Microcontrollers, the brains of embedded systems, have found their way into every aspect of our lives including medical devices such as pacemakers. Pacemakers provide life supporting functions to people therefore it is critical for these devices to meet their timing constraints. This thesis examines the use of hardware co-processing to accelerate the calculation time associated with the critical tasks of a pacemaker. In particular, we use an FPGA to accelerate a microcontroller’s calculation time of the Kendall Tau Rank Correlation Coefficient algorithm. The Kendall Tau Rank Correlation Coefficient is a statistical measure that determines the pacemaker’s voltage level for heart stimulation. This thesis explores three different hardware distributions of this algorithm between an FPGA and a pacemaker’s microcontroller. The first implementation uses one microcontroller to establish the baseline performance of the system. The next implementation executes the entire Kendall Tau algorithm on an FPGA with varying degrees of parallelism. The final implementation of the Kendall Tau algorithm splits the computational requirements between the microcontroller and FPGA. This thesis uses these implementations to compare system-level issues such as power consumption and other tradeoffs that arise when using an FPGA for co-processing.

Merlin.net Patient Care Network is a St. Jude Medical product that is used for remote patient management. The basic concept of Merlin.net is to allow the physician to view patient device follow-up information as well as general patient and device information on a web application. The Merlin.net system also interfaces with the patient and will send them notification if they miss a follow-up. All device information will be collected automatically while the patient is sleeping. This information is sent through a telephone line to a Merlin.net server to process a report package and display the collected information on the Merlin.net web application. The Merlin.net verification team ensures that all reports generated by the Merlin.net servers are processed and outputted correctly. There are currently 296 device parameters supported by Merlin.net, and the manual extraction and comparison of the expected parameter values takes several hours for each patient follow-up session. Currently there are 250 patient follow-up sessions used for verification testing. Each new release will continue to create additional patient follow-up sessions. Merlin.net releases are approximately 6 months apart, and each new release adds approximately 30-50 new patient follow-up records to support the new devices. In order to meet aggressive project deadlines, while ensuring that the Merlin.net system is processing and outputting patient follow-up data correctly, it is necessary to come up with an automated process to verify the contents of the processed data is correct. This will save a tremendous amount of time as well as improve on the quality of the verification process by eliminating human error and rework. It is critical for patient safety that the patient device follow-up information is processed and outputted correctly. In this thesis an automated process was developed to verify the correct content of the Merlin.net server generated reports for each patient follow-up session. This process leveraged different tools and scripting languages to achieve automation. TDE (Test Development Environment) tool was used to extract the device parameters from the patient follow-up sessions. The TDE script was written to extracts the desired parameter values from the patient follow-up session and automatically populates parameters in a device parameters spreadsheet. Once all the device parameter values are extracted in the spreadsheet, they are passed through a set of mapping rules, which form the expected values. The mapping rules were implemented as VBA (Visual Basic for Application) macros, one macro for each report. The VBA macros write the expected values back to the spreadsheet to form an “expected values spreadsheet”. The patient follow-up session is then sent to the Merlin.net server to process, which generates a processed patient follow-up session that contains a reports package in .zip format. A perl script was then written to compare the parameter values in the Merlinet.net generated reports with the corresponding expected values from the expected values spreadsheet. The perl script generates a comparison report displaying the discrepancies between the actual and the expected values.

