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Introdução: a fibrilação atrial (FA) é a arritmia mais frequente na prática clínica estando associada à elevada taxa de morbidade e mortalidade. O risco de acidente vascular cerebral (AVC) apresenta-se aumentado em pacientes com FA e há evidência de aumento progressivo do risco com o avançar da idade. A detecção precoce da FA pode permitir a antecipação terapêutica e consequente redução de morbimortalidade. Vários recursos diagnósticos têm sidos utilizados com essa finalidade incluindo o marca-passo cardíaco definitivo (MPD) que permite armazenar registros de elevada frequência no canal atrial. Sistemas atuais de monitoramento remoto contínuo (MRC) do portador de MPD permitem a identificação e o envio diário à distância destes eventos armazenados pelo dispositivo. Objetivo: definir o papel do MRC na detecção e no manejo da FA em idosos portadores de MPD. Método: foi um estudo prospectivo e randomizado com seleção consecutiva de 300 idosos (60 anos ou mais) entre março/2007 e janeiro/2010, em ritmo sinusal e com indicação para implante ou troca de MPD. Os pacientes (P) foram randomizados para grupo de intervenção (GI) em monitoramento remoto contínuo (n=150) e grupo controle (GC) em seguimento convencional (n=150) com consultas agendadas para 30, 90, 180 dias e posteriormente a cada seis meses até dois anos de seguimento. No GI foram realizadas consultas extras motivadas por alertas automáticos de FA com duração mínima de 2,5 horas enviados pelo sistema de MRC. Resultados: o tempo de seguimento médio foi de 435 dias. Não houve diferença entre os grupos (GI x GC) em relação à idade (75,5 x 74,3 anos, p=0,44), sexo (feminino 54,7% x 57,4%, p=0,46), indicação do MPD (BAV 89,7% x 88,7%; p=0,84) e eventos clínicos (incidência de FA 25,3% x 19,3%, p=0,42; AVC 1,4% x 0%, p=0,44 e óbitos 8,6% x 5,3%, p=0,16). Houve mais documentação eletrocardiográfica da FA no GI (10%) em comparação ao GC (4%), p=0,027 e o MPD detectou corretamente a FA em 95,2% desses casos. O tempo para a primeira recorrência da FA foi de 79 x 128 dias; p=0,005. O número de dias em FA foi menor no GI (16 dias; IConf 95%: 8,89 a 23,18) em relação ao GC (51,9 dias; IConf 95%: 21,89 a 81,93), p=0,028. Baseados no escore CHADS2 houve mais pacientes com indicação para terapia antitrombótica no GI (p=0,008). Foram realizadas 55 consultas extras motivadas pelo sistema de MRC com necessidade de mudança terapêutica em 81% dos casos (36% antitrombóticos, 20% antiarrítmicos, 13% reprogramação MPD e 12% cardioversão). Conclusões: o MRC proporcionou menor tempo para a detecção da FA reduzindo o número de dias em arritmia devido à antecipação da terapêutica. Houve mais pacientes com documentação eletrocardiográfica da FA e submetidos à terapia antitrombótica no GI. Os alertas automáticos do sistema de MRC apresentaram importância clínica na maioria das consultas extras havendo necessidade de modificações na terapia antiarrítmica e antitrombótica, assim como na reprogramação do MPD. Os resultados deste estudo destacam o MRC como ferramenta auxiliar no manejo da FA em idosos portadores de MPD / Introduction: atrial fibrillation (AF) is the most common arrhythmia in clinical practice and it is related to high prevalence of morbidity and mortality. The annual risk of stroke is increased in AF patients especially with advancing age. Early AF detection should anticipate the management of AF which can reduces morbidity and mortality. Atrial high rate episodes device detected is a good diagnostic tool in PM carriers and these events can be sent daily to the doctor by continuous remote monitoring (CRM) systems. The aim of this study was to determine the role of CRM to detect and in the management of AF in elderly pacemaker patients. Method: It was a randomized and prospective study. Between March/2007 and January/2010 we selected 300 consecutive patients with an indication to atrioventricular pacemaker implantation or generator change. There were included patients in sinus rhythm with 60 years old or more. They were randomized in remote group (RG=150) and control (CG=150). Follow-up (FU) was scheduled in 30, 90 and 180 days and after, 6/6 months until two years. Patients in RG had extra appointment if automatic AF alerts (minimum AF burden of 2.5 hours) were sent by CRM. Results: FU mean time was 435 days. There were no difference between studied groups (RG vs. CG) in age (75.5 vs. 74.3 years, P=0.44); gender (female 54.7% vs. 57.4%, P=0.46); pacemaker indication due to sick sinus syndrome 10.3% vs. 11.3% and AV block 89.7% vs. 88.7%, P=0.84; AF incidence 25.3% vs. 19.3%, P=0.42; stroke 1.4% vs. 0%, P=0.44 and death 8.6% vs. 5.3%, P=0.16. AF was documented by