Die Beurteilung der Wirkung von Cariporide auf dieEreignis-Wahrscheinlichkeit eines Herzinfarktes oder des Todes imRahmen einer Bypass-Operation ist Gegenstand der Arbeit. DasNHE-Austauschersystem in der Herzmuskelzelle induziert den unterIschämie durch den intrazellulären Protonenüberschusshervorgerufenen Na(+)- und Ca(2+)-Einstrom. Cariporide ist einNHE-Inhibitor, der den unter Ischämie durch die Ca(2+)-Überladunginduzierten Herzmuskelzelltod verzögern soll. In einer kombinierten Phase-II/III-Studie (GUARDIAN, n=11590) war derEinfluss verschiedener intravenöser Dosen von Cariporide auf dieHäufigkeit von Herzinfarkt oder Tod in ACS/NQMI, PTCA undCABG-Patientenkollektiven untersucht worden. Nur die höchstdosierteCABG-Gruppe zeigte eine signifikante Reduktion der Ereignisrate um24,7% (p=0,027) gegenüber Placebo. Diese schwacheDosis-Wirkungs-Beziehung konnte durch eine pharmakokinetische undpharmakodynamische Populationsanalyse in eineKonzentrations-Wirkungs-Beziehung überführt werden. Zur Entwicklungdes Populationsmodells waren verschiedene Submodelle notwendig: 1. Modell für den Zeitverlauf der Ereignisrate: Durch Kombination zweier Weibull-Verteilungen ist es möglich, die beobachteten Daten als Überlebenszeitfunktion nach CABG zu beschreiben. Ein akutes, unmittelbar auf die CABG-Operation zurückzuführendes Risiko wird hier von einem chronischen Risiko unterschieden. 2. Pharmakokinetisches Modell: Ein multiexponentielles populationspharmakokinetisches Modell ist notwendig zur Beschreibung der PK nach iv-Applikation von Cariporide bei Probanden und Patienten. 3. Pharmakodynamisches Modell: Über ein empirisches logistisches Modell wird die Reduktion des akuten Risikos mit der mittleren Cariporide Plasmakonzentration unter der Bypass-Operation verknüpft. In einer Substudie der GUARDIAN-Hauptstudie konnte daspopulationspharmakokinetische Modell aus der früherenPhase-I-Entwicklung mit Probanden für die Patienten validiert werden.Die mit Hilfe der individüllen Dosierung, der demographischen Datenund dem Populationsmodell für die Periode mit dem höchsten Risikowährend der CABG-Operation vorhergesagten mittlerenPlasmakonzentrationen flossen in die Analyse derKonzentrations-Zeit-Abhängigkeit der Ereignis-Wahrscheinlichkeit ein. Eine untere Schwellenkonzentration (0,5mg/l), unterhalb der mitkeinem Effekt zu rechnen ist, wurde bestimmt. Die Daten erlaubten dieSchätzung des maximalen Effekts nur unzureichend. Die maximaleRisikoreduktion von 60% wurde mit einem Konfidenzintervall von29% bis 100% geschätzt. Unter Einsatz einer linearen Näherungdes Hill-Modells wurde eine obere Schwellenkonzentration bei 0,9mg/lbestimmt. Nur 37% aller Patienten der 80mg-Dosisgruppe erreichtenmittlere Konzentrationen oberhalb der unteren Schwellenkonzentration,in der 120mg-Dosisgruppe waren es immerhin schon 75% allerPatienten. Die Infusion von 120mg Cariporide über eine Stunde gefolgt voneiner Erhaltungsdosis von 20mg/h für weitere 47 Stunden sollte bei95% der Patienten während der CABG-Operation zu mittlerenKonzentrationen über der minimal effektiven Konzentration von0,5mg/l führen. Eine auf diese Weise mittels Simulationenoptimierte Dosierungsregel sollte während der CABG-Operation zu einemerhöhten Schutz der Patienten gegen die Folgen ischämischerEreignisse führen. Eine weitere Erhöhung der Erhaltungsdosis aufbis zu 40mg/h mit einer entsprechenden Anpassung der Initialdosissollte 95% der Patienten sogar über die bisher nur unsicher zubestimmende obere Grenzkonzentration von 0,9mg/l bringen. Solltenkeine dosislimitierenden Nebenwirkungen auftreten, kann dieseErhöhung sowohl der Initialdosis als auch der Erhaltungsdosis zueiner weiteren Verbesserung während der Risikoperiode führen undeinen weiteren potentiellen klinischen Vorteil für Cariporideerbringen. / Subject of this analysis is the assessment of the effect of cariporideon the event probability of a myocardial infarction (MI) or death inthe scope of a coronary artery bypass graft. Thesodium-hydrogen-exchange system (NHE) in the myocardial cell inducesthe sodium and calcium influx caused by an ischaemia induced hydrogenoverload. Cariporide is a NHE-inhibitor which is seen to be delayingthe necrosis of myocardial cells caused by the ischaemia inducedcalcium influx. The influence of different intravenous doses of cariporide on thefrequency of MI and death in ACS/NQMI, PTCA, and CABG patients hadbeen investigated in a combined phase II/III trial (GUARDIAN,n=11590). Only the highest dosed CABG-subgroup showed a significantreduction of the event-rate compared to placebo of 24.7% (p=0.027).This weak dose-effect-relationship could be translated into aconcentration-effect relationship by using a populationpharmacokinetic/pharmacodynamic (PK/PD) analysis. To develop thispopulation model a series of sub-models were established: 1) Model for the time-to-event progression: using a combination of two Weibull-distributions, it was possible to describe the observed data following the CABG procedure by means of a survival-function. An acute risk, likely to be related to the CABG-procedure could be discriminated from a chronic risk. 2) Pharmacokinetic model: a multi-exponential population PK model was necessary to describe the PK after iv-application of cariporide in volunteers as well patients. 3) Pharmacodynamic model: using an empirical logistic model the reduction of the acute risk was linked to the cariporide plasma-concentrations. In a sub-study of the GUARDIAN-main study, the population PK model ofthe phase I development in volunteers had been be validated. Usingthe individual dosing, the individual demographic information and thepopulation PK model mean concentrations were calculated for the periodof the highest risk during the CABG procedure. Those concentrationswere then introduced into the analysis of the concentration timedependency of the event probability. A lower threshold concentration (0.5mg/l) was estimated beneath thatno effect would be expected. The data permitted the estimation of themaximum effect only insufficiently. A maximum risk reduction of 60%was estimated with a confidence interval from 29% to 100%. Using thelinear approximation of the Hill-model an upper thresholdconcentration of 0.9mg/l could be determined. Mean concentrationsunder risk were reached above the lower threshold concentration inonly 37% of all patients in the 80mg dose group, whereas in the 120mgdose-group already 75% of the patients exceeded the lower thresholdconcentration. The infusion of 120mg cariporide for an hour followed by a maintenancedose of 20mg/h for further 47 hours should maintain in 95% of thepatients during the CABG-procedure mean concentrations above theminimal effective concentration of 0.5mg/l. A dose regimen optimisedin this sense by means of simulations should lead to an increasedprotection against ischemic events during and after theCABG-operation. A further increase of the maintenance dose up to40mg/h with a corresponding adaptation of the initial dose shouldshift at least 95% of the patients above the so far impreciseestimated upper threshold concentration of 0.9mg. If no dose limitingside-effects occur, this increase of both the initial dose and themaintenance dose may lead to a further improvement during the riskperiod and may result in a further potential clinical advantage forcariporide.

