Les patients coronariens stables ou stabilisés sont à haut risque d’évènements cardiovasculaires. Ils représentent une population hétérogène avec une présentation clinique, un terrain et un pronostic pouvant être extrêmement variables d’un patient à l’autre. Pourtant, d’après les recommandations internationales, tous doivent bénéficier d’une prise en charge relativement comparable basée sur des essais cliniques réalisés dans des sous-populations restreintes de patients stables et instables, pour la plupart anciens, et ne correspondant plus à la prise en charge actuelle des patients. Préciser les déterminants du pronostic de cette population, et notamment les stratégies thérapeutiques, est un enjeu majeur.Les antagonistes du système rénine-angiotensine (IEC/ARA2) font partie de l’arsenal médicamenteux de tout patient coronarien. Pourtant leur intérêt, en association aux antiagrégants plaquettaires et statines, est incertain chez les patients sans dysfonction ventriculaire gauche qui constituent un sous-groupe important parmi les patients stables.Le registre international REACH a évalué l’impact des IEC/ARA2 dans cette population avec 4 ans de suivi. La méthodologie statistique utilisée a été une analyse observationnelle avec ajustement ou avec appariement selon le score de propension. Il n’a pas été mis en évidence de bénéfice des IEC/ARA2 sur le critère de jugement principal composite associant décès cardiovasculaire – IDM – AVC, de même que sur le critère de jugement secondaire associant décès cardiovasculaire – IDM – AVC – Hospitalisation pour évènement athéro-thrombotique ou sur les critères tertiaires comprenant individuellement chacun des critères de jugement secondaire ainsi que sur la mortalité toute cause. Enfin il n’est pas ressorti non plus de bénéfice franc dans les sous-groupes d’analyse. Les résultats ont été concordants lorsque les analyses ont été réalisées pour les IEC seuls ou pour les ARA2 seuls, et ont été confortés par diverses analyses de sensibilité.Ces données méritent confirmation dans une cohorte indépendante. C’est l’un des objectifs du registre CLARIFY, registre de 32703 patients coronariens stables ou stabilisés, dont le suivi à 5 ans est terminé. Dans ce registre contemporain international, le taux global à 5 ans de mortalité toute cause a été de 7,9%, de mortalité non cardiovasculaire de 5% et de mortalité cardiovasculaire de 2,9%. Un évènement cardiovasculaire comprenant infarctus du myocarde (fatal ou non), angor instable, revascularisation coronaire par angioplastie ou pontage est survenu chez 15,9% des patients.Tout comme les IEC/ARA2, l’impact des bétabloquants dans la prise en charge du coronarien stable ou stabilisé, sans dysfonction ventriculaire est également controversé. Cette classe médicamenteuse est en cours d’évaluation dans CLARIFY. L’analyse tient compte du type de bétabloquant, de la dose prescrite, des éventuelles intolérances amenant à modifier leur utilisation, de la présence et de l’ancienneté d’un infarctus du myocarde et la fraction d’éjection ventriculaire gauche.CLARIFY a également pour objectif d’approfondir les déterminants du pronostic de la maladie coronarienne stable, avec une analyse spécifiquement focalisée sur la présence de symptômes angineux, d’ischémie myocardique et sur leur combinaison, en fonction de l’utilisation des méthodes de revascularisation myocardiques, pour mieux comprendre les mécanismes responsables des évènements cardiovasculaires et évoluer vers une prise en charge plus personnalisée. / Stable or stabilized coronary artery disease patients are at high risk for cardiovascular events. They represent a heterogeneous population. The clinical presentation, the context and the prognosis can be extremely variable from one patient to another. However, according to the international guidelines, those patients should be given a relatively comparable treatment based on clinical trials realized in restricted subpopulations of stable and unstable patients. Most of these trials are old, and no longer correspond to the current management. Specifying the determinants of the prognosis of this population, and in particular the therapeutic strategies, is a major challenge.The antagonist receptors of renin-angiotensin system (ACEI/ARB) are a part of the treatment of any coronary artery disease patient. Yet their interest in the prognosis of this population without left ventricular dysfunction in association with antiplatelet agents and statins is uncertain.The contemporary REACH registry has assessed the impact of ACEI/ARB in this population with a 4-year of follow-up. The statistical methodology used was based on the propensity score. After adjustment or matching with the propensity score, there was no benefit of ACEI/ARB on