electrocardiogram in 21 patients (RG=10% vs. CG=4%, P=0.027) and the pacemakers detected AF correctly in 95,2%. Median time to first AF recurrence was 79 vs. 128 days, P=0.005. The mean AF days was 16.0 (IC95%; 8.89 to 23.18) vs. 51.91 (IC95%; 21.89 to 81.93); P=0.028. According CHADS2 score, there were more patients with an antithrombotic therapy indication in RG (P=0.008). In 55 extra appointments, there was a therapy change in 81% of them (36% antithrombotic therapy, 20% arrhythmic therapy, 13% pacemaker programming and 12% electrical cardioversion). Conclusion: CRM allowed earlier AF detection which reduced AF days by anticipated therapy. In RG, the time to detection of first AF recurrence was lower than in the conventional approach. There were more AF documented by EKG and more patients with an indication to antithrombotic therapy in RG. Most of extra appointment needed a therapy change with regard to antithrombotic or antiarrhythmic therapy and device programming. The results of this study point out the CRM like a good auxiliary tool in the management of AF in elderly pacemaker patients

Introdução: a fibrilação atrial (FA) é a arritmia mais frequente na prática clínica estando associada à elevada taxa de morbidade e mortalidade. O risco de acidente vascular cerebral (AVC) apresenta-se aumentado em pacientes com FA e há evidência de aumento progressivo do risco com o avançar da idade. A detecção precoce da FA pode permitir a antecipação terapêutica e consequente redução de morbimortalidade. Vários recursos diagnósticos têm sidos utilizados com essa finalidade incluindo o marca-passo cardíaco definitivo (MPD) que permite armazenar registros de elevada frequência no canal atrial. Sistemas atuais de monitoramento remoto contínuo (MRC) do portador de MPD permitem a identificação e o envio diário à distância destes eventos armazenados pelo dispositivo. Objetivo: definir o papel do MRC na detecção e no manejo da FA em idosos portadores de MPD. Método: foi um estudo prospectivo e randomizado com seleção consecutiva de 300 idosos (60 anos ou mais) entre março/2007 e janeiro/2010, em ritmo sinusal e com indicação para implante ou troca de MPD. Os pacientes (P) foram randomizados para grupo de intervenção (GI) em monitoramento remoto contínuo (n=150) e grupo controle (GC) em seguimento convencional (n=150) com consultas agendadas para 30, 90, 180 dias e posteriormente a cada seis meses até dois anos de seguimento. No GI foram realizadas consultas extras motivadas por alertas automáticos de FA com duração mínima de 2,5 horas enviados pelo sistema de MRC. Resultados: o tempo de seguimento médio foi de 435 dias. Não houve diferença entre os grupos (GI x GC) em relação à idade (75,5 x 74,3 anos, p=0,44), sexo (feminino 54,7% x 57,4%, p=0,46), indicação do MPD (BAV 89,7% x 88,7%; p=0,84) e eventos clínicos (incidência de FA 25,3% x 19,3%, p=0,42; AVC 1,4% x 0%, p=0,44 e óbitos 8,6% x 5,3%, p=0,16). Houve mais documentação eletrocardiográfica da FA no GI (10%) em comparação ao GC (4%), p=0,027 e o MPD detectou corretamente a FA em 95,2% desses casos. O tempo para a primeira recorrência da FA foi de 79 x 128 dias; p=0,005. O número de dias em FA foi menor no GI (16 dias; IConf 95%: 8,89 a 23,18) em relação ao GC (51,9 dias; IConf 95%: 21,89 a 81,93), p=0,028. Baseados no escore CHADS2 houve mais pacientes com indicação para terapia antitrombótica no GI (p=0,008). Foram realizadas 55 consultas extras motivadas pelo sistema de MRC com necessidade de mudança terapêutica em 81% dos casos (36% antitrombóticos, 20% antiarrítmicos, 13% reprogramação MPD e 12% cardioversão). Conclusões: o MRC proporcionou menor tempo para a detecção da FA reduzindo o número de dias em arritmia devido à antecipação da terapêutica. Houve mais pacientes com documentação eletrocardiográfica da FA e submetidos à terapia antitrombótica no GI. Os alertas automáticos do sistema de MRC apresentaram importância clínica na maioria das consultas extras havendo necessidade de modificações na terapia antiarrítmica e antitrombótica, assim como na reprogramação do MPD. Os resultados deste estudo destacam o MRC como ferramenta auxiliar no manejo da FA em idosos portadores de MPD / Introduction: atrial fibrillation (AF) is the most common arrhythmia in clinical practice and it is related to high prevalence of morbidity and mortality. The annual risk of stroke is increased in AF patients especially with advancing age. Early AF detection should anticipate the management of AF which can reduces morbidity and mortality. Atrial high rate episodes device detected is a good diagnostic tool in PM carriers and these events can be sent daily to the doctor by continuous remote monitoring (CRM) systems. The aim of this