nÃo hà / Enxertos compostos com artÃria torÃcica interna esquerda (ATIE) tem aumentado sua aplicabilidade na cirurgia de RevascularizaÃÃo MiocÃrdica (RM). A confirmaÃÃo de patÃncia do enxerto de ATIE à pedra fundamental na RM. O melhor parÃmetro de patÃncia calculado pelo ecoDopplercardiograma à a fraÃÃo diastÃlica (FD) ≥ 0,5. O objetivo geral deste estudo foi estabelecer parÃmetros ecoDopplercardiogrÃficos de patÃncia do enxerto composto de ATIE, quando revasculariza a artÃria interventricular anterior (AIA) e outro ramo do sistema coronariano esquerdo. O especÃfico foi definir a sensibilidade e a especificidade de trÃs variÃveis: RelaÃÃo da velocidade-pico na diÃstole sobre a velocidade-pico na sÃstole (VPD/VPS), integral da velocidade-tempo na diÃstole (VTID) e FD quanto à patÃncia do enxerto composto utilizando FD ≥ 0,5 como padrÃo de referÃncia. O estudo foi realizado segundo um desenho em duas fases, fase controle e fase estudo. Na fase controle, todos os pacientes tinham a patÃncia dos enxertos confirmadas por cineangiocoronariografia (CINE). Estes pacientes tinham registro das variÃveis VPD/VPS, VTID e FD. Foram entÃo estabelecidos pontos de cortes para essas variÃveis baseando-se nos cÃlculos de sensibilidade e especificidade atravÃs da curva ROC (ReceiverOperationCharacteristic) com o objetivo de diferenciar enxertos compostos de enxertos simples quando a ATIE somente revasculariza a AIA. Esses pontos de corte foram aplicados nos pacientes com enxerto composto da fase estudo. Foi construÃda uma tabela de contingÃncia 2x2 para o cÃlculo de sensibilidade e especificidade, tendo como indicador de patÃncia uma FD≥0,5. Na fase controle, observou-se diferenÃas estatisticamente significativas na anÃlise das trÃs variÃveis em diferenciar o enxerto simples do composto. Os parÃmetros de patÃncia do enxerto composto estabelecidos pela fase estudo foram VPD/VPS ≥ 0,71, VTId ≥ 0,09 e FD ≥ 0,58. A especificidade para todas essas variÃveis foi de 100%. A sensibilidade foi de 40% para VPD/VPS ≥ 0,71, 36,4% para VTId ≥ 0,09 e 68% para FD ≥ 0,58. Conclui-se que valores maiores ou iguais aos estabelecidos para cada variÃvel representam um provÃvel indicador de patÃncia do enxerto composto. Valores abaixo do estabelecido apresentam grande proporÃÃo de falsos negativos, nÃo sendo conclusivo quanto à patÃncia. / Composite grafts with left internal thoraic artery (LITA) has incresed its applicability in Coronary Artery Bypass Surgery (CAGB). Confirmation of patency of the LITA graft is the cornerstone of Miocardial Revascularization. The best measure of patency calculated by Doppler echocardiogram (Doppler) is the diastolic fraction (DF) ≥ 0.5. The aim of this study was to establish Doppler echocardiographic parameters which could suggest the presence of a composite graft of LITA, when it revascularizes the anterior interventricular artery (AIA) and another branch of the left coronary artery system. The endpoint of this study was to define sensitivity and specificity considering three variables: ratio of peak velocity in diastole over the systolic peak velocity (DPV / SPV), the mean velocity-time integral in diastole (VTID) and FD of the composite graft patency using FD ≥ 0.5 as the reference standard. The study was conducted according to a design in two stages. It was defined a control group and study group. In the control group, all patients had graft patencies confirmed by coronary angiography (CINE) and the variables DPV / SPV,VTID and DF measured. So, we use this data to establish cutoff points for these variables , based on the calculation of sensitivity and specificity using the ROC curve (Receiverv Operation Characteristic) in order to differentiate composite from simple graft when ATIE only revascularizes the AIA. These cutoff points were applied in patients with composite graft group study. We built a 2x2 contingency table to calculate sensitivity and specificity, considering the indicator of patency a DF ≥ 0.5. In the control group, we observed statistically significant differences in the analysis of the three variables in differentiating simple from composite grafts. The parameters of composite graft patency established by the study group were DPV / SPV ≥ 0.71,VTID ≥ 0.09 and FD ≥ 0.58. The specificity for all these variables was 100%. The sensitivity was 40% for DPV / SPV ≥ 0.71, ≥ 36.4% for VTId≥ 0.09 and 68% for FD ≥ 0.58. We conclude that values greater than or equal to those established for each variable represents a likely indicator of graft patency compound. Values below the established are not conclusive to exclude composite grafts due to a large proportion off alse negatives.

