Introdução: A falta de sistemas estruturados de custeio nas organizações hospitalares, principalmente filantrópicas, tem dificultado a análise da cobertura dos custos pelo repasse do Sistema Único de Saúde (SUS) aos procedimentos realizados. Objetivo: Identificar a percentagem de cobertura do repasse de verba do SUS para a cirurgia de revascularização miocárdica (CRM), em um hospital filantrópico do município de São Paulo, que possui um sistema de custeio consolidado. Método: Estudo de abordagem quantitativa, transversal e descritiva. Utilizou-se um banco de dados com registro de CRM denominado REVASC, criado pela instituição em 2009 e de inclusão contínua. As informações para a pesquisa foram coletadas de 13 de março a 30 de setembro de 2012. A escolha do período foi devido ao início da inclusão de informações sobre custo e repasse do SUS. A população alvo foi de 1913 pacientes e amostra de 1362 (71,2%). Resultados: O custo total médio da internação por paciente foi de R$16.196,91. A média de repasse pelo SUS foi de R$6.992,91(48,66%), observando-se um déficit de 9.204,00 (51,34%). A média de idade foi de 61,4 anos e 69,9% eram do sexo masculino. A média do tempo de permanência hospitalar (TPH) foi de 11,23 dias, sendo 2,42 dias na terapia intensiva e 8,49 dias no pós-operatório. A maioria dos pacientes (69,5%) apresentou um TPH maior que sete dias, considerada prolongada pela instituição. Ao comparar o Grupo 1 (TPH7dias) e Grupo 2 (TPH>7dias), este apresentou custo, receita, diferença entre custo-receita e diferença percentual significativamente maiores que os pacientes do Grupo1. Ao associar o TPH com fatores de risco houve diferença apenas no Grupo 2 que apresentou maior idade, maior número de diabetes e de insuficiência renal crônica. Em relação às complicações pós-operatórias houve diferença em relação a transfusão sanguínea, fibrilação atrial, sangramento importante, pneumonia, insuficiência renal aguda, infarto agudo do miocárdio perioperatório, hemodiálise, acidente vascular encefálico, ventilação mecânica prolongada e reoperação por sangramento / mediastinite, também com incidência maior no Grupo2. Conclusão: O repasse do SUS cobriu menos da metade do custo total médio da internação em CRM (48,66%). Embora o valor do repasse do SUS tenha aumentado conforme a elevação do custo, esse ressarcimento foi desproporcional ao custo total, resultando numa diferença percentual de receita cada vez mais negativa a cada aumento do custo e da permanência hospitalar. / Introduction: The lack of structured expense systems in hospital organizations, especially when philanthropic, has hindered the analysis of the coverage of costs by transfer of funds from the Unified Healthcare System (SUS) for the procedures performed. Objective: To identify the percentage of coverage of the transfer of funds from SUS for coronary artery bypass surgery (CABG) in a philanthropic hospital that has a consolidated expense system in the municipality of São Paulo. Method: A quantitative, cross-sectional, and descriptive study. A databank containing data with CABG records called REVASC was used, created by the institution in 2009 with ongoing data inclusion. Information for the research was collected from March 13 to September 30, 2012. The choice of that period was due to the start of inclusion of information on costs and the transfer of funds from SUS. The target population was made up of 1913 patients and a sample of 1362 (71.2%). Results: The total mean cost of hospitalization per patient was R$16,196.91. The mean transfer of funds by SUS was R$6,992.91 (48.66%), with a deficit of 9,204.00 (51.34%). The mean age of the subjects was 61.4 years, and 69.9% of them were men. The mean hospital stay (HS) was 11.23 days, in which 2.42 days were in intensive therapy, and 8.49 days in the postoperative unit. Most of the patients (69.5%) had a HS longer than seven days, considered prolonged by the institution. When comparing Group 1 (HS 7 days) and Group 2 (HS >7 days), the latter group showed costs, revenue, difference between cost and revenue, and percentage difference significantly greater than did the patients from Group 1. In associating the HS with risk factors, there was a greater difference only in Group 2, which showed a higher age, and greater number individuals with diabetes and chronic renal failure. As to postoperative complications, there was a difference as to blood transfusion, atrial fibrillation, significant bleeding, pneumonia, acute renal failure, perioperative acute myocardial infarct, hemodialysis, cerebrovascular accident, prolonged mechanical ventilation, and reoperation due to bleeding/mediastinitis, also with an incidence greater than in Group 2. Conclusion: The financial provision from SUS covered less than half the total mean cost of hospitalization for CABG (48.66%). Although the value transferred from SUS increased according to cost elevation, this reimbursement was disproportional to the total cost, resulting in an increasingly negative percentage difference of revenue for each increase in cost and in hospital stay.

