Academic literature on the topic 'Post-operative atriale fibrillation'

Atrial fibrillation is the most common arrhythmia observed following CoronaryArtery Bypass Graft surgery. Objectives: To determine the incidence of post-operative atrialfibrillation in patients undergoing coronary artery bypass grafting. Materials and Methods:Study Design: Non-randomized prospective. Setting: Cardiac Surgery Department ofMultan Institute of Cardiology, Multan. Period: 20-1-2014 to 01-05-2015. A total number offour hundred and ninety (490) patients having age more than 40 years undergoing isolatedcoronary artery bypass graft surgery were included in the study. Data was analyzed in SPSSV20 software. Frequency and percentages were used for Atrial Fibrillation. To see the impact ofAF on morbidity, patients developing AF was compared with those who do not develop AtrialFibrillation post-operatively using independent sample t-test for quantitative variables. Chisquaretest and Fischer’s Exact test (whenever appropriate) was used to compare qualitativevariables. Results: A total number of four hundred and ninety (490) patients were included inthis study. There were more 431 males (88.0%) in this study. of the patients 71.6% were in LVGrade I before surgery. Incidence of post-operative atrial fibrillation was 13.5%. In 4.5% patientsIABP was inserted due to hemodynamic instability. Ventilation time and hospital stay time wassignificantly higher in patients with AF postoperatively (p value 0.03 and 0.02 respectively).But duration of inotropic support, post-op CKMB levels and IABP use were not significantlydifferent in both groups. Conclusion: The incidence of post-operative Atrial Fibrillation is 13.5%according to this study. And these patients were associated with increased risk of morbidity.

Introduction: Atrial Fibrillation (AF) is one of the most common arrhythmiaafter coronary artery bypass grafting (CABG). Many risk factors have been identified for thedevelopment of postoperative AF with varied level of evidence. AF is associated with increasedrisk of morbidity and mortality causing prolong hospital stay and utilizing more resources.Our study was aimed to identify high risk population for developing post-operative AF andto draw recommendations for its prevention. Objectives: Our objective was to determine thefrequency of Atrial Fibrillation (AF) and its predisposing factors in patients after Coronary ArteryBypass Grafting (CABG). Setting: The study was conducted at Cardiac Surgery Department /Faisalabad Institute of Cardiology, Faisalabad. Duration of Study: 15-12-2014 to 14-07-2015.Study Design: Cross sectional study. Results: The result showed that out of 130 patientsundergoing CABG surgery, 104 (80.3%) male and 26 (19.7%) females, 9(7%) patients sufferedAF in post-operative phase. A significant association was found between postoperative AF andadvanced age (p = 0.011), obesity (p = 0.028), low EF (p = 0.000), and post-operative useof β-blocker (p = 0.007). Significant difference was found between postoperative AF and daysstayed in hospital (p = 0.000) and magnesium level at first day (p = 0.038). On the other handthere was no significant relationship found between AF and prolongs cross clamp and bypasstime. Conclusion: Advance age, obesity, congestive heart failure, low ejection fraction andwithdrawal from beta blockers in post-operative period have been identified as a significant riskfactors for the development of post-operative atrial fibrillation.

Background: Post-operative atrial fibrillation is a common post-operative complication and has significant morbidity and mortality. This study was done with an objective to determine the association of various medication use in patients undergoing coronary artery bypass graft (CABG) with post-operative atrial fibrillation (POAF).Methods: This was a prospective observational study done in the department of cardiovascular and thoracic surgery of GMC Kottayam from December 2019 to December 2020 after obtaining institutional review board clearance. A sample size of 334 was fixed and patients undergoing off pump (OP) CABG were consecutively recruited in the study. The association of intraoperative and postoperative medication use with occurrence of POAF were analysed using the univariate analysis with a p<0.05 using the SPSS 16 software.Results: Peri-operative inotrope use was found to be significantly associated with post operative atrial fibrillation odds ratio 1.08 (95% CI 1.02-1.13). We could not find any association with preoperative use of beta blockers/agonist, antidiabetics, levothyroxine, ACE inhibitors or antiplatelet drugs. All the patients 60 (18%) who developed POAF were given amiodarone as per protocol.Conclusions: Perioperative inotrope use was found to have significant association with the development of post operative atrial fibrillation following OPCABG. More multi-institutional studies with determination of association with individual drugs and doses with POAF need to be conducted in future.

