Background: Combined valvular and coronary artery bypass grafting (CAB G) surgery requires a long period of cardioplegic arrest (CA) that predisposes the heart to ischaemiareperfusion injury, low cardiac output syndrome, reperfusion dysrhythmias, inhospital mortality and increased costs. Procedures that can reduce the duration of CA would be expected to reduce intraoperative and postoperative complications. Mehods: Adults undergoing combined valvular and CABG surgery were randomized to either coronary surgery performed on the beating heart with cardiopulmonary bypass (CPB) support followed by CA for the valvular procedure (hybrid group) or surgery with both procedures carried out under CA (conventional group). The primary outcome was a composite of in-hospital death, postoperative myocardial infarction, cardiac dysrhythmias, requirements for cardiac pacing for more than 12 hours and/or inotropic support for more than 12 hours postoperativeiy. Results: One hundred and sixty patients (80 hybrid, 80 conventional) were randomized between March 2008 and July 2012. Mean age was 66.5 years and 74% were male. Valvular procedures included aortic (61.8%) and mitral (33.1%) alone or in combination (5.l %). The primary outcome occurred in 64/80 of the conventional group patients and 67/80 of the hybrid group patients (odds ratio 1.24, 95% Cl 0.54 to 2.86, p=0.61). The CA time was, on average, 16% shorter in the hybrid group (median 98 minutes vs. 89 minutes, geometric mean ration (GMR) 0.84, 95% Cl 0.77 to 0.93 , p=0.0004), but the overall duration of CPB was on average 7% longer in the hybrid group (GMR 1.07, 95% Cl 0.98 to 1.16, p=0.12). Cardiac troponin T plasma concentrations and levels of metabolites measured in heart biopsies were similar between the two treatment groups. Conclusion: The hybrid technique reduced the CA time, but this did not result in a significant reduction in the frequency of the primary outcome. In this trial the clinical outcomes and the extent of the myocardial injury were similar between the two surgical methods.

Introduction An increasing proportion of the patients undergoing cardiac surgery have diabetes mellitus, in particular type II diabetes. In spite of this, diabetic patients have received limited attention in this setting. Although diabetes is a metabolic disease cardiac metabolism in association with surgery has previously not been explored in diabetics. This investigation was carried out to describe the metabolic state of the heart in diabetics after cardiac surgery and to study if it is accessible to metabolic intervention with high-dose GIK. Also, the potential hazards associated with such a regime in clinical practice were evaluated. Furthermore, a comparison of the outcome in diabetic and nondiabetic patients after coronary surgery was done. Methods Myocardial metabolism and how it was influenced by high-dose GIK was assessed with coronary sinus catheter technique in a prospective randomized study on 20 type II diabetic patients undergoing CABG (paper I, II). Safety issues concerning high-dose GIK were assessed in two retrospective studies. The potential role of metabolic interventions for neurological injury was assessed in a cohort of 775 consecutive patients undergoing CABG or combined CABG + valve surgery, in whom metabolic interventions gradually replaced traditional treatment for postoperative heart failure (paper III). A detailed analysis of blood glucose and electrolyte control was done in all cases (n=89) receiving high-dose GIK during one year (paper IV). The hemodynamic impact of highdose GIK was assessed with standard postoperative monitoring including Swan-Ganz catheters (paper II, IV). Outcome and prognosis after CABG in diabetic patients (n=540) were compared with nondiabetics (n=2239) with the aid of the institutional database comprising all isolated CABG procedures from 1995-1999 (paper V). Results The metabolism of the diabetic heart after CABG was characterized by predominant uptake of FFA and restricted uptake of carbohydrate substrates. A high extraction rate of beta-hydroxybutyric acid and glutamate was also found. Alanine was released from the heart (paper I). High-dose GIK induced a shift towards uptake of carbohydrates, in particular lactate, at the expense of FFA and betahydroxybutyric acid (paper II). A substantial systemic glucose uptake was found during high-dose GIK treatment but the uptake tended to be lower and blood glucose higher if adrenergic drugs were used or/and if the patient was a diabetic (paper IV). High-dose GIK was associated with beneficial effects on cardiac output both in the prospective and retrospective analyses (paper II, IV). No evidence for untoward neurological effects associated with GIK treatment was found. History of cerebrovascular disease was the most important risk factor for postoperative cerebral complications and in general markers for advanced atherosclerotic disease were found to be of importance (paper III). High-dose GIK in clinical practice was associated with acceptable blood glucose and electrolyte control and no serious adverse events were recorded (paper IV). Patients with diabetes undergoing CABG had an acceptable short-term mortality that did not differ significantly from non-diabetic patients. However, diabetic patients had a higher early postoperative morbidity particularly with regard to stroke, renal- and infectious complications. Also, long-term survival was markedly reduced in diabetic patients, particularly in insulin treated patients (paper V). Comments FFA were the main source of energy for the heart in type II diabetics