Objetivo. Verificar se as características espectrais dos eletrogramas atriais (EgA) em ritmo sinusal (RS) se correlacionam com a presença de gânglios parassimpáticos cardíacos. Materiais e Resultados. Treze pacientes encaminhados para submeter-se a ablação de fibrilação atrial (FA) foram incluídos de forma prospectiva. Previamente ao início da ablação, realizou-se o registro de EgA em RS em uma série de regiões anatômicas pré-determinadas, seguindo-se uma ordem sequencial. Em seguida, aplicou-se estímulos elétricos de alta frequência (20 Hz de frequência, amplitude de 100 V e duração de pulso de 4 ms), nos mesmos locais. Uma resposta vagal evocada foi definida como um súbito aumento no intervalo RR ou a indução de bloqueio na condução átrio-ventricular imediatamente após a aplicação do estímulo de alta-frequência (EAF). Procedeu-se à análise espectral dos sinais atriais em RS registrados, com amostragem de 1000 Hz, janela Hanning. No total, 1488 EgA oriundos de 186 locais anatômicos foram registrados, sendo 129 de regiões com resposta vagal negativa e 57 correspondentes a regiões de resposta vagal positiva. A duração do eletrograma e o número de deflecções foram similares nos pontos com resposta vagal positiva e negativa. A densidade de potência espectral em locais de resposta vagal positiva, no entanto, foi menor entre 26 e 83 Hz, e maior entre 107 e 200 Hz, comparados com os locais de resposta negativa. A área sobre a curva entre 120 e 170 Hz normalizada para a área total do espectro foi testada como um novo parâmetro diagnóstico. A análise de curva ROC demonstrou que o valor area 120-170 / area total > 0,14 foi capaz de identificar locais de inervação vagal com sensibilidade de 70,9% e especificidade de 72,1%. Conclusão. A análise espectral de sinais atriais durante RS é um método factível e simples de mapear os locais de inervação parassimpática cardíaca, sem a necessidade de qualquer tipo de estimulação / Objective. To verify whether spectral components of atrial electrograms (AE) during sinus rhythm (SR) correlate with cardiac ganglionated plexus (GP) sites. Methods and Results. Thirteen patients undergoing atrial fibrillation (AF) ablation were prospectively enrolled. Prior to radio frequency application, endocardial AE were recorded with a sequential point-by-point approach. Electrical stimuli were delivered at 20 Hz, amplitude 100 V, and pulse width of 4 msec. A vagal response was defined as a high-frequency stimulation (HFS) evoked AV block or a prolongation of RR interval. Spectral analysis was performed on single AE during SR, sampling rate of 1000 Hz, Hanning window. Overall, 1488 SR electrograms were analyzed from 186 different left atrium sites, 129 of them corresponding to negative vagal response sites and 57 to positive response sites. The electrogram duration and the number of deflections were similar in positive and negative response sites. Spectral power density of sites with vagal response was lower between 26 and 83 Hz and higher between 107 and 200 Hz compared with negative response sites. The area between 120 and 170 Hz normalized to the total spectrum area was tested as a diagnostic parameter. ROC curve analysis demonstrated that an area 120-170 / area total value > 0,14 identified vagal sites with 70,9% sensitivity and 72,1% specificity. Conclusions. Spectral analysis of AE during SR is feasible and simple method of mapping the cardiac autonomic nervous system (ANS), with no stimulation required

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.