Atrial fibrillation (AF) occurs in almost 30% of patients undergoing coronary artery bypass grafting (CABG). Around 80% of these patients have decreased levels of total and ionized serum magnesium postoperatively. The association between magnesium deficiency and post CABG AF is still undetermined. Therefore, a large variety of prophylactic strategies have been assessed including perioperative magnesium administration. However, the efficacy is still questionable. The aim of this study was to find out any correlation of serum magnesium levels with the incidence of post-operative atrial fibrillation in patients undergoing off pump CABG and whether magnesium supplementation modifies the incidence. One hundred fifty patients undergoing CABG were selected and divided into treatment and control groups. Perioperative serum magnesium assays were done, and patients were monitored in the postoperative period for occurrence of Atrial Fibrillation. The risk of post CABG atrial fibrillation was more among females, obese patients, patients with EF &#60; 50% and RWMA. Post-operative AF occurred in 5 patients in the treatment group (n = 75) and 11 patients in the control group (n = 75). : The proportion of patients with post-operative atrial fibrillation among cases (6.7%) was lower than that of controls (14.7%) which may indicate an important role of magnesium in prevention of AF following cardiac surgeries. The results however didn’t reach a statistical significance which could be due to sample size, the duration and design of the study and the period of post-operative AF monitoring.

Post-operative atrial fibrillation (POAF) is a frequent entity increasing hospitalization duration, stroke and mortality. In the recent years, a few studies have sought to investigate the potential effect of colchicine in POAF prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In the present review article, we intend to provide a synopsis of clinical practice guidelines, summarize and critically approach current evidence for or against colchicine as a means of POAF prevention.

Atrial fibrillation (AF) affects up to 50% of post-operative cardiac surgery patients. AF is rarely fatal and most cases are transient and clinically benign. AF however could occasionally lead to many serious complications such as thromboembolic strokes, ischemic bowel, hypotension, or hemorrhage secondary to the required anticoagulation therapy. In addition, hospital length of stay is often prolonged due to the need to control this arrhythmia prior to discharge. Many strategies to prevent the onset of this condition have been the subject of intense research in recent years. Many pharmacologic and non-pharmacologic agents have been studied with varying degrees of success. Amiodarone, a very effective class III anti-arrhythmic agent, has been shown to reduce the onset of this condition by half in this patient population. Most Amiodarone studies were conducted on coronary artery bypass grafting (CABG) patients and the uptake of this intervention strategy by clinicians has been poor at best. The purpose of this study was to examine the possible benefit of using Amiodarone in a select group of cardiac surgery patients who were deemed to be at a higher risk of developing post-operative AF using a randomized controlled trial model. This select group of patients included valve patients, patients with poor left ventricular function, and the elderly. In addition, the possible economic benefit of such selective prophylactic strategy was evaluated. No clear clinical or economic benefits were demonstrated at the conclusion of the trial. The required a priori sample size was not achieved at the conclusion of the trial and hence many of the results did not achieve statistical significance.

Surgical myocardial revascularization remains the standard of care for patients with multi-vessel coronary artery disease. A growing body of evidence indicates that systemic inflammation and myocardial oxidative stress are associated with the development of postoperative atrial fibrillation (POAF) and low cardiac output syndrome in patients undergoing cardiac surgery. Statins have been shown to exert rapid anti-inflammatory and antioxidant effects by inhibiting myocardial NOX2 oxidases and by increasing the bioavailability of nitric oxide (NO). However, whether these so-called pleiotropic effects of statins result in improved patient outcomes remains to be established. To provide further insights into the mechanisms of action and impact on clinical outcomes of peri-operative statin treatment in patients undergoing cardiac surgery, I studied the molecular mechanisms underlying the myocardial nitroso-redox balance in samples of the right atrial appendages (RAA) obtained before (PRE) and after cardiopulmonary bypass (CPB) and reperfusion (POST) and setup two double-blind randomised placebo-controlled trials: 1) STARR (Statin Treatment on Atrial Refractoriness and Reperfusion injury), which tested the effect of Atorvastatin (80 mg once daily for up to 6 days before surgery and 5 days after) on the atrial effective refractory period (AERP, over 4 post-operative days) and superoxide production in paired PRE- and POST- RAA samples from 60 patients 2) STICS (Statin Treatment In Cardiac Surgery), which assessed the effects of peri-operative treatment with Rosuvastatin (20mg od) on POAF (assessed by continuous holter ECG monitoring for 5 days postoperatively) and myocardial injury (assessed by serial troponin I measurements) in 1922 patients undergoing elective cardiac surgery. I observed that atrial superoxide production increased significantly after reperfusion due to increased mitochondrial and NOX2 oxidase activity and to uncoupling of NOS activity. NOS activity in RAA samples decreased significantly after reperfusion (by 60%), but this reduction was not prevented by BH4 supplementation (10 μM) or NOX2 inhibition. Instead, I identified increased endothelial NOS S-glutathionylation as the main mechanism responsible for NOS uncoupling after reperfusion. In STARR, atorvastatin prevented increase in RAA superoxide production, maintained the functionally coupled status of NOS and NO bioavailability after reperfusion but had no measurable effect on postoperative AERP. In STICS, treatment with rosuvastatin significantly reduced LDL-C concentration by 48 hours after surgery but had no effect on the incidence of POAF (203 (21%) of the Rosuvastatinallocated patients vs. 197 (20%) of the placebo-allocated patients) or on perioperative myocardial damage (P = 0.80). Pre-defined subgroup analyses (age, sex, prior statin use, baseline troponin concentration, duration of randomized treatment before surgery, type of cardiac surgery, and postoperative use of anti-inflammatory drugs) did not identify any category of patient who benefited from perioperative rosuvastatin treatment. Nor were there beneficial effects on any of the other in-hospital clinical outcomes that were assessed. In conclusion, cardiac surgery on CPB is associated with myocardial nitroso redox imbalance that is reversed by perioperative intensive therapy with statins. However, these effects have no beneficial effects on common in-hospital complications after elective cardiac surgery. Although the benefits of long-term statin therapy in patients requiring myocardial revascularization are well established, the work presented in this thesis does not support routine use of perioperative intensive therapy with statins for the prevention of postoperative complications in patients undergoing elective cardiac surgery.