after CABG whereas the uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate may represent an adaptation to the unfavorable metabolic situation of the post-ischemic diabetic heart. High-dose GIK can be used in type II diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of FFA and beta-hydroxybutyric acid. The magnitude of this shift was sufficient to account for the entire myocardial oxygen consumption assuming that the substrates extracted were oxidized. This could have implications for the treatment of the diabetic heart in association with surgery and ischemia. Provided careful monitoring high-dose GIK can be safely used in clinical practice and this treatment deserves further evaluation in the treatment of postoperative heart failure. High-dose GIK also provides a means for strict blood glucose control and as substantial amounts of glucose can be infused even in critically ill patients, it may prove useful for nutrition in critical care. Several of the risk factors for neurological injury identified constitute markers for advanced atherosclerotic disease, thus, also providing an explanation for the increased risk of neurological injury in diabetics after cardiac surgery. Short-term mortality was acceptable in diabetics after CABG. However, further efforts are warranted to address postoperative morbidity and late outcome. This represents a challenge as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG. / On the day of the public defence the status of article IV was: Submitted and the title of article IV was in the printed version: High-dose GIK in cardiac surgery - clinical safety issues and lessons learned.

<p>The aims of this project were to investigate the impact of perioperative myocardial damage on morbidity and mortality after coronary artery bypass grafting (CABG), to determine whether biochemical marker levels after CABG correlate to perioperative myocardial infarct size, and to assess the long-term morbidity after CABG, in particular to determine whether women do worse.</p><p>The studies were conducted in patients who had undergone isolated, primary CABG. The correlation of postoperative cardiac marker levels to early and late survival was evaluated in 4,911 consecutive patients; this showed that elevated cardiac markers implied a highly increased risk of both early cardiac death and late death. Hospital readmission for any cause and effect of gender on the readmission rate were analysed in 7,493 patients; it was found that the risk of readmission was higher in women than in men, because of greater co-morbidity and higher age. In the same patient cohort, it was clearly demonstrated that perioperative myocardial damage increased the risk of heart failure independently, and that late mortality was greatly increased in patients readmitted for heart failure. Finally, in a prospective, clinical trial, creatine kinase MB (CK-MB) and troponin I and T levels were found to correlate to infarction mass, as quantified by magnetic resonance imaging postoperatively. The findings strongly suggested that CK-MB above five times the upper normal limit was the result of perioperative myocardial infarction.</p><p>In conclusion, perioperative myocardial damage is an important adverse event with a highly negative effect on early and late survival after CABG, and also entails an increased risk of subsequent heart failure, which markedly impairs long-term survival. Gender differences may be explained by patient characteristics and risk factors and not by female sex per se. Increases in biochemical markers after CABG correspond to the amount of perioperatively infarcted myocardium. </p>

The aims of this project were to investigate the impact of perioperative myocardial damage on morbidity and mortality after coronary artery bypass grafting (CABG), to determine whether biochemical marker levels after CABG correlate to perioperative myocardial infarct size, and to assess the long-term morbidity after CABG, in particular to determine whether women do worse. The studies were conducted in patients who had undergone isolated, primary CABG. The correlation of postoperative cardiac marker levels to early and late survival was evaluated in 4,911 consecutive patients; this showed that elevated cardiac markers implied a highly increased risk of both early cardiac death and late death. Hospital readmission for any cause and effect of gender on the readmission rate were analysed in 7,493 patients; it was found that the risk of readmission was higher in women than in men, because of greater co-morbidity and higher age. In the same patient cohort, it was clearly demonstrated that perioperative myocardial damage increased the risk of heart failure independently, and that late mortality was greatly increased in patients readmitted for heart failure. Finally, in a prospective, clinical trial, creatine kinase MB (CK-MB) and troponin I and T levels were found to correlate to infarction mass, as quantified by magnetic resonance imaging postoperatively. The findings strongly suggested that CK-MB above five times the upper normal limit was the result of perioperative myocardial infarction. In conclusion, perioperative myocardial damage is an important adverse event with a highly negative effect on early and late survival after CABG, and also entails an increased risk of subsequent heart failure, which markedly impairs long-term survival. Gender differences may be explained by patient characteristics and risk factors and not by female sex per se. Increases in biochemical markers after CABG correspond to the amount of perioperatively infarcted myocardium.