Submitted by Daniely Januário (daniely.januario@gmail.com) on 2018-03-02T12:31:14Z No. of bitstreams: 1 joseresendedecastrojunior.pdf: 3078753 bytes, checksum: f22309c68ef54befb8ce6682fdfa7d3e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-03-14T18:29:39Z (GMT) No. of bitstreams: 1 joseresendedecastrojunior.pdf: 3078753 bytes, checksum: f22309c68ef54befb8ce6682fdfa7d3e (MD5) / Made available in DSpace on 2018-03-14T18:29:39Z (GMT). No. of bitstreams: 1 joseresendedecastrojunior.pdf: 3078753 bytes, checksum: f22309c68ef54befb8ce6682fdfa7d3e (MD5) Previous issue date: 2016-09-30 / PROQUALI (UFJF) / A fibrilação atrial é a arritmia cardíaca sustentada mais comum, acometendo principalmente idosos e aumenta o risco de acidente vascular cerebral. É atualmente um problema de saúde pública pela sua elevada morbimortalidade e custos crescentes. A varfarina é o anticoagulante que se mostrou efetivo na prevenção deste evento, contudo apresenta limitações que contribuem para a sua baixa aderência e subutilização. O surgimento de novos anticoagulantes, como a rivaroxabana, evidenciou que esta medicação pode ser tão efetiva quanto à varfarina, mas, com menores taxas de complicações hemorrágicas graves, principalmente cerebrais, não havendo necessidade de exames de monitorização, porém com um custo maior. O objetivo deste estudo foi avaliar a custo-utilidade da rivaroxabana comparada à varfarina nesta arritmia, ou seja, comparar o custo da intervenção com sua efetividade medida como ganho em anos de vida ajustada pela qualidade. Inicialmente foi realizada uma revisão sistemática de estudos econômicos sugerindo que a rivaroxabana pode ser uma opção custo-efetiva, principalmente em países desenvolvidos. Houve apenas um estudo realizado em país em desenvolvimento que mostrou resultado divergente. Posteriormente, foi desenvolvido um modelo econômico de Markov, na perspectiva do Sistema Único de Saúde, que permitiu simular a evolução de uma coorte de idosos com fibrilação atrial, em ciclos trimestrais durante toda a vida. Os resultados evidenciaram que os custos incrementais da rivaroxabana foram superiores à varfarina (R$ 7.135,48), com um discreto aumento de utilidade, resultando numa razão de custo-utilidade incremental de R$ 206.816,45/anos de vida ajustada pela qualidade. Este valor encontra-se acima do limiar proposto pela Organização Mundial da Saúde, podendo não ser uma opção custo-efetiva. Apesar das limitações, este trabalho conseguiu reunir as evidências disponíveis e mostrou a necessidade de se ajustar os protocolos clínicos e diretrizes para uma prática clínica que possa conciliar os princípios de integralidade do cuidado à sustentabilidade do sistema de saúde. / Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting mainly the elderly and increases the risk of stroke. It is currently a public health problem because of its high morbidity and mortality and increasing costs. Warfarin is an anticoagulant that was effective in preventing this type of stroke, but has limitations that contribute to its low adhesion and underutilization. The emergence of new anticoagulants such as rivaroxaban, suggest that this drug may be as effective as warfarin, but with lower rates of major bleeding complications, mainly brain. Also, with this drug, there is no need for monitoring tests, but is more expensive. The aim of this study was to evaluate the cost-utility of rivaroxabana compared to warfarin in this arrhythmia, or compare the cost of a health intervention with effectiveness measured as a gain in years of life adjusted for quality. Initially, a systematic review of economic studies was performed that suggest that rivaroxaban can be a cost-effective option compared to warfarin, especially in developed countries. There was only one study in a developing country which showed divergent results. Later, it was developed an economic model of Markov was developed with the Unified Health System perspective, which allowed simulation of the evolution of a cohort of elderly patients with Atrial fibrillation in quarterly cycles throughout life. The results showed that the incremental costs of rivaroxaban was superior to warfarin (R$ 7.135,48), with a slight increase of utility, resulting in incremental cost-utility ratio of R$ 206.816,45/years of life adjusted for quality. This value is above the threshold proposed by the Wolrd Health Organization, may not be a cost-effective option. Despite the limitations, this study brought together the available evidence and showed the need to adjust the clinical protocols and guidelines for clinical practice that can reconcile the principles of comprehensive care to the sustainability of the health system.