Thesis (M.S.)--East Carolina University, 2009.
Presented to the faculty of the Department of Exercise and Sport Science. Advisor: Timothy P. Gavin. Title from PDF t.p. (viewed May 5, 2010). Includes bibliographical references.

A fibrilação atrial (FA) é a arritmia mais comum no pós-operatório de cirurgia cardíaca. Apesar de estar relacionada a alterações estruturais, alguns pacientes, mesmo que sem tais condições, ainda assim, cursam com fibrilação atrial no pós-operatório (FAPO) causando aumento no tempo de internação e custos. Estudos recentes vem ampliando o conhecimento sobre pequenos fragmentos de RNA, chamados de microRNAs (miRNAs) que podem interferir diretamente no aparecimento de algumas doenças na área cardiovascular. O objetivo do presente estudo é: 1) comparar a expressão dos miRNAs 1, 23 e 26 entre pacientes com e sem FAPO; 2) comparar nos grupos a expressão destes miRNAs entre os período pré e pós-cirúrgico; 3)comparar a expressão dos genes GJA1, KCNJ2, CACNB1, CACNA1C e KCNN3 entre os tempos pré e pós-cirúrgico no grupo FAPO; 4) comparar estes últimos genes no tecido atrial; 5) comparar os genes relacionados à produção de interleucinas (IL)-1, 6 e fator de necrose tumoral alfa (TNF?) entre os grupos e entre os tempos pré e pós-cirúrgico; 6)avaliar as características clínicas e evolutivas da população estudada. Pacientes submetidos à cirurgia de revascularização miocárdica foram submetidos à coleta de 20ml de sangue pré e pós-cirurgia bem como fragmento de tecido atrial. Um total de 143 pacientes compuseram os grupos: FAPO (24 pacientes), controle genético (24 pacientes) e controle total (97 pacientes + 24 grupo controle genético). Do ponto de vista clínico observou-se maior idade, tempo de anóxia, tempo de internação em terapia intensiva e hospitalar no grupo FAPO. A análise genética revelou menor expressão do miRNA-23 no grupo FAPO (p=0,02). A comparação entre os períodos pré e pós-cirúrgico revelou redução dos três miRNAs no tempo pós-cirúrgico (p<0,05) e dos genes relacionados às proteínas de canal (p<0,05). A comparação no tecido não evidenciou alterações entre os grupos. Os genes relacionados ás citocinas revelaram redução no período pós-cirúrgico (p<0,05) em ambos os grupos. Concluiu-se que o miRNA-23 pode ter implicação no surgimento da FAPO e outros miRNAs não estudados devem estar envolvidos neste processo uma vez que houve redução de outros genes de canais relacionados ao aparecimento de FAPO.
Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery. AF is related to cardiac structural changes although a group of patients still remains developing post-operative atrial fibrillation (FAPO) even without those changes, leading to more days in the hospital and costs. Recent studies showed that short fragments of RNA, called microRNA (miRNA) can contribute to the development of several diseases in the cardiovascular area. The aim of this study is to 1) compare the expression of miRNA-1, 23 and 26 between the group with and without FAPO; 2) compare, in the FAPO group, the expression of these miRNAs in the pre and post-surgery periods; 3) compare the expression of GJA1, KCNJ2, CACNB1, CACNA1C e KCNN3 genes between the pre and post-surgery periods; 4) compare this genes in atrial tissue; 5) compare the genes related to inflammation cytokines as interleukin(IL)-1, 6 and alpha tumoral necrosis factor between the groups in the pre and post-surgery periods; 6) evaluate clinical and evaluative patterns of the study population. Twenty milliliters of blood samples in the pre and post-operative periods and an atrial fragment were extracted from patients submitted to coronary artery bypass graft surgery. A total of 143 patients were divided in the FAPO group (24 patients), genetic control group (24 patients) and a total control (97 + 24 genetic control patients). The clinical analysis showed bigger age and clamp-time, more days in the intensive care unit and hospital in the FAPO group. The genetic analysis revealed less expression of miRNA-23 in the FAPO group (p=0.02). The comparison between the pre and post-surgery periods showed reduction in the three studied miRNAs (p<0.05) and reduction in the genes related to the production of the membrane protein channel sites. The comparisons in the atrial tissue didn´t show any difference in the study groups. The cytokines showed post-surgery reduction (p<0.05) in both groups. The conclusion is that miRNA-23 can be implicated in FAPO as others miRNAs not studied can also be, once there was a significative reduction in the genes related to FAPO development.

