Background - Regular exercise reduces the risk of cardiovascular disease and subsequent sudden cardiac death (SCD). However, a small, but notable proportion of athletes die suddenly due to inherited or congenital disorders of the heart that predispose to malignant ventricular arrhythmias. Such tragedies are highly publicised, particularly when high-profile athletes are involved. To date, limited evidence for the efficacy of cardiovascular pre-participation screening exists outside of the Italian experience. Furthermore, limited data exists examining the impact of ethnicity on cardiac adaptations to physical training. Whilst the cardiovascular benefits of exercise are well known, the impact of life-long endurance exercise is less well understood. Long term high-intensity endurance exercise is associated with changes in cardiac morphology together with electrocardiographic alterations that are believed to be physiologic in nature. Recent data however, has suggested a number of deleterious adaptive changes in cardiac structure, function and electrical activity in response to life-long endurance activity. Aims and Objectives - The aims of this PhD were; 1) To find an effective preparticipation screening method that would successfully identify pre-existing cardiovascular abnormalities, 2) To identify the prevalence of hypertrophic cardiomyopathy and Long QT syndrome in elite UK athletes; 3) To examine the impact and significance of ethnicity upon left ventricular remodelling in elite athletes, and 4) To examine the acute and chronic impact of ultra-endurance exercise across the life-span in male endurance athletes. Major Results and Conclusions – 1) Study 2 sought to confirm the efficacy of resting 12-Lead ECG ‘alongside’ personal/family history questionnaires and physical examinations as collective tools to identify diseases that have the potential of causing sudden death within a cohort of elite junior athletes (n=1074) and physically active school children (n=1646). Nine participants were identified with a positive diagnosis of a disease associated with SCD. None of those diagnosed with a disease associated with SCD were symptomatic or had a family history of note. Thus, personal symptoms and family history questionnaires alone are inadequate in the identification of individuals with diseases associated with SCD. In conclusion, resting 12-Lead ECG is paramount when screening for diseases that have the potential of causing sudden death in the young. 2) Study 3 examined 3,500 asymptomatic elite athletes (75% male) with a mean age of 20.5 ± 5.8 years with 12-lead ECG and 2-dimensional echocardiography. None had a known family history of HCM. Of the 3,500 athletes, 53 (1.5%) had LVH (mean 13.6 ± 0.9mm, range 13 to 16mm), and of these 50 had a dilated LV cavity with normal diastolic function to indicate physiological left ventricular hypertrophy. Three (0.08%) athletes with LVH had a non-dilated LV cavity and associated deep T-wave inversion that could have been consistent with HCM. However, none of the 3 athletes had any other phenotypic features of HCM on further non-invasive testing and none had first-degree relatives with features of HCM. In conclusion, the prevalence of HCM in elite athletes is significantly less than in the general population; with the demands of strenuous exercise on the cardiovascular system selecting out most individuals with HCM. Study 4 examined 2000 elite athletes in order to identify the prevalence of Long QT syndrome. Three athletes had a QTc value of >500 ms and all exhibited one of: paradoxical prolongation of QTc during exercise, a confirmatory genetic mutation, or prolonged QTc in a first-degree relative. In contrast, none of the athletes with a QTc value of <500 ms had any other features to indicate LQTS. Accordingly, the prevalence of a prolonged QTc interval in elite British athletes is 0.4%. 3) Study 6 examined 300 nationally ranked UK black male athletes (mean age 20.5 years) in comparison to 150 black and white sedentary individuals and 300 highly-trained white male athletes. Black athletes exhibited greater LV wall thickness and cavity size compared with sedentary black and white individuals. Black athletes had greater LV wall thickness compared with white athletes. A minority of black athlete’s exhibit LVH ≥15 mm; proposing that in the absence of cardiac symptoms or a family history of HCM, an LV wall thickness ≥15 mm in black athletes may represent physiologic LVH when the LV cavity is enlarged and diastolic indexes are normal. 7 black athletes (12%) with LVH displaying deep T-wave inversions in leads V1 to V4. In conclusion, in the absence of obvious pathology, these electrical anomalies in black athletes likely represent a normal spectrum of ECG changes in response to physical training. 4) Study 8 examined 17 male participants (age 33.5 ± 6.5 years, 26–40 years) using cardiac magnetic resonance (CMR) and echocardiography before and after a marathon to investigate the relationship between systolic function and diastolic function against biomarkers of cardiac damage. Results demonstrates biomarkers of myocardial cell damage following an acute bout of prolonged exercise are not associated with either systolic or diastolic functional measures, and do not seem to be associated with any detectable myocardial inflammation, oedema, or scarring using either gold standard techniques of gadolinium enhanced CMR or echocardiography respectively. The impact of multiple episodes of prolonged exercise, as experienced by highly trained veteran endurance athlete is not fully understood. 5) Study 10 examined the cardiac structure and function of 12 life-long, competitive endurance veteran athletes (> 50 yrs, mean ± SD marathons 178 ± 209 (range 20 – 650)) against 17 young male endurance athletes (<40 yrs) using echocardiography and CMR with late gadolinium enhancement (LGE) to assess myocardial fibrosis. Lifelong veteran athletes had smaller LV and RV end-diastolic and end-systolic volumes (p<0.05) but maintained LV and RV systolic function compared with young athletes. In 6 (50%) of the veteran athletes LGE of CMR indicated the presence of myocardial fibrosis; no LGE in the young athletes. The prevalence of LGE in veteran athletes was not associated with the number of competitive marathons or ultra-endurance marathons (>50 miles) completed, age, LV and RV end-diastolic volumes or LV mass (p>0.05). In conclusion, there is limited evidence at present demonstrating that cardiovascular re-modelling following lifelong endurance exercise leads to long-term disease progression, cardiovascular disability or SCD.