Hintergrund: Mit der stetig steigenden Zahl an Neuimplantationen von kardiovaskulären implantierbaren elektronischen Geräten (CIED) steigt auch die Anzahl der Komplikationen, die mit einem chirurgischen Zweiteingriff einhergehen. Nicht selten müssen die vorhandenen Sonden dabei extrahiert bzw. explantiert werden. Allein in Deutschland wurden laut Jahresbericht 2018 des Deutschen Herzschrittmacher und Defibrillatorregisters ca. 75 000 Schrittmacher (SM) und ca. 23 000 implantierbare Kardioverter und Defibrillatoren (ICD) neu implantiert. Zusätzlich wurden ca. 16 000 SM-Aggregatwechsel, ca. 11 000 ICD-Aggregatwechsel, ca. 11 000 SM-Revisionen und ca. 8 000 ICD-Revisionen durchgeführt. Die Hauptindikation zur Sondenextraktion ist die Infektion der Sonde oder der Schrittmachertasche mit dem Risiko einer Endokarditis der Trikuspidalklappe oder einer generalisierten Infektion mit einhergehender Sepsis. Daneben wird die Indikation zur Sondenextraktion bei Sondendysfunktion, Vorhandensein von mehreren Sonden, chronischen Schmerzen, Systemumstellungen oder Systemverlagerungen z. B. vor Bestrahlungen sowie bei symptomatischen venösen Thrombosen der Gefäße mit implantierten Sonden gestellt. Bis zur Jahrtausendwende wurden Sonden allein durch Zug an der Sonde (manuell oder mittels Extension), durch Kappen der Sonde und mittels endovaskulärer Methoden oder durch eine offene Operation entfernt. Nicht selten kam es dabei zu Komplikationen wie Rupturen an Gefäßen oder am Herzen, die größere Operationen zur Folge hatten. In den letzten Jahrzehnten wurden jedoch eine Vielzahl an Instrumenten und Geräten zur Sondenextraktion entwickelt, um diese schwerwiegenden Komplikationen zu vermeiden. Mittlerweile werden diese Hilfsmittel in „Powered traction tools“ und „Non powered traction tools“ unterschieden. Unter „Powered traction tools“ werden Laser armierte Schleusen bzw. Katheter, elektrochirurgische Schleusen und rotierende schneidende Schleusen verstanden. „Non powered traction tools“ sind sogenannte Locking-Stylets, mechanische dilatierende Schleusen sowie femorale Schlingensysteme zur Bergung von Sondenresten aus dem rechten Ventrikel oder Atrium. Fragestellung: In der folgenden prospektiven Registerstudie wird die Excimer-Laser-Technik als Methode zur Sondenextraktion monozentrisch analysiert. Primärer Endpunkt ist die Erfolgsrate unter der Laserextraktion. Sekundärer Endpunkt ist das Auftreten von Komplikationen. Methoden: Im Zeitraum vom 01.01.2012 bis 31.12.2017 wurden im Herzzentrum Coswig 149 CIED-Sondenextraktionen mittels Excimer-Laser bei 146 Patienten durchgeführt. Dabei wurden 257 Sonden extrahiert (86 SM-Sonden und 171 ICD-Sonden). Die prospektiv angelegte Registerdatenbank im Rahmen der hausinternen Qualitätssicherung wurde in SPSS transferiert und analysiert. Bei allen Patienten wurde der Eingriff im OP-Saal unter Allgemeinanästhesie unter intraoperativer Fluoroskopie und transösophagealer Echokardiographie(TEE)-Kontrolle durchgeführt. Postoperativ erfolgte eine Röntgenaufnahme des Thorax zum Ausschluss verbliebener Fremdmaterialien (Sondenreste) sowie eine transthorakale Echokardiographie (TTE) zum Ausschluss eines Perikardergusses. Ergebnisse: 226/257 (88 %) aller Sonden konnten mit dem Einsatz des Excimer-Lasers komplett entfernt werden. In 15/257 (6 %) war nur eine partielle Entfernung der Sonden möglich. Bei 16/257 (6 %) war der eingesetzte Excimer-Laser ohne Erfolg. Von diesen 16 verbliebenen Sonden wurden 6 Sonden mit einem transfemoralem Snare und 3 Sonden durch Sternotomie mit HLM-Anschluss entfernt. Die Gesamtkomplikationsrate betrug 23/149 (15 %) aller Eingriffe. Bei 2/149 (1 %) traten schwere Komplikationen auf: ein Patient entwickelte einen postoperativen Apoplex mit Hemiparese und eine Patientin entwickelte eine Perikardtamponade und verstarb aufgrund dessen. Außerdem traten 21/149 (14 %) nicht-schwerwiegende Komplikationen bei 20 Patienten auf: 5x postoperativer Pneumothorax (allerdings musste nur bei 3 Patienten eine Thorax-Drainage gelegt werden), 3x Sondendislokation mit notwendiger Sonden-Neuplatzierung/-Neuimplantation, 6x Taschenhämatom mit einer Hämatomausräumung im Verlauf des gleichen Aufenthaltes, 2x Perikarderguss (wobei es nur bei einem Patienten notwendig war, eine Perikardpunktion durchzuführen), 2x Hämatothorax mit Thorax-Drainagenanlage, 