Nos travaux montrent qu’au cours de la fibrillation atriale (FA), les microparticules (MP) reflètent et contribuent à un état d’hypercoagulabilité et pro-inflammatoire. Leurs concentrations similaires dans les deux oreillettes de patients en FA témoignent d’une absence de différence de statut pro-thrombotique entre ces deux cavités cardiaques. Au cours des procédures d’ablation de FA, les concentrations de MP évoluent parallèlement à l’augmentation de l’activation cellulaire et plaquettaire. Nous avons également montré dans l'altération tissulaire des oreillettes en FA, l'importance de la sénescence qui évolue avec la progression du trouble du rythme. Nous avons caractérisé un modèle cellulaire de sénescence réplicative de cellules endothéliales auriculaires de porc permettant d'identifier l'apparition d'un phénotype pro-thrombotique, pro-inflammatoire, pro-adhésif et de mieux comprendre la physiologie de la cellule endothéliale atriale sénescente et le rôle majeur du système rénine-angiotensine dans ces mécanismes. / Our data evidence that during atrial fibrillation (AF), microparticles (MP) contribute to an enhanced hypercoagulable and pro-inflammatory state. Similar concentrations of MP measured in left and right atria of AF patients highlight the absence of chamber-specific enhanced thrombogenic status. During AF ablation procedures, MP concentrations progress in parallel with cell and platelet activation. We also showed that AF progression is strongly related to human atrial senescence burden pointing toward a possible network that links in human atrium, senescence burden, endothelial dysfunction, thrombogenicity and atrial remodeling. We also developed a model of left atrium endothelial cell replicative senescence providing compelling evidences indicating that atrial endothelial senescence promotes thrombogenicity, inflammation and proteolysis. These data underline the major role of renin-angiotensin system in endothelial atrial cell senescence.

Abstract The identification of risk factors for major adverse events after coronary artery bypass surgery is of main importance as it allows outcome prediction, facilitates preoperative patient selection and improves the quality of care. In the present clinical studies we have evaluated the impact of preoperative angiographic severity of a coronary artery disease and preoperative C-reactive protein (CRP) on the immediate outcome after coronary artery bypass surgery. We have reviewed the results of off-pump (OPCAB) versus conventional on-pump coronary artery bypass surgery (CCAB) in high risk patients. We have evaluated the impact of postoperative pulmonary artery blood temperature on the immediate outcome as well. In addition, we have investigated the incidence, timing and outcome of an atrial fibrillation (AF) related stroke after surgery. The multivariate analysis showed that among 2233 patients, the overall coronary angiographic score was predictive of postoperative death (p = 0.03; OR 1.027, 95% CI: 1.003–1.052) and of a low cardiac output syndrome (p = 0.04; OR 1.172, 95% CI: 1.010–1.218). The poor status of the proximal segment of the left circumflex coronary artery, the diagonal branches and the left obtuse marginal artery were most closely associated with adverse postoperative outcome. Patients (114/764) with a preoperative serum concentration of CRP ≥ 1.0 mg/dL had a higher risk of overall postoperative death (5.3% vs. 1.1%, p = 0.001), cardiac death (4.4% vs. 0.8%, p = 0.002), a low cardiac output syndrome (8.8% vs. 3.7%, p = 0.01). Among 179 high risk patients with an additive EuroSCORE6, the 30-day postoperative death and stroke rates were 7.5% and 6.0% in the OPCAB group, and 5.4% (p = 0.75) and 8.0% (p = 0.77) in the CCAB group, respectively. No significant differences were observed in other major outcome end-points between these non-randomised groups either. High pulmonary artery blood temperature on admission to the ICU among 1639 patients was significantly associated with an increased risk of overall postoperative death (p = 0.002), cardiac death (p = 0.03), and a low cardiac output syndrome (p &lt; 0.0001), and was significantly correlated with prolonged length of the ICU stay (r = 0.095; p &lt; 0.0001), and postoperative bleeding (ρ = –0.091; p = 0.001). Among 2,630 patients who underwent coronary artery bypass grafting (CABG), 52 (2.0%) experienced a postoperative stroke. Twelve out of these 52 patients (23.1%) died postoperatively. The ischemic cerebral event occurred after a mean of 3.7 days (0–33). In 19 patients (36.5%), atrial fibrillation preceded the occurrence of neurological complication. The angiographic severity of the coronary artery disease and the preoperative serum concentration of CRP predict postoperative outcome after a CABG operation. OPCAB can be performed safely in high-risk patients with results as satisfactory as those achieved with CCAB. CABG patients with a high pulmonary artery blood temperature on admission to the ICU seem to have a higher risk of postoperative adverse events. Atrial fibrillation occurring after coronary artery bypass grafting is a major determinant of a postoperative stroke.