Whereas first line therapy for chronic obstructive pulmonary disease (COPD) usually includes a short-acting bronchodilator, there are suggestions that these agents may increase the risk of cardiac arrhythmias. In this thesis, we first assessed the risks associated with short-acting beta-agonists (SABA), long-acting beta-agonists (LABA), ipratropium bromide (IB), and methyl xanthines (MX) within a cohort of COPD patients using the health databases of Saskatchewan. In order to confirm these findings and to address some methodological issues we then replicated this analysis within a larger cohort of patients using the health databases of Quebec. / Our first study cohort consisted of 6,018 adults aged 55 and older, newly treated with bronchodilator medications. We found that new users of both IB and LABA increased the risk of arrhythmia (RR 2.39 [95% CI 1.42-4.05] and (RR 4.55 [95% CI 1.43-14.45] respectively). When the cohort was restricted by excluding subjects who had recently either been hospitalised or experienced an exacerbation, the elevated risk associated with the new use of IB persisted (RR 3.65 [95% CI 1.72-7.74]), an effect was detected with new use of MX (RR 5.17 [95% CI 1.38-19.30]), but there was insufficient power to detect an effect associated with the new use of LABA. / Due to both power issues and the limited availability of LABA within the Saskatchewan data, we replicated the analysis in a larger new-user cohort of 76,661 Quebec adults aged 67 and over. This study confirmed our earlier results, with an elevated risk of arrhythmia associated with the new use of both IB and LABA (RR 1.43 [95% CI 1.08-1.88]) and (RR 1.54 [95% CI 1.00-2.36]) respectively, as well as with new use of SABA (RR 1.28 [95% CI 1.02-1.61]). Finally, using marginal structural models, we demonstrated that both exacerbations of COPD as well as minor non-event arrhythmias were moderate time-dependent confounders within this setting. / In conclusion, we found that new use of bronchodilators in COPD, particularly IB and LABA, was associated with an increase in the risk of cardiac arrhythmias. We also demonstrated the method by which the time-dependent confounder status of specific model covariates may be evaluated.

