Work name: The analysis of the Health Rescue Service City of Prag trips for the period 2007 - 2009 Aim of work: The aim of this work is to describe and assess by graphs the analysis of the Health Rescue Service City of Prag trips in Prag for the period 2007 - 2009. Further to classify its historical progress, describe its current state including the modern equipment and also describe access of resuscitations for the same period. Method: In this work a method of data collection from avaiable literature of the Health Rescue Service City of Prag is used as well as the consultation with experienced rescue workers and people who work on the operation centre and who are processing the data and statistics of the Health Rescue Service City of Prag trips. Results: The result of this work is the graphical representation of the single trips for the urgent life - threatening events and their subsequent comparison for the period 2007 - 2009. There is also the evaluation of the success of interventions. Key words: the Health Rescue Service, the medical emergency, a rescue worker, an emergency event, a sudden cardiac arrest, the resuscitation

Sudden cardiac death (SCD) in a young person is a rare but tragic event, and the potential of prevention is unknown. The aim of this thesis is to contribute to the prevention by analysing SCD in the young in Sweden during the period 1992-1999. Data of SCD in the young based on a national registry is not previously reported. The approach is broad, covering the spectrum from epidemiology to supportive needs of families confronted with SCD. The survey methods comprised analyses of national registries, questionnaires, personal interviews, forensic-, police-, medical- and military conscription records. The SCD group selected from the database of the National Board of forensic Medicine consisted of 181 persons, 15 to 35 years old, who had suffered an SCD during 1992-1999 in Sweden, 132 men (73 %) and 49 women (27 %). The mean incidence was 0.93 per 100,000 per year. The trend showed no decrease during the surveyed years, 1992-1999. The most common diagnoses were the structurally normal heart (21 %), coronary artery disease (18 %), and dilated cardiomyopathy (12 %). In a study group of 162 individuals (19 cases of aortic aneurysm, 17 men and two women, were excluded), ECGs, symptoms and lifestyle factors were analysed and related to the autopsy findings. ECGs were available in 66 individuals (59 men and seven women) and 50 % of these were pathological. The most frequent aberrations were repolarisation abnormalities and in half of the cases with more than one ECG a development in a pathological direction was seen. In four out of ten seeking medical advice because of symptoms an ECG was taken and three of these were pathological. Possibly cardiac-related alpitations were common, but also non-specific symptoms such as fatigue after an influenza- like illness. It was not possible to link a certain sign or symptom to a specific diagnosis. In 26 (16 %) there was a family history of SCD. Physical activity and body mass index (BMI) in men were the same as in a control group, whilst women had a higher BMI and a lower level of physical activity than the controls. In coronary artery disease deaths there were a high percentage of smokers and BMI was higher than in the controls in both sexes. Competing athletes more often died during physical activity than non-athletes, but were not overrepresented in the SCD group. The majority of the athletes who died during physical activity had an underlying structural cardiac disease. Death during sleep was the most common mode of death in subjects with structurally normal heart. A lack of supportive structures in the handling of bereaved relatives were disclosed in the interviews. Most participants felt that they had been left mainly to themselves to find information and support. A common reflection from the bereaved was that there is a need of the same supportive routines in cases of a single death as in accidents where there are several casualties. The bereaved had a need of getting an explanation and a need of supportive structures. The cognitive dimension of understanding and the emotional dimension of being understood were found to be significant for the complex processes of mourning and recreating one’s life as a bereaved. In summary, SCD was uncommon in the young, but the incidence was not decreasing during the study period. The most common autopsy findings were the structurally normal heart and coronary artery disease. Symptoms preceding SCD were common but often misinterpreted. The SCD group was very similar to the normal population with regard to life style factors. In certain cardiac disorders physical activity seemed to trigger sudden death, whilst in others death during sleep was the most common mode of death. There is no single test which predicts if a person is at risk of SCD. A further cardiac evaluation in cases with pathological ECGs, and in cases with a positive family history or serious unexplained symptoms such as syncope, might permit the early identification of persons at risk of SCD. ECG is an underused tool in the investigation of symptoms, and a database with old ECGs available for comparison could be useful in the prevention of SCD. There is a need of better care of the bereaved, and based on our findings we propose the introduction of a supportive program.

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.