O enxerto de artéria torácica interna tem demonstrado capacidade de remodelamento devido a interação com o leito arterial coronariano. O objetivo deste estudo foi analisar a influência dos fatores clínicos e angiográficos no remodelamento dos enxertos, definido como variação no calibre vascular. Casuística e métodos: No período entre 1983 e 1999, 356 pacientes realizaram cirurgia de revascularização do miocárdio utilizando a artéria torácica interna esquerda para o ramo interventricular anterior e a artéria torácica interna direita para um ramo da circunflexa. Trinta e dois pacientes foram submetidos a cineangiocoronariografia pós-operatória, a qual foi posteriormente analisada com o aplicativo CASS II®. Este estudo observacional apresentou acompanhamento médio de 42 meses(6-204 meses). As variáveis angiográficas analisadas foram os diâmetros proximal e distal dos enxertos arteriais (variável dependente), área coronariana, pontuação de fluxo TIMI, diâmetro de estenose proximal, fluxo dominante distal e ramos patentes. Fatores de risco cardiovascular também foram incluídos. Resultados: O modelo de regressão linear múltiplo demonstrou um R2ajustado=0,69 (p=0,0001) para o modelo a direita e R2ajustado=0,46 (p=0,002) para a esquerda. Os enxertos apresentaram diâmetros proximal e distal de 2,67mm ±0,085 e 2,232mm ±0,085 à esquerda; 2,458mm ±0,088 e 2,010mm ± 0,091 (média±EP) à direita, respectivamente (p>0,05). Nenhuma variável clínica obteve correlação significante estatisticamente. A área coronariana apresentou coeficiente de beta=0,42 (0,14-0,6/IC-95%) e diâmetro de estenose proximal de 0,55 (0,40-0,65/IC-95%) para o remodelamento do lado direito. A área coronariana demonstrou coeficiente de beta=0,54 (0,3- 0,68/IC-95%) para o remodelamento do lado esquerdo. Conclusões: A artéria torácica interna não demonstrou diferença de calibre em relação a lateralidade (esquerda vs direita). O diâmetro de estenose proximal da artéria coronária revascularizada demonstrou correlação positiva com o remodelamento dos enxertos do lado direito. A área da artéria coronária revascularizada foi a única variável de influência para o remodelamento bilateral dos enxertos / Internal thoracic artery grafts has demonstrated capacity for remodeling due to interaction with the coronary artery bed. The goal was to analysis the influence of clinical and angiographic factors in this remodeling as defined as grafts caliber variation. Methods: In a period from 1983 to 1999, 356 patients underwent to coronary artery bypass surgery using the left internal thoracic artery anastomosed to interventricular anterior branch and the right internal thoracic artery to circumflex branches. Thirty two patients were submitted to postoperative coronary angiography which was further analysed by CASS II® software. The mean follow-up of this observational study was 42 months(6- 204 months). Angiographic variables analyzed was proximal and distal diameters of arterial grafts(dependent variable), coronary area, TIMI flow grade, proximal stenosis diameter, dominant distal flow and patent branches. Cardiovascular risk factors were included indeed. Results: The multiple regression model demonstrated R2adjusted=0.69 (p=0.0001) for right side and R2adjusted=0.46 (p=0.002) for left side. The grafts presented proximal and distal diameters of 2.67mm ±0.085 and 2.232mm ±0.085 from left side; 2.458mm ±0.088 and 2.010mm ±0.091 (mean±SE) from right side respectively (p > 0,05). None of the clinical variables had statistical significant correlation. The coronary area presented as a beta coefficient=0.42 (0.14-0.6/CI-95%) and proximal stenosis diameter of 0.55 (0.40-0.65/CI-95%) for right side remodeling. The coronary area shown a beta coefficient=0.54 (0.3- 0.68/CI-95%) for left side remodeling. Conclusions: The internal thoracic artery did not demonstrate difference in caliber about its laterality (left vs right). The proximal stenosis degree of the bypassed coronary artery demonstrated positive correlation with remodeling for the right side grafts. Bilateral grafts remodeling was only explained by positive correlation with the bypassed coronary area