The scientific novelty of the study A large number of reports have demonstrated that depressed heart rate variability after myocardial infarction (MI), left ventricular dysfunction and arrhythmias are powerful predictors of mortality. Nevertheless there is a lack of detailed assessment of heart rate variability in the acute period of MI, especially during the first 24 hours, from long-term (24-h) recordings, and the value of different parameters of heart rate variability in predicting dangerous complications of MI was not fully evaluated. The indications of complex and constant monitoring of heart rate variability, left ventricular function, arrhythmias in acute MI are not based on scientific studies as well as their value in predicting the effect of different methods of management, course and outcomes of critical cardiac conditions. Thus, the current study differs from all the earlier studies in that we assessed heart rate variability in the very early period of myocardial infarction (the first and the third day) using long time recordings (24 h), both – time-domain and frequency-domain –methods, and evaluated its changes in relation to arrhythmias and left ventricular function, using not only conventional 2D-echocardiography but also left ventricular long axis function assessment by M-mode and tissue Doppler imaging. The aim of the study The aim of the study was to determine the association between heart rate variability, cardiac arrhythmias and left ventricular... [to full text]

Radiofrequency catheter ablation (RFA) is a rapidly developing, minimally invasive method of treatment for heart arrhythmias. Its employment is however limited due to complications, including thromboembolic ones. The basic of seven objectives of this dissertation were to: 1. by using different agonists of aggregation, to evaluate alteration of platelet aggregation in the venous blood and platelet-rich plasma, fibrinogen and D-dimer levels before RFA, immediately after, 24 hours and 72 hours after RFA under the influence of RFA in patients suffering from heart arrhythmia; 2. to establish the influence of the total RFA energy, structural heart disease, antithrombotic medicines know in the alteration of platelet aggregation induced by different agonists and in the alteration before RFA, immediately after and 24 hours after RFA. The obtained data show that changes in PA after RFA depended on whether PA proceeded in the venous blood or plasma and on the agonist used to induce aggregation. According to the results, PA is suppressed immediately after RFA and increases in 24 hours. The level of the applied total energy had an effect on changes in platelet aggregation after RFA. The dynamics of PA in patients with and without a structural heart disease were similar. The obtained pre-RFA values of PA were lower in blood and even lower in plasma in the group of patients who used aspirin, as compared to those who used low molecular mass heparin or no antithrombotic medicines. Despite the... [to full text]

No description available.

Plusieurs maladies entraînent soit une augmentation soit une diminution du taux des acides gras (AG) et de leurs dérivés circulants, notamment les acyl-carnitines (AC). Ce changement a été soupçonné comme étant la cause de importants dérangements électriques. Nous avons montré que les AC à chaine longue (LCAC) du côté extracellulaire modulent le canal hERG de façon spécifique, modulant sa amplitude de courant et sa cinétique. Aucun AC testé n’a eu d’effet en intracellulaire. La CAR et les MCAC n’ont eu aucun effet. Les AC ne modulent pas les courants IKS et IK1. Le canal Cav1.2 est modulé par C16-CAR et le C16 dans la lignée HEK293-ICaL et dans des cardiomyocytes de rat. En condition physiologique il existe donc un lien strict entre le métabolisme énergétique et activité électrique cardiaque qui entraine une modulation permanente du canal hERG par les LCAC. La régulation par les LCAC du canal hERG et peut être celle du canal ICaL, pourraient participer au dérangement électrique à l’origine du déclenchement de troubles du rythme cardiaque retrouvé dans certaines maladies. / Several diseases can cause either an increase or a decrease in the rate of fatty acids (FAs) and their derivatives circulating, including acyl-carnitines (AC). This change is suspected as being the cause of major cardiac electrical perturbations. We have shown that long-chain AC (LCAC) modulate specifically by the extracellular side the hERG channel, regulating its current amplitude and kinetics. All AC tested had no effect when applied intracellularly. Carnitine and medium chain AC had no effect on hERG. LCAC does not modulate IK1 and IKS. Cav1.2 channel is modulated by C16 and C16-CAR in line HEK293-ICaL and rat cardiomyocytes. In physiological conditions there exists a strict link between energy metabolism and cardiac electrical activity which causes a permanent modulation of hERG channel by the LCAC. Regulation by the LCAC of the hERG channel and maybe ICaL, could participate in the electrical disturbance causing the onset of cardiac arrhythmia found in certain diseases.