<p>Boljom prevencijom aterosklerotskih bolesti i uvođenjem invazivnih procedura endoluminalnim pristupom u lečenju koronarne bolesti i karotidne bolesti, hirur&scaron;ke procedure u poslednje dve decenije postaju sve kompleksnije i teže. Profil pacijenata podvrgnutih revaskularizaciji miokarda postaje sve rizičniji i procentualno se povećava broj polivaskularnih pacijenata za koje je neophodno uraditi dodatne procedure na karotidnim arterijama, bilo da su one urađene simultano, u dva ili tri akta. To su pacijenati koji imaju značajne aterosklerotske lezije na jednoj ili obe karotidne arterije zajedno sa značajnim suženjima koronarnih arterija. Algoritmi koji se nude u projektovanju operativne taktike ni danas nisu strogo definisani i vrlo često zavise od individualne procene i stava hirurga koji izvode ove procedure. Ishod operativnog lečenja ovih pacijenata često zavisi od hirur&scaron;ke taktike i ustanove u kojoj se oni operativno leče. Prediktori ishoda operativnog lečenja bi mogli biti važan faktor u selekcioniranju pacijenata u preporuci taktike operativnog lečenja. U tezi su analizirani klinički aspekti preoperativno i postoperativno, postoperativni mortalitet - 30 dana posle operacije i jednu godinu posle operacije. Analiziran je uticaj faktora: starost, pol, neurolo&scaron;ka disfunkcija, infarkt miokarda do 90 dana pre operacije, nestabilna angina, diabetes mellitus, bilateralna stenoza karotidnih arterija kod 94 pacijenta koji su operisani u Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici u periodu 2007-2012g. Kod svih je, preoperativno, nađeno da imaju značajne promene na koronarnim i karotidnim arterijama. Pacijenti su podeljeni u dve grupe po tipu izvr&scaron;ene operacije. Prvu grupu su sačinjavali pacijenti koji su operisani u odvojenim operacijama karotidnih arterija i revakularizacije miokarda, a drugi su operisani simultano operacijom karotidnih arterija i revaskularizacijom miokarda. U metodologiji su kori&scaron;ćene metode retrospektivnog i prospektivnog istraživanja. Kori&scaron;ćena je elektronska baza podataka Instituta za kardiovaskularne bolesti Vojvodine, vođen je intervju sa pacijentima. Kori&scaron;ćeni su i pregledi doppler sonografije karotidnih arterija koji su rađeni u drugim ustanovama. Mortalitet-30 dana i jednu godinu posle operacije je bio prihvatljivo nizak, pacijenti su pobolj&scaron;ani u posmatranim parametrima. Neurolo&scaron;ki morbiditet na 30 dana i jednu godinu posle je bio prihvatljivo nizak. Prediktori mortaliteta su bili pu&scaron;enje 30 dana i godinu dana posle operacije u obe grupe. Prediktor morbiditeta 30 dana i jednu godinu nakon operacije bila je hiperlipoproteinemija. Ženski pol je bio nezavisni prediktor mortaliteta u grupi pacijenata operisanih u vi&scaron;e aktova. Pacijenti operisini simultano su bili teži po simptomima ( NYHAklasi) i u većem riziku (EU2 score), ali nisu imali statistički značajno veću smrtnost u odnosu na grupu operisanu u vi&scaron;e aktova.</p> / <p>Surgical procedures have become more complex and difficult in the past two decades due to the better prevention of atherosclerotic diseases and the introduction of invasive procedures with endoluminal approach to treating coronary and carotid artery diseases. The profile of patients undergoing myocardial revascularization is becoming riskier. There is also increase in the percentage of patients with polyvascular disease who need additional procedures on the carotid arteries, whether they are done simultaneously or in two or three acts. These are the patients who have significant atherosclerotic lesions in one or both of the carotid arteries along with the significant narrowing of the coronary arteries. Algorithms that are offered to plan operative tactics are still not strictly defined and often depend on the individual assessment of surgeons and the attitude of certain institutions that perform the procedure. The outcome of surgical treatment of these patients often depends on surgical tactics and the institution in which they are treated. Predictors of surgical treatment outcome could be an important factor for the selection of patients and the recommendation of operative treatment tactics. The thesis analyzed pre- and postoperative clinical aspect as well as 30-day and one-year postoperative mortality. The influence of the following factors was analyzed: age, sex, neurologic dysfunction, myocardial infarction occurring 90 days after surgery, unstable angina, diabetes mellitus, and bilateral carotid artery stenosis in 94 patients that underwent cardiac surgery at the Clinic of Cardiovascular Surgery of the Institute of Cardiovascular Diseases of Vojvodina in Sremska Kamenica in the period from 2007 to 2012. All patients had significant changes on the coronary and carotid arteries. The patients were divided into two groups according to the type of surgery. The first group consisted of the patients who underwent carotid artery surgery and myocardial revascularization separately. The second group of patients underwent carotid artery surgery and myocardial revascularization at the same time. Methods of retrospective and prospective research were used in the methodology. Electronic data base of the Institute of Cardiovascular Diseases of Vojvodina was also used and the patients were interviewed. Doppler of carotid arteries performed both in our institution and in other institutions was used. Mortality, 30-day and one-year post surgery, was acceptably low. The patients were improved in the observed parameters. Neurologic morbidity 30 days and one year after surgery was acceptably low. Smoking 30 days and one year after surgery was predictor of mortality in both groups. Hyperlipoproteinemia 30 days and one year after surgery was predictor of morbidity. Female sex was independent predictor of mortality for the first group of patients. The second group of patients were more complex according to the symptoms (NYHA class) and with greater risk (EU2 score), but their mortality rate was not statistically significant in relation to the first group of patients.</p>