A artéria radial (AR) constitui valiosa opção de enxerto na revascularização do miocárdio (RM), desde a retomada de seu uso, nos anos 1990. O objetivo deste estudo foi avaliar perviedade e remodelamento dos enxertos de AR e sua relação com lesão obstrutiva pré-operatória e parede miocárdica revascularizada, observando-se também os enxertos de artéria torácica interna (ATI). CASUÍSTICA E MÉTODO: Entre 1994 e 2007, 3.964 pacientes foram operados com uso da AR, no InCor/HCFMUSP. Foram selecionados os reestudos angiográficos (12 meses) de 100 pacientes, sendo 11 deles reestudados em duas épocas diferentes. Em 92 pacientes foi utilizada a ATI. Foram determinados os diâmetros médios de AR e ATI, através do software CASS-II®. RESULTADOS: O tempo médio de reestudo foi de 70,53 ±33,18 meses. Em 82 casos (82,0%), a AR revascularizou uma única coronária, mais freqüentemente (50,83%) os ramos marginal esquerdo (ME) ou ventricular posterior (VP/CX). As obstruções pré-operatórias entre 90 e 99% foram as mais prevalentes (39,0%). A perviedade observada foi de 80 casos para AR (80,0%) e 80 para ATIE (86,96%). Houve correlação entre as maiores obstruções pré-operatórias e maior perviedade da AR (p=0,024). Os diâmetros médios dos enxertos foram de 2,302mm ±0,479 (AR) e 2,262mm ±0,409 (ATI). Observaram-se AR maiores do que a média (>2,30mm) nas obstruções pré-operatórias de 100%, em comparação com as demais (p=0,017). As AR que revascularizaram a parede lateral apresentaram os maiores diâmetros, em comparação às demais (p=0,04). Nos 11 pacientes com 2 reestudos, os diâmetros médios das AR foram de: 2,482mm ±0,424 (primeiro reestudo) e 2,599mm ±0,532 (segundo reestudo)(p=n/s). Para as ATIE, observaram-se: 2,308mm ±0,459 (primeiro reestudo) e 2,326mm ±0,531 (segundo reestudo) (p=n/s). No segundo reestudo, observou-se maior número de AR com diâmetros maiores, relacionados às obstruções entre 90-100% (p=0,013). A parede miocárdica revascularizada não interferiu nos diâmetros dos enxertos. CONCLUSÕES: A obstrução pré-operatória interfere na perviedade e nos diâmetros dos enxertos de AR, especialmente nas obstruções de 90% ou mais. A parede miocárdica revascularizada não interfere na perviedade da AR, porém interfere nos diâmetros dos enxertos. Foi observado remodelamento dos enxertos de AR, estando as obstruções mais graves relacionadas aos maiores aumentos de diâmetros dos enxertos comportamento semelhante às ATI. / The radial artery (RA) is an invaluable option for coronary artery bypass grafting (CABG), since its re-introduction in the late 1990 s.The objective of this study was to assess patency and remodeling of RA grafts regarding the interference of pre-operative coronary obstruction and grafted myocardial wall, also observing the internal thoracic artery grafts (ITA). METHODS: Between 1994 and 2007, 3,964 patients were operated with RA grafts, at Heart Institute, University of São Paulo, Brazil. Post-operative coronary angiographies (12 months)of 100 patients were obtained, including 11 patients with two post-op exams, at different periods. In 92 patients the ITA was also used.The grafts medium diameters were obtained using the CASS-II® software. RESULTS: Mean time of post-op angiography was 70,53 ±33,18 months. In 82 cases (82,0%) the RA grafted a single coronary, more frequently (50,83%) the left marginal (LM) or posterior ventricular (PV) branches. Pre-op obstructions between 90 and 99% were more prevalent (39,0%). Patency was of 80 cases for the RA (80,0%) and 80 cases for the ATI grafts (86,96%). There was a correlation between more severe pre-op obstructions and greater patency of the RA grafts (p=0,024). The mean diameters were 2,302mm ±0,479 (RA) and 2,262mm ±0,409 (ITA). RA diameters were above the mean value (>2,30mm) in pre-op obstructions of 100%, compared to the rest (p=0,017). The RA grafting the lateral wall showed the larger diameters, compared to the rest (p=0,04). For the 11 patients with 2 post-op angiographies, mean diameters of RA grafts were: 2,482mm ±0,424 (first) and 2,599mm ±0,532 (second)(p=n/s). For ITA grafts, mean diameters were: 2,308mm ±0,459 (first) and 2,326mm ±0,531 (second)(p=n/s). For the second angiographies, RA grafts exhibited larger diameters, related to pre-op obstructions between 90 and 100% (p=0,013). The grafted myocardial wall showed no interference with graft diameter. CONCLUSIONS: Pre-op coronary obstruction interferes in patency and diameters of RA grafts, more evidently for obstructions of 90% or greater. The grafted myocardial wall does not interfere with RA patency, although it does interfere with graft diameter. Remodeling was observed in RA grafts, correlating greater pre-op coronary obstructions and more evident increase in graft diameter similarly to the ITA grafts.

