± 1,79 mm2, p<0,05). Sensitivity (S), Specificity (Sp), Predictive positive (PPV) and negative values (PNV) were calculated based upon discriminate values from visual, QCA and IVUS. The EKG response, related to percent diameter luminal stenosis by visual analysis of angiography showed S=37% and Sp=77%. Reversible uptake had S=75%; Sp=64%; PPV=43% and PNV=88%. The global ischemic findings that were discriminant are described bellow: Method Variable S (%) Sp (%) PPV (%) PNV (%) QCA DML 78 44 51 73 QCA AML 71 43 65 50 IVUS DML 93 39 50 90 IVUS AML 83 56 86 50 Considering the studied population with known coronary artery disease, perfusion and thickening adenosine SPECT results are associated with AS% by IVUS. When Clinical, EKG and scintigraphic findings are considered together as a dicotomic variable (ischemia x normal), correlation is observed between MLD and MLA by QCA and IVUS. Also, the method is considered feasible and safe, when clinical, hemodinamic and EKG abnormalities are evaluated

Orientador: Maria Jaqueline Mamprim / Banca: Carlos Roberto Teixeira / Banca: Maria Denise Lopes / Banca: Priscila Macedo de Souza / Banca: Raquel Sartor Marcelino / Resumo: A onça parda (Puma concolor) possui significativa expressão no controle de outros vertebrados. Ela está no topo da cadeia alimentar, o que demonstra a sua grande importância em seu habitat natural. A espécie apresenta-se na Lista nacional oficial de espécies da fauna ameaçadas de extinção - peixes e invertebrados aquáticos, do Ministério do Meio Ambiente brasileiro, publicada na Instrução Normativa n. 3, de 27 de maio de 2003, e atualizada pela Portaria n. 444, de 17 de dezembro de 2014. A análise ultrassonográfica abdominal em modo B, Doppler colorido e espectral, associada à avaliação clínico-laboratorial desses animais fornecerá valores de referências que auxiliarão na investigação de doenças, uma vez que, não existem relatos pretéritos no que tange a investigação sonográfica desses felinos. Foram realizados exames ultrassonográficos e laboratoriais em quatorze animais, sendo onze machos e três fêmeas, livres de Leishmania chagasi e provenientes do Centro de Reabilitação de Animais Silvestres, Campo Grande, MS, sendo calculadas as médias dos valores encontrados para título de análises. O fígado apresentou-se hipoecogênico. A parede da vesícula biliar hiperecogênica, medindo 0,21 cm. Os diâmetros da artéria aorta, veia cava caudal e veia portal foram respectivamente 1,42 cm, 1,43 cm, 0,84 cm e a fluxometria portal foi de 32,30 cm/s. O baço é hiperecogênico, medindo 3,25 cm em corte transversal. A velocidade da artéria esplênica foi 47,13 cm/s. A parede do estômago e intestino mediram 0,26 cm e 0,20 cm respectivamente. O comprimento da adrenal esquerda foi 3,52 cm e a direita 3,23 cm. A espessura da parede da bexiga foi de 0,22 cm, o comprimento renal direito 6,22 cm e o esquerdo 5,96 cm. O índice de resistividade da artéria renal direita foi de 0,51 e esquerda de 0,50. A ultrassonografia mostrou-se eficiente na avaliação abdominal de onças pardas e é promissora a utilização desta ... / Abstract: The cougar (Puma concolor) has significant expression in the control of other vertebrates. She is at the top of the food chain, which shows its importance in their natural habitat. The species present in the official national list of animal species threatened with extinction - fish and aquatic invertebrates, the Ministry of the Brazilian Environment, published in the Normative Ruling. 3 of 27 May 2003, and updated by Ordinance N. 444 of 17 December 2014. The abdominal ultrasound examination in B, color and spectral Doppler, associated with clinical and laboratory evaluation of these animals provide values of references that will assist in the investigation of diseases, since there are no reports in the past tense respect the sonographic investigation of these cats. Ultrasound and laboratory tests were performed in fourteen animals, which eleven males and three females, free of Leishmania chagasi and from the Rehabilitation Center of Wild Animals, Campo Grande, MS, and computed the average values found for under analysis. The liver was presented hypoechoic. The wall of the gallbladder hyperechogenic, measuring 0.21 cm. The diameter of the aorta, vena cava and portal vein were respectively 1.42 cm, 1.43 cm, 0.84 cm and flowmetry gate was 32.30 cm/s. The spleen is hyperechogenic, measuring 3.25 cm in cross section. The speed of the splenic artery was 47.13 cm/s. The wall of the stomach and intestine measured 0.26 cm and 0.20 cm, respectively. The length of the left adrenal was 3.52 cm and 3.23 cm right. The thickness of the bladder wall was 0.22 cm, the right renal length 6.22 cm and 5.96 cm left. The right renal artery resistance index was 0.51 and left 0.50. Ultrasonography was efficient in the abdominal assessment brown ounces and is promising to use this tool in the clinical routine of wild animal medicine / Doutor

Objetivos: 1.- Analizar las características biológicas de las células plasmáticas (CP) en sangre periférica (SP) y en médula ósea (MO) en un grupo control sano y en pacientes con discrasias de células plasmáticas y relacionarlas con las características clínico-patológicas y la evolución de la enfermedad de los pacientes. 2.- Estudiar la presencia y fenotipo de CP clonales en SP (aCPs), para establecer una relación con las características biológicas de las células plasmáticas de MO, el diagnóstico y la evolución de la enfermedad. 3.