INTRODUÇÃO: A inflamação atua diretamente na gênese, progressão e manutenção da aterosclerose. A proteína C reativa ultrassensível (PCRus) é um biomarcador inflamatório preditor de eventos cardiovasculares (ECVs). OBJETIVOS: Analisar o comportamento da PCRus na revascularização do miocárdio (RM) com e sem circulação extracorpórea (CEC) nos períodos pré e pós-operatório e correlacioná-los com as variáveis biológicas e laboratoriais. MÉTODOS: Estudo clínico prospectivo não-randomizado, com 136 pacientes pertencentes ao The Medicine, Angioplasty or Surgery Study V (MASS-V Trial) sendo 93 do sexo masculino e 43 do sexo feminino. Foram elencados 69 pacientes para Grupo 1 (G1= RM com CEC) com média de idade de 61,7 anos e 67 pacientes foram elencados para o Grupo 2 (G2= RM sem CEC) com média de idade de 62,6 anos. Todos os participantes do estudo tiveram amostras de sangue coletadas para análise de glicose, triglicérides (TG), creatinina, colesterol total (CT), high density lipoprotein (HDL), low density lipoprotein (LDL) e creatinofosfoquinase (CPK) no pré-operatório. A coleta das amostras de creatinofosfoquinase MB (CKMB), troponina I (TnI) e proteína C reativa ultrassensível (PCRus), foi realizada no pré-operatório e após 6h, 12h, 24h, 36h, 48h e 72h do ato cirúrgico. Também foram obtidas no pré-operatório as variáveis biológicas de cada paciente (idade, tabagismo, diabetes mellitus (DM), lesão de tronco em coronária esquerda (TCE), índice de massa corpórea (IMC), infarto do miocárdio prévio (IAM prévio), fibrose do miocárdio). A presença de fibrose miocárdica foi analisada através de ressonância magnética cardíaca (RMC) 2 dias antes da cirurgia (F1= fibrose pré-operatória) e com 6 dias após a cirurgia (F2= fibrose pós-operatória). A PCRus foi analisada de maneira uni e bivariada com as variáveis laboratoriais e biológicas elencadas para este estudo. Foram incluídos todos os pacientes angiograficamente documentados com estenose multiarterial proximal > 70% e isquemia documentada por teste de esforço (TE) ou classificação de angina estável (Classe II ou III) pela Canadian Cardiovascular Society (CCS). Não foram incluídos neste estudo reoperações, cirurgias combinadas, infarto agudo do miocárdio (IAM) recente ( <= 6 meses), doença inflamatória recente, trombose venosa profunda (TVP) ou tromboembolismo pulmonar recente (TEP), insuficiência renal aguda (IRA) ou insuficiência renal crônica (IRC). RESULTADOS: Os grupos foram considerados comparáveis em função das variáveis biológicas e laboratoriais analisadas, exceto pela maior ocorrência de hipertensão arterial no G1 e de IAM no G2. Observou-se que houve aumento dos valores da PCRus obtidos no pós em relão ao pré-operatório (p < 0,001). Essa alteração foi significativa em relação às técnicas de RM empregadas. Uma análise bivariada correlacionou a área sob a curva da PCRus e as demais variáveis analisadas e não foi observada significância estatística (p > 0,05) com exceção da área sob a curva encontrada da creatinofosfoquinase (CPK) que resultou em uma correlação positiva no G1 (p=0,015). CONCLUSÕES: Houve aumento da PCRus no pós em relação ao pré-operatório. Este aumento ocorreu em todos os momentos avaliados do pós-operatório. Não houve diferença de comportamento da PCRus entre as técnicas de revascularização do miocárdio empregadas / INTRODUCTION: The inflammation acts directly on atherosclerosis genesis, progression and maintenance. Ultrassensitive C- reactive protein (usCRP) is an inflammatory biomarker that predicts cardiovascular events (CVEs). OBJECTIVES: To analyze the behavior of the usPCR in the MR (myocardial revascularization) with and without extracorporeal circulation (ECC) in the pre and postoperative periods and correlate them with the biological and laboratory variables. METHODS: A prospective non-randomized clinical study with 136 patients belonging to The Medicine, Angioplasty or Surgery Study V (MASS-V Trial), 93 males and 43 females. Sixty-nine patients were enrolled for Group 1 (G1 = MR with ECC) with a mean age of 61.7 years and 67 patients were assigned to Group 2 (G2 = MR without ECC) with a mean age of 62.6 years. All participants in the study had blood samples collected to analyse of glucose, triglycerides (TG), creatinine, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and creatinephosphokinase (CPK) in the preoperative. The samples of creatinephosphokinase MB (CKMB), Troponin I (ITn) and usCRP were collected in the preoperative and after 6, 12, 24, 36, 48, and 72 hours from the surgery. The laboratory analysis provided