Introdução: Dos mecanismos fisiopatológicos à estratificação de risco e manejo, ainda persistem hoje muitas lacunas e debates sobre a miocardiopatia não compactada (MNC). Recentemente, a ressonância magnética cardiovascular (RMC) vem sendo amplamente utilizada para aumentar a precisão do diagnóstico de MNC em pacientes com alta probabilidade clínica pré-teste, com valor prognóstico e alta relevância na tomada de decisões clínicas. Objetivo: Este estudo teve como objetivo caracterizar o mapeamento T1 e o volume extracelular (VEC) miocárdico por RMC em pacientes com MNC e investigar como esses marcadores teciduais relacionam-se com a fração de ejeção do ventrículo esquerdo (FEVE) e arritmias ventriculares (AV). Métodos: Foram recrutados prospectivamente 36 pacientes com MNC e 18 controles saudáveis para realizarem uma RMC com mapeamento T1 entre julho de 2013 e setembro de 2016. O VEC foi avaliado apenas para os segmentos do ventrículo esquerdo sem áreas de fibrose macroscópica pela técnica do realce tardio (RT), objetivando-se investigar a presença de fibrose miocárdica intersticial difusa. Para avaliar as diferenças entre os parâmetros de RMC nos pacientes e controles, foram usados o teste t entre as amostras pareadas (Wilcoxon) e um modelo de regressão linear foi construído para investigar a relação entre a FEVE e os achados clínicos e de imagem (inclusive o VEC). Resultados: Os pacientes com MNC apresentaram maiores valores de T1 nativo (1.024 ± 43ms versus 995 ± 22ms, p = 0,01) e VEC (28,0 ± 4,5% vs. 23,5 ± 2,2%, p < 0,001) em relação aos controles. Apenas o VEC foi associado independentemente com a FEVE (beta = -1,3, p = 0,003) na regressão multivariada. Houve uma interessante tendência para a terapia betabloqueadora modificar positivamente a relação entre ECV e LVEF (beta = 4,1, intervalo de confiança de 95%, -0,6 a 8,8), porém com p alto (0,08). Além disso, entre pacientes com MNC e RT ausente (negativo), AV foram associadas com maior VEC (27,7% em pacientes com AV vs 25,8% em pacientes sem AV, p = 0,002). Conclusão: Nos pacientes com MNC, a caracterização tecidual miocárdica por mapeamento T1 sugere uma expansão extracelular por fibrose intersticial difusa no miocardio sem fibrose focal pelo RT, o que foi associada à disfunção ventricular e AV. Tais achados podem dar suporte a um potencial valor do mapeamento T1 no refino da estratificação de risco de pacientes com MNC / Background: From pathophysiological mechanisms to risk stratification and management, much debate and discussion persist regarding non-compaction cardiomyopathy (NCC). Recently, cardiovascular magnetic resonance (CMR) imaging has been widely used to more accurately diagnose NCC in patients with high clinical pre-test probability, with prognostic value and high relevance in the clinical decision making process. Purpose: This study aimed to characterize myocardial T1 mapping and extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR), as well as investigate how these tissue markers relate to left ventricular ejection fraction (LVEF) and ventricular arrhythmias (VA) in patients with NCC. Methods: We prospectively recruited 36 patients with NCC and 18 controls to perform a cardiovascular magnetic resonance (CMR) with T1 mapping between July 2013 and September 2016. ECV was quantified in LV segments without late gadolinium enhancement (LGE) areas to investigate diffuse myocardial fibrosis. Differences in CMR parameters between patients and controls were assessed using t-test or Wilcoxon rank-sum test, and a linear regression model was built for LVEF to test the association with ECV and clinical characteristics. Results: Patients with NCC had higher native T1 (1024±43ms vs. 995±22ms, p=0.01) and expanded ECV (28.0±4.5% vs. 23.5±2.2%, p < 0.001) compared to controls. ECV was independently associated with LVEF (beta=-1.3, p=0.003). There was a trend for beta-blocker therapy to modify the relationship between ECV and LVEF (beta=4.1, 95% confidence interval, 0.6 to 8.8, p=0.08). Moreover, among patients without LGE, VA were associated with higher ECV (27.7% with VA vs 25.8% without VA, p=0.002). Conclusion: In NCC patients, tissue characterization by T1 mapping suggests an extracellular expansion by diffuse fibrosis in myocardium without LGE, which was associated with myocardial dysfunction and VA. These findings lend support to the potential role of T1 mapping in refining NCC risk stratification