Estima-se que mais de 800.000 cirurgias cardíacas de revascularização do miocárdio por ano são realizadas no mundo. Nesta intervenção terapêutica uma das complicações mais comuns é a fibrilação atrial, que esta intimamente relacionada com aumento de risco de morbidade e mortalidade pós-operatória. Os fatores determinantes desta manifestação podem ser pré, intra e pós-operatórios que possivelmente se relaciona com as proteínas pró-inflamatórias, canais iônicos e sistema renina-angiotensina. Portanto, os polimorfismos nos genes que codificam essas proteínas podem ter importante papel no desenvolvimento da FAPo. O objetivo deste trabalho foi de avaliar a associação entre os polimorfismos dos genes IL6 (G-174C), KCNE5 (C97T) e AGT (A-217G) e a incidência da FAPo e seus efeitos na expressão de RNAm, em apêndice atrial direito e em sangue periférico. Para o estudo foram selecionados 76 indivíduos portadores de insuficiência coronariana obstrutiva com indicação de intervenção cirúrgica de revascularização do miocárdio. Desses, 16 com FAPo, 52 sem FAPo e 8 pacientes foram excluídos por motivo de óbito. Amostras de sangue periférico foram obtidas para análise de parâmetros bioquímicos e para extração de DNA genômico e RNA total, antes e 48 horas após a cirurgia cardíaca. Os polimorfismos de nucleotídeo único (SNP) dos genes da IL-6, KCNE5 e do AGT foram detectados pela PCR-RFLP e confirmados por sequenciamento de DNA. A expressão de RNAm em leucócitos totais de sangue periférico e de tecido foi analisada pela PCR em tempo real, utilizando o gene GAPDH como referência endógena. A freqüência do alelo -174G foi de 75 % no GFA e 69,2% no GC e não foi associada ao desenvolvimento de FAPo. A freqüência do alelo 97T foi de 0% no GFA e 10,8% no GC e não foi associada a menor incidência de FAPo. A freqüência do alelo -217A foi de 12,5% no GFA e 15,9% no GC e também não foi associado ao desenvolvimento de FAPo. A expressão de RNAm da IL-6 em LTSP foi reduzida do pré para o pós-operatório de cirurgia de RM em ambos os grupos e não houve correlação entre a expressão de RNAm da IL-6 em LTSP e apêndice auricular direito. A expressão de RNAm do KCNE5 em LTSP foi reduzida do pré para o pós-operatório de cirurgia de RM, exceto em indivíduos do gênero masculino do GC, sugerindo a influência do gênero na expressão desse gene. Não houve correlação entre a expressão de RNAm do KCNE5 em LTSP e apêndice auricular direito. Não se detectou expressão de RNAm do AGT em LTSP e sua expressão em apêndice auricular direito foi extremamente baixa, portanto não está associada ao desenvolvimento de FAPo.
It is estimated that more than 800,000 heart surgery coronary artery bypass grafting are performed annually in the world. This therapeutic intervention of the most common complication was atrial fibrillation, which is closely related to increased risk of morbidity and postoperative mortality. The determining factors of this event can be pre, intra and postoperative possibly relates to the pro-inflammatory proteins, ion channels and renin-angiotensin system. Therefore, polymorphisms in the genes encoding these proteins may play an important role in the development of PoAF. The objective of this study was to evaluate the association between polymorphisms of IL6 gene (G-174C), KCNE5 (C97T) and AGT (A-217G) and the incidence of PoAF and its effects on mRNA expression in right atrial appendage and peripheral blood. For the study we selected 76 individuals with obstructive coronary artery disease with indication for surgical myocardial revascularization. Of these, 16 with PoAF, 52 without PoAF and 8 patients were excluded because of death. Blood samples were obtained for biochemical analysis and extraction of genomic DNA and total RNA before and 48 hours after cardiac surgery. The single nucleotide polymorphisms (SNPs) of IL-6, KCNE5 and AGT were detected by PCR-RFLP and confirmed by DNA sequencing. mRNA expression in total leukocytes in peripheral blood and tissue were analyzed by real-time PCR, using GAPDH gene as endogenous reference. The frequency of-174G allele was 75% in the GFA and 69.2% in GC and was not associated with the development of FAPO. The 97T allele frequency was 0% in GFA and 10.8% in GC and was not associated with a lower incidence of PoAF. The frequency of allele-217A was 12.5% in the GFA and 15.9% in GC and was not associated with the development of PoAF. The mRNA expression of IL-6 on LTSP was reduced from preoperative to the postoperative period of CABG in both groups and no correlation between mRNA expression of IL-6 on LTSP and right atrial appendage. The mRNA expression of KCNE5 LTSP was reduced in the pre and postoperative CABG, except among males in the CG, suggesting the influence of gender on expression of this gene. There was no correlation between the expression of mRNA KCNE5 in LTSP and right auricular appendage. There was no mRNA expression of AGT in LTSP and its expression in right atrial appendage was extremely low, so it is associated with the development of PoFA.