La majorité des morts subites correspond à un infarctus du myocarde, c'est-à-dire à une occlusion aiguë d'une artère coronaire, compliqué de trouble du rythme ventriculaire. On ne sait pas pourquoi à degré d'ischémie myocardique équivalent, à âge, sexe et statut clinique égaux, un patient développera des arythmies ventriculaires alors qu'un autre n'aura aucune complication rythmique. Dans cette étude, nous aborderons deux approches de l'étude de la mort subite. D'une part, le recueil de données biologiques et cliniques et d'autre part une approche génétique. Ainsi, il a été mis en évidence que le polymorphisme Gln27Glu du gène ADRB2 semble prédisposer les patients à l'apparition rapide de la fibrillation ventriculaire dans le cadre d'une ischémie cardiaque. Cette étude suggère également que la présence de variants dans le gène GJA1 près de résidus soumis à la méthylation pourrait être liée à la survenue de la fibrillation ventriculaire chez les patients avec infarctus du myocarde. Ces nouvelles données permettent d'améliorer les connaissances sur la mort subite à la phase aiguë de l'infarctus du myocarde et d'envisager dans le futur de nouvelles stratégies de prévention / The majority of cardiac sudden deaths correspond to a myocardial infarction, ie an acute occlusion of a coronary artery, complicated by ventricular arrhythmia. It is not known why, at equivalent degree of myocardial ischemia, at equal age, sex and clinical status, one patient will develop ventricular arrhythmias while another will have no rhythmic complication.In this study, we will discuss two approaches to the study of sudden death. On the one hand, the collection of biological and clinical data and on the other hand a genetic approach.Thus, it has been shown that the Gln27Glu polymorphism in the ADRB2 gene seems to predispose patients to the rapid onset of ventricular fibrillation in the setting of cardiac ischemia. This study also suggests that the presence of variants in the GJA1 gene near residues subjected to methylation may be related to the occurrence of ventricular fibrillation in patients with myocardial infarction.These new data help to improve knowledge on sudden death in the acute phase of myocardial infarction and to consider new prevention strategies in the future

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.

Abstract Based on experimental studies, heterogeneous ventricular repolarization has been suggested to predispose to the onset of life-threatening ventricular arrhythmias and subsequent studies in various patient populations have associated it with poor clinical outcome. The aim of this study was to assess the dynamics of ventricular repolarization from electrocardiogram (ECG) during a standard exercise stress test with techniques based on principal component analysis, and to investigate whether they would yield valuable prognostic information on cardiac mortality and sudden cardiac death. Exercise ECG recordings from 40 healthy men and women were analyzed in order to establish normal dynamics and rate-dependence for the spatial QRS/T angle and total cosine R to T (TCRT), which reflects the spatial deviation between the depolarization and repolarization wave-fronts. Subsequently, exercise ECG recordings from 20 patients with previous myocardial infarction (MI) were compared with 20 controls in order to assess the modulation of previous MI on the dynamics of TCRT. The prognostic value of abnormal dynamics and rate-dependence of TCRT and spatial QRS/T angle were assessed in 1,297 patients referred to a clinically indicated exercise stress test. The spatial QRS/T angle and TCRT were found to be significantly rate-dependent during both exercise and recovery periods as TCRT and the cosine of the spatial QRS/T angle decreased at higher heart rates (HR), indicating increase in the global heterogeneity of the ventricular repolarization. In the post-MI group, the dynamics of TCRT were impaired with a significantly lower rate-dependence in contrast to the healthy and control groups. In the study cohort, impaired rate-dependence of TCRT during both exercise and recovery periods was an independent predictor of cardiac and sudden cardiac death during the follow up of the study. Similarly, reduction of