Abstract Coronary artery disease (CAD) is the leading cause of death in developed countries. In patients with complex CAD, coronary artery bypass grafting (CABG) remains the preferred treatment as it can provide long-lasting results. However, CABG carries a significant risk of excessive perioperative bleeding and other complications, which may deteriorate the prognosis. Transfusion of blood products is generally used to compensate blood loss. However, both bleeding and blood transfusions have been shown to be associated with an adverse outcome. This cohort study aimed to clarify the impact of perioperative bleeding and the use of different blood products in the development of perioperative complications in 2,764 patients undergoing isolated CABG. The universal definition of perioperative bleeding classification (UDPB) was employed to stratify the severity of bleeding. Additionally, the impact of storage time of transfused red blood cells (RBCs) on the outcome was investigated. Increased UDPB classes, particularly classes 3 and 4, were associated with significantly poorer immediate and late outcome. RBC transfusion in patients who underwent elective off-pump CABG was independently associated with increased troponin I release indicating myocardial injury. Prolonged storage duration of transfused RBCs did not affect immediate and late outcome of patients with moderate bleeding. The most remarkable risk factors for stroke after off-pump CABG were any degree of atherosclerosis of the ascending aorta as well as transfusion of platelets and/or solvent/detergent-treated plasma. The UDPB classification appears to be a promising research tool to stratify the severity of perioperative bleeding and to assess its prognostic impact after coronary surgery. Prevention of major bleeding that leads to blood transfusion may protect from myocardial injury and stroke and possibly result in better early and late outcomes. Patients with a diseased ascending aorta could be considered at high risk of stroke because of their risk of generalized atherosclerosis. In case of mildly diseased aorta, the “no-touch” aorta policy should be considered with the intention of preventing postoperative stroke. / Tiivistelmä Sepelvaltimotauti on yleisin kuolinsyy kehittyneissä maissa. Potilailla, joilla on vaikea monen suonen tai vasemman sepelvaltimon päärungon tauti, sepelvaltimoiden ohitusleikkaus on edelleen paras hoitovaihtoehto, koska sillä pystytään saavuttamaan pitkäkestoisia tuloksia. Kuitenkin ohitusleikkaukseen liittyy suuri riski leikkauksen aikaiselle tai jälkeiselle verenvuodolle ja muille haittatapahtumille, jotka osaltaan huonontavat potilaan ennustetta. Vuodon hoitona käytetään yleisesti verensiirtoa. Kuitenkin on osoitettu, että sekä verenvuoto että verituotteiden anto lisäävät riskiä komplikaatioille. Tämän kohorttitutkimuksen tavoitteena oli selvittää tarkemmin leikkauksen yhteydessä ilmenevän vuodon ja siihen liittyvän verensiirron vaikutuksia leikkauksen jälkeisten haittatapahtumien kehittymiseen 2764 ohitusleikatulla potilaalla. Universal Definition of Perioperative Bleeding (UDPB) -luokitusta käytettiin vuodon vaikeusasteen luokittelemiseen. Lisäksi tutkittiin siirrettyjen punasolujen varastointiajan vaikutusta potilaan ennusteeseen. Korkeammat UDPB-luokat, erityisesti luokat 3 ja 4, liittyivät merkittävästi huonompaan lyhyen ja pitkän aikavälin ennusteeseen. Potilailla, joille oli tehty kiireetön ohitusleikkaus ilman sydän-keuhkokoneen käyttöä, punasolujen anto oli itsenäinen riskitekijä suurentuneelle troponiini I -päästölle eli sydänlihasvauriolle. Pidentynyt punasolujen varastointiaika ei ollut yhteydessä lyhyen tai pitkän aikavälin ennusteeseen potilailla, jotka olivat vuotaneet kohtalaisesti. Merkittävimmät riskitekijät ilman sydän-keuhkokonetta tehdyn leikkauksen jälkeiselle aivoinfarktille olivat minkä tahansa asteinen nousevan aortan ateroskleroosi sekä verihiutaleiden ja/tai jääplasman anto. UDPB-luokitus vaikuttaa lupaavalta tutkimustyökalulta verenvuodon vaikeusasteen luokitteluun. Lisäksi sitä voidaan käyttää vuodon ennusteellisen vaikutuksen arvioimiseen ohitusleikkauksen jälkeen. Runsaan verenvuodon ja siihen liittyvän verensiirron ehkäiseminen saattaa suojata potilasta sydänlihasvauriolta ja aivoinfarktilta ja mahdollisesti johtaa parempaan lyhyen ja pitkän aikavälin ennusteeseen. Potilaita, joilla on nousevan aortan ateroskleroosi, voisi pitää suuressa aivoinfarktiriskissä yleisen ateroskleroosiriskin vuoksi. Potilailla, joilla on lieväkin nousevan aortan ateroskleroosi, tulisi harkita aortan jättämistä pihdittämättä aivoinfarktin ehkäisemiseksi.