À l’heure actuelle, plusieurs centres de chirurgie cardiaque ont noté une augmentation du nombre de patients âgés orientés pour une chirurgie. Les baisses majeures de la natalité et de la mortalité dans tous les groupes d’âge ont contribué au vieillissement progressif des populations des pays industrialisés. Il est bien connu que la prévalence des pathologies cardiovasculaires augmente avec l’âge et fait en sorte que ce groupe de patients âgés soit à haut risque opératoire. Trois études ont été réalisées dans le cadre de ce travail dédié aux deux types de chirurgie les plus fréquemment pratiquées pour ce groupe de population : la chirurgie de la valve aortique et la chirurgie de revascularisation coronarienne. Le substitut valvulaire aortique idéal pour une personne âgée considérée à risque opératoire élevé suscite toujours un débat. Depuis quelques années, avec les progrès technologiques en chirurgie cardiaque, les valves sans suture (V-SS) en général et la Perceval en particulier, constituent une excellente alternative à la prothèse standard chez ce sous-groupe de patients. Tout en diminuant le temps opératoire, la Perceval ne compromet ni la qualité ni la sécurité de l’acte chirurgical et elle présente des bénéfices cliniques et hémodynamiques aussi bien à court et à long terme. Pour le démontrer nous vous présentons les résultats d’une étude de cohorte regroupant 215 patients consécutifs qui a permis d’évaluer l’efficacité et la durabilité de la Perceval. Notre étude se veut l’appui qui soutiendra la place et l’apport de la Perceval dans l’arsenal thérapeutique du remplacement valvulaire aortique (RVA). Comme toutes les bioprothèses, la Perceval est soumise à un risque faible, mais constant à long terme de dégénérescence structurale et qui pourrait éventuellement nécessiter une réintervention. Pour clarifier cette problématique, nous vous présentons une étude descriptive rapportant notre expérience dans la prise en charge de la détérioration structurale de la prothèse Perceval. De plus, cette étude a permis de mettre en lumière la complémentarité parfois inattendue (dans des conditions urgentes) de ces approches thérapeutiques ( TAVI et Perceval) chez les patients à risque élevé. De nos jours, un certain pourcentage des malades orientés vers une revascularisation chirurgicale présente une pathologie coronarienne assez diffuse et complexe qui peut compromettre la revascularisation coronarienne souhaitable. A cet effet, l’endartériectomie coronarienne (EC), une ancienne technique largement utilisée auparavant, puis délaissée par la suite, mérite d’être reconsidérée chez ces patients. La troisième étude présentée dans ce mémoire rapporte les résultats d’une cohorte de 147 patients atteints de maladie coronarienne diffuse. En plus d’être sécuritaire, notre étude documente la perméabilité à court et à moyen terme d’un sous groupe de patient étudié avec un angioscanner coronaire. / Currently, several cardiac surgery centers have noted an increase in the number of elderly patients referred for surgery. The major decline in birth rates and deaths in all age groups has contributed to the gradual aging of populations in industrialized countries. It is well known that the prevalence of cardiovascular pathologies increases with age and puts this group of elderly patients at high risk for surgery. Three studies were carried out as part of this work dedicated to the two types of surgery most frequently performed for this population group: aortic valve surgery and coronary revascularization surgery. The ideal aortic valve substitute for an elderly person considered to be at high operative risk is still a subject of debate. In recent years, with technological advances in cardiac surgery, sutureless valves (V-SS) in general and the Perceval in particular have been an excellent alternative to the standard prosthesis in this subgroup of patients. While reducing operating time, Perceval does not compromise the quality or safety of the surgical procedure and it offers clinical and hemodynamic benefits both in the short and long term. To demonstrate this, we present to you the results of a cohort study involving 215 consecutive patients which made it possible to