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The geraniol (C10H18O) is an acyclic monoterpene alcohol, present in the essential oil of some medicinal plants, herbs and citrus fruits, especially species of the genus Cymbopogon. Were described biochemical and pharmacological properties such as anticonvulsant action, analgesic, antinflammatory, antioxidant, anticancer and antimicrobial activities. In this study we sought to characterize the effects produced by geraniol on contractility, electrical activity and its possible antiarrhythmic potential in mammalian heart. For this, we used guinea-pig (Cavia porcellus) and mice (Mus musculus) of C57Bl/6J strain. The contractile studies were performed in the left atria drawn 1GF and stimulated with pulses of suprathreshold current, maintained in Cuba for isolated organ submerged in modified Tyrode solution (8 mL) and aerated with carbogenic mixture (95% O2 and 5% CO2). The force of atrial contraction was recorded by an isometric transducer. Electrocardiographic recordings were performed on isolated heart under constant aortic perfusion flow (8 mL/min) in a Langendorff system. To study the effects of geraniol on current membrane, experiments were performed using the technique of patch-clamp in rat ventricular cardiomyocytes setup whole-cell. In the atrium, geraniol reduced the force of contraction (~ 98%, EC50 = 1510 ± 160 M) whereas nifedipine, used as positive control, showed a EC50 of 0.90 ± 0.66 M. Geraniol, at 3 mM, decreased the positive inotropism of both CaCl2 and BAY K8644. In ventricular cardiomyocytes, the ICa,L was reduced by 50.7% (n = 5, p < 0.0001) after perfusion with 300 M of geraniol. Furthermore, geraniol prolonged the action potential duration (APD) measured at 50% of repolarization (49.7%, n = 5, p < 0.05), without changing the resting potential. The increase in APD can be attributed to blockade of K+ channel transient outward (Ito) (59.7%, n = 4, p < 0.001), the K+ current non-inactivated (Iss) (39.2 %, n = 4, p < 0.05) and K+ current to inward rectifier (Ik1) (33.7%, n = 4, p < 0.0001). In isolated heart, geraniol increased PRi and QTi without affecting the QRS (n = 6) complex, and reduced both left ventricular pressure (83%) and heart rate (16.5%). Furthermore, geraniol delayed time for the start of ouabain-induced arrhythmias in 128%, preventing in 30% the increase of diastolic tension, however, without affect the positive inotropic effect induced by ouabain (n = 6). Geraniol exerts negative inotropic and chronotropic responses in the mammalian heart by decreasing the L-type Ca2+ current and prolongs the duration of ventricular action potential by reducing potassium currents voltage-dependent. Such effects may be responsible for the antiarrhythmic effect of geraniol front the arrhythmias induced by ouabain in vitro. / O geraniol (C10H18O) é um monoterpeno alcoólico acíclico, presente no óleo essencial de algumas plantas medicinais, frutas cítricas e ervas aromáticas, principalmente espécies do gênero Cymbopogon. São descritas propriedades bioquímicas e farmacológicas, tais como ação anticonvulsivante, analgésica, anti-inflamatória, antioxidante, anticancerígena e antimicrobiana. Neste trabalho buscou-se caracterizar os efeitos produzidos pelo geraniol sobre a contratilidade, atividade elétrica e seu possível potencial antiarrítmico em coração de mamífero. Para tanto, foram utilizados cobaia (Cavia porcellus) e camundongos (Mus musculus) da linhagem C57Bl/6J. Os estudos contráteis foram realizados em átrio esquerdo estirado a 1gf e estimulados com pulsos de corrente supralimiares, mantido em cuba para órgão isolado, submerso em solução de Tyrode modificada (8 mL) e aerado com mistura carbogênica (95 % O2 e 5 % CO2). A força de contração atrial foi captada por um transdutor isométrico. Os registros eletrocardiográficos foram realizados em coração isolado, sob perfusão aórtica de fluxo constante (8 mL/min), em sistema de Langendorff. Para estudar os efeitos do geraniol sobre as correntes de membrana, foram executados experimentos através da técnica de patch-clamp , na configuração whole-cell , em cardiomiócitos ventriculares de camundongo. No átrio, o geraniol reduziu a força de contração (~ 98%, EC50 = 1510 ± 160 M) enquanto que a nifedipina, usada como controle positivo, apresentou uma EC50 de 0,90 ± 0,66 M. O geraniol, na concentração de 3 mM, diminuiu o inotropismo positivo de ambos CaCl2 e BAY K8644. Em cardiomiócito ventricular, a ICa,L foi reduzida em 50,7% (n = 5, p < 0,0001), após a perfusão com 300 μM de geraniol. Além disso, o geraniol prolongou a duração do potencial de ação (DPA), medida a 50 % da repolarização (49,7%, n = 5, p < 0,05), sem alterar o potencial de repouso. O aumento da DPA pode ser atribuído ao bloqueio dos canais para K+ transient-outward (Ito) (59,7 %, n = 4, p < 0,001), canal de K+ não-inativado (Iss) (39,2 %, n = 4, p < 0,05) e do canal para K+ inward rectifier (IK1) (33,7% , n = 4, p < 0,0001). Em coração isolado (n = 6), o geraniol aumentou o PRi e QTi sem afetar a duração do complexo QRS, reduzindo a pressão ventricular esquerda (83%) e a frequência cardíaca (16,5%). Além disso, o geraniol retardou o tempo para o início das arritmias induzidas por ouabaína em 128%, evitando em 30% o aumento da tensão diastólica sem, contudo, afetar o efeito inotrópico positivo da ouabaína (n = 6). O geraniol exerce respostas inotrópicas e cronotrópicas negativas no coração de mamífero, por meio da diminuição das correntes para Ca2+ tipo-L e, prolonga a duração do potencial de ação ventricular por reduzir as correntes para K+ dependentes de voltagem. Tais efeitos podem ser responsáveis pelo efeito antiarrítmico do geraniol frente às arritmias induzidas por ouabaína in vitro .