ABSTRACT Background: The epicardial adipose tissue is located between the myocardium and the visceral pericardium, lying directly above the myocardium without any fascia. Epicardial adipose tissue presents itself with histological features typical of the brown adipose tissue. It plays a cardioprotective role through thermoregulation, energy homeostasis and anti-inflammatory regulation. However, in pathological conditions, epicardial adipose tissue may have a pro-inflammatory effect. Less is known about the role played by epicardial adipose tissue in patients with a history of atrial fibrillation. Some studies suggest an association between increased epicardial adipose tissue (volume and thickness) and atrial fibrillation. Nonetheless, there is little data about histological characterisation of epicardial adipose tissue in patients with a history of atrial fibrillation. Aim of the study: To evaluate the quantitative (using echocardiography) and qualitative characteristics (intra-operatory biopsy for histological characterisation) of epicardial adipose tissue in relation to atrial fibrillation burden after coronary artery bypass graft. Patients and methods: Prospective single-centre study approved by the ethics committee of Verona and Rovigo in July 2018. Patients undergoing coronary artery bypass graft with preserved left ventricular ejection fraction were included, after giving informed consent. Patients with atrial fibrillation and immunosuppressive therapy history were excluded. All enrolled patients underwent a medical evaluation to collect clinical history, a transthoracic echocardiography to measure epicardial adipose tissue thickness and collection of a bioptic sample containing right appendage and epicardial adipose tissue during coronary artery bypass graft. After surgery post-surgical clinical course and telemetry were collected. Lastly, histological characterisation (PLIN1 and fibrosis) of the bioptic samples was performed. Results: 56 patients undergoing coronary artery bypass graft were enrolled between 10th September 2018 and 3rd September 2019 in Cardiology and Cardiac Surgery departments. The mean hospitalisation was 11,9 ± 6,9 days and the postsurgical hospitalisation was 7,9 ± 3,7 days. 44 (78,6%) patients were male and the median age was 68,45 ± 9,2 years. All patients were continuously monitored with telemetry from the day of cardiac surgery until discharge. No major complications occurred, only one death unrelated to the surgery. Out of the total number of patients, 22 (39%) had at least one episode of atrial fibrillation. In the population that developed atrial fibrillation there was a bigger atrial volume, a higher degree of diastolic disfunction (E/A rate), a thicker layer of epicardial adipose tissue and an older median age in comparison to the group that did not develop it. Epicardial adipose tissue measured using echocardiogram with a cut off of 4 mm was a predictor of atrial fibrillation with an OR of 1,49 [1,09-2,04], 73% of sensibility and 89% of specificity. Furthermore, from the histological analyses of biopsies, the patients with atrial fibrillation had a significantly higher percentage of fibrosis, while adipose infiltration was not significantly higher. Through univariate analysis, atrial volume (OR 1,05 CI 1,01-1,09, p 0,022), E/A rate (OR 0,04 CI 0,02-0,72 p 0,29), the percentage of fibrosis (OR 1,12 CI 1,00-1,25 p 0,045) and age (OR 1,17 CI 1,07-1,28 p 0,001) were predictors of atrial fibrillation as well as the thickness of the epicardial adipose tissue. Through multivariate analysis atrial volume (p 0,027), fibrosis (p 0,003) and age (p 0,039) were independent predictors of atrial fibrillation. Conclusion: Post cardiac surgical atrial fibrillation is frequent. Epicardial adipose tissue measured by echocardiogram, atrial volume, fibrosis and age are predictors of post cardiac surgical atrial fibrillation.