Les activités électriques ectopiques à l’origine des épisodes de fibrillation atriale pourraient être dues à des échanges calciques anormaux dans les cardiomyocytes (CM) de veine pulmonaire (VP). Le cycle du calcium des CM de VP a donc été caractérisé et comparé à celui des CM d’oreillette gauche (OG) et de ventricule gauche (VG). Des outils ont été développés pour mesurer la régularité d’organisation des réseaux de tubules transverses et la contractilité des CM de VP. Contrairement aux CM d’OG et de VG, l’organisation hétérogène du réseau de tubules dans la population des CM de VP conduit à une grande variabilité de forme des transitoires calciques et d’amplitude de contraction. Au sein des VP, ces différents types de CM sont regroupés en îlots. La fréquence des libérations calciques spontanées est également plus grande dans les CM de VP que dans ceux d’OG et de VG. La population des CM de VP présente une dynamique calcique aux caractéristiques uniques pouvant être source d’arythmies. / Ectopic foci leading to atrial fibrillation episodes might be due to abnormal calcium handling by the pulmonary vein (PV) cardiomyocytes (CM). Therefore, the calcium cycle of PV CM was characterized and compared to those of left atria (LA) and left ventricle (LV) CM. Some tools have been developed to measure the organization of transverse tubular networks and contractility of PV CM. Unlike LA and LV CM, the heterogeneous organization of the tubular networks in the PV CM population leads to wide ranges of calcium transient shapes and contraction amplitudes. Within the whole PV, these different types of CM are gathered in islets. The frequency of spontaneous calcium release is also higher in PV CM than in LA and LV CM. The special features of the calcium handling properties of the PV CM population could be a source of arrhythmias.

Background Many risk factors for stroke are well characterized and might, at least to some extent, be similar for first-ever stroke and for recurrent stroke events. However, previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. Patients who survive spontaneous intracerebral hemorrhage (ICH) often have compelling indications for antithrombotic (AT) treatment (antiplatelet (AP) and/or anticoagulant (AC) treatment), but due to controversy of the decision to treat, a large proportion of these patients are untreated. In the absence of evidence from randomized controlled trials (RCTs), there is need for more high- quality observational data on the clinical impact of, and optimal timing of AT in ICH survivors. The aims of this thesis were to assess time trends in stroke recurrence, to determine the factors associated with an increased risk of stroke recurrence – including socioeconomic factors – and to determine to what extent ICH survivors with and without atrial fibrillation (AF) receive AT treatment and to determine the optimal timing (if any) of such treatment.  Methods The population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence register was used to assess the epidemiology and predictors of stroke recurrence after ischemic stroke (IS) and ICH from 1995 to 2008 in northern Sweden. Riksstroke, the Swedish stroke register, linked with the National Patient Register and the Swedish Dispensed Drug Register, made it possible to identify survivors of first-ever ICH from 2005 to 2012 with and without concomitant AF to investigate to what extent these patients were prescribed AP and AC therapy. The optimal timing of initiating treatment following ICH in patients with AF 2005–2012 was described through separate cumulative incidence functions for severe thrombotic and hemorrhagic events and for the combined endpoint “vascular death or non-fatal stroke”. Riksstroke data on first-ever stroke patients from 2001 to 2012 was linked to the Longitudinal Integration Database for Health Insurance and Labour market studies to add information on education and income to investigate the relationship between socioeconomic status and risk of recurrence. Results Comparison between the cohorts of 1995–1998 and 2004–2008 showed declining risk of stroke recurrence (hazard ratio: 0.64, 95% confidence interval (CI): 0.52-0.78) in northern Sweden. Significant factors associated with an increased risk of stroke recurrence were age and diabetes. Following ICH, a majority (62%) of recurrent stroke events were ischemic.  