Abstract Cardiovascular diseases are the leading cause of death worldwide, and coronary artery disease accounts for the majority of them. The treatment of choice for complex coronary artery disease is coronary artery bypass grafting. However, as surgery in general, cardiac surgery is associated with an increased risk of perioperative bleeding and utilization of blood products. The present study aimed to investigate the impact of preoperative anemia, perioperative bleeding and retained blood syndrome as well as blood transfusion on the outcomes after isolated coronary surgery. The severity of perioperative bleeding was assessed mainly using the E-CABG and UDPB stratification criteria. Our analyses showed that severe bleeding is associated with a significantly increased risk of stroke. Furthermore, severe bleeding increased the risk of several adverse events even in low-risk patients. Retained blood syndrome was observed to be a common complication after coronary surgery and was associated with an increased risk of postoperative complications. Preoperative anemia seems to have no significant impact on patient early and late survival. Instead, the frequent exposure to blood products may be the determinant of poorer survival observed among anemic patients. Perioperative blood loss and exposure to allogeneic blood has been shown to increase adverse events. Therefore, prevention of bleeding and measures to optimize patient blood management could improve patient outcomes after cardiac surgery. / Tiivistelmä Sydän ja verisuonitaudit ovat maailmanlaajuisesti yleisin kuoleman aiheuttaja, joista sepelvaltimotaudilla on suurin vaikutus. Sepelvaltimoiden ohitusleikkaus on käypä hoito vakavassa sepelvaltimotaudissa. Kuten kirurgiassa yleisestikin, erityisesti sydänkirurgia on yhdistetty suurentuneeseen verenevuodon ja verituotteiden saannin riskiin. Tutkimukseni tavoitteena oli selvittää preoperatiivisen anemian, perioperatiivisen verenvuodon, verituotteiden annon, sekä leikkausalueelle jääneen veren itsenäisiä vaikutuksia potilaiden lopputulemiin sepelvaltimoiden ohitusleikkauksen jälkeen. Verituotteiden ja perioperatiivisen verenvuodon määrää arvioitiin pääsääntöisesti käyttäen E-CABG ja UDPB verenvuotoluokituksia. Tuloksenamme oli, että vakava verenvuoto lisää merkitsevästi aivoinfarktin riskiä. Lisäksi vakava perioperatiivinen verenvuoto on yhteydessä useisiin komplikaatioihin myös matalan leikkausriskin potilailla. Leikkausalueelle jääneen veren huomattiin olevan yleinen ongelma sepelvaltimoiden ohitusleikkauksen jälkeen, minkä lisäksi se lisäsi riskiä useille haitta-tapahtumille. Preoperatiivisella anemialla ei ollut tilastollisesti merkitsevää vaikutusta potilaiden lyhyen ja pitkän aikavälin ennusteisiin. Sen sijaan, aneemisille potilaille annetut verensiirrot saattaisivat aiheuttaa näillä potilailla huomatun alentuneen elinajan ennusteen. Perioperatiivisen verenvuodon ja altistumisen verituotteille on osoitettu lisäävän haittatapahtumia. Siispä verenvuodon vähentäminen ja verituotteiden säästäminen voisi parantaa potilaiden ennustetta sydänkirurgiassa.