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.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2021
Contextualização. A fibrilhação auricular pós-operatória (POAF) é uma das complicações mais frequentes após cirurgia. Apesar de ter sido vista como uma situação benigna por muito tempo, vários estudos têm demonstrado que a POAF tem consequências importantes para a morbimortalidade a longo prazo, por aumentar o risco de eventos tromboembólicos. No entanto, não existem estudos que avaliem a eficácia e segurança da anticoagulação oral (ACO) na redução de eventos tromboembólicos e mortalidade em doentes com POAF. Métodos. Pesquisa sistemática no CENTRAL e MEDLINE de RCTs e estudos observacionais. Os dados foram selecionados e extraídos por dois revisores independentes. O risco de viés foi avaliado pela ferramenta ROBINS-I. Realizámos um modelo de efeitos aleatórios para estimar os Odds Ratios (OR) combinados com intervalos de confiança a 95% (IC), e a heterogeneidade foi avaliada pela estatística I2. O outcome primário considerado foi tromboembolismo. Resultados. Sete estudos observacionais incluindo 177,141 doentes com POAF foram incluídos na meta-análise. O uso de ACO foi associado a um menor risco de eventos tromboembólicos (OR = 0,67; IC 95% 0,46-0,99; I2 = 65%). O efeito da ACO não foi estatisticamente significativo na análise conjunta de mortalidade (OR = 0,73; IC 95% 0,49 a 0,50; I2 = 95%) e de hemorragia (OR = 2,18; IC 95% 0,55 a 8,66; I2 = 0%). Conclusão. A ACO foi associada a um menor risco de eventos tromboembólicos em pacientes com POAF após cirurgia cardíaca.
Background. Post-operative atrial fibrillation (POAF) is one of the most frequent complications after surgery. Although it was thought to be a benign situation for a long time, several studies have shown that POAF has important consequences for long-term morbidity and mortality, by increasing the risk of thromboembolic events. However, there is no study evaluating the efficacy and safety of oral anticoagulation (OAC) in reducing thromboembolic events and mortality in patients with POAF. Methods. We searched CENTRAL and MEDLINE for RCTs and observational studies. Data were screened and extracted by two independent reviewers. The risk of bias was evaluated by ROBINS-I tool. We performed a random-effects model to estimate the pooled Odds Ratios (OR) with 95% Confidence Intervals (CI), and heterogeneity was evaluated by I2 statistics. The primary outcome was thromboembolic events. Results. Seven observational studies including 177,141 patients with POAF were included in the meta-analysis. OAC use was associated with lower risk of thromboembolic events (OR = 0.67; 95% CI 0.46 to 0.99; I2 = 65%). The effect of OAC was not statistically significant in a pooled analysis of all-cause mortality (OR = 0.73; 95% CI 0.49 to 0.50; I2 = 95%) and bleeding (OR = 2.18; 95% CI 0.55 to 8.66; I2 = 0%). Conclusion. Oral anticoagulation was associated with a lower risk of thromboembolic events in patients with POAF following cardiac surgery.

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Background: Oral anticoagulation is essential following post-operative atrial fibrillation. Although warfarin is commonly used, its efficacy is dependent on the achievement of a time in therapeutic range above 65%. Non-vitamin K oral anticoagulants are an alternative option, however the optimal time to initiate post-operatively is unknown, due to 'recent surgery' often being cited as an exclusion criteria within phase III clinical trials. Purpose: To compare the management of oral anticoagulation for stroke prevention in postoperative atrial fibrillation after cardiothoracic surgery. Methods: An ambispective study was conducted at large tertiary centre analysing patients that developed postoperative atrial fibrillation after cardiothoracic surgery from January 2016 to January 2017 reviewing both patient and surgical data. Results: Sixty-four patients developed postoperative atrial fibrillation, of which 39 (60.9%) and 25 (39.1%) were prescribed warfarin and non-vitamin K oral anticoagulants (NOACs), respectively. 14 (51.9%) patients had a confirmed time in therapeutic range below 65%, reflecting poor anticoagulant control with warfarin. NOACs were initiated on an average of 8.36 ± 3.74 days post-operatively. 22 (62.9%) patients in the warfarin group and 13 (65.9%) patients in the NOAC group were confirmed to be in sinus rhythm six weeks after discharge. Among these patients, 14 (40.0%) stopped the anticoagulation after restoration of sinus rhythm, of which were more likely to continue if were receiving a NOAC. Conclusion: Whilst warfarin is commonly initiated for post-operative atrial fibrillation, a time in therapeutic range below 65% for warfarin shows that acute optimal anticoagulation management is difficult to achieve, especially for the short term patients that revert back in to sinus rhythm. NOACs may possibly be a more effective alternative, initiating eight days post operatively. However further studies need to be conducted to ensure optimal dose of these agents as well as the ideal timeframe to initiate anticoagulation in the acute post-operative phase.