1x neu aufgetretene postoperative Trikuspidalklappeninsuffizienz ohne Indikation zur Operation, 1x Perforation der oberen Hohlvene (SVC) ohne Nachweis eines Perikardergusses und 1x Sondenrest-Embolisierung mit Entfernung mittels transfemoralem Snare. Schlussfolgerung: Die Sondenextraktion mittels Excimer-Laser ist eine effektive und sichere Methode zur Entfernung von Sonden bei Patienten mit Herzschrittmacher (SM) und Implantierbaren Kardiovertern und Defibrillatoren (ICD). Die prospektive Registeranalyse des monozentrischen Patientenkollektivs zeigt mit 122/149 (93 %) eine hohe Erfolgsrate.:Abbildungsverzeichnis 5 Tabellenverzeichnis 6 Abkürzungsverzeichnis 7 1. Einleitung 9 1.1 Hintergrund 10 1.1.1 Kardiovaskuläre implantierbare elektronische Geräte (CIED) 10 1.1.1.1 Herzschrittmacher 10 1.1.1.2 Implantierbare Kardioverter-Defibrillatoren (ICD) 12 1.1.1.3 Elektroden 12 1.2 Sondenextraktion 14 1.2.1 Definitionen 14 1.2.2 Indikation zur Sondenextraktion 14 1.2.2.1 CIED-Infektion 14 1.2.3 Komplikationen 17 1.2.4 Sondenextraktionsmethoden 19 2. Fragestellung 22 3. Material und Methoden 22 3.1 Definitionen 23 3.2 Peri- Operative Standards 24 3.2.1 Elektrodenextraktionsvorgehen 25 3.3 SLS II Excimer-Laser-Schleuse 27 3.4 Datenerhebung und Statistik 28 4. Ergebnisse 31 4.1 Patientenchraktaristika 31 4.2 Indikation zur Extraktion 32 4.3 Aggregat- und Sondencharakteristika 33 4.4 Primärer Endpunkt: Effektivität 34 4.5 Sekundärer Endpunkt: Komplikationen 37 5. Diskussion 41 5.1 Indikationen zur CIED-Sondenextraktion 41 5.2 Standards gemäß der Heart Rhythm Society-Empfehlungen 42 5.3 Patientenkollektiv 43 5.4 Primärer Endpunkt: Erfolgsrate der Laser-Sondenextraktionen 44 5.5 Sekundärer Endpunkt: Komplikationen der Laser-Sondenextraktionen 45 5.6 Vergleich mit den Studienergebnissen aus dem GALLERY-Register 48 5.7 Limitationen 48 6. Schlussfolgerung 49 7. Zusammenfassung 50 8. Literaturverzeichnis 54 9. Danksagung 59 11. Eidesstattliche Erklärung 63

This thesis focuses on elucidating the electrical mechanisms underlying excitation of small intestinal and colonic smooth muscle initiated by interstitial cells of Cajal (ICC). All the ICC subtypes are involved in the orchestration, generation, and/or transmission of electrical signals to smooth muscle to pace gut motor patterns. Some ICC types have intrinsic activity leading to omnipresent rhythmic changes in smooth muscle excitability; others respond to stimuli, inducing pacemaker activity as required. Together they orchestrate motor patterns such as propulsion and segmentation, essential functions of the gut. To study ICC electrophysiology, I utilized patch clamping to record ion channel currents from single intestinal ICC and sharp microelectrodes to record colonic smooth muscle membrane potentials. I have made several discoveries contributing to our understanding of ICC electrophysiology. Firstly, my research increased our understanding of the properties of intrinsic pace-maker activity. I showed that maxi Cl– channels from small intestinal ICC make a significant contribution to slow wave depolarization triggered by intracellular calcium. Secondly, I showed that colonic intramuscular ICC (ICC-IM) selectively express KV7.5 channels, which are suppressed by cholinergic agonists, meaning that excitatory stimuli triggering acetylcholine release deactivate KV7.5 channels, leading to increased excitability. Thirdly, I have shown that the bile acid chenodeoxycholic acid and the nitric oxide donor sodium ni-troprusside both induce pacemaker activity, rhythmic transient depolarisations in mouse colonic muscle, which led to the hypothesis that nitrergic nerves are involved in generating inducible myenteric plexus ICC (ICC-MP) pacemaker activity. It is only when ICC are suitably stimulated by intracellular processes such as rhythmic Ca2+ transients or extracellular signalling from neurotransmitters or small molecules, that ICC produce membrane potential rhythmicity, required for generation of intrinsic slow waves, low-frequency rhythmic transient depolarisations and transmission of excitation into the muscle. / Thesis / Doctor of Philosophy (PhD) / The gut is essential for digestion and absorption of food. The gut has special cells called interstitial cells of Cajal (ICC), which control the contractions of the gut muscle. ICC are