- Analizar en SP la expresión de moléculas de activación/adhesión CD62L, HLA-DR y CD56 en linfocitos T y la expresión de moléculas KIR2DL en linfocitos T (CD4+ y CD8+) y células NK, en relación con las características biológicas de las células plasmáticas de sangre periférica y médula ósea, el tipo de gammapatía y la evolución clínica. Metodología: Se incluyeron un total de 164 pacientes procedentes de tres hospitales de la Región de Murcia de nuevo diagnóstico de discrasia de células plasmáticas (MGUS, SMM y MM) y aquellos que sin ser de nuevo diagnóstico no han recibido tratamiento, siguiendo los criterios del IMWG 2003. También se estudias 30 controles sanos. Las células fueron analizadas por histología, citometría de flujo (CMF) y por FISH. Resultados: Los diagnósticos fueron: 86 MGUS, 25 SMM y 53 MM. El porcentaje de CPs y la ratio proliferación/apoptosis de CPs, en MO, son de ayuda para orientar el diagnóstico de MGUS frente a Mieloma (SMM+MM) y tienen capacidad predictiva de progresión y SG. La combinación de ambos permite establecer un modelo de estimación de riesgo basado en parámetros de MO: CPs≥1.78% y ratios proliferación/apoptosis≥1.77 discriminan pacientes de bajo, intermedio y alto riesgo en SMM+MM. Incluso tiene capacidad pronóstica independientemente del tratamiento aplicado. De las alteraciones analizadas por FISH (aneuploidía, deleción 13q, rotura IHG, ganancia 1q y deleción p53), son estas dos últimas las que impactan de forma negativa en progresión y SG. La presencia de aCPs en SP ≥ 0.0035% son útiles para discriminar MGUS de mieloma y es un parámetro predictivo de progresión y supervivencia independiente a otros parámetros bien establecidos. Hemos establecido un modelo de estimación de riesgo basado en parámetros de SP como son edad, ISS y presencia de aCP en SP que identifica pacientes de bajo, intermedio y alto riesgo, reduciendo el porcentaje de pacientes de riesgo intermedio e incrementando los de alto riesgo en comparación al modelo propuesto por el IMWG-2014 con basado en citogenética e impacta con mayor fuerza en el riesgo de progresión y SG que el propuesto por IMWG-2014. Las células T CD8+ que expresan CD57, CD62L y/o HLA-DR, en SP, tiene una reducida utilidad en diagnóstico y/o pronóstico. La detección de la expansión de linfocitos T CD8+CD57+DR+, si se ha podido asociar tanto con la carga tumoral como con la frecuencia de aCPs en SP. Conclusiones: 1. El porcentaje de CPs en MO por CMF y el ratio proliferación/apoptosis son factores pronósticos que permiten establecer un modelo de predicción de riesgo en mieloma (SMM+MM). 2. La deleción de P53 y la amplificación de 1q (por FISH) son los principales marcadores de mal pronóstico para progresión y SG. 3. Cifras de aCPs en SP discriminan MGUS de mieloma y permiten establecer un modelo de predicción de riesgo en Mieloma 4. En ambos modelos de predicción de riesgo estimada con parámetros de CMF en SP o MO, mantiene su valor pronóstico con independencia del tratamiento administrado. 5. Los linfocitos T CD8+CD57+DR+, asocian tanto con la carga tumoral como con la frecuencia de aCPs en SP. 6. La presencia del ligando específico para KIR2DS1-HLA-C2 parece condicionar la susceptibilidad a padecer mieloma. / Objectives: 1. To analyze the biological characteristics of the plasma cells (CP) in peripheral blood (PB) and bone marrow (BM) in a healthy control group and patients with plasma cell dyscrasias and relate clinicopathological features and the evolution of the disease of patients. 2. Study the presence and phenotype in clonal CP SP (ACPs) to establish a relationship with the biological characteristics of the plasma cells in MO, diagnosis and disease progression. 3. Scan molecule expression SP activation / adhesion CD62L, HLA-DR and CD56 on T lymphocytes and KIR2DL molecule expression in T lymphocytes (CD4 + and CD8 +) and NK cells in relation to the biological characteristics of plasma cells in peripheral blood and bone marrow, gammopathy type and clinical outcome. Methodology: A total of 164 patients from three hospitals in the Murcia region of new diagnosis of plasma cell dyscrasias (MGUS, SMM and MM) and those that will be newly diagnosed untreated been included following criteria IMWG 2003. 30 healthy controls were also studying. Cells were analyzed by histology, flow cytometry (FCM) and by FISH Results: The diagnoses were: 86 MGUS, SMM 25 and 53 MM. The percentage of CPs and proliferation / apoptosis of CPs, MO, ratio are helpful to guide the diagnosis of MGUS versus myeloma (SMM + MM) and are predictive of progression and OS. The combination of both allows for a risk estimate model parameters based on MO: CPs≥1.78% and ratios proliferation / apoptosis≥1.77 discriminate patients at low, intermediate and high risk SMM + MM. It even has prognostic applied regardless of treatment analyzed by FISH abnormalities (aneuploidy, deletion 13q, gain 1q and deletion p53), the latter two are impacting negatively on progression and SG. The presence of ACPs in SP S ≥ 0.0035% are useful to discriminate myeloma and MGUS is a parameter predictive of progression and survival independent other well established parameters. We have established an estimation model based risk parameters SP as are age, ISS and presence of ACP SP identifies patients at low, intermediate and high risk, reducing the percentage of patients with intermediate risk and increasing high-risk compared to that proposed by the IMWG-2014 based on cytogenetic and impacts most strongly in the risk of progression and SG model proposed by IMWG-2014. CD8 + T cells and / or cells expressing CD57, HLA-DR CD62L, SP, has little use in diagnosis and / or prognosis. Detecting the expansion of CD8 + T lymphocyte CD57 + DR +, if it has been associated with both tumor burden as often as ACPS SP. Conclusions: 1. The percentage of CPs in MO by multiparametric flow cytometry and proliferation/apoptosis ratio are prognostic factors that allow to establish a risk prediction model Myeloma (SMM + MM). 2. Deletion of p53 and amplification of 1q (FISH) are the main markers of poor prognosis for the progression and OS. 3. aCPs figures MGUS to myeloma SP discriminate and allow for a prediction model Myeloma risk 4. In both models of risk prediction parameters estimated with either CMF or SP in MO, maintains its prognostic value regardless of the type of treatment given. 5. T CD8 + DR + CD57 + lymphocytes associated with both tumor burden as often as aCPS SP. 6. The presence of the ligand specific for HLA-C2-KIR2DS1 seems to condition susceptibility to myeloma