The nationwide Riksstroke study confirmed the declining incidence, and it further concluded that low income, primary school as highest attained level of education, and living alone were associated with a higher risk of recurrence beyond the acute phase. The inverse effects of socioeconomic status on risk of recurrence did not differ between men and women and persisted over the study period. Of Swedish ICH-survivors with AF, 8.5% were prescribed AC and 36.6% AP treatment, within 6 months of ICH. In patients with AF, predictors of AC treatment were less severe ICH, younger age, previous anticoagulation, valvular disease and previous IS. High CHA2DS2-VASc scores did not seem to correlate with AC treatment. We observed both an increasing proportion of AC treatment at time of the initial ICH (8.1% in 2006 compared with 14.6% in 2012) and a secular trend of increasing AC use one year after discharge (8.3% in 2006 versus 17.2% in 2011) (p&lt;0.001 assuming linear trends). In patients with high cardiovascular event risk, AC treatment was associated with a reduced risk of vascular death and non-fatal stroke with no significantly increased risk of severe hemorrhage. The benefit appeared to be greatest when treatment was started 7–8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within three years was 17.0% when AC treatment was initiated eight weeks after ICH and 28.6% without any antithrombotic treatment (95% CI for difference: 1.4% to 21.8%). For high-risk men, the corresponding risks were 14.3% vs. 23.6% (95% CI for difference: 0.4% to 18.2%). Conclusion Stroke recurrence is declining in Sweden, but it is still common among stroke survivors and has a severe impact on patient morbidity and mortality. Age, diabetes and low socioeconomic status are predictors of stroke recurrence. Regarding ICH survivors with concomitant AF, physicians face the clinical dilemma of balancing the risks of thrombosis and bleeding. In awaiting evidence from RCTs, our results show that AC treatment in ICH survivors with AF was initiated more frequently over the study period, which seems beneficial, particularly in high-risk patients. The optimal timing of anticoagulation following ICH in AF patients seems to be around 7–8 weeks following the hemorrhage.

No description available.

Background: The risk of ischaemic stroke in patients with atrial fibrillation (AF) and mechanical heart valve (MHV) prostheses can be reduced by oral anticoagulation (OAC), which increases the risk of serious bleeding. The aims of this thesis were [1] to find out how effective and safe warfarin is where treatment quality is high, i.e. Sweden, with proportion of time that patients spend within the therapeutic range (TTR) &gt;70%, [2] whether there is evidence for administering low-molecular-weight heparin (LMWH) during temporary interruptions of OAC (bridging therapy), and whether non-vitamin K-dependent oral anticoagulants (NOACs) as a group, [3] or individually, [4] are more effective and safer than warfarin when used for stroke prevention in patients with AF. Materials and methods: All four studies were retrospective, based on the Swedish anticoagulation register Auricula, and done with merging of data from some or all of the National Patient Register, the Prescribed Drug Register, the Swedish Stroke Register (Riksstroke), and the Cause of Death Register. In studies 2–4, propensity score matching was performed to obtain treatment groups with similar risk profiles. Outcomes were defined as haemorrhages or thromboses requiring specialist care, or death. Haemorrhages were intracranial, gastrointestinal, or other. Thromboses were ischaemic stroke, systemic embolism, myocardial infarction, or venous thromboembolism (VTE). Study 1 described all patients on warfarin during 2006–2011, which was before the introduction of NOACs. Study 2 was a cohort study of all patients who had a planned interruption of warfarin during the same period. Study 3 included all 49,011 patients