pacemaker cells, like those that pace heart beats. To pace gut muscle contractions, ICC generate electrical signals which cause the muscle to contract in an organized rhythmic manner, which promotes mixing or propulsion of gut contents, called motility. I used tiny electrodes to record electrical activity from ICC or gut muscle, to improve our understanding of how ICC pacemaker activity controls motility. My research characterised ion channels, which are microscopic protein pores that allow cells to make electrical currents, that enable generation of pacemaker signals by ICC. I also investigated activation of ICC electrical activity that causes propulsive colonic motility. This will hopefully lead to treatment improvements for patients with motility disorders in the future.

By exploiting the concept of emergent network properties and the hierarchical nature of networks, we have constructed several levels of models facilitating the investigations of issues in the area of respiratory neural control. The first of such models is an intracellular second messenger pathway model, which has been shown to be an important contributor to intracellular calcium metabolism and mediate responses to neuromodulators such as serotonin. At the next level, we have constructed new single neuron models of respiratory-related neurons (e.g. the pre-Btzinger complex neuron and the Hypoglossal motoneuron), where the electrical activities of the neurons are linked to intracellular mechanisms responsible for chemical homeostasis. Beyond the level of individual neurons, we have constructed models of neuron populations where the effects of different component neurons, varying strengths and types of inter-neuron couplings, as well as network topology are investigated. Our results from these simulation studies at different structural levels are in line with experiment observations. The small-world topology, as observed in previous anatomical studies, has been shown here to support rhythm generation along with a variety of other network-level phenomena. The interactions between different inter-neuron coupling types simultaneously manifesting at time-scales orders of magnitude apart suggest possible explanations for variations in the outputs measured from the XII rootlet in experiments. In addition, we have demonstrated the significance of pacemakers, along with the importance of considering neuromodulations and second-messenger pathways in an attempt to understand important physiological functions such as breathing activities.

Abstrakt Bakgrund: Användning av i implanterbar kardioverter-defibrillator (ICD) och pacemaker ökar i samhället då fler överlever hjärtkomplikationer. Många av dessa patienter överlever genom att patienten har fått en pacemaker eller ICD implanterad. Samtidigt som implanterbar kardioverter-defibrillator ökar så ökar även MR-undersökningarna i samhället. MR - modaliteten är en undersökning som inte ger patienter joniserande strålning samt ger denna modalitet bättre bildkvalité på människans mjukvävnader till jämförelse med en DTundersökning. MR - undersökningarna har blivit en populär metod att diagnostisera patienter och även patienter med pacemaker eller ICD. Trots detta har externa magnetfältet påverkat pacemakern och ICD till den grad att patienter har avlidit. Syftet: Syfte med studien är att belysa befintlig kunskap om säkerhetsrutiner och risker vid MR-undersökningar av patienter som har pacemaker eller implanterbar kardioverter-defibrillator. Metod: Studien genomfördes som en allmän litteraturöversikt. Artikelsökningar gjordes i databaserna Pubmed och Cinahl. Tolv kvantitativa artiklar valdes som sedan granskades och analyserades för att svara mot syftet. Resultat: Säkerhetsrutiner och risker kring pacemaker och ICD sammanställdes i två huvudkategorier vilka är säkerhetsrutiner och risker. Slutsats: I röntgensjuksköterskans yrkesroll är det viktigt att följa det lokala säkerhetsrutiner såsom att följa sjukhusets protokoll och att ha bra kommunikation med patienter med pacemaker eller ICD för att följa upp så patienten inte får några symtom under eller efter undersökningen. Genom att följa dessa säkerhetsrutiner förebygger vårdpersonalen symtom hos patienter och riskerna minimeras. / Abstract Introduction: The use of implanted cardiovascular devices such as pacemaker