INTRODUÇÃO: pacientes com doença renal crônica em diálise apresentam elevada mortalidade anual, principalmente decorrente de eventos cardiovasculares, com destaque para morte súbita cardíaca (MSC). Os eventos arrítmicos (EA) são considerados os principais responsáveis pela MSC, tornando relevante a sua avaliação. Dispositivos cardíacos modernos como o looper implantável, que tem capacidade de monitorar o ritmo cardíaco por longo período de tempo e diagnosticar EA, podem contribuir na estratificação de risco desta população. OBJETIVOS: avaliar a taxa de ocorrência dos EA em candidatos a transplante renal com looper implantável e identificar fatores associados; determinar a significância prognóstica dos EA na MSC e mortalidade total; avaliar eficiência diagnóstica do looper e o papel da diálise. MÉTODOS: estudo clínico observacional, prospectivo e aberto que incluiu cem candidatos a transplante renal, em hemodiálise e com alto risco para transplante (idade >=50 anos, DM ou doença cardiovascular). Entre junho/2009 e janeiro/2010, os pacientes foram submetidos ao implante do looper para detecção dos EA e seguimento clínico de um ano. A idade média do grupo foi 59 anos; 65% homens; 97% hipertensos, 70% diabéticos, 34% com infarto prévio e tempo médio de 53,8 meses em hemodiálise. O diagnóstico dos EA seguiu protocolo específico e foram descritos todos os eventos clínicos fatais e não fatais. A estatística incluiu: análise descritiva dos EA, associação destes com variáveis exploratórias pelos testes de qui-quadrado, exato de Fischer, t-Student, Mann-Whitney e regressão logística stepwise selection para análise multivariada (p<0,05). RESULTADOS: foram diagnosticados 5075 EA em 98 pacientes em seguimento médio de 425 dias. A taxa de ocorrência dos EA na casuística foi: bradiarritmias (25%), arritmias supraventriculares (94%) e arritmias ventriculares (79%). Os EA mais comuns foram: taquicardia sinusal (39%) e atrial não sustentada (27%), extrassístoles ventriculares e atriais isoladas (16% e 5,4%) e taquicardia ventricular não sustentada (TVNS - 5,3%). Foram preditores para ocorrência dos EA: duração intervalo PR (p=0,0008; OR=1,05; IC-95%=1,02-1,08) e QT longo (p=0,002; OR=7,28; IC- 95%=2,01-26,35) para bradiarritmias; duração intervalo QTc (p=0,022; OR=1,02; IC-95%=1,01-1,04) e presença de insuficiência cardíaca (p=0,034; OR=9,87; IC- 95%=1,17-82,79) para arritmias ventriculares e dilatação ventricular esquerda (p=0,041; OR=2,83; IC-95%=1,01-7,96) para TVNS. Ocorreram 35 eventos clínicos não fatais, 14 transplantes renais e 18 óbitos. Dentre os óbitos, 38,9% foram cardiovasculares súbitos: quatro arritmogênicos, um IAM e dois indeterminados. Não houve associação entre EA e eventos fatais; fibrilação atrial e bradiarritmias tiveram associação significativa com eventos não fatais. O mecanismo de morte (arritmogênico) foi elucidado pelo looper em quatro pacientes com MSC; um paciente apresentou bloqueio atrioventricular e necessitou de marca-passo. A taxa de EA foi superior no período intradiálise em comparação ao interdiálise (p<0,001). CONCLUSÕES: neste estudo, que avaliou a monitorização cardíaca prolongada com looper implantável em candidatos a transplante renal, a taxa de ocorrência de EA foi elevada; foram preditores dos EA: a duração intervalo PR e presença de QT longo para bradiarritmias, duração intervalo QTc e insuficiência cardíaca para arritmias ventriculares e dilatação ventricular para TVNS; a taxa de mortalidade foi elevada, com importante contribuição da MSC; não houve associação entre EA e mortalidade total ou súbita; houve associação entre as bradiarritmias e a fibrilação atrial com a ocorrência de eventos não fatais; os EA foram mais frequentes no período intradiálise; o looper implantável foi eficiente na elucidação diagnóstica, com poucas complicações. / INTRODUCTION: chronic kidney disease patients undergoing