Introdução: A fibrilhação auricular (FA) é a arritmia sustentada mais comum na prática clínica e está associada ao aumento da mortalidade e morbilidade, assim como a hospitalizações frequentes e à redução da qualidade de vida. A fibrilhação auricular pós-operatória (FAPO) é uma variante da FA clássica que se caracteriza pelo diagnóstico de um novo caso de FA, habitualmente auto-limitada, após realização de cirurgia-major (tipicamente cardíaca) em doentes que se encontravam em ritmo sinusal previamente ao procedimento cirurgico e sem historial clínico prévio desta arritmia. Estima-se que a FAPO ocorra em cerca de 30% das cirurgias-major. Neste sentido, a terapêutica anticoagulante é essencial como profilaxia para o acidente vascular cerebral, sendo que tanto os anticoagulantes orais não antagonistas da vitamina K (NACOs) (apixabano; dabigatrano; edoxabano; rivaroxabano) como os antagonistas da vitamina K (AVK) (varfarina; acenocumarol) se revelam eficazes na prevenção do acidente vascular cerebral na fibrilhação auricular. Embora a varfarina seja amplamente usada na prática clínica, a sua eficácia está dependente da manutenção da percentagem de tempo no intervalo terapêutico a um nível superior a 65%. Por sua vez, os NACOs revelam-se como uma alternativa à varfarina, sendo referidos como opção preferencial nos normativos das mais reconhecidas sociedades de cardiologia. No entanto, o tempo ideal para iniciar a terapêutica com estes agentes no perído pós-operatório carece de investigação, devido à exclusão desta população dos ensaios clínicos randomisados de fase III. Desta forma, no âmbito do programa Erasmus, este projeto foi desenvolvido durante os três meses em que tive a oportunidade de integrar o Departamento de Farmácia do Hospital St. Bartholomew sediado em Londres, Reino Unido. Tendo sido proposto pelo responsável deste departamento, este estudo teve como objetivo aprofundar o conhecimento relativamente ao tratamento ótimo e efetivo com anticoagulantes orais e, em última análise, permitir a otimização, eficácia e segurança destes agentes. Além disso, refletindo o importante papel do farmacêutico enquanto membro integrado numa equipa multidisciplinar de profissionais de saúde, este projeto permitiu de igual forma, a promoção da discussão com cirurgiões, médicos e enfermeiros acerca do potencial de possíveis mudanças a adotar futuramente na prática clínica de modo a garantir uma melhor gestão da FAPO, e consequentemente proporcionar os melhores cuidados em saúde a estes utentes. Objetivos: Este estudo teve como propósito comparar a gestão da terapêutica anticoagulante oral na fibrilhação auricular pós-cirurgia cardiotorácica. Deste modo, foram formuladas quatro questões de investigação: 1. Qual percentagem de pacientes prescritos com varfarina que demonstrou um tempo no intervalo terapêutico superior a 65%, seis semanas após a alta hospitalar? 2. Qual é a dosagem adequada de NACOs no período pós-operatório? 3. Qual é o momento ideal para iniciar terapêutica com NACOs no período pós-operatório? 4. Os anticoagulantes orais foram descontinuados nos doentes que revelaram reversão para ritmo sinusal seis semanas após a alta hospitalar? Assim, tendo como ponto de partida as questões supracitadas, foram definidos os seguintes objetivos específicos para este estudo: i) Avaliar a eficácia da varfarina no período pós-operatório; ii) Investigar as tendências e padrões na prática clínica em relação à NACOs (i.e., escolha do NACO prescrito, dosagem, período pós-operatório de iniciação terapêutica); iii) Esclarecer as características envolvidas na hipótese de considerar a redução da dose de NACOs, bem como o prazo ideal para iniciar a terapêutica com estes fármacos no período pós-operatório; iv) Identificar o número de doentes que revertem para ritmo sinusal (RS) seis semanas após a cirurgia cardiotorácica; v) Analisar as taxas de descontinuação de anticoagulantes orais, quando é verificada a reversão para RS. Métodos: Foi conduzido um estudo ambiespectivo em doentes que desenvolveram fibrilhação auricular pós operatória entre janeiro de 2016 e janeiro de 2017. O estudo compreendeu duas fases distintas; Uma retrospetiva e uma prospectiva (desenho ambiespectivo). As informações presentes nos registos médicos dos utentes submetidos a cirurgia entre os dias 1 de janeiro de 2016 e 31 de janeiro de 2017 foram avaliadas retrospectivamente para determinar a amostra de interesse para estudo com base nos critérios de eligibilidade definidos. Foram igualmente consultados retrospectivamente os registos de distribuição da farmácia e os relatórios de controlo de stocks para identificar todos os doentes com prescrições de varfarina ou novos anticoagulantes orais nas alas cardiotorácicas durante o período de coleção de dados. Foram assim constituídos dois coortes de exposição, de acordo com o subgrupo