starting OAC for stroke prevention due to AF between 1 July 2011 and 31 December 2014, and study 4 all 64,382 patients with the same indication between 1 January 2013 and 31 December 2015. Results: Study 1 showed that for the 77,423 patients on warfarin with 217,804 treatment years, TTR was 77.4% for patients with AF, 74.5% with MHV, and 75.9% with VTE. Annual rates of intracranial bleeding were 0.38%, 0.51%, and 0.30%. In study 2, with 14,556 warfarin interruptions, the 30-day risk of a bleeding requiring specialist care was 0.64% for LMWH treated and 0.46% for controls. For patients with VTE as indication for OAC, bleeding rate with LMWH was significantly higher at 0.85% vs. 0.16% (hazard ratio 5.24, 95% confidence interval 1.39–19.77), but with no difference for patients with MHV or AF. The incidence of ischaemic complications was higher in the LMWH bridging group overall and for patients with MHV and AF, but not for patients with VTE. In study 3, for the 12,694 patients starting NOAC (10,392 treatment years) or matched warfarin patients (9,835 treatment years, TTR 70%) due to AF, annual incidence of ischaemic stroke and systemic embolism did not differ between the groups (1.35% vs. 1.58%), but risks of major bleedings and intracranial bleedings were significantly lower: 2.76% vs. 3.61% and 0.40% vs. 0.69%. In study 4, patients on individual NOACs (6,574 dabigatran, 8,323 rivaroxaban, 12,311 apixaban) were compared to 37,174 patients starting warfarin (in total 81,176 treatment years). No NOAC showed any difference in risk of ischaemic stroke or systemic embolism, but there were fewer intracranial bleedings, serious bleedings overall, and deaths for dabigatran and apixaban compared to warfarin. For patients starting rivaroxaban the risk of gastrointestinal bleeding was higher than for matched warfarin counterparts, with no significant differences in other bleeding risks, or mortality. Conclusions: Swedish warfarin treatment shows TTR levels that are high by international standards, correlating to low incidences of ischaemic and haemorrhagic events. LMWH bridging has not been proven beneficial, even for patients with MHV, meaning that bridging in general cannot be recommended. NOACs as a group were safer than high-quality warfarin treatment. Efficacy did not differ, even when comparing individual NOACs to warfarin, but there were fewer bleedings on dabigatran and apixaban. Although not more efficient than warfarin with a high TTR, NOACs should be the recommended first choice for OAC in AF, on the merit of lower bleeding risks. / <p>Finansiär: Forskning och Utveckling, Region Västernorrland</p>

Omega 3 poly unsaturated fatty acids (n-3 PUFA) have been shown to protect against sudden cardiac death following myocardial infarction and reduce the risk of ventricular arrhythmias in patients with heart failure. At the inception of this study, there was one clinical study that reported n-3 PUFA supplementation reduced the risk of atrial fibrillation (AF) following CABG. As AF is a very common arrhythmia and as there are no safe and effective means of preventing AF, we designed this study to further validate the findings of the previous study in a more robust study design. In addition, this study also aimed to evaluate the cellular changes that underpin the beneficial anti-arrhythmic effect of n-3 PUFA.The outcome of this study shows that n-3 PUFA does not reduce the risk of AF following CABG. However, short term supplementation with n-3 PUFA reliably increases the membrane incorporation in phospholipids and results in alteration in the expression levels of cardiac calcium handling proteins phospholamban and ryanodine receptors. In addition, such incorporation in animal (rat) ventricular myocytes leads to changes in the rate of decay of the systolic calcium transient and an increase in the amplitude of the caffeine induced calcium transient thereby indicating a greater activity of SERCA. These findings needs further evaluation but is clearly interesting as the clinical situations where n-3 PUFA have been shown to be anti-arrhythmic are situations where cellular calcium overload is the main mechanism of arrhythmogenesis.