The usability of computer models of the heart depends mostly on their capacity to accurately represent heart anatomy, microstructure and function. However, integrating such a variety of biological data is often not possible. This is the case of the cardiac conduction system (CCS), which is responsible for the fast and coordinated distribution of the electrical impulses. The CCS cannot be observed in-vivo but it is mandatory in several cardiac modeling applications involving arrhythmias. The aims of this thesis are to show the importance of explicitly modeling the CCS structure and function for an accurate description of the electrical activation of the ventricles and to present a novel technique to build automatically a CCS structure that meets physiological observations. Pursuing that goal has required a multidisciplinary effort to build models for cardiac electrophysiology, and imaging techniques to acquire and analyze data of the CCS at different scales. / La usabilidad de modelos computacionales cardíacos depende del poder representar con precisión la anatomía del corazón, su microestructura y su función. Sin embargo, la integración de tal variedad de datos biológicos no siempre es posible. Este es el caso del sistema de conducción cardiaco (CCS), que es responsable de la distribución rápida y coordinada de los impulsos eléctricos. El CCS no puede ser observado in vivo pero es imprescindible en los modelos del corazón que involucran las arritmias. Los objetivos de esta tesis son el modelar la estructura y función del CCS para obtener una descripción precisa de la activación eléctrica del corazón y el construir la estructura de un CCS que cumpla con las observaciones fisiológicas. La persecución de este objetivo ha requerido un esfuerzo multidisciplinar para construir modelos de la electrofisiología cardiaca y las técnicas de imagen necesarias para adquirir y analizar datos del CCS a diferentes escalas.

Al nostre estudi avaluem l' estratègia de revascularització percutània com a tractament de la cardiopatia isquèmica crònica i estable al nostre medi. Estudiem els predictors independents per a la prolongació de l'ingrés després de la realització de l'intervencionisme coronari percutani. Amb això es dibuixen els criteris d'exclusió d'un programa d'angioplàstia ambulatòria. També s'identifiquen els pacients amb un major risc per a reingressar al mes i al cap de tres mesos post procediment. Finalment s'analitza la mortalitat a l'any. Els predictors independents per la prolongació de l'ingrés són: realitzar el procediment via femoral, que a la nostra població selecciona pacients amb procediments més complexos, els pacients de més edat, la hipertensió arterial, la insuficiència renal crònica, la malaltia vascular perifèrica i el tractament del tronc coronari esquerra. L'accés femoral i realitzar intervencionisme per insuficiència cardíaca o miocardiopatia dilatada, varen augmentar de forma significativa el risc de reingrés al mes. Els factors que es relacionen de manera significativa amb la mortalitat a l'any per totes les causes, varen ser el reingrés al mes, l'intervencionisme per insuficiència cardíaca, la no utilització de stent farmacoactiu i tractar un vas diferent de la coronària dreta. / En nuestro estudio evaluamos la estrategia de la revascularización percutánea como tratamiento de la cardiopatía isquémica crónica y estable en nuestro medio. Estudiamos los predictores independientes para la prolongación del ingreso tras realización de intervencionismo coronario percutáneo. Con ello se dibujan los criterios de exclusión de un programa de angioplastia ambulatoria. También se identifican los pacientes de mayor riesgo para reingresar al mes y tres meses postprocedimiento. Finalmente se analiza la mortalidad al año. Los predictores independientes para la prolongación del ingreso son: realizar el procedimiento por vía femoral, que en nuestra población selecciona pacientes con procedimientos más complejos, los pacientes más añosos, la hipertensión arterial, la insuficiencia renal crónica, la enfermedad vascular periférica y el tratamiento de tronco coronario izquierdo. El acceso femoral y realizar intervencionismo por insuficiencia cardiaca o miocardiopatía dilatada, aumentaron de manera significativa el riesgo de reingreso al mes. Los factores que se relacionaron de manera significativa con la mortalidad al año por todas las causas fueron el reingreso al mes, el intervencionismo por insuficiencia cardiaca, la no utilización de stent farmacoactivo y el tratar un vaso diferente a la coronaria derecha. / Our study evaluates percutaneous revascularization strategy as a treatment for chronic stable cardiac ischemic disease in our environment. We study independent predictors for prolonging hospitalization after percutaneous coronary revascularization. These predictors are used in the design of exclusion criteria for a same day discharge angioplasty program. We also identify the profile of patients who have a higher risk for readmission at one month and at three months. Finally, we analyse mortality after one year follow up. The independent predictors for prolonging hospitalization were femoral approach (this approach is used for more complex procedures in our sample), older people, hypertension, chronic renal failure, peripheral vascular disease and percutaneous treatment of left main coronary artery. Femoral approach and percutaneous revascularization for the treatment of heart failure or dilated cardiomyopathy were significant factors for one-month readmission. Significant factors related to one-year overall mortality were one-month readmission, percutaneous coronary intervention in heart failure context, non-use of drug eluting stent and the treatment of a different vessel than right coronary artery.