Abstract Coronary artery disease is the leading cause of death in the world. The outcome of patients at a very high operative risk undergoing coronary artery bypass surgery has not been thoroughly investigated. Cohorts of patients underwent coronary surgery between January 1997 and December 2013 at the Oulu University Hospital, Finland. Data was acquired from electronic patient records. Statistical analysis was performed on the collected data to evaluate outcome and identify predictors of adverse events. Very high-risk patients who underwent isolated coronary artery bypass surgery had a high 30-day mortality (16.2%), but their 5-year survival was satisfactory (66.8%). Survivors of out-of-hospital cardiac arrest were compared to a control group. Immediate postoperative mortality was slightly higher in out-of-hospital cardiac arrest patients (6.3% vs. 0%, p = 0.24), but the overall 5-year survival rates were similar (80.7% vs. 84.5%). Patients with preoperative stage 3 chronic kidney disease have a higher mortality than patients with stage 1-2 chronic kidney disease. Kidney function decline/year was predictive of all-cause mortality, cardiovascular mortality and also tended to predict fatal and non-fatal cardiovascular events. The E-CABG postoperative complication grading system was used to stratify the severity and prognostic impact of postoperative complications and was shown to predict early and late mortality for these patients. The outcome of emergency coronary artery bypass surgery was studied in a multi-center setting. Increasing emergency classes, left ventricular ejection fraction ≤30%, on-pump surgery, and participating centers were independent predictors of in-hospital mortality. Survival rates at 1, 3 and 5 years were 86.4%, 81.6%, and 76.1%. Despite the high preoperative risk of these patients, the long-term outcome for coronary surgery is satisfactory. Patients with stage 3 chronic kidney disease may experience a significant decline in kidney function and poor outcome. Early referral to a nephrologist may be beneficial for these patients. The E-CABG complication grading system seems to be a promising tool for stratifying the severity and prognostic impact of complications occurring after coronary surgery. / Tiivistelmä Sepelvaltimotauti on johtavia kuolinsyitä Maailmassa. Ohitusleikkauksen tuloksia ei ole täysin selvitetty erittäin korkean riskin potilailla. Potilaat leikattiin vuosina 1997-2013. Potilastiedot hankittiin sairauskertomuksista ja kuolinsyytiedot kansallisista rekistereistä. Erittäin korkean riskin potilaiden välitön kuolleisuus ohitusleikkauksen jälkeen on korkea (30 päivän kuolleisuus 16,2 %). Viiden vuoden kuluttua leikkauksesta elossa oli 66,8% leikatuista. Ohitusleikkausta edeltävästi elvytettyjä potilaita verrattiin kontrolliryhmään. Välittömät leikkauksen jälkeinen kuolleisuus oli 6,3% vs. 0% (p = 0,24). Viiden vuoden kuluttua leikkauksesta elossa oli tutkimusryhmästä 80,7% ja kontrolliryhmästä 80,7%. Leikkausta edeltävästi keskivaikean munuaisten vajaatoiminnan omaavilla potilailla on korkeampi kuolleisuus verrattuna potilaisiin, joiden munuaistoiminta on normaalia tai lievästi heikentynyt. Munuaisten vajaatoiminnan eteneminen ennusti kokonaiskuolleisuutta, sydän- ja verisuonikuolleisuutta ja enteili sydän- ja verisuonitapahtumia. E-CABG leikkauksen jälkeisten komplikaatioiden luokittelujärjestelmällä luokiteltiin leikkauksen jälkeisten komplikaatioiden vaikeusastetta ja ennusteellista vaikutusta. E-CABG luokat ja pisteytys ennustivat 1kk, 3kk kuolleisuutta ja kuolleisuutta pidemmällä aikavälillä. Päivystysohitusleikkauksen tuloksia tutkittiin monikeskusasetelmassa. Sairaalakuolleisuutta ennustivat päivystysleikkausluokitteluluokan vakavuus, vasemman kammion ejektiofraktio ≤30%, perfuusiossa tehty leikkaus ja leikkaava keskus. Potilaiden elossaololuvut olivat 1, 3 ja 5 vuoden kohdalla 86,4%, 81,6%, and 76,1%. Leikkaustulokset erittäin korkean riskin potilailla ohitusleikkauksesta ovat kohtuullisia leikkausta edeltävään riskiarvioon suhteutettuna. Näin ollen tämän potilasryhmän sepelvaltimotaudin hoito leikkaamalla on perusteltua. Keskivaikean munuaisten vajaatoiminnan omaavien potilaiden munuaissairauden etenemiseen seuranta-aikana liittyy kuolleisuutta ja sydän- ja verisuonitapahtumia. Aikaisessa vaiheessa tehty nefrolgin konsultaatio voi parantaa näiden potilaiden munuaisfunktiota. E-CABG komplikaatioiden luokittelujärjestelmä vaikuttaa lupaavalta työkalulta ohitusleikkauksen jälkeisten komplikaatioiden luokitteluun ja ennustevaikutuksien arviointiin.