Abstract Coronary artery bypass grafting (CABG) is the treatment of choice for patients with three-vessel disease or left main stenosis. However, it is associated with considerable risk of perioperative complications such as myocardial infarction, stroke, infections, and mortality to which excessive bleeding is a contributing factor. This thesis aims to determine the factors involved in and clinical implications of bleeding after CABG. The 1st study evaluated the effects of preoperative ASA discontinuation on the patient’s outcome after CABG. The results showed that late or no discontinuation of low-dose ASA before CABG may decrease the risk of postoperative stroke without increasing the risk of postoperative bleeding. In the 2nd study the use of warfarin was found to be a safe during CABG with no excess bleeding nor other major complications. The 3rd study estimated the impact of surgeons´ performances on blood loss and need for re-exploration after CABG. With 2001 study patients, this study clearly demonstrated that an individual surgeon is a powerful determinant of postoperative bleeding and need for re-exploration after CABG. Using systematic review and meta-analysis, we estimated the risk of complications related to re-exploration for bleeding after CABG. In literature search in 2011, 8 articles with 557 923 patients fulfilled the inclusion criteria. Re-exploration for bleeding after cardiac surgery carries a significantly increased risk of postoperative mortality and morbidity, and thus has a major impact on the patient’s immediate postoperative outcome. We also studied the impact of blood transfusion on the development of post-operative stroke after CABG. Of the study population of 2 226 CABG patients, stroke occurred postoperatively in 53 patients (2.4%). The statistical analysis showed that transfusion of blood products after CABG has a strong, dose-dependent association with the risk of stroke. The use of Octaplas® and platelet transfusions seem to have an even larger impact on the development of stroke than red blood cell transfusions. The 6th study investigated the impact of transfusion of blood products on intermediate outcome after CABG in 2001 patients. The findings indicated that transfusion of any blood product is associated with a significant risk of all-cause and cardiac mortality after CABG. / Tiivistelmä Sepelvaltimotauti on yleisin kuolinsyy ja sepelvaltimoiden ohitusleikkaus hyvine pitkäaikaistuloksineen on todettu parhaaksi hoidoksi potilailla, joilla on monen suonen tai vasemman päärungon tauti. Ohitusleikkaukseen liittyy kuitenkin verenvuodon sekä näihin kytkeytyvien komplikaatioiden riski. Tämän väitöskirjan tavoitteena oli määrittää verenvuodon riskitekijöitä sekä verituotteiden siirtojen vaikutusta ohitusleikkauspotilaiden ennusteeseen. Verenhyytymistä estävien lääkkeiden tiedetään lisäävän verenvuotoja. Ensimmäinen tutkimus osoitti, että ASA:n jatkaminen keskeytyksettä ohitusleikkauksissa vähentää aivoinfarktien riskiä lisäämättä silti verenvuodon riskiä. Toisessa tutkimuksessa pitkäaikainen warfariinihoito osoittautui turvalliseksi ohitusleikkauksen aikana eikä sen käyttö lisännyt verenvuotoja eikä muita komplikaatioita. Kolmas tutkimus osoitti kirurgin taidon merkityksen verenvuotojen ja uusintaleikkausten määrään 2001 potilaalla. Verenvuotojen vuoksi tehtävien uusintaleikkausten negatiivinen vaikutus postoperatiiviseen mortaliteettiin sekä morbiditeettiin on todettu yksiselitteisesti useissa tutkimuksissa. Vuonna 2011 tehdyllä systemaattisella kirjallisuuskatsauksella ja meta-analyysillä selvitimme yhteensä 557 923 ohitusleikkauspotilaan aineistosta, että verenvuodon jälkeisiin uusintaleikkauksiin liittyy huomattava kuoleman ja komplikaatioiden riski. Verenvuotoja hoidetaan yleisesti verensiirroilla, vaikkakin useat tutkimukset ovat osoittaneet verituotteiden annon lisäävän mortaliteettia sekä komplikaatioriskiä. Viides tutkimus selvitteli sepelvaltimoleikkauksissa potilaalle annettujen verituotteiden ja leikkauksen yhteydessä sairastettujen aivoinfarktien välistä yhteyttä. Osoittautui, että verituotteiden käyttöön liittyy annosriippuvaisesti lisääntynyt riski saada aivoinfarkti leikkauksen yhteydessä. Varsinkin verihiutale- ja jääplasmasiirtoihin on todettu liittyvän vielä suurempi aivoinfarktin riski kuin punasolusiirtoihin. Kuudes tutkimus selvitteli sepelvaltimoleikkauksien yhteydessä annettujen verituotteiden vaikutusta 2001 potilaan keskipitkään ennusteeseen. Tutkimus osoitti, että minkä tahansa verituotteen antoon sepelvaltimoleikkauksissa liittyy lisääntynyt kuoleman ja sydänkuoleman riski.