Objetivos Este estudio plantea la hipótesis de que la cirugía cardíaca minimamente invasiva para recambio valvular aórtico por miniesternotomía en “J” no es inferior en términos de morbimortalidad perioperatoria en relación al abordaje convencional, y que podría presentar ventajas en cuanto a la recuperación de los pacientes y a una disminución en las necesidades transfusionales. Además, podría ser una opción válida para los pacientes de alto riesgo incluidos en la llamada “zona gris” sometidos actualmente a recambios valvulares transcateter (TAVI) . Métodos Estudio retrospectivo realizado en un solo centro (Consorcio Hospital General Universitario de Valencia, España), se recogen los pacientes intervenidos de recambio valvular aórtico aislado de forma consecutiva entre los años 2005 y 2013. Con un total de 618 pacientes, se conformaron dos grupos, 498 en el grupo intervenido por esternotomía media (grupo E) y 120 en el de abordaje minimamente invasivo (grupo M). Tras emparejamiento por “propensity score matching” teniendo en cuenta las variables preoperatorias se identificaron 120 casos controles dentro del grupo E para los 120 del grupo M. Se realizó un análisis estadístico entre los grupos para variables preoperatorias, morbilidad y mortalidad peroperatoria e intrahospitalaria, requerimientos transfusionales y duración de estancias hospitalarias. Se realizó también un análisis univariante y multivariante para identificar predictores independientes de morbilidad, mortalidad y requerimientos transfusionales. Se analizaron además los resultados intra y postoperatorios de un subgrupo de pacientes de alto riesgo (EuroScore Logístico I = o > a 15) en cuanto a morbilidad y mortalidad hospitalaria. Resultados No se hallaron diferencias significativas en cuanto al score de riesgo quirúrgico ni otras variables preoperatorias entre ambos grupos. Los tiempos de circulación extracorpórea (CEC) y de pinzamiento aórtico fueron significativamente mayores en el grupo E; 94,44 ± 32,55 vs 82,19 ± 24,53 y 73,06 ± 26,87 vs 63,26 ± 16,24 respectivamente. No se encontraron diferencias significativas entre ambos grupos en mortalidad ni en compliaciones postoperatorias. La estancia tanto en Unidad de Cuidados Intensivos (UCI) como la estancia hospitalaria total fue significativamente mayor en el grupo E; 4,61 ± 6,92 vs 3,09 ± 1,69 (p 0,020) y 10,51 ± 7,82 vs 7,35 ± 3,21 (p <0,001) respectivamente. El grupo E registró mayor necesidad transfusional que el grupo M, 63,3% vs 52,5% (p 0,089) de pacientes transfundidos con concentrados de hematíes, 24,1% vs 11,6% (p 0,012) para unidades de plaquetas y 27,5% vs 14,1% (p 0,011) para plasma fresco congelado. El tiempo de CEC se presentó como factor predictivo de morbilidad, la transfusión de plasma para mortalidad y el abordaje minimamente invasivo como factor protector ante necesidades transfusionales de plaquetas. El grupo de alto riesgo no registró mortalidad. La estancia hospitalaria total y en UCI fue ligeramente más prolongada que la media del grupo total. Se registraron un 14,3% de complicaciones hemodinámicas y de herida. Discusión El interés por este abordaje viene asociado al cambio en la esfera de pacientes sometidos a cirugías cardiacas, siendo cada vez más añosos y con mayor comorbildad. Como nueva técnica, debe garantizar los mismos resultados de seguridad en cuanto a morbimortalidad en relación a la técnica estandarizada. Este trabajo, refuerza la premisa de que este abordaje es igual de seguro que el convencional; demostrando ventajas en cuanto a la recuperación en el postoperatorio y a una disminución de la necesidades transfusionales. En los pacientes de alto riesgo, considerados ahora como “zona gris” queda por consensuar el mejor tratamiento a aplicar. Con el advenimiento de nuevos dispositivos de implante como las prótesis “sutureless”, los abordajes minimamente invasivos podrían convertirse en una opción válida de tratamiento para estos pacientes. / “OUTCOMES IN MINIMALLY INVASIVE AORTIC VALVE SURGERY” SUMMARY Objective This study hypothesizes that cardiac surgery minimally invasive aortic valve replacement by ministernotomy "J" is not inferior in terms of perioperative morbidity and mortality comparing to the conventional approach. Minimmally invasive approach could be advantageous in terms of recovery and less transfusion requirements. It could also be an option for high-risk patients included in the "gray area" currently undergoing transcatheter valve replacements (TAVI). Methods Retrospective study at a single center (Consortium General Hospital Universitario de Valencia, Spain). We collected patients undergoing isolated aortic valve replacement between 2005 and 2013. 618 patients were included: 498 in the median sternotomy group (E group) and 120 in the minimally invasive approach (group M). After a propensity score matching considering the main preoperative variables, 120 cases were included in the control group E and 120 for group M. We performed a statistical analysis between groups for preoperative variables, perioperative morbidity and hospital mortality, transfusion requirements and hospital length of stay. A univariate and multivariate analysis was also performed to identify independent predictors of morbidity, mortality and transfusion requirements. A subgroup of patients at high risk with EuroScore Logistics I = or> 15 were identified and analyzed in terms of morbidity and hospital mortality. Results No significant differences in the score of surgical risk or other preoperative variables between the groups were found. Times of cardiopulmonary bypass (CPB) and aortic clamping were significantly higher in group E; 94.44 ± 32.55 vs 82.19 ± 24.53 and 73.06 ± 26.87 vs 63.26 ± 16.24 respectively. No significant differences in mortality or postoperative morbidity was found between groups. Intensive Care Unit (ICU) and the total hospital length of stay were significantly higher in group E; 4.61 ± 6.92 vs 3.09 ± 1.69 (p 0.020) and 10.51 ± 7.82 vs 7.35 ± 3.21 (p <0.001) respectively. The group E registered the highest packed red blood cells transfusion rate 63.3% vs 52.5% (p 0.089), units of platelets 24.1% vs 11.6% (p 0.012) and fresh frozen plasma 27.5% vs 14.1% (p 0.011). CPB time was found as a predictor of morbidity, mortality plasma transfusion and minimally invasive approach as a protective factor against platelet transfusion requirements. The high-risk group reported no mortality. Total hospital and ICU length of stay was slightly longer than the average for the whole group. hemodynamic and wound complications were recorded in the 14,3% of patients in this group. Discussion The increasing patients with high comorbidity undergoing cardiac surgery has increased the interest in minimally invasive aortic approach As new technique should guarantee the same outcomes in terms of morbidity and mortality safety comparing to the standardized technique. This study supports the hypothesis that this approach is as safe as conventional; demonstrating advantages in the postoperative recovery and decreased transfusion requirements. In high-risk patients, now considered "gray area", this treatment might be the best. With the advent of new implant devices such as prosthetics "sutureless" valves, minimally invasive approaches could become a valid treatment option for these patients.