dialysis have a high annual mortality rate, mainly due to cardiovascular disease. Sudden cardiac death (SCD), attributed to arrhythmic mechanisms, is considered the major cause of these high death rates. The implantable loop recorder (ILR), a modern cardiac device has the ability for long-term cardiac rhythm monitoring and diagnosing arrhythmic events (AE), which in fact may contribute to the risk stratification of this population. OBJECTIVES: this study was designed to evaluate the incidence and predictors of AE in renal transplant candidates with ILR; to determine the prognostic significance of AE in SCD and all-cause mortality, evaluate the diagnostic effectiveness of ILR and the role of dialysis. METHODS: a prospective, open, observational clinical study was conducted, including one hundred renal transplant candidates undergoing hemodialysis, at high risk for transplantation (age >=50 years, diabetes or cardiovascular disease). Between June/2009 and January/2010, patients received an ILR for detection of AE with a one-year follow-up. Mean age of the group was 59 years; 65% were men; 97% hypertensive, 70% diabetic, 34% had previous myocardial infarction and mean hemodialysis time was 53.8 months. The diagnosis of AE followed specific protocol and all fatal and non-fatal clinical events were described. The statistical analysis included: descriptive analysis of AE, an association between these events and exploratory variables by chi-square tests, Fisher exact test, Student\'s t test, Mann-Whitney test and logistic regression using stepwise selection for multivariate analysis (p<0.05). RESULTS: during mean follow-up of 425 days, 5075 AE were diagnosed by ILR in 98 patients. The rate of occurrence of EA in this patients was: bradyarrhythmias (25%), supraventricular arrhythmias (94%) and ventricular arrhythmias (79%). The most common AE were: sinus tachycardia (39%), nonsustained atrial tachycardia (27%), isolated premature ventricular beats (16%), isolated premature atrial beats (5.4%) and nonsustained ventricular tachycardia (NSVT - 5.3%). Predictors for the occurrence of AE were: duration of PR interval (p=0.0008; OR=1.05; 95%CI=1.02-1.08) and long QT (p=0.002; OR=7.28; 95%CI=2.01-26.35) for bradyarrhythmia; duration of QTc interval (p=0.022; OR=1.02; 95%CI=1.01-1.04) and presence of heart failure (p=0.034; OR=9.87; 95%CI=1.17-82.79) for ventricular arrhythmia and left ventricular dilatation (p=0.041; OR=2.83; 95%CI=1.01-7.96) for NSVT. There were 35 non-fatal clinical events, 14 renal transplantations and 18 deaths during follow-up. Regarding causes of death, 38.9% were due to sudden cardiovascular event: four were arrhythmogenic, one resulted from acute myocardial infarction and two were indeterminate. There was no association between AE and all cause or sudden mortality; bradyarrhythmias and atrial fibrillation were associated with the occurrence of non-fatal clinical events. The mechanism of death (arrhythmogenic) was elucidated by ILR in four patients with SCD; one patient had atrioventricular block and required pacemaker insertion. The rate of AE was higher in the intradyalitic period compared to interdialytic (p <0.001). CONCLUSIONS: in this study, which evaluate long-term cardiac rhythm monitoring with ILR in renal transplant candidates, the incidence of AE was high; predictors for the occurrence of AE were: duration of PR interval and presence of long QT for bradyarrhythmia, duration of QTc interval and heart failure for ventricular arrhythmia and left ventricular dilatation for NSVT; mortality rate was high and SCD made an important contribution. There was no association between AE and all-cause mortality and SCD; bradyarrhythmias and atrial fibrillation were associated with non-fatal events; the EA rate was higher at intradialytic period; the ILR was efficient in elucidating diagnoses and had few complications.