Mild cognitive deficits that negatively impact self-management education-related outcomes may be present in a proportion of cardiac rehabilitation patients and the degree of impairment may vary by the type of coronary revascularization procedure. The purpose of this study was to compare cognitive function, as measured by the Montreal Cognitive Assessment (MoCA), between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) patients, and to determine independent variables of MoCA score. In a cross-sectional study, 78 cardiac rehabilitation patients (CABG n = 38, PCI n = 40) completed the MoCA. Demographics were collected and disease burden was calculated using the age-adjusted Charlson Comorbidity Index (ACCI). Mild cognitive deficits (MoCA ≤26) were present in 55.3% CABG and 30.0% PCI patients. An independent Student’s t test showed that MoCA scores were significantly lower among CABG patients (mean = 24.5, SD = 3.3) compared to PCI patients (M = 26.7, SD = 2.7), t (76) = 3.15, p < 0.01. Descriptive analyses of cognitive domain scores indicated that deficits in short-term memory and language were present among CABG patients. Using a backward regression, coronary revascularization procedure (CABG vs. PCI) (p = 0.006) and disease burden (ACCI) (p = 0.015) remained significant, while heart failure diagnosis became non-significant and was removed from the model (F (2, 75) = 8.382, p < 0.001). The final model explained 16.1% of the total variance in MoCA score (adjusted R2 = 0.161). Results indicate that cognitive deficits were present in cardiac rehabilitation participants and associated with the type of coronary revascularization procedure, suggesting the need for formal cognitive screening and adaptation of education interventions in cardiac rehabilitation. A future prospective cohort study is required to establish temporality, and to measure education-related outcomes, such as health-related quality of life (HRQOL) and self-management. / Thesis / Master of Science (MSc) / Cardiac rehabilitation (CR) is a multifaceted program consisting of exercise and education that is essential to the care of post-coronary revascularization patients. While exercise has shown to improve health outcomes, education has demonstrated inconsistent effects. Since education has imposed cognitive demands, this discrepancy in outcomes may, in part, be due to cognitive deficits present in a proportion of program attendees: the degree of impairment may vary by type of coronary revascularization procedure prior to CR. This study compared cognitive function between two groups of coronary revascularization patients, post-coronary bypass surgery and post-coronary angioplasty, and determined independent variables for cognitive function. Results showed that coronary bypass surgery patients had significantly lower cognitive function than coronary angioplasty patients at program intake. Coronary bypass surgery and accumulated disease burden were weakly associated with decreased cognitive function. Cognitive screening and adapted education for patients with cognitive deficits should be considered to improve CR outcomes.

Coronary artery disease represents a leading cause of death worldwide, to which the coronary artery bypass graft (CABG) is the main method of treatment in advanced multiple vessel disease. The use of the internal mammary artery (IMA) as a graft insures an improved long-term survival, but impairment of chest wall perfusion often leads to surgical site infection and increased morbidity and mortality. Infrared thermography (IRT) has established itself in the past decades as a non-invasive diagnostic technique. The applications vary from veterinary to human medicine and from head to toe. In this study we used IRT in 42 patients receiving CABG to determine the changes in skin surface temperature preoperatively, two hours, 24 h and 6 days after surgery. The results showed a significant and independent drop of surface temperature 2 h after surgery on the whole surface of the chest wall, as well as a further reduction on the left side after harvesting the IMA. The temperature returned to normal after 24 h and remained so after 6 days. The study has shown that IRT is sufficiently sensitive to demonstrate the known, subtle reduction in chest wall perfusion associated with IMA harvesting.

背景與目的： 每一項疾病都有其潛在的風險，但要有效的降低死亡率及併發症發生率，必須找出關鍵性指標加以改善或預防。我們以心臟冠狀動脈繞道手術之患者為例，希望藉由統計分析的方式，找出造成死亡以及術後併發症最相關的因素，目的不只在預測，而在於防範。 研究對象與方法： 在我們的實驗設計上，風險因子分布在手術前、手術中、以及手術後三個階段，對象是某醫學中心接受心臟冠狀動脈繞道手術的220例患者。分析採用迴歸統計建立模型，其中羅吉斯迴歸中的依變數為死亡率與罹病率，線性迴歸的依變數為加護病房留置天數以及總住院日數。ROC curve亦將被建立，以判斷模型是否能區別病患是否罹病或死亡。所得資料亦計算EuroScore及其ROC曲線面積，並與歷史資料做比較。 結果： 所建立的死亡估計模型的有兩個，預測值都在97%以上，ROC曲線面積亦都超過0.96；併發症估計模型由六個變數所構成，預測率及ROC曲線面積分別為94%和0.984。加護病房留置天數及住院天數估計模型分別由八個及十三個因子來解釋，調整後的R square分別為0.527及0.6。EuroScore對死亡與併發症的預測率，分別為93.7%和82%，ROC曲線面積分別是0.864和0.797，均高於歷史文獻記錄，未來應該廣泛應用。 結論與建議： 經由適當的風險分級和危險因子分析，我們可以找出風險高低的標準和依據，了解影響死亡率與罹病率的關鍵因子是什麼，儘可能的做事前的防範與處置，希望能夠改善結果並提高手術的存活率。 EuroScore是個值得採用的預測工具，可以廣泛應用在死亡率與併發症發生率的估計，但是必須搭配風險因子的改善，才能發揮實際的功效。我們認為，體外循環時間與再次手術是最具有空間來降低死亡率與罹病率的兩個要素，有效率的控制時間、改善造成再手術的前因後果，除了死亡率與併發症發生率的下降外，還可以及早脫離對加護病房照顧的需求並減少留置的天數。