evaluate the effectiveness and durability of Perceval. Our study is intended to support the place and contribution of Perceval in the therapeutic arsenal of aortic valve replacement (AVR). Like all bioprostheses, Perceval is subject to a low, but constant long-term risk of structural degeneration which may eventually require reoperation. To clarify this problem, we present to you a descriptive study reporting our experience in the management of structural deterioration of the Perceval prosthesis. In addition, this study shed light on the sometimes unexpected complementarity (in urgent conditions) of these therapeutic approaches (TAVI and Perceval) in high-risk patients. Nowadays, a certain percentage of patients referred for surgical revascularization present a fairly diffuse and complex coronary pathology which can compromise the desirable coronary revascularization. To this end, coronary endarterectomy (CE), an old technique widely used before, then abandoned thereafter, deserves to be reconsidered in these patients. The third study presented in this thesis reports the results of a cohort of 147 patients with diffuse coronary artery disease. In addition to being safe, our study documents the short- and medium-term patency of a subgroup of patients studied with a coronary CT angiography.

L'objectiu d'aquest treball era avaluar la mortalitat hospitalària de la cirurgia coronaria en malalts de la sanitat pública operats en centres de gestió pública i privada de Catalunya, mitjançant l'ús de dues escales de risc (l'EuroSCORE i un model d'àmbit local). S'analitzà també la validesa dels mètodes d'avaluació i es comparà el resultat de la cirurgia sense circulació extracorpòria respecte de la cirurgia amb circulació extracorpòria. Es van incloure tots els malalts consecutius (1.605) sotmesos a una primera intervenció d'empelt coronari aïllat durant dos anys en cinc hospitals. Els resultats indiquen que a Catalunya: 1) La gestió privada del centre s'associa marginalment amb una millor supervivència. 2) L'efectivitat de la cirurgia coronària a millorat en els últims anys. 3) Ambdós instruments d'ajust del risc son útils per a l'avaluació d'aquests resultats. 4) La cirurgia sense circulació extracorpòria s'associa a millors resultats, sobre tot en els pacients amb risc preoperatori baix. / El objetivo de este trabajo era evaluar la mortalidad hospitalaria de la cirugía coronaria de los pacientes de la sanidad pública operados en centros de gestión pública y privada de Cataluña, mediante dos escalas de riesgo (el EuroSCORE y una de ámbito local). Se analizó también la validez de los métodos de evaluación y se comparó el resultado de la cirugía sin circulación extracorporea con el de la cirugía con circulación extracorporea.Se incluyeron los pacientes (1.605) sometidos a una primera intervención de implante aortocoronario aislado durante dos años en cinco centros.Los resultados indican que en Cataluña: La gestión privada se asocia marginalmente a mejor supervivencia. La efectividad de la cirugía coronaria ha mejorado en los últimos años. Ambos instrumentos de ajuste del riesgo resultan útiles para la evaluación de estos resultados. La cirugía sin circulación extracorporea se asocia a mejores resultados, sobre todo en pacientes de riesgo bajo. / The objective of the present study was to evaluate hospital mortality after coronary surgery in patients from the public health system operated on in public and private centers, using two risk scores (the EuroSCORE and a locally derived model). In addition, validity of such evaluating methods was assessed and the results of off-pump and on-pump coronary surgery were compared.All consecutive patients (1.605) undergoing a first isolated coronary by-pass procedure during two years were recruited in five hospitals.The results show that in Catalonia: 1) Private hospital management is associated to a maginal increase in hospital survival. 2) Effectiveness of coronary by-pass surgery has increased compared to previous evaluations. 3) Both risk scores showed complementary properties fort he evaluation of results. 4) Off-pump coronary surgery is associated to better results and the association is grater in low risk patients.