Introdução: a revascularização miocárdica (RM) sem circulação extracorpórea (CEC) tem sido associada a menores complicações quando comparadas à com CEC. Objetivos: determinar os efeitos da CEC em marcadores de hemostasia, fibrinólise, inflamação e correlacionar com eventos clínicos. Método: os pacientes foram incluídos de forma prospectiva e randomizada para cirurgia de RM com (n=41) ou sem CEC (n=51). As concentrações de proteína C reativa (PCR), fibrinogênio, dímero-D e inibidor do ativador do plasminogênio tipo 1 (PAI1) foram quantificadas antes e após (1 e 24 horas) a RM. As técnicas cirúrgicas e anestésicas foram padronizadas para ambos os grupos. Eventos clínicos foram avaliados durante a hospitalização inicial e após 1 ano de seguimento. Resultados: as concentrações de PAI1 e dímeros-d foram maiores quando comparados os valores pré-operatórios com os de 1 e 24 h, após a RM em ambos os grupos, porém as concentrações de PAI1 aumentadas estenderam-se por 24 h após a RM com CEC (p<0,01). A concentração de PCR teve um aumento de pequena magnitude imediatamente após a cirurgia em ambos os grupos e aumentou de modo similar 24h após a RM (p<0,01). A RM com CEC foi associada com maior perda sanguínea durante a cirurgia e mais sangramento pós-operatório (p<0,01). A incidência de todas as outras complicações foi similar nos dois grupos. Conclusão: a RM com CEC apresentou evidências bioquímicas de um estado pró-trombótico precoce após a cirurgia, porém, sem evidências no aumento no número de eventos trombóticos. O estado pró-trombótico pode ser consequência do circuito extracorpóreo, resposta compensatória ao sangramento, ou a ambos em pacientes submetidos à cirurgia com CEC. / Objective: To delineate the effects of extracorporeal bypass on biomarkers of hemostasis, fibrinolysis, and inflammation and clinical sequelae. Methods: Patients were assigned prospectively and randomly to either on-pump (n=41) or off-pump (n=51) coronary bypass surgery. The concentrations of C-reactive protein (CRP), fibrinogen, D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) in blood were quantified before and after (1 hour and 24 hours) surgery. Similar surgical and anesthetic procedures were used for both groups. Clinical events were assessed during initial hospitalization and at the end of 1 year. Results: The concentrations of PAI-1 and d-dimer were greater compared with preoperative values 1 hour and 24 hours after surgery in both groups, but their concentrations increased to a greater extent 24 hours after surgery in the on-pump group (p<0.01). The concentration of CRP did not change appreciably immediately after surgery in either group but increased in a parallel fashion 24 hours after either on-pump or off-pump surgery (p<0.01). Bypass surgery in the on-pump group was associated with greater blood loss during surgery and more bleeding after surgery (p0.01). The incidence of all other complications was similar in the 2 groups. Conclusion: On-pump surgery was associated with biochemical evidence of a pro-thrombotic state early after surgery but no greater incidence of thrombotic events. The pro-thrombotic state may have been a consequence of extracorporeal bypass, compensation in response to more bleeding, or both in patients undergoing on-pump surgery.

La maladie coronaire stable est une maladie chronique pour laquelle de nombreuses stratégies thérapeutiques sont disponibles, dont le traitement par médicaments seuls et les traitements invasifs par angioplastie avec stent ou par pontage aortocoronaire. Face aux résultats de plusieurs méta-analyses mettant en évidence un taux de mortalité comparable entre ces traitements, nous avons décidé d’effectuer un travail de recherche comparant leurs coûts. Dans la première partie de mon travail, nous avons comparé, après une période de un an et une autre de 3 ans de suivi des patients, les données cliniques et économiques publiées pour 5 traitements de l’angor stable : les médicaments seuls, le pontage aortocoronaire, l’angioplastie sans stent, l’angioplastie avec stent nu et l’angioplastie avec stent actif. La mortalité et le taux d’IDM étaient nos critères de jugement clinique. Les coûts directs, liés au traitement effectué et liés à la prise en charge des éventuelles complications, ont été uniformisés via la parité de pouvoir d’achat et exprimés en US $ 2008. Il s’agissait de notre critère de jugement économique. Un total de 19 études cliniques a été retenu dans notre méta-analyse en réseau. Nos résultats mettent en évidence une absence de différence significative sur le critère clinique. En revanche, nous avons observé une différence concernant le coût moyen de chaque traitement après un an et 3 ans de suivi. Le traitement le moins onéreux était le traitement par médicaments seuls, après un an et 3 ans de suivi, avec respectivement un coût moyen par patient de 3 069 US $ et 13 854 US $. Le coût moyen le plus élevé a toujours été obtenu avec le traitement par pontage aortocoronaire : 27 003 US $ après un an et 28 670 US $ après 3 ans de suivi. Cependant, nos conclusions sont limitées d’une part, par la variabilité des méthodes économiques utilisées dans les études sélectionnées dans notre méta-analyse et, d’autre part, par l’évolution des traitements dans le temps. Dans la seconde partie de mon travail de recherche, nous avons calculé le coût