study was to determine the role of CRM to detect and in the management of AF in elderly pacemaker patients. Method: It was a randomized and prospective study. Between March/2007 and January/2010 we selected 300 consecutive patients with an indication to atrioventricular pacemaker implantation or generator change. There were included patients in sinus rhythm with 60 years old or more. They were randomized in remote group (RG=150) and control (CG=150). Follow-up (FU) was scheduled in 30, 90 and 180 days and after, 6/6 months until two years. Patients in RG had extra appointment if automatic AF alerts (minimum AF burden of 2.5 hours) were sent by CRM. Results: FU mean time was 435 days. There were no difference between studied groups (RG vs. CG) in age (75.5 vs. 74.3 years, P=0.44); gender (female 54.7% vs. 57.4%, P=0.46); pacemaker indication due to sick sinus syndrome 10.3% vs. 11.3% and AV block 89.7% vs. 88.7%, P=0.84; AF incidence 25.3% vs. 19.3%, P=0.42; stroke 1.4% vs. 0%, P=0.44 and death 8.6% vs. 5.3%, P=0.16. AF was documented by electrocardiogram in 21 patients (RG=10% vs. CG=4%, P=0.027) and the pacemakers detected AF correctly in 95,2%. Median time to first AF recurrence was 79 vs. 128 days, P=0.005. The mean AF days was 16.0 (IC95%; 8.89 to 23.18) vs. 51.91 (IC95%; 21.89 to 81.93); P=0.028. According CHADS2 score, there were more patients with an antithrombotic therapy indication in RG (P=0.008). In 55 extra appointments, there was a therapy change in 81% of them (36% antithrombotic therapy, 20% arrhythmic therapy, 13% pacemaker programming and 12% electrical cardioversion). Conclusion: CRM allowed earlier AF detection which reduced AF days by anticipated therapy. In RG, the time to detection of first AF recurrence was lower than in the conventional approach. There were more AF documented by EKG and more patients with an indication to antithrombotic therapy in RG. Most of extra appointment needed a therapy change with regard to antithrombotic or antiarrhythmic therapy and device programming. The results of this study point out the CRM like a good auxiliary tool in the management of AF in elderly pacemaker patients

Correction de la bradycardie et des troubles de conduction dans des modèles de dysfonction congénitale de l’automatisme cardiaque par l’inhibition pharmacologique du courant IKAChLa dysfonction du nœud sinusal (DNS) est l’une des principales pathologies de l’automatisme cardiaque. La DNS désigne une multitude de troubles caractérisées par l’incapacité du nœud sinusal (SAN) à générer ou à conduire l’impulsion cardiaque. La seule thérapie actuellement disponible pour la DNS est l’implantation d’un pacemaker électronique. Des études épidémiologiques prévoient un besoin croissant d’implantation de pacemaker électroniques au cours des 50 prochaines années à cause du vieillissement de la population. Le développement des thérapies innovantes pour la DNS est donc un enjeu médical et sociétal important. L’inhibition pharmacologique du courant potassique activé par l’acétylcholine (IKACh) pourrait constituer une nouvelle option thérapeutique pour traiter la DNS.Nous avons donc testé l’inhibition du courant IKACh par un peptide de venin d’abeille, la Tertiapine-Q, pour corriger le DNS et le dysfonctionnement de la conduction chez des souris modèle de pathologies cardiaque humaine en particulier les souris portant l’inactivation des canaux L Cav1.3 (Cav1.3-/-), les souris portant simultanément l’ablation de Cav1.3 et des canaux de type-T Cav3.1 (Cav1.3-/-/Cav3.1-/-), les souris porteuses de la perte de fonction des canaux f- (HCN4-CNBD) et les souris haplo-suffisantes Nav1.5 (Scn5a+/-).Nous avons enregistré par télémétrie, l’ECG, chez ces modèles murins avant et après l’administration de différentes doses de Tertiapine-Q.L’inhibition du courant IKACh par la Tertiapine-Q prévient des dysfonctions sinusales et améliore la conduction dans ces modèles de bradycardie congénitale suggérant la possibilité d’un développement d’un ciblage pharmacologique d’IKACh afin de parvenir à corriger la DNS et les troubles de la conduction. / Inhibition of KACh channels by the bee venom peptide tertiapin-Q rescues inherited cardiac conduction defects, sino-atrial bradycardia, and atrioventricular block in models of congenital dysfunctionSinus node dysfunction (SND) is a widespread disease of heart automaticity. SND refers to a multitude of sinus node (SAN) disorders characterized by failure to generate or conduct the cardiac impulse. The only currently available therapy for chronic SND is the implantation of an electronic pacemaker. Epidemiological studies forecast an increasing need for pacemaker implantation during the next 50 years, with the ageing of the