the usCRP that was analyzed in a univariate and bivariate way. We also analyzed in the preoperative biological variables of each patient (age, smoking, diabetes mellitus (DM), left coronary trunk lesion (LCT), body mass index (BMI), previous myocardial infarction (previous AMI), myocardial fibrosis). The presence of myocardial fibrosis was analyzed by cardiac magnetic resonance imaging (CMR) 2 days before surgery (F1 = preoperative fibrosis) and 6 days after surgery (F2 = postoperative fibrosis). The usCRP was analyzed in a univariate and bivariate way using with the laboratory and biological variables listed for this study. All angiographically documented patients with > 70% proximal multiarterial stenosis and ischemia, documented by stress test (ST) or classification of stable angina (Class II or III), according to the Canadian Cardiovascular Society (CCS), were included. Reoperations, combined surgeries, recent acute myocardial infarction (AMI) ( <=6 months), recent inflammatory disease, deep venous thrombosis (DVT) or recent pulmonary thromboembolism (PTE), acute renal failure (ARF), or chronic renal failure (CRF), were not included. RESULTS: The groups were considered comparable according to the biological and laboratory variables analyzed, except for the greater occurrence of SAH in G1 and AMI in G2. It was observed that there was an increase in the usCRP values obtained in the postoperative period in relation to the preoperative period (p < 0.001). This change was significant in relation to the MR techniques employed. A bivariate analysis correlated the area under the usCRP curve and the other variables analyzed and no statistical significance was observed (p > 0.05) except for the area under the creatine phosphokinase (CPK) curve that resulted in a positive correlation in G1 (p=0.015). CONCLUSIONS: There was an increase in usCRP in the postoperative period compared to the preoperative period. This increase occurred in all moments assessed postoperatively. There was no difference in the usCRP behavior between the two myocardial revascularization techniques employed

Objetivos: O objetivo desse estudo foi comparar a perviedade da artéria torácica interna esquerda (ATIE) dissecada por videotoracoscopia robótica para revascularização minimamente invasiva do ramo interventricular anterior (RIA) com a revascularização do miocárdio convencional. Métodos: De 2007 a 2010, 36 pacientes foram randomizados para revascularização do miocárdio minimamente invasiva (RMMI) ou revascularização do miocárdio convencional (RMC). Pacientes randomizados para o grupo RMMI foram submetidos à dissecção da ATIE por videotoracoscopia auxiliada pelo braço robótico AESOP seguida de uma minitoracotomia anterior esquerda no 4º espaço intercostal para anastomose com o RIA. Pacientes randomizados para o grupo RMC foram submetidos a revascularização do miocárdio convencional com esternotomia mediana completa, dissecção aberta da ATIE e anastomose ao RIA. Fluxometria por tempo de trânsito (FTT) foi utilizada para avaliação da perviedade da ATIE imediata. Após 24 meses uma tomografia multislice foi utilizada para avaliar a perviedade a médio prazo da ATIE. Resultados: O tempo médio de dissecção da ATIE no grupo RMMI foi de 50,1 ± 11,2 vs. 22,7 ± 3,3 min no grupo RMC. Não houve diferença significativa no fluxo médio da ATIE para o RIA entre os grupos estudados (46,17 ± 20,11 vs. 48,61 ± 23,42 mL/min, p=0,86) respectivamente. Não houve diferença significante na incidência de infecção de ferida profunda (0 vs. 2, p=0,48) e necessidade de reoperação por sangramento (0 vs. 1, p=1,00) nos grupos RMMI e RMC respectivamente. A angiotomografia mostrou perviedade da ATIE em 100% dos pacientes do grupo RMMI vs. 94,1% no grupo RMC (p=1,00). Não houve mortalidade nos grupos estudados. Conclusão: A revascularização do miocárdio minimamente invasiva do ramo interventricular anterior com dissecção da artéria torácica interna esquerda por videotoracoscopia robótica foi segura e factível. A perviedade da artéria torácica interna esquerda imediata e a médio prazo foi similar entre ambas as técnicas / Objective: The aim of this study was to compare the patency of left internal mammary artery (LIMA) robotically harvested for left anterior descendent (LAD) artery minimally invasive bypass with conventional LIMA to LAD off-pump bypass. Method: From 2007 to 2010, 36 patients were randomized to either LIMA robotically harvested to LAD artery minimally invasive bypass or standard LIMA to LAD off-pump bypass. Patients assigned to robotic group underwent robotic endoscopic harvesting of LIMA with the AESOP system followed by a small left thoracotomy in the 4th intercostal space for off-pump LAD bypass. Patients assigned to standard group underwent full median sternotomy, open LIMA harvesting followed by off-pump LAD bypass. Transit time flow measurement was used for intraoperative evaluation of LIMA to LAD patency. After a mean 24-month follow-up, Multislice Computed Tomography was used to evaluate LIMA to LAD midterm patency. Results: The mean LIMA harvesting time in robotic group was 50.1 ± 11.2 min vs. 22.7 ± 3.3 min in conventional group. There was no significant difference in intraoperative LIMA to LAD flow between robotic and conventional groups (46.17 ± 20.11 mL/min vs. 48.61 ± 23.42 mL/min, p=0.86). There were no significant differences in incidence of wound infection (0 vs. 2, p=0,48) and reoperation for bleeding (0 vs. 1, p=1.00) between robotic and conventional groups respectively. In robotic group, Multislice CT revealed patent LIMA graft in 100% patients vs. 94.1% patients in conventional group (p=1.00). There was no mortality in the study group. Conclusions: Minimally invasive LAD bypass using LIMA graft robotically harvested was safe and feasible. Early and mid-term LIMA patency was similar between both techniques