de prise en charge d’un patient angoreux stable traité par l’une des 4 stratégies thérapeutiques suivantes : médicaments seuls, pontage aortocoronaire, angioplastie avec stent nu et angioplastie avec stent actif. Pour se faire, nous avons défini d’une part 6 situations cliniques correspondant aux possibles états cliniques du patient un an après l’instauration du traitement étudié et, d’autre part, déterminé les quantités de soins consommés pour chacune de ces situations cliniques. La perspective retenue était celle de l’Assurance Maladie. Les coûts calculés étaient liés aux hospitalisations, aux soins ambulatoires et aux moyens de transport utilisés pour accéder à l’hôpital. La stratégie médicamenteuse était la moins onéreuse avec un coût moyen annuel de 1 518 € ; ce coût prenant en compte les probabilités de survenue des 6 états cliniques. Le traitement par pontage aortocoronaire était le plus onéreux des 4 traitements étudiés, avec un coût moyen annuel de 15 237 €. La perspective de mes travaux est de modéliser la prise en charge d’un patient angoreux stable en envisageant un second traitement si le premier traitement effectué conduit à une situation d’échec thérapeutique. Les arbres que nous avons construits nous permettront ensuite d’effectuer une analyse coût-efficacité de deux stratégies thérapeutiques avec une durée totale de suivi des patients de 2 ans. Enfin, si nos travaux mettent en avant l’intérêt économique du traitement par médicaments, nous soulignons que ces résultats sont obtenus après avoir suivi les patients sur une courte durée (études à un an et à 3 ans), alors que l’angor stable est une maladie chronique où les stratégies thérapeutiques peuvent se succéder en cas d’échec à l’un des traitements... / Stable coronary artery disease is a chronic disease for which many treatment strategies are available, treatment with drugs alone and invasive treatment by stenting or coronary artery bypass graft. With the results of several meta-analyzes showing a mortality rate comparable between treatments, we decided to conduct a research comparing costs. In the first part of my work, we compared, after a period of one year and of 3 years of patient follow-up, clinical and economic data for five treatment of stable angina: medication alone, coronary artery bypass graft, angioplasty without stent, angioplasty with bare metal stent and angioplasty with drug-eluting stent. Mortality and MI rates were our clinical end point. Direct costs related to the treatment performed and related to the management of complications, have been standardized using the purchasing power parity and expressed in U.S. $ 2008. It was our criterion for economic analysis. A total of 19 clinical studies have been selected in our network meta-analysis. Our results show there is no significant difference in clinical end point. In contrast, we observed a difference in the average cost of each treatment after one year and three year follow-up. The least expensive treatment was the only treatment with drugs, after a year and 3 years of follow-up, each with an average cost per patient of U.S. $ 3,069 and U.S. $ 13,854. The highest average cost has been obtained with the treatment coronary artery bypass graft: U.S. $ 27,003 after one year and U.S. $ 28,670 after 3 years of follow-up. However, our conclusions are limited due to the high variability of the economic methods used in the selected studies and because of the evolution of revascularization techniques. In the second part of my research work, we calculated the cost of management of stable angina pectoris patients treated with one of the following four treatment strategies: medication alone, coronary artery bypass graft, angioplasty with bare metal stent and angioplasty with stent active. We defined a part 6 clinical situations corresponding to the possible clinical conditions of the patient one year after the treatment. We have defined the quantities of care consumed for each of these clinical situations. The perspective selected was the statutory health insurance in 2011. The calculated costs were related to hospitalization, ambulatory care and medical transport used to reach the hospital. The drug strategy was the least expensive with an average annual cost of € 1,518, the cost taking into account the probability of occurrence of 6 clinical conditions. Treatment with coronary artery bypass graft was the most expensive of the four treatments studied, with an average annual cost of € 15,237. The prospect of my work is to model the management of stable angina pectoris patient considering a second treatment if the first treatment led to a situation of treatment failure. The trees we built then allow us to perform a cost-effectiveness analysis of two strategies with a total duration of patient follow-up of 2 years. Finally, if our work highlights the economic benefits of drug treatment, we emphasize that these results are obtained after following patients over a short period (1 year and 3 years), while stable angina is a chronic disease where therapeutic strategies may succeed in case of failure to one of the treatments. In addition, we keep in mind that the choice of treatment, whether conservative or by drugs, by invasive myocardial revascularization should be done individually, i.e. taking into account the individual characteristics of each patient.