Coronary artery disease (CAD) is the leading cause of mortality worldwide and atrial fibrillation (AF) is a prevalent arrhythmia associated with increased risk of mortality and morbidity. Despite improved outcome in both diseases, there is a need to further describe the prevalence, outcome and management of CAD in patients with concomitant AF. AF was a common finding among patients with MI, with 16% having new-onset, paroxysmal or chronic AF. Patients post-MI with concomitant AF, regardless of subtype, were at increased risk of composite cardiovascular outcome of mortality, MI or ischemic stroke, including mortality and ischemic stroke alone. No major difference in outcome was observed between AF subtypes. At discharge, an oral anticoagulant was prescribed to 27% of the patients with MI and AF undergoing percutaneous coronary intervention (PCI). Aspirin or clopidogrel plus warfarin versus dual antiplatelet therapy with aspirin plus clopidogrel were associated with similar 0-90-day and lower 91-365-day risk of cardiovascular outcome, without increased risk of major bleeding events. Triple therapy with aspirin, clopidogrel plus warfarin versus dual antiplatelet therapy was associated with non-significant lower risk of cardiovascular outcome, but with increased risk of bleeding events. Treatment with renin-angiotensin system (RAS) inhibitors post-MI was associated with lower risk of all-cause and cardiovascular mortality in patients with and without congestive heart failure and/or AF. However, RAS inhibition in patients without AF was not associated with lower risk of new-onset AF. Approximately 1 in 3 patients undergoing isolated coronary artery bypass grafting (CABG) had pre- or postoperative AF. Patients with AF, regardless of subtype, were at higher risk of all-cause mortality, cardiovascular mortality and congestive heart failure. Furthermore, postoperative AF was associated with higher risk of recurrent AF. In conclusion, AF was a common finding in the setting of MI and CABG. AF, irrespectively if in the setting of MI or CABG was associated with higher risk of ischemic events and mortality. Also, postoperative AF was associated with recurrent AF. Oral anticoagulants post-MI and PCI in patients with AF was underutilized, however, optimal antithrombotic therapy is still unknown. RAS inhibition post-MI seems beneficial, however, it was not associated with lower incidence of new-onset AF.

La fibrillation auriculaire (FA) est une arythmie touchant les oreillettes. En FA, la contraction auriculaire est rapide et irrégulière. Le remplissage des ventricules devient incomplet, ce qui réduit le débit cardiaque. La FA peut entraîner des palpitations, des évanouissements, des douleurs thoraciques ou l’insuffisance cardiaque. Elle augmente aussi le risque d'accident vasculaire. Le pontage coronarien est une intervention chirurgicale réalisée pour restaurer le flux sanguin dans les cas de maladie coronarienne sévère. 10% à 65% des patients qui n'ont jamais subi de FA, en sont victime le plus souvent lors du deuxième ou troisième jour postopératoire. La FA est particulièrement fréquente après une chirurgie de la valve mitrale, survenant alors dans environ 64% des patients. L'apparition de la FA postopératoire est associée à une augmentation de la morbidité, de la durée et des coûts d'hospitalisation. Les mécanismes responsables de la FA postopératoire ne sont pas bien compris. L'identification des patients à haut risque de FA après un pontage coronarien serait utile pour sa prévention. Le présent projet est basé sur l'analyse d’électrogrammes cardiaques enregistrées chez les patients après pontage un aorte-coronaire. Le premier objectif de la recherche est d'étudier si les enregistrements affichent des changements typiques avant l'apparition de la FA. Le deuxième objectif est d'identifier des facteurs prédictifs permettant d’identifier les patients qui vont développer une FA. Les enregistrements ont été réalisés par l'équipe du Dr Pierre Pagé sur 137 patients traités par pontage coronarien. Trois électrodes unipolaires ont été suturées sur l'épicarde des oreillettes pour enregistrer en continu pendant les 4 premiers jours postopératoires. La première tâche était de développer un algorithme pour détecter et distinguer les activations auriculaires et ventriculaires sur chaque canal, et pour combiner les activations des trois canaux appartenant à un même événement cardiaque. L'algorithme a été développé et optimisé sur un premier ensemble de marqueurs, et sa performance évaluée sur un second ensemble. Un logiciel de validation a été développé pour préparer ces deux ensembles et pour corriger les détections sur tous les enregistrements qui ont été utilisés plus tard dans les analyses. Il a été complété par des outils pour former, étiqueter et valider les battements sinusaux normaux, les activations auriculaires et ventriculaires prématurées (PAA, PVA), ainsi que les épisodes d'arythmie. Les données cliniques préopératoires ont ensuite été analysées pour établir le risque préopératoire de FA. L’âge, le niveau de créatinine sérique et un diagnostic d'infarctus du myocarde se sont révélés être les plus importants facteurs de prédiction. Bien que le niveau du risque préopératoire puisse dans une certaine mesure prédire qui développera la FA, il n'était pas corrélé avec le temps de l'apparition de la FA postopératoire. Pour l'ensemble des patients ayant eu au moins un épisode de FA d’une durée de 10 minutes ou plus, les deux heures précédant la première FA prolongée ont été analysées. Cette première FA prolongée était toujours déclenchée par un PAA dont l’origine était le plus souvent sur l'oreillette gauche. Cependant, au cours des deux heures pré-FA, la distribution des PAA et de la fraction de ceux-ci provenant de l'oreillette gauche était large et inhomogène parmi les patients. Le nombre de PAA, la