Made available in DSpace on 2016-01-26T12:51:15Z (GMT). No. of bitstreams: 1 isabelathomaztakakura_dissert.pdf: 1870282 bytes, checksum: 871ee642969bbc10aeb356aeefd91988 (MD5) Previous issue date: 2007-05-10 / Recent studies have shown that low heart rate variability (HRV) is a clear indication of an increased risk for severe ventricular arrhytmia and sudden cardiac. However, the traditional techniques of data analysis in time and frequency domain are often not sufficient to characterize the complex dynamics of heart beat generation. Hence, different attempts have been reported to apply the concept of nonlinear dynamics (chaos domain) to this problem as the methods Detrended Fluctuation Analysis (DFA), Autocorrelation (Tau), Hurst Exponent (HE), Lyapunov Exponent (LE), Poincaré Plot (SD1 e SD2). Objective: We speculated that patients with decreased chaotic behavior in the preoperative period would tend to present higher morbidity and mortality in the length of postoperative stay. Methods: Seventy-two non-selected patients (mean age 58.4±10.2 years) with coronary artery disease and elective coronary artery bypass graft surgery (CABG) indication, were studied. We had their HRV with Polar Advanced S810 and analyzed with the above chaos, time and frequency domain variables. The occurrences of relevant events during the length of postoperative stay as neurological, infectious and renal complications, severe arrhytmias or death were compared. The Fisher s Test was used to compare the occurrence of events. We described Sensibility, Specificity, Positive Predictive Value, Positive Likelihood Ratio and ODDS Ratio (CI 95%). Results: In comparison of groups death versus no death (Scenario 1) of the Lyapunov Exponent, for example, the ODDS Ratio was 11.5 (CI 95% 1.261 to 104.92, P=0.0171). The Scenario 3 (2 or more events versus 0 to 1 event) xxiv showed the Odds Ratio 12.414 (CI 95% 1.515 to 101.72, P=0.0048). Conclusions: The patients with decreased HRV evaluated from some nonlinear dynamic analysis methods before CABG surgery present higher morbidity and mortality in the length of postoperative stay. / Estudos recentes têm mostrado que a baixa variabilidade da freqüência cardíaca (VFC) é um claro indicador de maior risco para arritmia ventricular grave e morte súbita. Contudo, as técnicas tradicionais de análises de dados no domínio do tempo e da freqüência nem sempre são suficientes para caracterizar a dinâmica complexa da geração do batimento cardíaco. Conseqüentemente, diferentes tentativas têm sido feitas para aplicar o conceito de dinâmica não-linear (domínio do caos) para este problema, como os métodos não-lineares: Análise de Flutuações Depurada de Tendências (DFA), Autocorrelação (Tau), Expoente de Hurst (HE), Expoente de Lyapunov (LE), Desvio-padrão da perpendicular à linha de identidade no gráfico de Poincaré (SD1e SD2). Objetivo: Assim, o objetivo deste trabalho foi demonstrar se a redução do comportamento caótico (avaliado por métodos de dinâmica nãolinear) no período pré-operatório à revascularização do miocárdio acarretaria maior morbidade e mortalidade no período pós-operatório, durante a internação. Método: No presente estudo, 72 pacientes não-selecionados (média de idade de 58,4±10,2 anos) com doença arterial coronária e indicação eletiva de cirurgia foram incluídos e sua VFC foi captada pelo Polar Advanced S810 por meio da análise dos intervalos RR. A VFC foi analisada por variáveis do domínio do tempo (SDNN, RMSSD), do domínio da freqüência (LF nu, HF nu, a relação LF/HF) e do domínio do caos, citadas acima. A ocorrência de eventos relevantes durante o pós-operatório foi avaliada, como complicações neurológicas, infecciosas e renais, arritmias graves ou morte. O Teste Exato de xxii Fisher foi usado para comparar a ocorrência de eventos. Também foram registrados a Sensibilidade, Especificidade, Valor Preditivo Positivo, Valor Preditivo Negativo, Likelihood Ratio Positivo e ODDS Ratio com 95% de Intervalo de Confiança para a ocorrência de eventos. Um valor de P &#8804; 0.05 foi considerado significante. Resultados: De acordo com medidas feitas pelo Expoente de Lyapunov, por exemplo, o Cenário 1 (comparando grupo de pacientes que faleceram no pós-operatório hospitalar com o grupo dos que não faleceram) evidenciou Odds Ratio de 11,5 (IC 95% 1,261 a 104,92) com valor de P de 0,0171 e o Cenário 3 (2 ou mais eventos contra 0 a 1 evento) evidenciou Odds Ratio de 12,414 (IC 95% 1,515 a 101,72) com valor de P de 0,0048. Conclusão: A avaliação da VFC por métodos de dinâmica não-linear em pacientes no período pré-operatório da cirurgia de revascularização do miocárdico, mostrou tratar-se de ferramenta promissora como preditora de maior morbidade e mortalidade durante o período de pós-operatório hospitalar.