Introduction: Coronary artery bypass grafts are most commonly performed using saphenous vein grafts to complement the internal thoracic artery. The saphenous vein will remain popular despite its lower patency rate because it is easily accessible and lengthy enough to perform multiple bypasses. Therefore, several approaches have been studied, with the common goal of finding the optimal conditions that reduce graft failure. They include novel harvest techniques, new preservation preparations, innovative genetic therapies and experimental drugs. We believe a pharmacological pre-conditioning with an anti-oxidative and anti-inflammatory drug during the crucial time of harvest may spark beneficial survival response from the endothelial cells. One particular compound is Celastrol, an HSP90 inhibitor, which displays those antioxidant and anti-inflammatory properties. Methods: Human umbilical vein endothelial cells (HUVEC) were pretreated with various concentrations of Celastrol (10-10M, 10-8M and 10-6M). In order to reproduce oxidative stress found in ischemia/reperfusion, cells were exposed to hydrogen peroxide for a short and extended period (1h and 24h). To mimic storage condition encountered in clinical settings, cells were also exposed in heparinized normal saline. The viability was assessed by LIVE/DEAD assay. As for migrative and proliferative properties, scratch tests were performed. Finally, various protective intracellular pathways were evaluated by Western blot. Results: This study shows that pre-treatment with Celastrol promotes survival in HUVEC submitted to oxidative stress. Notable improvement in cellular viability was detected as early as 1 hour after oxidative stress (H2O2 4 mM), 76.6% vs 66.1% (p=0.005). Significant survival benefits are also reported after prolonged oxidative stress (H2O2 0.5 mM for 24 hours); viability was 93.7% vs 76.9% (p=0.001) for Cel 10- 8 M and 96.6% vs 76.9% (p=0.002) for Celastrol 10-10M when compared to the vehicle. Celastrol, however, did not significantly affect viability of HUVEC stored in heparinized normal saline. Celastrol at 10-6 M promotes faster and more complete wound closure compared to the vehicle or to lower dosages. Celastrol triggers early activation of the RISK pathway, inducing activation of both Akt and ERK1/2 within the first 15 minutes of treatment. Celastrol also induces the expression of HSP70 and HO-1, effectors of the Heat Shock Response and the anti-oxidative response respectively. Conclusion: Pre-treatment by Celastrol provides survival benefits in endothelial cells under oxidative stress. It also stimulates endothelial cell proliferation and migration, promoting faster and more complete re-endothelialisation. Celastrol can potentially be used as an additive to storage solutions to limit endothelial injury and promote graft protection. / Introduction: La chirurgie de pontage coronarien requiert, dans la grande majorité des cas, l’utilisation de l’artère mammaire interne en combinaison avec un ou des greffons provenant de la grande veine saphène. Malgré le taux de perméabilité inférieur aux artères, la veine saphène reste un choix populaire de conduit en raison de son accessibilité et de sa longueur. De ce fait, le greffon veineux devient la cible de multiples approches et le sujet de nombreuses études visant à optimiser sa perméabilité. Celles-ci incluent le raffinement des techniques de prélèvement, les solutions de préservations, les agents pharmacologiques ainsi que la thérapie génique. Il est davantage intéressant de combiner les approches afin de joindre leurs bénéfices, comme, par exemple, ajouter un agent pharmacologique à une solution de préservation. Un agent potentiel serait le Celastrol, connu pour être un inhibiteur du HSP90 et possède des propriétés antioxydantes et anti-inflammatoires. Méthodologie: Des cellules endothéliales humaines provenant de la veine ombilicale (HUVEC) sont pré-conditionnées à de multiples concentrations de Celastrol (10-10M, 10-8M and 10-6M) pendant une heure avant d’être soumises aux conditions de stress. Pour reproduire les conditions per-opératoires de prélèvement, les cellules endothéliales ont été préservées dans du salin (NS) héparinisé. Pour mimer le stress secondaire à l’ischémie/reperfusion, les cellules ont aussi été soumises à diverses concentrations de H2O2. Une analyse de la viabilité cellulaire fut conduite par le test de LIVE/DEAD. La capacité de ré-endothélialisation est étudiée grâce à l’épreuve de scratch test. Les voies intracellulaires de survie telles que le RISK pathway (Akt, ERK1/2), le Heat