and ICD is increasing in society as more people survive cardiac complications. Many of these patients survive by having a pacemaker or ICD implant. While implanted cardiovascular devices are increasing, so are MRI scans in society. MRI is an examination that does not give patients ionizing radiation and provides better image quality of human soft tissues compared to CT scan. MRI scans have become a popular method of diagnosing patients and also patients with pacemaker or ICD. Despite this the external magnetic field affects the pacemaker and ICD to the point where patients have died. Aim:The purpose of the study is to shed light on existing knowledge about safety routines and risks in MRI examinations of patients who have a pacemaker or implantable cardioverter-defibrillator. Method: The study was conducted as a general literature overview. Article searches were made in the Pubmed and Cinahl databases. Twelve quantitative articles were selected which were then reviewed and analysed to meet the purpose. Results: Safety routines and risks around pacemaker and ICD were compiled into two main categories, which are safety routines and risks. Conclusion: In the professional role of the radiographer, it is important to follow local safety procedures such as following hospital protocols, monitoring and also having good communication with patients who have pacemaker or ICD during and after examinations so the patient does not experience any symptoms. By following these safety procedures the healthcare professionals will minimize the risks and symptoms in patients with cardiovascular implantable during and after MRI scan.

L'activité électrique du coeur est initiée par la génération spontanée de potentiels d'action venant des cellules pacemaker du noeud sinusal (SN). Toute dysfonction au niveau de cette région entraîne une instabilité électrique du coeur. La majorité des patients souffrant d'un noeud sinusal déficient nécessitent l'implantation chirurgicale d'un pacemaker électronique; cependant, les limitations de cette approche incitent à la recherche d'une alternative thérapeutique. La base moléculaire des courants ioniques jouant un rôle crucial dans l'activité du noeud sinusal sont de plus en plus connues. Une composante importante de l'activité des cellules pacemakers semble être le canal HCN, responsable du courant pacemaker If. Le facteur T-box 3 (Tbx3), un facteur de transcription conservé durant le processus de l'évolution, est nécessaire au développement du système de conduction cardiaque. De précédentes études ont démontré que dans différentes lignées cellulaires le Phorbol 12-myristate 13-acetate (PMA) active l'expression du gène codant Tbx3 via des réactions en cascade partant de la protéine kinase C (PKC). L'objectif principal de cette étude est de tester si le PMA peut augmenter la fréquence et la synchronisation de l'activité spontanée du pacemaker biologique en culture. Plus précisément, nous avons étudié les effets de l'exposition chronique au PMA sur l'expression du facteur de transcription Tbx3, sur HCN4 et l'activité spontanée chez des monocouches de culture de myocytes ventriculaires de rats néonataux (MVRN). Nos résultats démontrent que le PMA augmente significativement le facteur transcription de Tbx3 et l'expression ARNm de HCN4, favorisant ainsi l'augmentation du rythme et de la stabilité de l'activité autonome. De plus, une diminution significative de la vitesse de conduction a été relevée et est attribuée à la diminution du couplage intercellulaire. La diminution de la vitesse de conduction pourrait expliquer l'effet négatif du PMA sur la synchronisation de l'activité autonome du pacemaker biologique. Ces résultats ont été confirmés par un modèle mathématique multicellulaire suggérant que des fréquences et résistances intercellulaires plus élevée pourraient induire une activité plus stable et moins synchrone. Cette étude amène de nouvelles connaissances très importantes destinées à la production d'un pacemaker biologique efficient et robuste. / The normal heartbeat is initiated by the spontaneous generation of action potentials in pacemaker cells of the sinoatrial node (SAN) region. Dysfunction of this region leads to electrical instability of the heart. The majority of the patients with sinus node dysfunction require surgical implantation of