This thesis presents the results of five studies that share a common bond; the analysis of organic complications (respiratory, renal and neurological) in a homogeneous cohort of recipients who received an Allo-HSCT-RIC at a single institution. The chosen scope is of particular interest to the extent that patients receiving this type of transplant are usually older, having more comorbidities, having received a greater number of previous treatments. This conditions might influence a higher risk of organic complications. Thus, the study of the organic complications could properly determine the Allo-HSCT-RIC’s tolerance in this specific group of patients. The first paper analyzed the development of pulmonary complications. The second analyzed respiratory viral infections and invasive pulmonary invasive aspergillosis (IA). The third paper evaluated the kidney complications after Allo-HSCT-RIC. The fourth paper was focused on neurological complications in the same cohort of patients. Results: The first study included 188 recipients of Allo-HSCT-RIC and analyzed the predictive value of pulmonary function test (PFT) in pulmopnary complications (PC). The cumulate incidence of PC was 45% [95% confidence interval (CI.), 38–53%]. Multivariate analysis showed that TLC was significantly associated with PC, nonrelapse mortality (NRM) and overall survival (OS), (Hazard Ratio (HR) 4.2, 95% CI. 2–8.5; HR 3.8, 95% CI. 1.7–8.5; HR 2.3, 95% CI. 1.3–4.1, respectively, P = 0.01), while abnormal FVC had a negative impact on PPC and OS (HR 1.8, 95% CI. 0.98–3.6, P = 0.06 and HR 1.7, 95% CI. 1.1–2.6, P = 0.008). The second included 219 consecutive recipients of Allo-HSCT-RIC. The 4-year incidence of IA was 13% (95% CI, 4–24%). In multivariate analysis, risk factors for developing IA were steroid therapy for moderate-to-severe graft vs host disease (HR 2.9, P<0.03), occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). The occurrence of IA had no effect on survival (P=0.5). The third manuscript include 188 Allo-HSCT-RIC recipients. The cumulative incidence of acute renal failure (ARF) at 1 year was 52%. The risk factors associated with ARF in multivariate analysis were: administration of MTX (HR 1.9, P =0.02), more than 3 lines of therapy prior to Allo-RIC (HR 1.8, P <0.01), diabetes mellitus (HR 2.1, P<0.01), and GVHD grade III-IV (HR 2.1, P =0.015). Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P<0.05). In the fourth, the author analyzes the characteristics, incidence and risk factors of neurological complications (NC) (both CNS and PNS) in the same patient population Alo-TPH-AIR and how they affect overall survival. The 4-year cumulative incidence of NC was16% (95% CI, 11-23). CNS complications included nonfocal encephalopathies in 11 patients, meningoencephalitis in 5 patients, and stroke or hemorrhage in 4. PNS complications consisted of 5 cases of mononeuropathies and 3 cases of polyneuropathies. Drug-related toxicity was responsible for 10 of the 31 events (32%) (8 caused by CsA). Overall, patients presenting NC showed a trend for higher 1-year nonrelapse mortality (NRM) (37% versus 20%, P=0.08). In patients with CNS involvement, 1-year NRM was significantly worse (42% versus 20%, P5.02). CNS NC also had a negative impact on 4-year overall survival (OS; 33% versus 45%, P5.05). Conclusions: The organic complications in the Allo-HSCT-RIC setting were diverses, frequent but did not seem more common compared to those reported in the myeloablative Allo-HSCT. The identification of several risk factors for these complications opens a window to explore further protocol modifications by reducing the conditioning doses or the application of prophilactic actions for patients at higher risk of organic complications and NRM.