population. It is thus an important medical and societal issue, to develop innovative therapies for SND. Pharmacologic inhibition of the G-protein activated K+ current (IKACh) could be a new therapeutic option to treat bradycardia and SND associated with other cardiac pathologies.We tested whether inhibition of IKAch by the peptide Tertiapin-Q could rescue SND and conduction dysfunction in Cav1.3-/- mice carrying concurrent ablation of L-type Cav1.3 and T-type Cav3.1 channels (Cav1.3-/-/Cav3.1-/-), mice carrying loss-of-function of f-channels (HCN4-CNBD) and Nav1.5 haploinsufficient (Scn5a+/-) mice.We employed telemetric ECG recordings of heart rate (HR), SAN pacemaking and AV dysfunction in mice before and after administration of different doses of Tertiapin-Q.Tertiapin-Q significantly improves the HR of Cav1.3-/-, Cav1.3-/-/Cav3.1-/-, and HCN4-CNBD from doses of 0.1 to 5 mg/kg. HRs of Tertiapin-Q-treated mice were similar to those recorded in untreated wild-type mice. Tertiapin-Q also improved cardiac conduction of Scn5a+/- mice by 24%.Pharmacological inhibition of IKAch by Tertiapin-Q prevents SAN dysfunction and improves conduction in three models of congenital bradycardia suggesting the possibility of pharmacologic development of IKACh targeting to manage SND and conduction disease, to delay or replace the implantation of an electronic pacemaker.

In mammalian hearts, initiation of the heartbeat occurs in a region of specialised pacemaker cells known as the sinoatrial node (SAN). The SAN is a highly complex spatially distributed structure which displays considerable cellular heterogeneity and is subject to complex electrotonic interactions with the surrounding atrial tissue. In this study, biophysically detailed ionic models of central and peripheral SAN pacemaker cells are described. These models are able to accurately reproduce experimental recordings of the membrane potential from central and peripheral SAN tissue. These models are used to investigate frequency synchronisation of electrically coupled cardiac pacemaker cells. Based on simulation results presented, it is proposed that cellular heterogeneity in the SAN plays an important role in achieving rhythm coordination and possibly contributes to the efficient activation of the surrounding atrial myocardium. This represents an important, previously unexplored, mechanism underlying pacemaker synchronisation and cardiac activation in vivo. A spatial-gradient model of action potential heterogeneity within the SAN is then formulated using a large-scale least squares optimisation technique. This model accurately reproduces the smooth spatial variation in action potential characteristics observed in the SAN. One and two dimensional models of the intact SAN are then formulated and three proposed models of SAN heterogeneity are investigated: 1) the discrete-region model, in which the SAN consists of a compact central region surrounded by a region of transitional pacemaker cells, 2) the gradient model, in which cells of the SAN exhibit a smooth variation in properties from the centre to the periphery of the SAN, and 3) the mosaic model, in which SAN and atrial cells are scattered throughout the SAN region with the proportion of atrial cells increasing towards the periphery. Simulation results suggest that the gradient model achieves frequency entrainment more easily than the other models of SAN heterogeneity. The gradient model also reproduces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. It is therefore proposed that the gradient model of SAN heterogeneity represents the most plausible model of SAN organisation.

The work deals with implantable devices and possibilities of interference of elektromagnetic field. At first, the electromagnetic compatibility is discussed. Basic terms are explained, followed by insisting on resources of possible distrurbing of implantable devices and standards dealing with this issue. Furthermore, short chapter about devices affecting function of implantable devices is introduced. It means devices which patients with implantable devices may meet in common life, as well as devices used in common life, also devices used jn medical environment. In the next part, measuring process of electromamagnetic effect in working compartment of FN Brno magnetotheraphy and elektrotheraphy is devised. There is a concept of measuring card thanks to which impulses of implantable devices are measured. Finally, a description of measuring on implantable devices in FN Brno. MIKULA, D. EMD instruments and electromagnetic immunity. Brno, 2009. 74 s. Master’s thesis in Brno University of technology on faculty of elektrical engeenerig and communication. Supervisor Ing. Marie Havlíková , Ph.D.