electronic pacemaker devices; however, limitations of this therapeutic approach lead to a need to search for alternatives. To date, the molecular basis of the ionic currents which play pivotal role in SAN action potential has been discovered. It is thought that an important component of the pacemaker cells are HCN channels, responsible for the funny current (If) in the SAN. Meanwhile, T-box factor 3 known as an evolutionary conserved transcription factors is necessary for development of the conduction system. In previous studies, it has been shown that Phorbol 12-myristate 13-acetate (PMA) activates Tbx3 gene expression in a PKC-dependent manner in several cell lines. The main objective of this study is to test if PMA can increase the frequency and synchronization of spontaneous activity of cultured biopacemakers. More precisely, we studied the effects of chronic exposure to PMA on the expression of the Tbx3 transcription factor and HCN4 in neonatal rat ventricular myocytes monolayers and how spontaneous activity was altered. Our results show that PMA significantly increases the Tbx3 transcription factor and HCN4 mRNA expression favoring an increased in the rate and spatial-temporal stability of the spontaneous activity. In addition, a significant decrease in conduction velocity was found that is attributed to decrease electrical intercellular coupling of the cells. The decrease in the conduction velocity could explain the negative effect PMA has on synchronization of spontaneous activity of the biopacemaker. These findings are confirmed by a multicellular mathematical model implying that faster frequency and higher intercellular resistance of the pacemaker cells may lead to a more stable and less synchronous activity. This study provides important new knowledge to produce efficient and robust biological pacemakers.

A disfunção ventricular esquerda (VE) é o principal determinante de mau prognóstico nos pacientes com bloqueio atrioventricular completo congênito (BAVTC) e marcapasso (MP). A dissincronia mecânica do VE pode desempenhar um papel importante no desenvolvimento da disfunção ventricular. Como o uso do MP é um fator de risco para dissincronia, nosso(s) objetivo(s) foram: (1) avaliar a dissincronia do VE pelo ecocardiograma tridimensional (3D) em tempo real e comparar com os parâmetros de dissincronia pelo Doppler tecidual ; (2) verificar a possível correlação entre o local do estímulo e o segmento ativado tardiamente; (3) correlacionar o tempo de marcapasso e a presença de dissincronia e remodelamento ventricular. Avaliamos 50 pacientes com BAVTC e MP através do ecocardiograma bidimensional (2D), Doppler tecidual e ecocardiograma tridimensional. Dados clínicos e anteriores ao implante do MP foram revistos pelos prontuários. Houve 12 (23,5%) pacientes com dissincronia pelo 3D e 14 (28%) pelo Doppler tecidual. Em 16 (32%) e 20 (40%) havia disfunção ventricular esquerda pelos 2D e 3D respectivamente. O remodelamento ventricular ocorreu em 50% dos pacientes. Houve uma excelente correlação entre o Doppler tecidual e o 3D para diagnóstico de dissincronia (kappa = 0,735, p <0,001). A fração de ejeção do VE (FEVE) correlacionou-se negativamente com a dissincronia pelo eco 3D (r= -0,58, p = 0,000001). A duração do ciclo cardíaco medida pelo intervalo RR teve também uma significante correlação negativa com o índice de dissincronia pelo 3D (r=-0,74, p=0,0011). O remodelamento do VE pelo Eco 3D (índices de esfericidade e conicidade) teve uma boa correlação com a disfunção do VE (p = 0,005 e 0,003 respectivamente). O tempo de marcapasso, a idade do implante e o local do eletrodo não se correlacionaram com a dissincronia. Comparando os pacientes com BAVTC e MP menores que 18 anos com um grupo controle de crianças normais, houve uma significante diferença em relação aos volumes do VE, índices de dissincronia, esfericidade e conicidade. Em conclusão, neste estudo transversal de pacientes com BAVTC e uso crônico de MP, o ecocardiograma tridimensional teve uma excelente correlação com o Doppler tecidual no diagnóstico de dissincronia mecânica. A posição do eletrodo não foi preditora do segmento ativado tardiamente. O tempo de MP não se correlacionou com a presença de dissincronia e disfunção do VE. Houve uma boa correlação entre a dissincronia, remodelamento e disfunção do