Desde la inclusión de la miocardiopatía no compactada como subtipo de miocardiopatía no clasificable por la OMS en 1990, existe controversia sobre definición, umbrales de enfermedad, técnica y criterios de medida, prevalencia y pronóstico. Objetivos: Definir la prevalencia de hipertrabeculación y miocardiopatía no compactada del VI en pacientes remitidos para realización de resonancia magnética en nuestro hospital. Valorar la asociación con miocardiopatía dilatada o hipertrófica. Describir la evolución de la FEVI en estos pacientes de forma prospectiva. Validar una herramienta diagnóstica de cuantificación automática que agilice el proceso de medida. Definir puntos de corte cuantitativos para discriminar entre sanos y afectados. Metodología: Se definió hipertrabeculación como existencia de trabéculas en ≥2 cortes y ≥2 segmentos del VI. Para definir miocardiopatía no compactada se usaron los criterios de Jenni y de Petersen, basados en la relación lineal entre la pared compacta y la pared trabeculada. Se contabilizaron los pacientes con hipertrabeculación y con miocardiopatía no compactada entre 2003 y 2010, buscándose las asociaciones con la presencia de hipertrofia, dilatación, ambas o ninguna. Se cuantificó la reducción de la FEVI ente dos estudios por ecocardiografía, calculándose la tasa anual de cambio de la FEVI (variación de la FEVI dividido por años entre ecocardiografías). Se desarrolló una herramienta de cuantificación automática de las trabéculas del VI. Para validar la herramienta se utilizaron pacientes sanos, no portadores (grupo control) y pacientes con MCNC y portadores de mutaciones de distintas miocardiopatías (mho, dilatadas, arritmogénica y displasias) en sus respectivas familias (grupo afectados). La cuantificación de las trabéculas se expresó en masa de miocardio trabeculado y compactado y en porcentaje de trabeculación con respecto a la masa total de miocardio. Se realizó un test subjetivo de calificación de la exactitud de la herramienta para discriminar las trabéculas y la pared compactada. Resultados: Encontramos hipertrabeculación en el VI en 103 de un total de 764 pacientes (13,4%). La prevalencia de miocardiopatía no compactada fue del 6% siguiendo criterios de Jenni o del 5% siguiendo criterios de Petersen. Las miocardiopatías asociadas a hipertrabeculación ó a miocardiopatía no compactada fueron hipertróficas (15% y 11%), dilatadas (21% y 27%) o ambas (12% y 10%). Un 51% de los corazones con hipertrabeculación y un 52% de los no compactados mostraban dimensiones de VI normales. La FEVI de los pacientes con hipertrabeculación (50%) y no compactados (46%) fue algo menor que la de los controles (53%) sin alcanzar diferencias significativas. La hipertrabeculación se asoció con una tasa anual de caída en la FEVI del 1% al año mientras que la no compactación del 2% al año respecto a los pacientes que no tienen trabéculas. La medida automática de la pared del ventrículo izquierdo tuvo una excelente concordancia con la observación subjetiva. Mediante esta herramienta, el porcentaje de trabeculación y la masa global de trabéculas indexada por superficie corporal, con puntos de corte de 27.4% y de 39.9 gr/m2, obtuvieron una sensibilidad del 80% y una especificidad del 78% para el diagnóstico de Miocardiopatía NO Compactada. Conclusiones: La prevalencia de hipertrabeculación en nuestra población general es del 13,4% y de la miocardiopatía no compactada del 5-6%. Las trabéculas son un factor pronóstico independiente de la caída de la FEVI en el seguimiento. La herramienta desarrollada permite identificar a los pacientes con Miocardiopatía No compactada, mediante el porcentaje de trabeculación y el índice de capa trabeculada. / Introduction: Since the inclusion of non-compaction cardiomyopathy as unclassifiable subtype by WHO in 1990, there is controversy about definition, threshold disease, technique and measurement criteria, prevalence and prognosis. Goals: Define the prevalence of hypertrabeculation and non-compaction cardiomyopathy in patients referred for performing MRI in our hospital. Assess the association with dilated or hypertrophic cardiomyopathy. Describe the evolution of LVEF in these patients prospectively. Validate a diagnostic tool for automatic quantification that expedites the measurement process. Define quantitative cutoffs to discriminate between healthy and affected. Methodology: Hypertrabeculation was defined as existence of trabeculae in ≥2 segments and ≥2 slices of the left ventricle. To define non-compaction cardiomyopathy were used Jenni and Petersen criteria, based on the linear relationship between the solid and trabecular wall. Hypertrabeculation and non-compaction cardiomyopathy patients, between 2003 and 2010, were counted. We classified patients according to the presence of dilated, hypertrophic cardiomyopathy (HC), both or neither. Reduction of LVEF between two echocardiographic studies was quantified and calculated the annual rate of change of LVEF (LVEF variation between two echocardiography studies and divided by years between studies). A tool for automatic quantification of trabeculae was developed. To validate the tool, healthy patients non-carriers (control group) and patients with LVNC and mutation carriers of various cardiomyopathies (HC, dilated, and arrhythmogenic dysplasia) in their families (affected group) were used. Quantification of trabeculae was expressed in trabecular and compacted mass and percentage of trabeculae respect to the total mass of the myocardium. A subjective test of qualification for the accuracy of the tool to discriminate trabecular and compacted wall was performed. Results: We found LV hypertrabeculation in 103 of a total of 764 patients (13.4%). The prevalence of non-compaction cardiomyopathy was 6% following Jenni criteria or 5% following Petersen criteria. We detected hypertrabeculation and non-compaction cardiomyopathy associated with hypertrophic cardiomyopathy (15% and 11%), dilated (21% and 27%) or both (12% and 10%). 51% of hearts with hypertrabeculation and 52% of non- compacted showed normal LV dimensions. LVEF in hypertrabeculation patients (50%) and uncompacted patients (46%) was somewhat lower than that of controls (53%) but difference was not significant. Hypertrabeculation was associated with an annual rate of decline in LVEF of 1% per year while non- compaction of 2% per year compared to patients without trabeculae. The automatic measurement of left ventricular wall was excellent agreement with the subjective observation. Using this tool, the percentage of the total mass trabeculation and trabecular indexed by body surface, with cutoffs of 27.4 % and 39.9 g / m2, obtained a sensitivity of 80 % and a specificity of 78% for the diagnosis of non compaction cardiomyopathy. Conclusions: Hypertrabeculation prevalence in our general population is 13.4 % and non -compaction cardiomyopathy 5-6%. The trabeculae are an independent predictor of the decline in LVEF at follow-up. The tool developed can identify patients with non-compaction cardiomyopathy, by the percentage of trabeculation and trabecular index layer. LVNC: Left Ventricular Non Compaction; LVEF: Left Ventricular Ejection Fraction; HC: Hypertrophic Cardiomyopathy; WHO: World Health Organization.