INTRODUÇÃO: A inflamação atua diretamente na gênese, progressão e manutenção da aterosclerose. A proteína C reativa ultrassensível (PCRus) é um biomarcador inflamatório preditor de eventos cardiovasculares (ECVs). OBJETIVOS: Analisar o comportamento da PCRus na revascularização do miocárdio (RM) com e sem circulação extracorpórea (CEC) nos períodos pré e pós-operatório e correlacioná-los com as variáveis biológicas e laboratoriais. MÉTODOS: Estudo clínico prospectivo não-randomizado, com 136 pacientes pertencentes ao The Medicine, Angioplasty or Surgery Study V (MASS-V Trial) sendo 93 do sexo masculino e 43 do sexo feminino. Foram elencados 69 pacientes para Grupo 1 (G1= RM com CEC) com média de idade de 61,7 anos e 67 pacientes foram elencados para o Grupo 2 (G2= RM sem CEC) com média de idade de 62,6 anos. Todos os participantes do estudo tiveram amostras de sangue coletadas para análise de glicose, triglicérides (TG), creatinina, colesterol total (CT), high density lipoprotein (HDL), low density lipoprotein (LDL) e creatinofosfoquinase (CPK) no pré-operatório. A coleta das amostras de creatinofosfoquinase MB (CKMB), troponina I (TnI) e proteína C reativa ultrassensível (PCRus), foi realizada no pré-operatório e após 6h, 12h, 24h, 36h, 48h e 72h do ato cirúrgico. Também foram obtidas no pré-operatório as variáveis biológicas de cada paciente (idade, tabagismo, diabetes mellitus (DM), lesão de tronco em coronária esquerda (TCE), índice de massa corpórea (IMC), infarto do miocárdio prévio (IAM prévio), fibrose do miocárdio). A presença de fibrose miocárdica foi analisada através de ressonância magnética cardíaca (RMC) 2 dias antes da cirurgia (F1= fibrose pré-operatória) e com 6 dias após a cirurgia (F2= fibrose pós-operatória). A PCRus foi analisada de maneira uni e bivariada com as variáveis laboratoriais e biológicas elencadas para este estudo. Foram incluídos todos os pacientes angiograficamente documentados com estenose multiarterial proximal > 70% e isquemia documentada por teste de esforço (TE) ou classificação de angina estável (Classe II ou III) pela Canadian Cardiovascular Society (CCS). Não foram incluídos neste estudo reoperações, cirurgias combinadas, infarto agudo do miocárdio (IAM) recente ( <= 6 meses), doença inflamatória recente, trombose venosa profunda (TVP) ou tromboembolismo pulmonar recente (TEP), insuficiência renal aguda (IRA) ou insuficiência renal crônica (IRC). RESULTADOS: Os grupos foram considerados comparáveis em função das variáveis biológicas e laboratoriais analisadas, exceto pela maior ocorrência de hipertensão arterial no G1 e de IAM no G2. Observou-se que houve aumento dos valores da PCRus obtidos no pós em relão ao pré-operatório (p < 0,001). Essa alteração foi significativa em relação às técnicas de RM empregadas. Uma análise bivariada correlacionou a área sob a curva da PCRus e as demais variáveis analisadas e não foi observada significância estatística (p > 0,05) com exceção da área sob a curva encontrada da creatinofosfoquinase (CPK) que resultou em uma correlação positiva no G1 (p=0,015). CONCLUSÕES: Houve aumento da PCRus no pós em relação ao pré-operatório. Este aumento ocorreu em todos os momentos avaliados do pós-operatório. Não houve diferença de comportamento da PCRus entre as técnicas de revascularização do miocárdio empregadas / INTRODUCTION: The inflammation acts directly on atherosclerosis genesis, progression and maintenance. Ultrassensitive C- reactive protein (usCRP) is an inflammatory biomarker that predicts cardiovascular events (CVEs). OBJECTIVES: To analyze the behavior of the usPCR in the MR (myocardial revascularization) with and without extracorporeal circulation (ECC) in the pre and postoperative periods and correlate them with the biological and laboratory variables. METHODS: A prospective non-randomized clinical study with 136 patients belonging to The Medicine, Angioplasty or Surgery Study V (MASS-V Trial), 93 males and 43 females. Sixty-nine patients were enrolled for Group 1 (G1 = MR with ECC) with a mean age of 61.7 years and 67 patients were assigned to Group 2 (G2 = MR without ECC) with a mean age of 62.6 years. All participants in the study had blood samples collected to analyse of glucose, triglycerides (TG), creatinine, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and creatinephosphokinase (CPK) in the preoperative. The samples of creatinephosphokinase MB (CKMB), Troponin I (ITn) and usCRP were collected in the preoperative and after 6, 12, 24, 36, 48, and 72 hours from the surgery. The laboratory analysis provided the usCRP that was analyzed in a univariate and bivariate way. We also analyzed in the preoperative biological variables of each patient (age, smoking, diabetes mellitus (DM), left coronary trunk lesion (LCT), body mass index (BMI), previous myocardial infarction (previous AMI), myocardial fibrosis). The presence of myocardial fibrosis was analyzed by cardiac magnetic resonance imaging (CMR) 2 days before surgery (F1 = preoperative fibrosis) and 6 days after surgery (F2 = postoperative fibrosis). The usCRP was analyzed in a univariate and bivariate way using with the laboratory and biological variables listed for this study. All angiographically documented patients with > 70% proximal multiarterial stenosis and ischemia, documented by stress test (ST) or classification of stable angina (Class II or III), according to the Canadian Cardiovascular Society (CCS), were included. Reoperations, combined surgeries, recent acute myocardial infarction (AMI) ( <=6 months), recent inflammatory disease, deep venous thrombosis (DVT) or recent pulmonary thromboembolism (PTE), acute renal failure (ARF), or chronic renal failure (CRF), were not included. RESULTS: The groups were considered comparable according to the biological and laboratory variables analyzed, except for the greater occurrence of SAH in G1 and AMI in G2. It was observed that there was an increase in the usCRP values obtained in the postoperative period in relation to the preoperative period (p < 0.001). This change was significant in relation to the MR techniques employed. A bivariate analysis correlated the area under the usCRP curve and the other variables analyzed and no statistical significance was observed (p > 0.05) except for the area under the creatine phosphokinase (CPK) curve that resulted in a positive correlation in G1 (p=0.015). CONCLUSIONS: There was an increase in usCRP in the postoperative period compared to the preoperative period. This increase occurred in all moments assessed postoperatively. There was no difference in the usCRP behavior between the two myocardial revascularization techniques employed

