Mechanism and Prediction of Post-Operative Atrial Fibrillation Based on Atrial Electrograms

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

Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the most common clinical arrhythmia, posing a major risk for occurrence of ischemic stroke. Oral anticoagulation and antiplatelet agents are used to prevent stroke. One major complication related to these therapies is the development of a hemorrhage. Providers are faced with treating older adults with AF who have concomitant geriatric syndromes that potentially alter treatment outcomes. This study involved examining records of subjects age ≥ 65 diagnosed with AF and concomitant geriatric syndromes (dementia, frailty, and/or falls) to describe differences in incidence of strokes and hemorrhages, depending upon the type of prevention therapy, and differences in incidences of stroke in patients with and without geriatric syndromes. Older adult patients with geriatric syndromes were divided into three groups based on the type of antithrombotic therapy prescribed at diagnosis of AF: oral anticoagulation, antiplatelet agents, or no oral anticoagulants or antiplatelet agents, with primary outcomes of a stroke or hemorrhage. In a separate analysis, older adults with and without geriatric syndromes across the three therapy groups were compared with primary outcome for stroke. Multivariable Cox hazard, logistic regression, and Kaplan Meier survival curves were utilized to determine association of treatment with risk-adjusted stroke and hemorrhage incidence. Compared to patients prescribed no antithrombotic therapy, the reduced stroke occurrence was 75% to 82% oral anticoagulants and 70% to 74% in those prescribed iv antiplatelet agents (both p < .001), after controlling for risk. Patients prescribed antiplatelet agents and oral anticoagulants were 3.28 and 3.19 times more likely, respectively, than patients not prescribed antithrombotics to develop noncranial hemorrhage (p < .05). Patients with geriatric syndromes experienced higher incidence of stroke when prescribed oral anticoagulants (p = 0.00) and antiplatelet agents (p < 0.001), compared to patients without geriatric syndromes. Subjects with geriatric syndromes had benefit and risk profiles when prescribed oral anticoagulant and antiplatelet therapies to prevent thromboembolism similar to other populations recorded, although overall stroke incidence was greater. This suggests that populations with geriatric syndromes should be specifically incorporated into the guidelines clinicians use to tailor antithrombotic therapies to individual patient risk

Secundum atrial septal defect in the adult. Clinical, haemodynamic and electrophysiological aspects.

Atrial septal defect (ASD) is the most common congenital heart malformation diagnosed in adult life. In this thesis important clinical, haemodynamic and electrophysiological aspects of ASD in the adult are explored. The diagnostic accuracy of magnetic resonance velocity mapping (MRvm)in calculating the pulmonary/systemic flow ratio (QP/QS)was assessed (I). The mean and maximal error by MRvm was 1±1% and ≤4% respectively in the whole range of different QP/QS and repeatability showed a difference of 1±5%. Interobserver variability was four times higher for radionuclide angiography than MRvm, 16% vs. 4%, demonstrating the superiority of MRvm. Atrial electrophysiological properties before and 8±6 months after ASD closure were examined by means of high-resolution orthogonal P-wave signal-averaged ECG (II and III). P-wave duration was significantly longer in ASD patients than in controls and overall, it was not significantly affected by ASD closure. P-wave duration did not relate to echocardiographic atrial sizes, suggesting atrial conduction delay which seems more or less irreversible in middle-aged ASD patients. The remodelling potential and its speed were investigated by repeated echocardiograms before and during the 1st year after ASD closure (IV). Right ventricular and right atrial sizes as well as the pulmonary pressure levels were markedly reduced after ASD closure and became normal in a majority of the patients. In contrast, the left atrial size did not change and remained abnormal in 44%. When changes occurred they came early. Outcome of ASD closure was compared to medical management 6 and 30 years after the initial assessment (V). Closure of the defect was superior to medical management in terms of functional class, heart size and pulmonary pressure in the intermediate term. Early ASD closure also seemed beneficial in terms of late cardiovascular morbidity and mortality, in spite of a high frequency of late ASD closure, after the intermediate exam, in the medically managed group. In summary, the findings favour timely closure of the ASD if to reduce the risk of late mortality and morbidity

Optimising cardiac services using routinely collected data and discrete event simulation