VE / The left ventricle (LV) dysfunction is the major reason for poor outcome in patients with congenital complete atrioventricular block (CCAVB) and pacemaker (PM). The LV mechanical dyssynchrony may play a significant role in the development of LV dysfunction in this population. As the long-term pacing is a potential risk factor for dyssynchrony, we sought to: (1) evaluate by real time three-dimensional echocardiography (RT3DE) the LV dyssynchrony and compare with Tissue Doppler (TDI) parameters; (2) verify the potential correlation between the electrode location and the latest segment activated; (3) correlate the time of pacing and LV dyssynchrony and LV remodeling. Two-dimensional (2D), TDI and RT3DE were performed in 50 patients with CCAVB and PM (mean age of 21,4 years DP 13,4). Clinical data were reviewed. Twelve (23,5%) had LV dyssynchrony by RT3DE and 14 (28%) by Tissue Doppler criteria. Sixteen (32%) and 20 (40%) had LV dysfunction by 2D and 3D, respectively. LV remodeling occurred in 50% of patients. There was an excellent correlation between RT3DE and TDI (Kappa = 0,735; p <0,001). The LV ejection fraction (LVEF) had a significant negative correlation with the dyssynchrony index by 3D (r = -0,58, p = 0,000001). The duration of the cardiac cycle measured by RR interval had a significant negative correlation with the LV dyssynchrony index by 3D (r = - 0,74, p = 0,0011). LV remodeling demonstrated by the sphericity and conic indexes had a good correlation with the presence of LV dysfunction (p = 0,005 and 0,003 respectively). The pacing time, the age at pacemaker implantation and the location of the electrode did not correlate with LV dyssynchrony. Patients bellow 18 years of age were significantly different in terms of LV dyssynchrony indexes, LV remodeling and LV volumes when compared with a control group with similar age and body surface area. In conclusion, in a cohort study of patients with CCAVB and long-term pacing, the RT3DE had an excellent correlation with TDI to evaluate LV dyssynchrony. The pacing site was not a predictor of the latest segment activation. The pacing time did not correlate with LV dyssynchrony and dysfunction. There was a correlation between the LV dyssynchrony and the presence of remodeling and dysfunction

O sistema Holter é considerado padrão ouro para detecção de arritmias cardíacas, possibilitando o seu diagnóstico e sua relação com os sintomas do paciente. As novas gerações de marcapassos (MP) detectam e registram eletrogramas intracavitários e poderiam dispensar o Holter no seguimento dos pacientes. Os diferentes MP dispõem de algoritmos de detecção de arritmias ventriculares (AV) que variam de acordo com o modelo e sua correlação diagnóstica com Holter foi pouco estudada. O objetivo desse estudo foi avaliar 1. a correlação entre o monitor de eventos dos MP e do Holter na detecção de AV e 2. a concordância das AV detectadas nos dois sistemas. Foram estudados129 pacientes portadores de MP com função de detecção de arritmias, com idade média de 68,6+19.1 anos (entre 19 e 94), 54,8% do sexo feminino. Os pacientes foram submetidos à monitorização com Holter por 72 horas. Assim que o sistema foi ligado, os contadores de eventos dos marcapassos foram reiniciados e os relógios sincronizados, para que ambos os sistemas detectassem os eventos simultaneamente. Os MP foram programados para detecção de eventos com o menor valor de frequência ventricular (FV) e o menor número de batimentos sequenciais (BT) possíveis. Depois de 72 horas, os sistemas Holter foram retirados e os registros analisados, assim como os registros simultâneos dos gravadores dos MP. Foram qualificados como eventos arrítmicos no Holter e MP, respectivamente: EV isoladas e \"PVC\"; extra-sístoles em pares e \"couplets\"; TVNS (> 3BT) e \"triplets\"(3BT), \"runs\"(3 a 8 ou > 8 BT) e \"HVR\" (3 ou 4 BT). As correlações de Spearman foram utilizadas para avaliar se o marcapasso acompanha a detecção dos parâmetros do Holter. Os coeficientes de correlação intraclasse e os respectivos intervalos com 95% de confiança, calculados para avaliar a concordâncias entre os parâmetros equivalentes do marcapasso e do Holter. Foram calculados os coeficientes Kappa para avaliar a concordância na detecção de > 10 \"PVC\"/h com > 10 EV/h. Resultados: Os monitores dos marcapassos