Endotelio funkcijos sutrikimas (disfunkcija) - būklė, apibūdinama padidėjusia adhezijos molekulių ekspresija, padidėjusia prouždegiminių veiksnių ir protrombotinių faktorių sinteze bei sutrikusia kraujagyslių tono reguliacija - yra mirties dėl kardiovaskulinės patologijos, miokardo infarkto bei poreikio revaskuliarizacijos procedūroms išsivystymo rizikos veiksnys. Darbo tikslas buvo nustatyti endotelio pažeidimą atspindinčių žymenų, hs-CRP, sVCAM-1 ir sICAM-1 reikšmę, nuspėjant kardiovaskulines komplikacijas po aortos vainikinių jungčių suformavimo operacijos, atliktos dirbtinės kraujo apytakos sąlygomis. Nustatėme, kad didesnės priešoperacinės hs-CRP ir sVCAM-1 koncentracijos buvo nepriklausomi didesnės kardiovaskulinių komplikacijų po aortos vainikinių jungčių suformavimo operacijų rizikos žymenys. Po aortos vainikinių jungčių suformavimo operacijos nustatyta reikšmingai didesnė hs-CRP, sVCAM-1 ir sICAM-1 koncentracija, palyginus su priešoperaciniu koncentracijos lygiu. Patikimos žymenų koreliacijos su aortos užspaudimo, dirbtinės kraujo apytakos bei operacijos trukme neradome. Pacientams po aortos vainikinių jungčių suformavimo operacijos koreliacijos tarp pooperacinio sICAM-1, sVCAM-1 bei hs-CRP koncentracijos lygio ir kardiovaskulinių komplikacijų išsivystymo rizikos nebuvo nenustatyta. / The endothelial cell damage/dysfunction is associated with increased expression of adhesion molecules, synthesis of proinflammatory, prothrombotic factors and abnormal modulation of vascular tone. A growing body of evidence suggests that endothelial dysfunction is associated with future cardiovascular events including cardiac death, myocardial infarction and the need for revascularization procedures. The aim of the study was to evaluate the impact of markers of endothelial damage as predictors of cardiovascular events after on-pump coronary artery bypass grafting surgery. We found that higher concentrations preoperatively of hs-CRP and sVCAM-1 were independent markers for higher risk of cardiovascular events after coronary artery bypass grafting surgery. Concentration of hs-CRP, sVCAM-1 and sICAM-1 increased significantly after on-pump coronary artery bypass grafting surgery compared to preoperative level. However correlation between the duration of aortic cross-clamp, cardiopulmonary bypass or surgery and markers of endothelial damage was not found. Correlation between postoperative concentration of hs-CRP, sVCAM-1 and sICAM-1 and risk for cardiovascular events after coronary artery bypass grafting surgery was not found.

Endotelio funkcijos sutrikimas (disfunkcija) - būklė, apibūdinama padidėjusia adhezijos molekulių ekspresija, padidėjusia prouždegiminių veiksnių ir protrombotinių faktorių sinteze bei sutrikusia kraujagyslių tono reguliacija - yra mirties dėl kardiovaskulinės patologijos, miokardo infarkto bei poreikio revaskuliarizacijos procedūroms išsivystymo rizikos veiksnys. Darbo tikslas buvo nustatyti endotelio pažeidimą atspindinčių žymenų, hs-CRP, sVCAM-1 ir sICAM-1 reikšmę, nuspėjant kardiovaskulines komplikacijas po aortos vainikinių jungčių suformavimo operacijos, atliktos dirbtinės kraujo apytakos sąlygomis. Nustatėme, kad didesnės priešoperacinės hs-CRP ir sVCAM-1 koncentracijos buvo nepriklausomi didesnės kardiovaskulinių komplikacijų po aortos vainikinių jungčių suformavimo operacijų rizikos žymenys. Po aortos vainikinių jungčių suformavimo operacijos nustatyta reikšmingai didesnė hs-CRP, sVCAM-1 ir sICAM-1 koncentracija, palyginus su priešoperaciniu koncentracijos lygiu. Patikimos žymenų koreliacijos su aortos užspaudimo, dirbtinės kraujo apytakos bei operacijos trukme neradome. Pacientams po aortos vainikinių jungčių suformavimo operacijos koreliacijos tarp pooperacinio sICAM-1, sVCAM-1 bei hs-CRP koncentracijos lygio ir kardiovaskulinių komplikacijų išsivystymo rizikos nebuvo nenustatyta. / The endothelial cell damage/dysfunction is associated with increased expression of adhesion molecules, synthesis of proinflammatory, prothrombotic factors and abnormal modulation of vascular tone. A growing body of evidence suggests that endothelial dysfunction is associated with future cardiovascular events including cardiac death, myocardial infarction and the need for revascularization procedures. The aim of the study was to evaluate the impact of markers of endothelial damage as predictors of cardiovascular events after on-pump coronary artery bypass grafting surgery. We found that higher concentrations preoperatively of hs-CRP and sVCAM-1 were independent markers for higher risk of cardiovascular events after coronary artery bypass grafting surgery. Concentration of hs-CRP, sVCAM-1 and sICAM-1 increased significantly after on-pump coronary artery bypass grafting surgery compared to preoperative level. However correlation between the duration of aortic cross-clamp, cardiopulmonary bypass or surgery and markers of endothelial damage was not found. Correlation between postoperative concentration of hs-CRP, sVCAM-1 and sICAM-1 and risk for cardiovascular events after coronary artery bypass grafting surgery was not found.