the primary endpoint of cardiovascular death - MI - stroke. No benefit was found on the secondary endpoint of cardiovascular death - MI - stroke - hospitalization for atherothrombotic events. No benefit was found on the tertiary criteria including individually each of the secondary endpoints and on any cause mortality. Finally,there was no clear benefit in the analyzes subgroups. These results were consistent when the analyzes were performed for ACEI alone or for ARB alone. They were also supported by sensitivity analyzes.These data should be confirmed or reversed in an independent cohort. This will be one of the many objectives of the CLARIFY registry, that enrolled 32,703 stable or stabilized coronary artery disease patients. The 5-year follow-up is complete. In this international contemporary registry, the overall 5-year rate of total mortality was 7.9%, non-cardiovascular mortality was 5% and cardiovascular mortality was 2.9%. A cardiovascular event including myocardial infarction (fatal or not), unstable angina, coronary revascularization by angioplasty or bypass surgery occured in 15.9% of patients.Like ACEI/ARB, the impact of betablockers on the management of stable or stabilized coronary artery disease without left ventricular dysfunction is also controversial. This drug class is being evaluated in CLARIFY. The analyzis takes into account the type of beta-blocker, the prescribed dose, any intolerance leading to changes in their use, the history of a myocardial infarction, and the left ventricular ejection fraction.CLARIFY will help to more define the determinants of the prognosis of stable coronary artery disease, with a more particular focus on symptomatic or not, ischemic or not, and revascularized or not, in order to better understand the mechanisms responsible for cardiovascular events, and evolve towards a more personalized and cost-effective care.

<p>Kranskärlsoperationen är för patienten en stor händelse som leder till många frågor och funderingar. Tidigare forskning har visat att patienter som genomgått en ranskärlsoperation har stort behov av information. Vårt syfte med studien var att beskriva informationen vid en kranskärlsoperation. Studien gjordes som en itteraturstudie. Resultatet av studien utföll i tre kategorier, informationsmetoder, vad informationen innehöll samt olika faktorer som påverkade patientinformationen. Information gavs skriftligt, muntligt, som videofilm, med Internet eller av en patient som tidigare gjort en kranskärlsoperation, ofta i kombination med varandra. Vad patienten ville att informationen skulle innehålla varierade från person till person beroende på i vilken fas patienten befann sig, pre- eller postoperativt. Flera faktorer framkom som var av betydelse. Det var viktigt för patienterna att personalen tog sig tid att lyssna och svara på frågor och funderingar. Patienter med litet socialt nätverk hade större behov av information än andra med stort socialt nätverk. En annan betydelsefull sak var att patienterna lätt skulle kunna komma i kontakt med kompetent personal både innan operationen och efter utskrivningen. Slutsatsen av resultatet var att informationen bör vara individuellt anpassad utifrån varje patients behov. Fortsatt forskning behövs för utveckling av en god patientinformation kring patienternas upplevelse av olika sorters informationssätt, samt att utveckla kontakt med patienter som tidigare gjort en kranskärlsoperation</p> / <p>Coronary artery bypass is for the patient a major event leading to many questions and concerns. Previous research has shown that patients who have undergone coronary artery bypass have great needs of information. Our aim of this study was to describe information before and after a coronary artery bypass. The study was done as a literature review. The results of the study were distributed into three categories, information methods, information content and the various factors that affect patient information. Information was given in writing, orally, by video, by Internet or by a patient previously undergoing a coronary artery surgery, usually in combination with each other. What the patient wanted the information should contain varied from person to person depending on what stage the patient was, pre- or postoperatively. Several factors emerged that were relevant. It was important for the patients that the staff took the time to listen and respond to questions and concerns. Patients with small social networks had a greater need for information than others with larger social network. Another important thing was that patients could easily get in touch with competent personnel both before surgery and after discharge. The conclusion of the result was that the information should be individualized based on each patient's needs. Continued research is needed to develop good patient information on patients' experience of different types of information means, and to develop contact with patients who have previously done a coronary artery bypass.</p>