shock response (HSP70) et la réponse anti-oxydante (via l’activité de HO-1) ont été examinées par immunoblot. Résultats: Les résultats démontrent que la préservation des cellules endothéliales dans du NS héparinisé est associée à une augmentation de la mortalité comparativement au milieu de culture (20.4% vs 1.9%, p=0.004). Toutefois, un traitement au Celastrol n’affecte pas significativement la survie des cellules endothéliales dans le NS héparinisé. Le stress oxydatif induit aussi une augmentation de la mortalité, et ce à dose-dépendante. Suivant un court stress 6 oxydatif (H2O2 4 mM), un pré-traitement au Celastrol 10-10M est associé à une meilleure viabilité comparativement au véhicule (76.6% vs 66.1%, p=0.005). Lorsque soumises à un stress oxydatif prolongé (H2O2 0.5 mM pendant 24h), les HUVEC pré-traitées au Celastrol à 10-8M et 10-10M démontrent une amélioration significative de la viabilité, 93.7% vs 76.9% (p=0.001) et 93.6% vs 76.9% (p=0.002) respectivement. Quant à la ré-endothélialisation, un traitement au Celastrol 10- 6M est associé à une fermeture plus rapide et complète comparativement au véhicule. Un court traitement au Celastrol active précocement les kinases de la voie de RISK (Akt et ERK). Le traitement induit aussi l’expression de HSP70 et HO-1 qui reste soutenue jusqu’à 48 heures posttraitement. Conclusion: Le Celastrol active plusieurs voies de protection intracellulaire tels que le RISK pathway, le Heat Shock Response et la réponse antioxydante via l’activité de HO-1. En corrélation avec cette réponse, il améliore la survie des cellules endothéliales dans un milieu oxydatif. Le Celastrol promeut aussi une ré-endothélialisation plus complète et rapide. Cette étude met en valeur les bénéfices potentiels du Celastrol sur les cellules endothéliales. Afin d’optimiser la protection du greffon, le Celastrol pourrait donc être considéré comme agent adjuvant à une solution de préservation.

No description available.

Introduction: Cardiovascular surgery is a relatively young but progressively evolving field in medicine. More specifically, in the past decades, cardiac surgery achieved significant advances in understanding the causes, progression and treatments of ischemic heart disease (IHD). The IHD is the most common coronary disease, and it ranks first in morbidity and mortality in the developed world. It justifies the need for significant fundamental research as well as its study in clinical practice. It now includes specialized cardiovascular centres with the complex specialized treatments. A group of interventional cardiologists capable of performing routine examinations of the coronary veins using selective angiography has been established. They can eventually also perform percutaneous coronary interventions with direct stent implants. Thus the advances have been made in comprehensive indication of the patients towards their optimal treatments under the regime of a cardio-team. Such team comprises of a cardio-surgeon, interventional cardiologist, echocardiography specialist and the attending physician who is usually the cardiologist. The IHD treatments involve preventive cardiology with the regime measures and checks, pharmacotherapy, interventional cardiology and cardiac surgery to spa treatment and...

Introduction: Cardiovascular surgery is a relatively young but progressively evolving field in medicine. More specifically, in the past decades, cardiac surgery achieved significant advances in understanding the causes, progression and treatments of ischemic heart disease (IHD). The IHD is the most common coronary disease, and it ranks first in morbidity and mortality in the developed world. It justifies the need for significant fundamental research as well as its study in clinical practice. It now includes specialized cardiovascular centres with the complex specialized treatments. A group of interventional cardiologists capable of performing routine examinations of the coronary veins using selective angiography has been established. They can eventually also perform percutaneous coronary interventions with direct stent implants. Thus the advances have been made in comprehensive indication of the patients towards their optimal treatments under the regime of a cardio-team. Such team comprises of a cardio-surgeon, interventional cardiologist, echocardiography specialist and the attending physician who is usually the cardiologist. The IHD treatments involve preventive cardiology with the regime measures and checks, pharmacotherapy, interventional cardiology and cardiac surgery to spa treatment and...