Abstract The incidence of sudden cardiac death (SCDs) in the western countries is 50 – 100 in a population of 100,000. The most common disease causing SCDs is coronary heart disease. A large proportion of the victims are unaware of the underlying cardiac disease or only mildly symptomatic. Many SCDs could be prevented with therapies targeted to the underlying cardiac disease and with implantable cardioverter defibrillators. However, current protocols identify only patients at highest risk and only a minority of SCDs occur in this group. Thus, markers for identifying subjects at risk for SCD are needed. The aim of this thesis was to study the roles of abnormalities in the electrocardiogram (ECG), obesity, and diabetes in SCD risk stratification. The prevalence and prognostic significance of the location of QRS transition zone (the chest lead in the ECG in which R wave amplitude ≥ S wave amplitude) and abnormal P terminal force in lead V1 of the ECG were assessed. In addition, the value of ECG abnormalities in SCD risk stratification in subjects with different relative weights were studied. These topics were assessed in a cohort of 10,000 middle-aged Finnish subjects followed over 30 years from national registers. Delayed QRS transition (occurring at V4 or leftwards) occurred in 16.4% of subjects and a markedly delayed QRS transition (at V5 or leftwards) occurred in 1.3% of subjects. Delayed QRS transition was associated with an increased risk of death and SCD and the risk of SCD was over 1.5-fold among those with markedly delayed QRS transition. An abnormal PTF (≥ 0.04mm∙s) was present in 4.8% of subjects and a markedly abnormal PTF (≥ 0.06mm∙s) in 1.2% of subjects. A markedly abnormal PTF was associated with an almost 2-fold risk of death and atrial fibrillation, but it did not predict SCDs. Both obesity and diabetes were associated with an increased risk of SCD, but the proportion of SCDs of all cardiac deaths did not increase in subjects with either of these conditions. ECG abnormalities provided most value in SCD risk stratification among normal weight subjects with a low level of risk factors. Overall, these studies provide information on the predictive value of some ECG risk markers and cardiovascular risk factors. However, the definite role of these risk markers in predicting the risk of SCD in general population at an individual level remains indecisive. / Tiivistelmä Sydänperäisten äkkikuolemien ilmaantuvuus länsimaissa on 50 – 100 tapausta 100000 ihmisen väestössä vuodessa. Suurin osa näistä kuolemista kohdistuu henkilöihin, joilla ei ole todettu sydänsairautta tai jotka ovat vähäoireisia. Yleisin sydänperäisen äkkikuoleman taustasairaus on sepelvaltimotauti. Näitä kuolemia voidaan ehkäistä sydänsairauksien hoidolla ja rytmihäiriötahdistimilla, mutta vain suurimman riskin potilaat tunnistetaan nykymenetelmin. Toimivia riskimarkkereita tarvitaan, jotta lisää potilaita saataisiin prevention piiriin. Tämän tutkimuksen tavoite oli tutkia 12-kytkentäisestä EKG:sta määritettävien QRS-transitioalueen (rintakytkentä, jossa R-aallon amplitudi ≥ S-aallon amplitudi) ja poikkeavan P terminal forcen (PTF) yleisyyttä ja yhteyttä sydänperäisiin äkkikuolemiin. Lisäksi tavoitteena oli tutkia lihavuuden ja diabeteksen vaikutusta sydänperäisen äkkikuoleman riskiin ja EKG-muutosten ennustearvoa eri painoisilla henkilöillä sydänperäisen äkkikuoleman riskiarviossa. Tutkimusaineistona käytettiin yli 10000:n keski-ikäisen suomalaisen väestökohorttia, jota seurattiin kansallisista rekistereistä. QRS-transitio tapahtui myöhään (V4:ssä tai siitä vasemmalle) 16.4 %:lla tutkituista ja huomattavan myöhään (V5:ssä tai siitä vasemmalle) 1.3 %:lla tutkituista. Myöhäinen QRS-transitio liittyi kuoleman ja sydänperäisen äkkikuoleman riskiin. Sydänperäisen äkkikuoleman riski oli yli 1.5-kertainen henkilöillä, joilla oli huomattavan myöhäinen QRS-transitio. Poikkeava PTF (≥ 0.04 mm∙s) todettiin 4.8 %:lla väestöstä ja huomattavan poikkeava PTF (≥ 0.06 mm∙s) 1.2 %:lla väestöstä. Huomattavan poikkeavaan PTF:en liittyi lähes kaksinkertainen kuoleman ja eteisvärinän riski, mutta ei äkkikuolemariskiä. Lihavuuteen ja diabetekseen liittyi kohonnut sydänperäisen äkkikuoleman riski. Toisaalta lihavilla ja diabeetikoilla myös ei-äkillisten sydänkuolemien riski oli suurentunut, eikä äkillisten kuolemien osuus sydänkuolemista korostunut. Sydänperäisen äkkikuoleman riskiin liitetyt EKG-muutokset paransivat riskiarviota eniten normaalipainoisilla henkilöillä, joilla oli vähemmän sydän- ja verisuonitautien riskitekijöitä. Kokonaisuutena nämä tutkimukset luovat uutta tietoa EKG-riskimarkkereista, lihavuudesta ja diabeteksesta sydänperäisen äkkikuoleman riskiarviossa. Näiden biomarkkereiden lopullinen rooli yksilötasolla perusväestössä vaatii kuitenkin vielä lisätutkimuksia.