<p>Transesophageal echocardiography (TEE) has become a useful tool in monitoring the heart in patients during open-heart surgery. This study was undertaken to evaluate whether it is feasible to use TEE to assess left ventricular myocardial viability in anesthetized patients scheduled for coronary artery bypass grafting (CABG).</p><p>A total of 84 patients were studied. To test myocardial viability, TEE and a low-dose dobutamine stress regimen were used. Echocardiographic data were analyzed off-line using a visual or semiautomatic analysis of segmental left ventricular wall motion (LVWM). Visual assessment was performed by readers blinded to the sequence of events. The agreement between readers in visual analysis of segmental LVWM in the transgastric short-axis view was 73% or higher. Segmental LVWM assessed by TEE was compared to hemodynamic data obtained by thermodilution pulmonary artery catheter (PAC) and coronary angiographic data. Also, using the same low-dose dobutamine stress regimen, TEE findings in the anesthetized patient perioperatively were compared with preoperative transthoracic echocardiography (TTE) findings in the awake patient.</p><p>TEE was found to be feasible and adequate for testing left segmental ventricular viability. A concomitant increase in stroke volume assessed by PAC and decrease in LVWM-score assessed by TEE was found with dobutamine stimulation. Abnormal segmental LVWM corresponded to angiographically stenosed supplying coronary artery vessels. During dobutamine stimulation, 69% of the corresponding segments responded which is a sign of viability. The LVWM response to preoperative TTE and perioperative TEE dobutamine stress was comparable except for a significant difference in the apical segments.</p><p>This study showed that perioperative TEE dobutamine stress could be used to test left ventricular viability and was also a valuable supplement to PAC, angiography and TTE. The acquired knowledge is important and suggest that further development of transesophageal ultrasound technology is warranted.</p>

This thesis describes the management of patients treated with mechanical circulatory support devices for short- or long-term use. Twenty-four patients suffering from postcardiotomy heart failure were treated with a minimally invasive axial flow pump. The device was effective in unloading the failing left ventricle and in maintaining an adequate systemic circulation. The principles of perioperative monitoring, and pharmacological therapy are outlined. The pump was also used as an alternative to the heart-lung machine in conjunction with coronary artery bypass surgery. Together with a short-acting β-blocker, esmolol, the heart was decompressed and heart motion was reduced, facilitating bypass surgery on the beating heart. The anesthesiological considerations using this method are described. An implantable left ventricular assist device was used as a bridge to heart transplantation in 10 patients. We were interested in assessing the possibility to establish such a treatment program at a non-transplanting center. A multidisciplinary approach was enabled thanks to the organization of our Heart Center and due the close collaboration with our transplant center at Lund University. As one of the first centers in Europe, we established a well-functioning program with good results. Nine out of 10 of the bridge patients, with treatment times varying between 53 to 873 days, survived pump treatment and were eventually transplanted. The device proved to be powerful enough to support the failing heart and enable rehabilitation of the patients. Outpatient management became simpler when using the electrical device with belt-worn batteries. The uncertain durability and the high risk of device-related complications are shortcomings that limit its potential for more permanent treatment of heart failure. A new generation of small implantable axial blood flow pumps has therefore been developed. The principles of these pumps are based on the first generation axial flow pumps evaluated in this thesis. After several years of basic research and experimental studies, the first human implants have been performed. In the thesis, the hemodynamic effects of such a novel axial flow pump have been evaluated in an acute heart failure model. This technology holds great promise, both as a bridge to heart transplantation, and as a permanent circulatory support system. / On the day of the public defence the status of the article IV was: Submitted for publication.