subestimaram o Holter. Os registros de \"PVC\", \"triplet\" e \"HVR\" por TVNS apresentaram correlações positivas em relação aos parâmetros do Holter, sendo a mais alta aquela entre \"PVC\" e EV (r=0,501). Porém, a concordância entre os tipos de arritmias detectadas foi baixa (CCI < 0,5), exceção feita à concordância de \"triplet\" com TVNS de três batimentos (CCI=0.984). A concordância na detecção de mais de 10 PVC/h e mais de 10 EV/h foi moderada (kappa= 0,483), embora para os MP da Medtronic, o coeficiente de concordância foi alto (kappa=0.877). Para os MP com algoritmo de detecção de sequências de três batimentos com FV menor que 140bpm ( < 140/3), a correlação entre HVR e TVNS foi expressiva (r = 1), sendo a concordância entre esses parâmetros também bastante alta (CCI = 0,800). Conclusões: A correlação e a concordância na detecção de AV registradas nos MP e no Holter foram inconsistentes. Padronização dos algoritmos de detecção de AV, semelhantes os do sistema Holter, é necessária para que os pacientes portadores de dispositivos implantáveis possam se beneficiar dessa função para seguimento clínico e estratificação de risco / The Holter monitoring is considered the gold standard method for detection of cardiac arrhythmias, enabling its diagnosis and its correlation with the patient\'s symptoms. New generations of artificial pacemakers can detect and record intracavitary electrograms and, theoretically, could discard the Holter during the follow-up of the patients. Pacemakers have different ventricular arrhythmias (VA) detection algorithms, varying according to the model. Their diagnosis capacity comparing to Holter monitoring has been poorly studied. The aim of this study was to evaluate 1. the correlation between the event monitor of the pacemaker and the Holter in VA detection and 2. the agreement between the VA detected in both systems. We studied 129 patients with implanted pacemakers, which had arrhythmia detection function, mean age of 68.6 + 19.1 years (19 to 94), 54.8% female. The patients underwent Holter monitoring for 72 hours. Once the system was connected, event counters of pacemakers were reset and the clocks synchronized, so that both systems could detect the arrhythmic events simultaneously. The pacemakers were programmed to detect events with the lowest ventricular rate and lowest number of sequential beats allowed for each model. After 72 hours, Holter systems were removed and the records analyzed, as well as the simultaneous records of the pacemakers. Were considered as arrhythmic events: PVC isolated (in the pacemaker described as \"PVC\"); premature beats in pairs (pacemaker described as \"couplets\"); NSVT (pacemaker described as \"triplets\"- 3beats, \"runs\"- 4 to 8 or > 8 beats and \"HVR\"- 3 to 4 beats). Spearman rank correlations were used to assess whether the pacemaker and Holter identified the same parameters. The intraclass correlation coefficients and the respective intervals with 95% confidence were calculated to evaluate the concordance between the equivalent parameters of the pacemaker and Holter. Kappa coefficients were calculated to assess the agreement in the detection of > 10 PVC/h by the pacemakers and by the Holter. Results: The pacemakers underestimated the arrhythmias detection of Holter. Records of \"PVC\", \"triplet\" and \"HVR\" by NSVT showed positive correlations with the Holter parameters, and the highest one was among \"PVC\" and EV (r = 0.501). The agreement between the types of arrhythmias detected was quite low (CCI < 0.5), except for \"triplet\" detected by pacemakers and three beats NSVT by Holter (ICC = 0.984). The correlation detection for more than 10 PVC /h was moderate (kappa = 0.483), except for Medtronic pacemakers (kappa=0.877). When the pacemaker was programmed to detect sequences of three beats with heart rate lower than 140bpm ( < 140/3), the correlation between HVR and NSVT was perfect (r = 1) and the agreement between these parameters was also quite high (ICC = 0.800). Conclusions: The correlation and agreement between pacemakers and Holter monitoring in the detection of VA were not consistent. A standardization of the pacemakers\' detection algorithms is necessary before using this function for clinical follow-up and risk stratification of the 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