farmacoterapêutico adotado (AVK vs NACO). Foram analisados os registos de prescrição de fármacos e notas médicas eletrónicas, a fim de selecionar de entre os pacientes prescritos com estes anticoagulantes orais, os que foram dispensados do hospital com um diagnóstico confirmado de fibrilhação auricular pós-operatória. Dados demográficos, historial médico e estudos laboratoriais foram analisados. Foram definidas como variáveis de interesse, os valores de tempo no intervalo terapêutico especificamente para o grupo-varfarina; o NACO prescrito, respetiva dose e dia de inicio da terapêutica no período pós-operatório para o grupo-NACO; CHA2DS2‐VASc score, tendo sido realizada a estratificação de risco para tromboembolismo e acidente vascular cerebral para ambas as coortes através da análise dos fatores de risco individuais. A fase prospetiva decorreu desde 31 de Janeiro até 28 de abril de 2017 e serviu para recolher os dados das consultas de follow-up, realizadas em média cerca de seis semanas após cirurgia no Hospital St. Bartolomew. Através da consulta deste dados obteve-se assim informação sobre a reversão para ritmo sinusal (ou não), a consequente descontinuição dos anticoagulantes orais. Os valores de International Normalized Ratio (INR) que estão na origem do cálculo do tempo no intervalo terapêutico foram obtidos através de contactos estabelecidos com as clínicas de anticoagulação onde estes utentes realizavam as mediações do INR. Estes valores foram obtidos prospetivamente para os doentes que continuaram a terapia com varfarina e consequente monitorização de INR coincidente com a fase prospetiva do estudo. Os dados recolhidos foram analisados recorrendo a estatística descritiva univariada e bivariada. Os dados discretos são apresentados como frequências absolutas e relativas, enquanto que os dados contínuos são apresentados através da tendência central e medidas de dispersão, incluindo média, mediana e desvio padrão. A análise bivariada serviu para comparar as características dos utentes das duas coortes de doentes expostas aos dois diferentes tratamentos e verificar se as características dos doentes, nomeadamente o seu perfil de risco de AVC ou risco hemorrágico, poderiam justificar a sua inclusão num ou noutro grupo farmacoterapêutico. Dado o tamanho amostral e a distribuição não-normal dos dados, foram selecionados testes não-paramétricos; o chi-quadrado e a sua extensão peloo teste Exacto de Fisher foram utilizados para analisar dados categóricos e o teste Wilcoxon Mann-Whitney para analisar dados contínuos. O intervalo de confiança considerado foi de 95%. Todos os dados foram analisados usando o IBM Statistical Software Package for Social Sciences (SPSS, versão 24). O protocolo deste estudo foi aprovado pela Comissão de Ética do Hospital St. Bartolomew, sob o número 8021. Resultados: Sessenta e quatro utentes desenvolveram fibrilhação pós-operatória, dos quais 39 (60.9%) e 25 (39.1%) foram medicados com varfarina e NACOs, respetivamente. Foram obtidos 27 dados de valores de tempo no intervalo terapêutico (69% dos medicados com varfarina), sendo que 14 doentes (52%) demonstraram valores de tempo no intervalo terapêutico inferiores a 65%, refletindo fraco controlo e pouca eficácia da terapêutica anticoagulante com varfarina. No que concerne à iniciação de NACOs no período pós-operatório, foi revelado que a terapêutica com estes anticoagulantes teve inicio, em média, 8.36 ± 3.74 dias após realização do procedimento cirurgico. Relativamente à reversão para RS, 22 doentes (62.9%) do grupo da varfarina e 13 doentes (65.0%) do grupo dos NACOs tinham revertido para RS seis semanas após a alta hospitalar. De entre estes doentes, um total de 14 (40.0)% discontinuou os anticoagulantes orais após confirmação de ritmo sinusal. Conclusões: Alcançar um tempo no intervalo terapêutico superior a 65% revela-se desafiante e díficil de alcançar no que diz respeito à terapêutica com varfarina, sendo tal facto demonstrado pela proporção de pacientes que demonstraram valores que expressam a baixa eficácia deste agente, ainda que eventualmente resultante da sua utilização em contexto real onde questões associadas ao estilo de vida, inclusivamente alimentares e de adesão à terapêutica, poderão influenciar profundamente a capacidade de autogestão do doente. Deste modo, os anticoagulantes orais não antagonistas da vitamina K, iniciados oito dias após cirurgia cardiotorácica, podem constituir uma alternativa mais efetiva na tromboprofilaxia associada à fibrilhação auricular. No entanto, será prudente confirmar estes dados em amostras de maior dimensão dadas as limitações deste exercício académico. Estudos adicionais devem igualmente ser realizados de modo a estabelecer a dose ideal, bem como o período apropriado para iniciar a terapêutica anticoagulante com estes agentes na fase aguda do pós-operatório.