durée des arythmies transitoires, le rythme cardiaque sinusal, la portion basse fréquence de la variabilité du rythme cardiaque (LF portion) montraient des changements significatifs dans la dernière heure avant le début de la FA. La dernière étape consistait à comparer les patients avec et sans FA prolongée pour trouver des facteurs permettant de discriminer les deux groupes. Cinq types de modèles de régression logistique ont été comparés. Ils avaient une sensibilité, une spécificité et une courbe opérateur-receveur similaires, et tous avaient un niveau de prédiction des patients sans FA très faible. Une méthode de moyenne glissante a été proposée pour améliorer la discrimination, surtout pour les patients sans FA. Deux modèles ont été retenus, sélectionnés sur les critères de robustesse, de précision, et d’applicabilité. Autour 70% patients sans FA et 75% de patients avec FA ont été correctement identifiés dans la dernière heure avant la FA. Le taux de PAA, la fraction des PAA initiés dans l'oreillette gauche, le pNN50, le temps de conduction auriculo-ventriculaire, et la corrélation entre ce dernier et le rythme cardiaque étaient les variables de prédiction communes à ces deux modèles. / Atrial fibrillation (AF) is an abnormal heart rhythm (cardiac arrhythmia). In AF, the atrial contraction is rapid and irregular, and the filling of the ventricles becomes incomplete, leading to reduce cardiac output. Atrial fibrillation may result in symptoms of palpitations, fainting, chest pain, or even heart failure. AF is an also an important risk factor for stroke. Coronary artery bypass graft surgery (CABG) is a surgical procedure to restore the perfusion of the cardiac tissue in case of severe coronary heart disease. 10% to 65% of patients who never had a history of AF develop AF on the second or third post CABG surgery day. The occurrence of postoperative AF is associated with worse morbidity and longer and more expensive intensive-care hospitalization. The fundamental mechanism responsible of AF, especially for post-surgery patients, is not well understood. Identification of patients at high risk of AF after CABG would be helpful in prevention of postoperative AF. The present project is based on the analysis of cardiac electrograms recorded in patients after CABG surgery. The first aim of the research is to investigate whether the recordings display typical changes prior to the onset of AF. A second aim is to identify predictors that can discriminate the patients that will develop AF. Recordings were made by the team of Dr. Pierre Pagé on 137 patients treated with CABG surgery. Three unipolar electrodes were sutured on the epicardium of the atria to record continuously during the first 4 post-surgery days. As a first stage of the research, an automatic and unsupervised algorithm was developed to detect and distinguish atrial and ventricular activations on each channel, and join together the activation of the different channels belonging to the same cardiac event. The algorithm was developed and optimized on a training set, and its performance assessed on a test set. Validation software was developed to prepare these two sets and to correct the detections over all recordings that were later used in the analyses. It was complemented with tools to detect, label and validate normal sinus beats, atrial and ventricular premature activations (PAA, PVC) as well as episodes of arrhythmia. Pre-CABG clinical data were then analyzed to establish the preoperative risk of AF. Age, serum creatinine and prior myocardial infarct were found to be the most important predictors. While the preoperative risk score could to a certain extent predict who will develop AF, it was not correlated with the post-operative time of AF onset. Then the set of AF patients was analyzed, considering the last two hours before the onset of the first AF lasting for more than 10 minutes. This prolonged AF was found to be usually triggered by a premature atrial PAA most often originating from the left atrium. However, along the two pre-AF hours, the distribution of PAA and of the fraction of these coming from the left atrium was wide and inhomogeneous among the patients. PAA rate, duration of transient atrial arrhythmia, sinus heart rate, and low frequency portion of heart rate variability (LF portion) showed significant changes in last hour before the onset of AF. Comparing all other PAA, the triggering PAA were characterized by their prematurity, the small value of the maximum derivative of the electrogram nearest to the site of origin, as well as the presence of transient arrhythmia and increase LF portion of the sinus heart rate variation prior to the onset of the arrhythmia. The final step was to compare AF and Non-AF patients to find predictors to discriminate the two groups. Five types of logistic regression models were compared, achieving similar sensitivity, specificity, and ROC curve area, but very low prediction accuracy for Non-AF patients. A weighted moving average method was proposed to design to improve the accuracy for Non-AF patient. Two models were favoured, selected on the criteria of robustness, accuracy, and practicability. Around 70% Non-AF patients were correctly classified, and around 75% of AF patients in the last hour before AF. The PAA rate, the fraction of PAA initiated in the left atrium, pNN50, the atrio-ventricular conduction time, and the correlation between the latter and the heart rhythm were common predictors of these two models.