Objetivos: O objetivo desse estudo foi comparar a perviedade da artéria torácica interna esquerda (ATIE) dissecada por videotoracoscopia robótica para revascularização minimamente invasiva do ramo interventricular anterior (RIA) com a revascularização do miocárdio convencional. Métodos: De 2007 a 2010, 36 pacientes foram randomizados para revascularização do miocárdio minimamente invasiva (RMMI) ou revascularização do miocárdio convencional (RMC). Pacientes randomizados para o grupo RMMI foram submetidos à dissecção da ATIE por videotoracoscopia auxiliada pelo braço robótico AESOP seguida de uma minitoracotomia anterior esquerda no 4º espaço intercostal para anastomose com o RIA. Pacientes randomizados para o grupo RMC foram submetidos a revascularização do miocárdio convencional com esternotomia mediana completa, dissecção aberta da ATIE e anastomose ao RIA. Fluxometria por tempo de trânsito (FTT) foi utilizada para avaliação da perviedade da ATIE imediata. Após 24 meses uma tomografia multislice foi utilizada para avaliar a perviedade a médio prazo da ATIE. Resultados: O tempo médio de dissecção da ATIE no grupo RMMI foi de 50,1 ± 11,2 vs. 22,7 ± 3,3 min no grupo RMC. Não houve diferença significativa no fluxo médio da ATIE para o RIA entre os grupos estudados (46,17 ± 20,11 vs. 48,61 ± 23,42 mL/min, p=0,86) respectivamente. Não houve diferença significante na incidência de infecção de ferida profunda (0 vs. 2, p=0,48) e necessidade de reoperação por sangramento (0 vs. 1, p=1,00) nos grupos RMMI e RMC respectivamente. A angiotomografia mostrou perviedade da ATIE em 100% dos pacientes do grupo RMMI vs. 94,1% no grupo RMC (p=1,00). Não houve mortalidade nos grupos estudados. Conclusão: A revascularização do miocárdio minimamente invasiva do ramo interventricular anterior com dissecção da artéria torácica interna esquerda por videotoracoscopia robótica foi segura e factível. A perviedade da artéria torácica interna esquerda imediata e a médio prazo foi similar entre ambas as técnicas / Objective: The aim of this study was to compare the patency of left internal mammary artery (LIMA) robotically harvested for left anterior descendent (LAD) artery minimally invasive bypass with conventional LIMA to LAD off-pump bypass. Method: From 2007 to 2010, 36 patients were randomized to either LIMA robotically harvested to LAD artery minimally invasive bypass or standard LIMA to LAD off-pump bypass. Patients assigned to robotic group underwent robotic endoscopic harvesting of LIMA with the AESOP system followed by a small left thoracotomy in the 4th intercostal space for off-pump LAD bypass. Patients assigned to standard group underwent full median sternotomy, open LIMA harvesting followed by off-pump LAD bypass. Transit time flow measurement was used for intraoperative evaluation of LIMA to LAD patency. After a mean 24-month follow-up, Multislice Computed Tomography was used to evaluate LIMA to LAD midterm patency. Results: The mean LIMA harvesting time in robotic group was 50.1 ± 11.2 min vs. 22.7 ± 3.3 min in conventional group. There was no significant difference in intraoperative LIMA to LAD flow between robotic and conventional groups (46.17 ± 20.11 mL/min vs. 48.61 ± 23.42 mL/min, p=0.86). There were no significant differences in incidence of wound infection (0 vs. 2, p=0,48) and reoperation for bleeding (0 vs. 1, p=1.00) between robotic and conventional groups respectively. In robotic group, Multislice CT revealed patent LIMA graft in 100% patients vs. 94.1% patients in conventional group (p=1.00). There was no mortality in the study group. Conclusions: Minimally invasive LAD bypass using LIMA graft robotically harvested was safe and feasible. Early and mid-term LIMA patency was similar between both techniques

Ce mémoire adresse la problématique de la présentation des résultats chirurgicaux en chirurgie cardiaque. Les complications postopératoires sont d’étiologie et de sévérité variées, peuvent atteindre plusieurs systèmes physiologiques et nécessitent différents degrés de traitements. Elles consistent en une source importante de morbidités pour le patient, mais ne sont toutefois pas toujours présentées de manière optimale dans les essais cliniques. En effet, les complications sont actuellement rapportées dans les études de manière hétérogène, ce qui nuit à la recherche en compliquant les comparaisons d’études, les revues systématiques et les méta-analyses. Plusieurs complications individuelles ont des systèmes de classification utilisés sporadiquement dans certains articles en chirurgie cardiaque, mais ceux-ci ne sont pas déployés de manière répandue. D’autre part, des classifications universelles s’appliquant à toutes les complications potentielles ont été adoptées dans la littérature chirurgicale, mais n’ont toutefois pas été implémentées en chirurgie cardiaque. L’étude menée dans le cadre de ce travail a adapté et appliqué la classification de Clavien-Dindo (CCD) et le Comprehensive Complication Index (CCI) pour la première fois en chirurgie cardiaque. Mon étude démontre que les comorbidités importantes en chirurgie cardiaque et les chirurgies plus complexes sont prédictives de la sévérité des complications selon ces deux échelles. Également, le CCD et le CCI corrèlent avec les durées de séjour aux soins intensifs et à l’hôpital après une chirurgie cardiaque. En conclusion, la CCD et le CCI représentent de manière fiable la complexité de l’évolution postopératoire en chirurgie cardiaque. Cela pourrait adresser le manque de standardisation dans la présentation des complications dans les essais cliniques et uniformiser la manière de rapporter les événements adverses en chirurgie cardiaque. Cela aurait également de multiples applications dans les initiatives d'amélioration de la qualité des soins, dans les évaluations des procédures et des procédés, ainsi que dans l'avancement de la recherche. / This memoir addresses the challenge of outcome reporting in cardiac surgery. Postoperative complications are of varying etiology and severity, can affect several physiological systems and require different degrees of treatment. They are an important source of morbidity for the patient but are not always optimally presented in clinical trials. Indeed, complications are currently reported in studies in a heterogeneous manner, which hampers research by complicating study comparisons, systematic reviews and meta-analyses. Many individual complications have classification systems that are used sporadically in some articles in cardiac surgery, but these are not widely used. On the other hand, universal classifications that apply to all potential complications have been adopted in the surgical literature, but none have been implemented in cardiac surgery yet. The study conducted as part of this work adapted and applied the Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) for the first time in cardiac surgery. My study shows that the important comorbidities in cardiac surgery and more complex surgeries are predictive of the severity of complications according to both scales. Moreover, the CCD and CCI also correlate with the lengths of stay in the intensive care unit and hospital after cardiac surgery. In conclusion, the CDCC and CCI reliably represent the complexity of the postoperative evolution in cardiac surgery. This could address the inconsistency with which complications are currently presented in surgical trials and standardize the way adverse outcomes are reported in cardiac surgery. This would have multiple applications in quality of care improvement initiatives, in evaluations of procedures and processes, and in advancement of research.