Sleep is a basic need, important to physical and psychological recovery. Insomnia implies sleep-related complaints, such as difficulty falling asleep, difficulty staying asleep, early awakening, or non-restorative sleep (NRS) in an individual who has adequate circumstances and opportunity to sleep.  Insomnia is also related to impairment of daytime functions. The prevalence of reported sleep disturbances varies between 15% and 60% in patients with coronary artery disease (CAD) up to five years after intervention. Disturbed sleep may have a negative impact on self-care capacity and behaviours. Little attention has been given to evaluation of sleep promotion through individualized non-pharmacological interventions among CAD patients. The overall aim of this thesis was to describe the impact of sleep quality and disrupted sleep on health-related quality of life (HRQoL) in patients with stable CAD, in comparison to a population-based group. The objective was also to evaluate an individualized non-pharmacological programme to promote self-care in sleep. Four studies were conducted during seven years, starting in 2001. Patients from six hospitals in the south of Sweden were invited to participate. In addition, an age and gender matched population-based group was randomly selected during the same period as the patients and was used for comparison with the CAD patients in two of the studies. Data was collected through interviews, self-reported questionnaires, a study specific sleep diary and actigraphy registrations. A pretest-posttest control design was used to evaluate whether an individualized non-pharmacological intervention programme could promote self-care in sleep-activity in CAD patients. The results showed a high prevalence of insomniac CAD patients out of whom a large proportion were non-rested insomniacs. This showed that NRS is one of the core symptoms of insomnia. On the other hand there were weak or non-significant gender differences with increasing insomnia severity. Severe insomniac CAD patients displayed a two or threefold higher presleep arousal or anxiety score and were more limited in taking physical exercise than the general population. Generally low sleep efficiency (SE%) was revealed in the studies, particularly among severe non-rested insomniac CAD patients. Among CAD patients, the individualized non-pharmacological programme to promote self-care in sleep-activity indicated improvements in sleep and HRQoL. This thesis elucidates the importance of focusing on the individual’s perception of their sleep-activity and health in their local context and supporting self-care management. Furthermore, it is of importance that nurses set individual goals together with the patient in order to increase self-efficacy to promote HRQoL.

Transesophageal echocardiography (TEE) has become a useful tool in monitoring the heart in patients during open-heart surgery. This study was undertaken to evaluate whether it is feasible to use TEE to assess left ventricular myocardial viability in anesthetized patients scheduled for coronary artery bypass grafting (CABG). A total of 84 patients were studied. To test myocardial viability, TEE and a low-dose dobutamine stress regimen were used. Echocardiographic data were analyzed off-line using a visual or semiautomatic analysis of segmental left ventricular wall motion (LVWM). Visual assessment was performed by readers blinded to the sequence of events. The agreement between readers in visual analysis of segmental LVWM in the transgastric short-axis view was 73% or higher. Segmental LVWM assessed by TEE was compared to hemodynamic data obtained by thermodilution pulmonary artery catheter (PAC) and coronary angiographic data. Also, using the same low-dose dobutamine stress regimen, TEE findings in the anesthetized patient perioperatively were compared with preoperative transthoracic echocardiography (TTE) findings in the awake patient. TEE was found to be feasible and adequate for testing left segmental ventricular viability. A concomitant increase in stroke volume assessed by PAC and decrease in LVWM-score assessed by TEE was found with dobutamine stimulation. Abnormal segmental LVWM corresponded to angiographically stenosed supplying coronary artery vessels. During dobutamine stimulation, 69% of the corresponding segments responded which is a sign of viability. The LVWM response to preoperative TTE and perioperative TEE dobutamine stress was comparable except for a significant difference in the apical segments. This study showed that perioperative TEE dobutamine stress could be used to test left ventricular viability and was also a valuable supplement to PAC, angiography and TTE. The acquired knowledge is important and suggest that further development of transesophageal ultrasound technology is warranted.