Durante a cirurgia de revascularização do miocárdio com circulação extracorpórea e hipotermia (CEC-H) ocorre alteração na efetividade do propofol e na sua farmacocinética realizada a partir das concentrações plasmáticas do propofol total no decurso do tempo. A ligação do propofol à proteína plasmática parece estar alterada em consequência de diversos fatores incluindo a hemodiluição e a heparinização que ocorre no início da circulação extracorpórea, uma vez que se reportou anteriormente que a concentração plasmática do propofol livre aumentou durante a realização da circulação extracorpórea normotérmica. Por outro lado, a infusão alvo controlada é recomendada para manter a concentração plasmática do propofol equivalente ao alvo de 2 &#181g/mL durante a intervenção cirúrgica com CEC-H. Se alterações significativas na hipnose do propofol ocorrem nesses pacientes, então o efeito aumentado desse agente hipnótico poderia estar relacionado à redução na extensão da ligação do fármaco as proteínas plasmáticas; entretanto, o assunto ainda permanece em discussão e necessita de investigações adicionais. Assim, o objetivo do estudo foi investigar as concentrações plasmáticas de propofol livre em pacientes durante a revascularização do miocárdio com e sem o procedimento de CEC-H através da abordagem PK-PD. Dezenove pacientes foram alocados e estratificados para realização de cirurgia de revascularização do miocárdio com circulação extracorpórea (CEC-H, n=10) ou sem circulação extracorpórea (NCEC, n=9). Os pacientes foram anestesiados com sufentanil e propofol alvo de 2 &#181g/mL. Realizou-se coleta seriada de sangue para estudo farmacocinético e o efeito foi monitorado através do índice bispectral (BIS) para medida da profundidade da hipnose no período desde a indução da anestesia até 12 horas após o término da infusão de propofol, em intervalos de tempo pré-determinados no protocolo de estudo. As concentrações plasmáticas foram determinadas através de método bioanalítico pela técnica de cromatografia líquida de alta eficiência. A farmacocinética foi investigada a partir da aplicação do modelo aberto de dois compartimentos, PK Solutions v. 2. A análise PK-PD foi realizada no Graph Pad Prisma v.5.0 após a escolha do modelo do efeito máximo (EMAX sigmóide, slope variável). Os dados foram analisados utilizando o Prisma v. 5.0, p<0,05, significância estatística. As concentrações plasmáticas de propofol total foram comparáveis nos dois grupos (CEC-H e NCEC); entretanto o grupo CEC-H evidenciou aumento na concentração do propofol livre de 2 a 5 vezes em função da redução na ligação do fármaco às proteínas plasmáticas. A farmacocinética do propofol livre mostrou diferença significativa entre os grupos no processo de distribuição pelo prolongamento da meia vida e aumento do volume aparente, e no processo de eliminação em função do aumento na depuração plasmática e redução na meia vida biológica no grupo CEC-H. A escolha do modelo EMAX sigmóide, slope variável foi adequada uma vez que se evidenciou alta correlação entre os valores do índice bispectral e as concentrações plasmáticas do propofol livre (r2>0.90, P<0.001) para os pacientes investigados. / During coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB) profound changes occur on propofol effect and on kinetic disposition related to total drug plasma measurements in these patients. It was reported that drug plasma binding could be altered as a consequence of hemodilution and heparinization before starts CPB since free propofol plasma levels was increased by twice under normothermic procedure. In addition, the target controlled infusion (TCI) is recommended to maintain propofol plasma concentration (2 &#181g/mL) during CABG CPB-H intervention. However, whether significant changes that occur in propofol hypnosis in these patients could be related to the reduction on the extension of drug plasma binding remain unclear and under discussion until now. Then, the objective of this study was to investigate propofol free plasma levels in patients undergoing CABG with and without CPB by a pharmacokinetics-pharmacodynamics (PK-PD) approach. Nineteen patients were scheduled for on-pump coronary artery bypass grafting (CABG-CPB, n=10) or off-pump coronary artery bypass grafting (OPCABG, n=9) were anesthetized with sufentanil and propofol TCI (2 &#181g/mL). Blood samples were collected for drug plasma measurements and BIS were applied to access the depth of hypnosis from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma drug concentrations were measured using high-performance liquid chromatography, followed by a propofol pharmacokinetic analysis based on two compartment open model, PK Solutions v.2; PK-PD analysis was performed by applying EMAX model, sigmoid shape-variable slope and data were analyzed using Prisma v. 5.0, considering p<0.05 as significant difference between groups. The total propofol plasma concentrations were comparable in both groups during CABG; however it was shown in CPB-group significant increases in propofol free plasma concentration by twice to fivefold occur as a consequence of drug plasma protein binding reduced in these patients. Pharmacokinetics of free propofol in CPB-H group compared to OPCAB group based on two compartment open model was significantly different by the prolongation of distribution half-life, increases on plasma clearance, and biological half-life shortened. In addition, the kinetic disposition of propofol changes in a different manner considering free drug levels in the CPB-H group against OPCAB group as follows: prolongation of distribution half-life and increases on volume of distribution, remaining unchanged biological half-life in spite of plasma clearance increased. BIS values showed a strong correlation with free drug levels (r2>0.90, P<0.001) in CPB-H group and also in OPCAB group by the chosen EMAX model sigmoid shape-variable slope analyzed by GraphPad Prisma v.5.0.