the area between the exercise and three-minute recovery TCRT/HR curves was associated with an increased risk of cardiac and sudden cardiac death. In conclusion, dynamics and rate-dependence of TCRT and spatial QRS/T angle are able to discriminate subjects with an increased risk of cardiac and sudden cardiac death. Reduced rate-dependence of TCRT during exercise and recovery periods, as well as decreased exercise-recovery hysteresis of TCRT, are significant predictors of cardiac and sudden cardiac death. / Tiivistelmä Sydämen kammioiden poikkeavan palautumisen on kokeellisissa tutkimuksissa havaittu altistavan kammioperäisille rytmihäiriöille. Lisäksi, useat tutkimukset erilaisissa potilasaineistoissa ovat osoittaneet sen olevan yhteydessä heikkoon kliiniseen ennusteeseen. Tämän työn tarkoituksena oli analysoida sydämen kammioiden repolarisaation dynamiikkaa sydänsähkökäyrästä (EKG) rasituskokeen aikana pääkomponenttianalyysiin perustuvilla menetelmillä sekä tutkia, ennustavatko uudet muuttujat sydänperäistä kuolemaa tai sydänperäistä äkkikuolemaa. Neljänkymmenen terveen miehen ja naisen rasitus-EKG:t analysoitiin depolarisaatio- ja repolarisaatioaaltojen välistä avaruudellista kulmaa kuvaavan ’total cosine R to T’:n (TCRT) sekä kolmiulotteisen QRS/T-kulman dynamiikan sekä sykeriippuvuuden normaaliarvojen määrittämiseksi. Lisäksi, vertailtiin 20 sydäninfarktin sairastaneen sekä 20 kontrollipotilaan rasitusmittauksia aiemman infarktin TCRT:n dynamiikkaan sekä sykeriippuvuuteen aiheuttaman modulaation määrittämiseksi. Muuttujien poikkeavan dynamiikan ennustearvoa testattiin 1297 rasitus-EKG-mittaukseen lähetteen saaneella potilaalla. Sekä TCRT että avaruudellisen QRS/T-kulman kosini olivat molemmat erittäin sykeriippuvaisia sekä rasituksessa että palautumisessa. Molemmat muuttujat pienenivät sykkeen (HR) kasvaessa, osoittaen kammioiden repolarisaation heterogeenisyyden kasvua korkeammilla syketaajuuksilla. Sydäninfarktin sairastaneilla potilailla muuttujien dynamiikka ja sykeriippuvuus olivat heikentyneitä. Kohorttiaineistossa heikentynyt sykeriippuvuus sekä rasituksen että palautumisen aikana ennustivat myöhempää sydänperäistä kuolemaa sekä sydänperäistä äkkikuolemaa itsenäisesti. Vastaavasti, rasituksen ja kolmen minuutin palautumisen aikaisten TCRT/HR kuvaajien väliin jäävän pinta-alan pienentyminen oli yhteydessä korkeampaan sydänperäisen kuoleman sekä sydänperäisen äkkikuoleman riskiin. Kammioiden repolarisaation dynamiikkaa kuvaavat muuttujat pystyvät erottelemaan potilaat, joilla on korkeampi riski kokea sydänperäinen kuolema tai sydänperäinen äkkikuolema. Poikkeavan alhainen sykeriippuvuus rasituksen ja palautumisen aikana sekä alentunut rasituksen ja palautumisen välinen hystereesi olivat merkittäviä sydänperäisen kuoleman sekä sydänperäisen äkkikuoleman ennustajia.

Abstract A non-ischemic etiology of sudden cardiac death (SCD), mostly due to various cardiomyopathies (CMP), accounts for about 20% of all SCDs. Most of the major studies of risk factors for SCD have focused on coronary artery disease (CAD). The aim of the present study was to clarify the characteristics of non-ischemic SCD in Northern Finland. In this study, consecutive victims of SCD (n=2661) were prospectively collected, and among whom post-mortem examinations were performed between 1998 and 2007. Information about the SCD victims was obtained from a combination of available medical records, postmortem examination reports, medication used at the time of SCD, and standardized questionnaire filled out by the closest family members of the victims of SCD. We also screened the candidate genes from a Finnish family in which fatal arrhythmias was first manifestation of a cardiac disease. The collagen content of the myocardium from histological samples in victims of SCD due to idiopathic myocardial fibrosis (IMF) was also evaluated. CAD was the most common cause of death (2082 victims, 78.2%). The prevalence of non-ischemic SCDs was 21.8% of all the SCDs. After sub-grouping the non-ischemic SCDs into various categories, the most common cause of death was CMP related to obesity (23.7%), followed by alcoholic CMP (19.0%), hypertensive CMP (15.5%) and IMF (13.6%). The association of SCD with IMF is notably frequent among victims &#60;40 years old (28.3%). The prevalence of family history of SCD was significantly higher in the victims of ischemic (34.2%) than non-ischemic SCD (13.4%, P&#60;0.001) or controls (17.6%, P&#60;0.001). Lamin A/C gene mutation R541C was found from Finnish SCD family, in which the IMF was predominant pathologic-anatomic finding. Myocardial type I collagen synthesis was increased in victims of SCD due to IMF. In conclusion, the characteristics of non-ischemic SCD in Finland differ from those reported previously. Higher prevalences of CMP-associated SCDs related to obesity, IMF and alcoholic CMP were observed as clinical and/or pathologic bases for non-ischemic SCD. The family history of SCD is not significantly increased in victims of non-ischemic SCD, suggesting a larger role of sporadic occurrence than inherited traits as the cause of non-ischemic SCD. Replacement of cardiac myocytes by fibrosis can be responsible for fatal cardiac arrhythmias in subjects with the lamin A/C gene mutation. The victims of SCD due to IMF have increased myocardial type I collagen synthesis. / Tiivistelmä Ei-iskeeminen sydänperäinen äkkikuolema aiheuttaa noin 20&#160;% kaikista sydänperäisistä äkkikuolemista. Suurin osa ei-iskeemisistä sydänperäisistä äkkikuolemista johtuu erilaisista sydänlihassairauksista, kardiomyopatioista. Useimmat sydänperäisen äkkikuoleman riskitekijöitä kartoittavista tutkimuksista ovat keskittyneet sepelvaltimotautiin. Tämän tutkimuksen tarkoituksena oli selvittää ei-iskeemisen sydänperäisen äkkikuoleman tunnuspiirteitä pohjoissuomalaisessa väestössä. Tutkimuksessa käytettiin potilasaineistona sydänperäiseen äkkikuolemaan menehtyneitä vainajia (n=2661), joille on tehty oikeuslääketieteellinen ruumiinavaus. Tiedot vainajista saatiin saatavilla olevista potilaskertomuksista, ruumiinavauspöytäkirjoista, äkkikuoleman aikaisesta lääkityksestä ja lähiomaisille lähetetystä standardisoidusta kyselylomakkeesta. Kandidaattigeenit tutkittiin pohjoissuomalaisesta perheestä, jossa ensimmäinen oire sydänsairaudesta oli hengenvaarallinen rytmihäiriö. Lisäksi sydänlihaksen kollageenikoostumus analysoitiin histologisista näytteistä potilailta, joiden sydänperäinen äkillinen kuolema johtui idiopaattisesta sydänlihaksen sidekudoskasvusta. Sepelvaltimotauti oli yleisin sydänperäisen äkkikuoleman aiheuttaja (n=2082, 78,2&#160;%). Ei-iskeemisten sydänperäisten äkkikuolemien osuus oli 21,8&#160;% (n=579) kaikista sydänperäisistä äkkikuolemista. Ei-iskeemiset sydänperäiset äkkikuolemat jaettiin alaryhmiin, joista yleisimmät olivat lihavuuteen assosioituva kardiomyopatia (23,7&#160;%), alkoholikardiomyopatia (19,0&#160;%), korkeaan verenpaineeseen assosioituva kardiomyopatia (15,5&#160;%) sekä idiopaattinen sydänlihaksen sidekudoskasvu (13,6 %), joka myös oli yleisin ei-iskeemiseen sydänperäiseen äkkikuolemaan johtava syy alle 40-vuotiailla (28,3&#160;%). Positiivinen sydänperäisen äkkikuoleman sukuhistoria oli tilastollisesti merkitsevästi yleisempää iskeemisillä (34,2&#160;%) kuin ei-iskeemisillä (13,4&#160;%) sydänperäisen äkkikuoleman uhreilla. Lamin A/C – geenin mutaatio löydettiin pohjoissuomalaisesta äkkikuolemaperheestä, jossa idiopaattinen sydänlihaksen sidekudoskasvu todettiin pääasialliseksi patologiseksi löydökseksi. Tyypin I kollageenin synteesi todettiin kohonneeksi idiopaattiseen sydänlihaksen sidekudoskasvuun menehtyneillä vainajilla. Yhteenvetona voidaan todeta, pohjoissuomalaisen väestön ei-iskeemisen sydänperäisen äkkikuoleman tunnuspiirteet eroavat aiemmin raportoiduista; lihavuuteen assosioituva kardiomyopatia, alkoholikardiomyopatia, sekä idiopaattinen sydänlihaksen sidekudoskasvu olivat aiempaa yleisempiä ei-iskeemisen äkkikuoleman aiheuttajia. Positiivinen sydänperäisen äkkikuoleman sukuhistoria ei ollut tilastollisesti merkitsevästi kohonnut ei-iskeemisen sydänperäiseen äkkikuolemaan menehtyneillä. Tämä tarkoittaa, että perinnöllinen syy ei-iskeemisen sydänperäisen äkkikuoleman aiheuttajana on luultua harvinaisempi. Lamin A/C – geenimutaation kantajilla sydänlihassolujen korvautuminen sidekudoksella todettiin hengenvaarallisen rytmihäiriön aiheuttajaksi. Lisäksi, tyypin I kollageenin synteesi todettiin kohonneeksi idiopaattiseen sydänlihaksen sidekudoskasvuun menehtyneillä vainajilla.