Objetivos: 1. Estudiar el efecto de varios polimorfismos localizados en genes no sarcoméricos en la fibrosis cardiaca en pacientes con miocardiopatía hipertrófica: 1.1 Estudiar la asociación de los polimorfismos con el grado de fibrosis miocárdica mediante resonancia magnética cardiaca utilizando realce de gadolinio. 1.2 Estudiar la implicación de los polimorfismos en el grado de fibrosis miocárdica observado en tejidos miocárdicos de pacientes con MCH obtenidos por miectomía. 2. Estudiar el efecto de varios polimorfismos localizados en genes no sarcoméricos en el desarrollo de fibrilación auricular en pacientes con MCH. 3. Estudiar el efecto de varios polimorfismos localizados en genes no sarcoméricos en el ingreso hospitalario urgente en pacientes con MCH. Metodología: Se realizó un estudio de cohortes incluyendo pacientes estables con MCH en tres hospitales terciarios del sudeste de España. Se incluyó de forma consecutiva todos los pacientes mayores de 18 años con diagnóstico de MCH tras la realización de una resonancia magnética cardiaca. A todos los pacientes se realizó una evaluación clínica con anamnesis, exploración clínica y exploraciones complementarias (electrocardiograma, ecocardiografía, holter-ECG, ergometría, resonancia magnética cardiaca). Se realizó la determinación de 9 polimorfismos en genes no sarcoméricos (ACE D/I, AGTR1 1166A>C, CYP11B2 -344C>T, COL1A1 2046G>T, RETN -420C>G, ADRB1 1165G>C, PPARGC1A 1444G>A, NOS3 894T>G y CALM3 -34T>A). Se determinó la concentración de resistina en suero mediante técnica de ELISA (Enzyme-linked immunosorbent assay). Los valores de aldosterona en suero fueron determinados mediante RIA (radioinmuinoassay) directo. Se determinó el grado de fibrosis en muestras de tejido miocárdico procedente de miectomía septal empleando la tinción tricrómica de Masson. Resultados: La población del estudio la constituyeron 168 pacientes y 136 controles con una mediana de seguimiento de 49,5 meses (RIC 25,8 - 77,0). La presencia del polimorfismo RETN -420C>G se mantuvo como predictor independiente del número de segmentos con realce tardío con gadolinio en el análisis multivariante (R² corregido 0,031, p:0,038). La asociación entre el polimorfismo -420C>G del gen RETN y la fibrosis intersticial en el tejido miocárdico fue estadísticamente significativa [Coeficiente B: 0,488 (IC 95% 0,015-0,962), p: 0,044]. En el análisis multivariante la presencia del polimorfismo en la región promotora del gen CYP11B2 (-344T>C) [HR: 3,02 (IC 95% 1,01-8,99); p=0,047], el antecedente de FA previa [HR: 2,81 (IC 95% 1,09-7,23); p=0,033] y el diámetro de la AI ≥42 mm [HR: 2,69 (IC 95% 1,01-7,18); p=0,048] continuaron siendo predictores independientes del desarrollo de la FA. En el análisis multivariado tanto la edad [HR: 1,03 (IC 95% 1,00-1,05); p=0,047] como la ausencia del polimorfismo del gen COL1A1 (genotipo 2046G/G) [HR: 2,76 (1,26-6,05), p=0,011] continuaron asociados de forma independiente con el ingreso hospitalario. Conclusiones: CONCLUSIÓN 1: El polimorfismo en la región promotora del gen de la resistina, RETN -420C>G, se asocia de manera significativa con la fibrosis cardiaca en pacientes con miocardiopatía hipertrófica. Conclusión 1.1: El polimorfismo en la región promotora del gen de la resistina, RETN -420C>G, se asocia de manera significativa con un incremento en el número de segmentos que presentan realce tardío con gadolinio en la resonancia magnética cardiaca. Conclusión 1.2: El polimorfismo en la región promotora del gen de la resistina, RETN -420C>G, se asocia de manera significativa con el grado de fibrosis miocárdica en muestras de tejido miocárdico obtenidas por miectomía. CONCLUSIÓN 2: La presencia del polimorfismo de la región promotora de la aldosterona sintetasa, CYP11B2 -344C>T, se asocia de manera significativa con el desarrollo de fibrilación auricular en los pacientes con miocardiopatía hipertrófica. CONCLUSIÓN 3: El polimorfismo del gen de la cadena α1 del colágeno tipo I, COL1A1 2046G>T, es un predictor independiente del pronóstico en pacientes con miocardiopatía hipertrófica, evaluado mediante la necesidad de ingreso hospitalario urgente. / Objectives: 1. To study the effect of several polymorphisms located in non sarcomeric genes in cardiac fibrosis in patients with hypertrophic cardiomyopathy (HCM): 1.1 To study the association of polymorphisms with the degree of myocardial fibrosis by cardiac MRI using gadolinium enhancement. 1.2 To study the involvement of the polymorphisms in the degree of myocardial fibrosis observed in myocardial tissues obtained from patients with HCM by septal myectomy. 