Background: The current practice of managing hospital resources, including beds, is very much driven by measuring past or expected utilisation of resources. This practice, however, doesn’t reflect variability among patients. Consequently, managers and clinicians cannot make fully informed decisions based upon these measures which are considered inadequate in planning and managing complex systems. Aim: to analyse how variation related to patient conditions and adverse events affect resource utilisation and operational performance. Methods: Data pertaining to cardiac patients (cardiothoracic and cardiology, n=2241) were collected from two major hospitals in Oman. Factors influential to resource utilisation were assessed using logistic regressions. Other analysis related to classifying patients based on their resource utilisation was carried out using decision tree to assist in predicting hospital stay. Finally, discrete event simulation modelling was used to evaluate how patient factors and postoperative complications are affecting operational performance. Results: 26.5% of the patients experienced prolonged Length of Stay (LOS) in intensive care units and 30% in the ward. Patients with prolonged postoperative LOS had 60% of the total patient days. Some of the factors that explained the largest amount of variance in resource use following cardiac procedure included body mass index, type of surgery, Cardiopulmonary Bypass (CPB) use, non-elective surgery, number of complications, blood transfusion, chronic heart failure, and previous angioplasty. Allocating resources based on patient expected LOS has resulted in a reduction of surgery cancellations and waiting times while overall throughput has increased. Complications had a significant effect on perioperative operational performance such as surgery cancellations. The effect was profound when complications occurred in the intensive care unit where a limited capacity was observed. Based on the simulation model, eliminating some complications can enlarge patient population. Conclusion: Integrating influential factors into resource planning through simulation modelling is an effective way to estimate and manage hospital capacity.Open Acces

Computational Cardiology: Improving Markers and Models to Stratify Patients with Heart Disease.

Heart disease is the leading cause of death around the world, claiming over 17 million lives each year (30% of all global deaths). The burden of heart disease can be attributed, in part, to the lack of clinically useful tools that can accurately stratify patients and match them to appropriate therapies. In this thesis, we explore the use of computation as a solution to this problem. Specifically, the goal of our work is to develop novel approaches that can be applied to cardiovascular datasets to discover diagnostic markers and to improve models for predicting adverse cardiovascular outcomes. Our research focuses on the following opportunities: (1) improving the computational efficiency of existing ECG markers while maintaining clinically useful discrimination; (2) developing new ECG markers based on short-term heart rate structure that are complementary to existing markers; (3) building more accurate models in the presence of small training cohorts with class-imbalance; and (4) proposing approaches to decompose ECG signals into atrial and ventricular components to predict arrhythmias arising from specific anatomical regions. When evaluated on multiple cohorts comprising patients with coronary artery disease and patients undergoing cardiothoracic surgery, our work substantially improves the ability to deliver cardiac care.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108791/1/jazzchia_1.pd

Front Lines of Thoracic Surgery

Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field

Interventional techniques in the management of persistent atrial fibrillation

Atrial fibrillation (AF) is a common cardiac rhythm problem experienced by patients and comprises an increasing demand on healthcare systems. AF is characterised by advanced neurohormonal remodelling in the atria resulting in dilation and variable degree of atrial fibrosis that can be measured by imaging techniques with difficulty in developing methods of identifying and quantifying left atrial (LA) fibrosis. LA fibrosis can be estimated by measuring LA scar using non-invasive imaging methods such as strain imaging in advanced echocardiography and in cardiac magnetic resonance (CMR) imaging. Achieving rhythm control strategy utilising catheter ablation (CA) has shown to be advantageous in improving quality of life (QOL) in patients with paroxysmal AF. The most effective method in management of AF has remained elusive in non-paroxysmal AF. Thoracoscopic surgical ablation (TSA) has been developed over the last decade by experienced surgeons with some promising early results but has not been investigated in long-standing persistent AF (LSPAF). I have attempted to answer some of the relevant questions that have remained in management of LSPAF by conducting a multicentre randomised control trial comparing efficacy between CA and TSA (CASA-AF RCT) and improvements in quality of life indices. In a sub-study, I measured LA volumes using echocardiography and CMR to determine reverse remodelling and LA function using tissue Doppler imaging and strain imaging to predict AF recurrence. In a CMR sub-study, a novel automatic LA segmentation algorithm was used to quantify LA fibrosis before and after ablation. I was able to quantify the response of the autonomic nervous system to targeted ganglionic plexi (GP) ablation as part of TSA compared to CA by measuring heart rate variability. I am hopeful that the knowledge gained from this thesis will help with an appropriate selection that will improve the management of patients with LSPAF.Open Acces