Kranskärlsoperationen är för patienten en stor händelse som leder till många frågor och funderingar. Tidigare forskning har visat att patienter som genomgått en ranskärlsoperation har stort behov av information. Vårt syfte med studien var att beskriva informationen vid en kranskärlsoperation. Studien gjordes som en itteraturstudie. Resultatet av studien utföll i tre kategorier, informationsmetoder, vad informationen innehöll samt olika faktorer som påverkade patientinformationen. Information gavs skriftligt, muntligt, som videofilm, med Internet eller av en patient som tidigare gjort en kranskärlsoperation, ofta i kombination med varandra. Vad patienten ville att informationen skulle innehålla varierade från person till person beroende på i vilken fas patienten befann sig, pre- eller postoperativt. Flera faktorer framkom som var av betydelse. Det var viktigt för patienterna att personalen tog sig tid att lyssna och svara på frågor och funderingar. Patienter med litet socialt nätverk hade större behov av information än andra med stort socialt nätverk. En annan betydelsefull sak var att patienterna lätt skulle kunna komma i kontakt med kompetent personal både innan operationen och efter utskrivningen. Slutsatsen av resultatet var att informationen bör vara individuellt anpassad utifrån varje patients behov. Fortsatt forskning behövs för utveckling av en god patientinformation kring patienternas upplevelse av olika sorters informationssätt, samt att utveckla kontakt med patienter som tidigare gjort en kranskärlsoperation / Coronary artery bypass is for the patient a major event leading to many questions and concerns. Previous research has shown that patients who have undergone coronary artery bypass have great needs of information. Our aim of this study was to describe information before and after a coronary artery bypass. The study was done as a literature review. The results of the study were distributed into three categories, information methods, information content and the various factors that affect patient information. Information was given in writing, orally, by video, by Internet or by a patient previously undergoing a coronary artery surgery, usually in combination with each other. What the patient wanted the information should contain varied from person to person depending on what stage the patient was, pre- or postoperatively. Several factors emerged that were relevant. It was important for the patients that the staff took the time to listen and respond to questions and concerns. Patients with small social networks had a greater need for information than others with larger social network. Another important thing was that patients could easily get in touch with competent personnel both before surgery and after discharge. The conclusion of the result was that the information should be individualized based on each patient's needs. Continued research is needed to develop good patient information on patients' experience of different types of information means, and to develop contact with patients who have previously done a coronary artery bypass.

Background: Despite the recent improvements in surgical techniques and postoperative patient care, atrial fibrillation (AF) remains the most frequent complication after cardiac surgery. Although postoperative AF is often regarded as a benign clinical condition, this arrhythmia has significant adverse effects on patient recovery and postoperative survival. Its exact pathophysiology has not yet been elucidated. The present thesis aims to analyze AF risk factors and their interaction, pre-existing histological explanatory alterations of the atrium, the AF impact on postoperative survival and the compliance of a prophylactic drug regimen. Methods: During a 10-year period, consecutive cardiac surgery cases with complete data on AF occurrence and postoperative survival were extracted. All patients were operated on for coronary or valvular surgery, with cardiopulmonary bypass (CPB). Hospital and long-term survival data were obtained from Swedish population registry. Study I) Isolated coronary artery bypass grafting (CABG, n=7056), aortic valve replacement (n=690) and their combination (n=688) were considered. Independent AF risk factors and AF effects on early and 1 year mortality were investigated. Study II) Patients affected by postoperative AF among isolated CABG patients (n=7621), valvular surgeries (n=995) and their combination (n=879) were studied. Long-term survival was obtained and prognostic factors identified. Study III) Seventy patients were randomized to on-pump (n=35) or off-pump (n=35) CABG. Samples from the right atrial appendage were collected and histology was evaluated by means of light and electronic microscopy with reference to preexistent alterations related to postoperative AF. Study