2. Study the effect of several polymorphisms located in non sarcomeric genes in the development of atrial fibrillation in patients with HCM. 3. Study the effect of several polymorphisms located in non sarcomeric genes in urgent hospitalization in patients with HCM. Methods: A cohort study including patients with stable HCM in three tertiary hospitals in southeastern Spain was performed. All patients older than 18 years diagnosed with HCM were consecutively included after completion of a cardiac MRI. All patients underwent a clinical evaluation: anamnesis, clinical examination and complementary examinations (electrocardiogram, echocardiography, Holter-ECG, effort test and cardiac MRI). The presence of nine polymorphisms in non sarcomeric genes were determined (ACE D/I, AGTR1 1166A>C, CYP11B2 -344C>T, COL1A1 2046G>T, RETN -420C>G, ADRB1 1165G>C, PPARGC1A 1444G>A, NOS3 894T>G y CALM3 -34T>A). The serum resistin concentration is determined by ELISA (Enzyme-linked immunosorbent assay). Aldosterone levels in serum were determined by direct radioinmuinoassay. The fibrosis is determined in tissue samples from myocardial septal myectomy using the Masson's trichrome staining. Results: The study population was constituted by 168 patients and 136 controls with a median follow up of 49.5 months (IQR 25.8 to 77.0). The presence of the polymorphism RETN -420C>G gene remained an independent predictor of the number of segments with late gadolinium enhancement in the multivariate analysis (adjusted R² 0.031, p: 0.038). The association between polymorphism RETN -420C>G gene and interstitial fibrosis in myocardial tissue was statistically significant [B coefficient: 0.488 (95% CI 0.015 to 0.962), p: 0.044]. In the multivariate analysis, the presence of the polymorphism in the promoter region of CYP11B2 (-344T> C) [HR: 3.02 (95% CI 1.01 to 8.99); p = 0.047], the history of previous AF [HR: 2.81 (95% CI 1.09 to 7.23); p = 0.033] and the diameter of the AI ≥42 mm [HR: 2.69 (95% CI 1.01 to 7.18); p = 0.048] remained independent predictors of the development of AF. In the multivariate analysis, both age [HR 1.03 (95% CI 1.00-1.05); p = 0.047] and the absence of COL1A1 gene polymorphism (genotype 2046G / G) [HR: 2.76 (1.26 to 6.05), p = 0.011] remained independently associated with hospitalization. Conclusions: CONCLUSION 1: The polymorphism in the promoter region of the resistin gene, RETN -420C> G, was significantly associated with cardiac fibrosis in patients with hypertrophic cardiomyopathy. Conclusion 1.1: The polymorphism in the promoter region of the resistin gene, RETN -420C> G, was significantly associated with an increase in the number of segments presenting late gadolinium enhancement on cardiac MRI. Conclusion 1.2: The polymorphism in the promoter region of resistin gene, RETN -420C> G is associated significantly with the degree of myocardial fibrosis in myocardial tissue samples obtained by Myectomy. CONCLUSION 2: The presence of the polymorphism in the promoter region of aldosterone synthase gene, CYP11B2 -344C> T, was significantly associated with the development of atrial fibrillation in patients with hypertrophic cardiomyopathy. CONCLUSION 3: The polymorphism of α1 chain of type I collagen, COL1A1 2046G> T, is an independent predictor of prognosis in patients with hypertrophic cardiomyopathy, assessed by the need for urgent hospitalization.

El presente trabajo está dirigido a conocer la utilidad de la implementación de las normativas de la Sociedad Española de Neumología (SEPAR) y del tratamiento empírico en la neumonía adquirida en la comunidad (NAC). Las normativas elaboradas por las sociedades científicas proporcionan una ayuda al clínico en el manejo de la infección y proporcionan una mejor calidad asistencial. Su implementación tiene efectos directos sobre la duración de la estancia, reingreso y mortalidad. De hecho, existen diferencias entre la elección de un determinado tipo de antibiótico en el pronóstico de la NAC. Este trabajo incluye una segunda parte dirigida al análisis fármaco-económico e implicación de la elección del tratamiento antibiótico empírico en términos de costes y eficacia durante la hospitalización de la NAC. Estos estudios coste-eficacia permiten evaluar la práctica clínica para maximizar el beneficio de salud frente al paciente a partir del cálculo de costes para las distintas alternativas de tratamiento. Esta tesis supone una aportación desde el punto de vista clínico a la búsqueda de medidas eficaces en el tratamiento de pacientes con NAC. Este estudio ha ayudado a demostrar la eficacia de las normativas SEPAR en términos de mejora de calidad asistencial y pronostico. Ha ayudado a demostrar la eficacia en términos de coste-efectividad de las diferentes alternativas de tratamiento según la adherencia a las directrices y como consecuencia una reducción de los costes hospitalarios / This work is aimed to determine the usefulness of implementing the spanish guidelines in community-acquired pneumonia (CAP). The guidelines developed by scientific societies, provide the clinicians support in the management of infections and provide better quality care. Its implementation has direct effects on the length of stay, readmission and mortality. In fact, there are differences between the choice of a specific type of antibiotic and the prognosis of CAP. This work includes a second part addressed to pharmacoeconomic analysis and involvement of empiric treatment in terms of cost and efficiency during CAP hospitalization. These cost-effectiveness analysis assess clinical practice to maximize health benefit to the patient based on the calculation of costs for various treatment alternatives. This thesis is a contribution, from the clinical point of view, to the search of effective measures in the treatment of patients with CAP. This study has helped to prove the efficacy of the SEPAR guidelines in terms of improved quality of care and prognosis. It has also helped to show efficacy in terms of cost-effectiveness of different treatment options, according to adherence to the guidelines, and as a consequence, a reduction in hospital costs.