Introduktion: Anestesisjuksköterskor arbetar inom flera olika delar av sjukvården. Tack vare deras kunskaper om luftvägar och omhändertagande av kritiskt sjuka patienter så anställs anestesisjuksköterskor inom olika prehospitala verksamheter så som exempelvis resursenheter. Vid plötsliga hjärtstopp är upprättandet av en fri luftväg kritiskt. Detta görs vanligen genom användandet av olika medicintekniska hjälpmedel som larynxmask eller endotrachealtub. De respektive hjälpmedlen har olika styrkor och svagheter som är väl studerade, men upplevelser av att använda dessa metoder finns det lite forskning om. Syfte: Syftet med studien var att studera anestesisjuksköterskans upplevelser av att använda larynxmask och endotrachealtub vid plötsliga hjärtstopp utanför sjukhuset. Metod: En kvalitativ induktiv enkätstudie med öppna semistrukturerade frågor genomfördes för att fånga användarnas upplevelser av skillnader mellan dessa metoder av luftvägshantering. 14 anestesisjuksköterskor med minst två års erfarenhet samt erfarenhet av att arbeta prehospitalt deltog i studien. Deltagarna arbetar i tre regioner vilka har stora skillnader i resurser och arbetsrutiner. Resultat: Larynxmask var mest använt, trots att nästan alla deltagare föredrog att ha patienten intuberad. Orsaken till att laynxmasken användes trots att deltagarna föredrog att patienten skulle ha en endotrachealtub varierade något men hade flera gemensamma faktorer så som tidsåtgång och enkel användning. / Introduction: Nurse anesthesias work in different parts of healthcare. In various prehospital activities and different resource units these specialist nurses are often hired for their knowledge of the airways and critical patients. In case of sudden cardiac arrest, the establishment of a free airway is critical. This is usually done using various medical aids such as a laryngeal mask or endotracheal tube. These have their different strengths and weaknesses that are well studied, but there is little research on experiences of using these methods. Aim: The aim of the study was to study anesthesia nurses' experiences of using a laryngeal mask and endotracheal tube in sudden cardiac arrest outside the hospital. Method: A qualitative inductive survey with open semistructural questions, was done to capture the users’ experiences of the differences between these methods of airway management. This study included 14 nurse anesthetists, with at least 2 years of experience and experience of working in a prehospital setting. Participants from three regions participated, those regions differ in resources and ways of working routines. Result: The laryngeal mask is most commonly used, even though almost all participants prefer to have an intubated patient. The reasons for that varies between the participants but have several common factors such as time of application and ease of use.

In recent years, clinical studies have shown that the most effective method of treatment to reduce the incidence of sudden cardiac death in patients at increased risk of malignant arrhythmias is to provide the patient with an implantable cardioverter-defibrillator (ICD). Complications associated with the transvenous implanted system, especially lead disorders and systemic infections, and have led to the development of a so-called subcutaneous defibrillator, which is thought to minimize these complications. Despite the medical benefits of implantable defibrillator treatment, which is generally well accepted by patients, anxiety, depression, and deterioration in their quality of life have been reported in clinical trials examining patients' psychopathology and quality of life after defibrillator implantation. Methodology: The objective of the diploma thesis was to find out which group of patients better assesses the quality of life depending on the type of implanted defibrillation device (ICD and S-ICD). For the purposes of the survey, the method of quantitative research was chosen in the form of its own questionnaire survey. The questionnaire contained a total of seventeen questions in which patients evaluated quality of life in five areas. Patients who met the following criteria were included in...