IV) Cardiac surgery patients with complete data on smoking status (n=3245) were reviewed. Effects of smoking on AF development and interaction among variables were explored. Study V) CABG patients without clinical contraindications to receive oral sotalol (80 mg twice daily) and magnesium were prospectively enrolled (n = 49) and compared with a matched contemporary control CABG group (n = 844). The clinical compliance to the AF prophylactic drug regimen was tested. Results: The overall AF incidence was around 26%, subdivided into 23%, 40% and 45% for isolated CABG, valve procedures and their combined surgeries, respectively. Age was the strongest predictor of postoperative AF. Coronary disease superimposed risk factors with reference to myocardial conditions at CPB weaning. Considering the preoperative smoking condition, smokers demonstrated a reduced AF incidence compared to non-smokers (20% versus 27%, p&lt;0.001). An interaction between smoking status and inotropic support was observed: without this interaction smoking conferred a 46% risk reduction of AF (p=0.011). At the histological level, myocyte vacuolization and nuclear derangement represented anatomical independent AF predictors (p=0.002 and p=0.016, respectively). CPB exposure was not associated to postoperative AF nor histological changes. Although, postoperative AF increases the length of hospitalization in all patient groups, it did not affect the hospital survival. However, AF independently impaired the late survival, a phenomenon seen in the CABG group only. With reference to the tested sotalolmagnesium drug regimen, only 55% of CABG patients were compliant to the treatment, with marginal effects on AF occurrence. Conclusions: In addition to age, details at the CPB weaning period, pre-existing histopathological changes, the hyperadrenergic state and catecholamines are key mechanisms in the pathophysiology of postoperative AF. In particular, the CPB period hides valuable information for timely AF prophylactic stratifications. Further, compliance effects due to patient selection should also be considered in a prophylactic therapy model. Postoperative AF increases late mortality after isolated CABG surgery, but not after valvular procedures. Although the mechanisms are unclear, our results draw the attention to possible AF recurrence after hospital discharge, indicating a strict postoperative surveillance.

Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.

Atherosclerosis is a systemic disease of the vessel wall that occurs in the aorta, carotid, coronary and peripheral arteries. Atherosclerotic plaques in coronary arteries may cause the narrowing (stenosis) or complete occlusion of the arteries and lead to serious results such as heart attacks and strokes. Medical imaging techniques such as X-ray angiography and computed tomography angiography (CTA) have greatly assisted the diagnosis of atherosclerosis in living patients. Analyzing and quantifying vessels in these images, however, is an extremely laborious and time consuming task if done manually. A novel image segmentation approach and a quantitative shape analysis approach are proposed to automatically isolate the coronary arteries and measure important parameters along the vessels. The segmentation method is based on the active contour model using the level set formulation. Regional statistical information is incorporated in the framework through Bayesian pixel classification. A new conformal factor and an adaptive speed term are proposed to counter the problems of contour leakage and narrowed vessels resulting from the conventional geometric active contours. The proposed segmentation framework is tested and evaluated on a large amount of 2D and 3D, including synthetic and real 2D vessels, 2D non-vessel objects, and eighteen 3D clinical CTA datasets of coronary arteries. The centerlines of the vessels are proposed to be extracted using harmonic skeletonization technique based on the level contour sets of the harmonic function, which is the solution of the Laplace equation on the triangulated surface of the segmented vessels. The cross-sectional areas along the vessels can be measured while the centerline is being extracted. Local cross-sectional areas can be used as a direct indicator of stenosis for diagnosis. A comprehensive validation is performed by using digital phantoms and real CTA datasets. This study provides the possibility of fully automatic analysis of coronary atherosclerosis from CTA images, and has the potential to be used in a real clinical setting along with a friendly user interface. Comparing to the manual segmentation which takes approximately an hour for a single dataset, the automatic approach on average takes less than five minutes to complete, and gives more consistent results across datasets.