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An accumulation of sudden unexpected cardiac deaths (SUCD) occurred in young Swedish orienteers, most of whom were elite athletes. From 1979 to 1992 the incidence in 18 to 34 year old male elite orienteers ranked on the national level the same year as death was calculated to 30 (per 100,000), which represents a 20 to 40 fold increase from the expected rate. From 1989 to 1992, the incidence was 50. There were, however, no indications on any similar clusters of SUCD in other sports. A special program to alter behaviour in orienteers was implemented in 1992-1993, after which there have been no more cases of SUCD in orienteers below 35 years of age. A histopathological re-evaluation of 16 cases of SUCD revealed myocarditis in 75% of these cases. In parallel, four of those cases also had changes mimicing arrhythmogenic right ventricular cardiomyopathy (ARVC). The combination of an increased incidence and myocarditis suggested that infection may be a pathogenetic factor. A broad search for different microorganisms in archival sera from five cases and tissues from the autopsies in two of those cases revealed the only common finding that all had antibodies to Chlamydia pneumoniae. DNA from C. pneumoniae was detected in the lung and heart in one of two cases. The intimate contact with nature of orienteers suggested possible zoonotic/vectorborne pathogens. Bartonella is such a pathogen and known to cross-react with C. pneumoniae. The use of PCR to test for DNA from the gltA gene of Bartonella in the two formerly mentioned cases of SUCD, and in three additional cases, gave positive bands from the hearts in four cases and the lung in a fifth case. The PCR products were sequenced and found to be identical to B. henselae in three cases and almost identical to B. quintana in the remaining two cases. Four of the five cases had antibodies to Bartonella when using micro immunofluorescence test with the antigens B. henselae, B. quintana, and B. elizabethae. The total prevalence of antibodies to Bartonella was 31% in 1,136 elite orienteers vs. 6.8% in 322 healthy blood donors (p<0.001), suggesting widespread exposure in the elite. It is hypothesized that subacute or reactivated Bartonella infection has a pathogenetic role in SUCD in orienteers, and may be involved in the development of ARVC-like disease.

Electrical restitution has been shown to inaccurately predict the occurrence of alternans of action potential duration. A new method using the spatial gradient of alternans (SGA) is proposed to predict alternans and cardiac electrical stability. A simulated 1-D strand of tissue was used to compare indexes computed from restitution methods and the SGA method to changes in the amplitude of alternans using different electro-physiological alterations. The SGA method correlated better with changes in the amplitude of alternans than restitution methods for a decrease in the transient outward current (Ito) and conduction velocity. Restitution methods correlated better with changes in the amplitude of alternans than the SGA method when the inward rectifier potassium current (Ik1) and the delayed rectifier potassium current (Ikr) were decreased. Restitution methods and the SGA method correlated well with changes in the amplitude of alternans when the L-type calcium channel current (ICaL) was altered and when Ikr, Ik1, and the sodium/calcium exchange current (INaCa) were increased. The SGA method includes the effect of conduction in tissue and reveals other features that provide advantages in predicting stability over currently used restitution methods.

Bakgrund: År 2016 drabbades 7 934 personer i Sverige av plötsligt hjärtstopp där någon slags behandling påbörjats. På grund av ökade kunskaper kring plötsligt hjärtstopp ökar antalet överlevare. Plötsligt hjärtstopp kan upplevas som en traumatisk kris och kan påverka personens liv. Detta medför ett behov av att förbättra kunskapen och förståelsen för hur personer upplever livet efter plötsligt hjärtstopp. Syfte: Att beskriva personers upplevelser av livet efter plötsligt hjärtstopp. Metod: Litteraturöversikt där nio artiklar med kvalitativ ansats analyserats induktivt. Resultat: Tre teman identifierades. Existentiellt kaos med subteman; Varför jag? och Närheten till döden. Tillbaka till tryggheten med subteman; Behov av närhet och Behov av information. Ett nytt liv med subteman; Livet förändras och Livet omprioriteras. Personerna som drabbats av hjärtstopp hade behov av att fylla i minnesluckor, försöka förstå vad som hade hänt samt finna en mening med händelsen. Slutsats: Resultatet visade att personer som genomgått plötsligt hjärtstopp upplevde att det nya livet innebar fysiska, kognitiva och emotionella svårigheter. Att lära sig leva igen innebar omprioriteringar i livet.

Abstract There is substantial evidence on the associations between cold ambient temperature and adverse health effects. Less is known about the role of prolonged episodes of cold weather denoted as cold spells. This study assessed relations between cold spells and adverse health effects globally, and quantified and elaborated the associations between cold spells and sudden cardiac death (SCD) in northern Finland. Based on random-effects models in the meta-analyses of evidence from 9 studies around the world, cold spells were associated with increased mortality rates from all or all non-accidental causes (RR 1.10; 95% CI: 1.04–1.17), cardiovascular diseases (RR 1.11; 95% CI: 1.03–1.19), and respiratory diseases (RR 1.21; 95% CI: 0.97–1.51). Suggestive evidence of other health effects was identified. Investigating 51-years of coordinate-specific weather data at the home coordinates of autopsy-verified cases of SCD, conditional logistic regression in a case-crossover setting produced an estimate for the association between cold spells and the risk of SCD (OR 1.33; 95% CI: 1.00–1.78). A greater number of cold days preceding death increased the risk of SCD approximately 19% per day (OR 1.19; 95% CI: 1.07–1.32). The association between season-specific cold spells and SCD was strongest during autumn and winter, and lowest during spring and summer. The association was stronger for ischemic (OR 1.55; 95% CI: 1.12–2.13) than for non-ischemic SCD (OR 0.68; 95% CI: 0.32–1.45) (Q-statistic 3.85, p 0.05), confirmed by the autopsy finding. Among cases suffering ischemic SCD, the association seemed stronger in those without a prior diagnosis of ischemic heart disease than in those diagnosed during lifetime. The association seemed stronger with severe coronary stenosis (OR 1.60; 95% CI: 1.11–2.30), and weaker with moderate stenosis (OR 0.97; 95% CI: 0.37–2.55). The use of aspirin, β-blockers, and nitrates seemed to decrease the risk of ischemic SCD during cold spells. In conclusion, cold spells increased the risk of ischemic SCD, and patients without appropriate diagnosis and medications for ischemic heart disease seemed most susceptible. The results indicate that coronary stenosis plays a central role in the cold-related pathogenesis of SCD. Timely diagnosis and treatment of ischemic heart disease might reduce weather-related SCDs in a community. / Tiivistelmä Kylmän lämpötilan ja terveyshaittojen välisistä yhteyksistä on vahva tutkimusnäyttö. Vähemmän tiedetään pitkittyneiden kylmäjaksojen ja terveyshaittojen välisistä yhteyksistä. Tutkimuksessa arvioitiin kylmäjaksojen ja terveyshaittojen välisiä yhteyksiä globaalisti, ja määritettiin kylmäjaksojen ja sydänperäisen äkkikuoleman (SÄK) välisiä yhteyksiä Pohjois-Suomessa. Yhdeksän eri puolella maailmaa toteutetun tutkimuksen tulosten meta-analyysissa satunnaisvaikutusten malli osoitti yhteyden kylmäjaksojen ja kaikkien tai luonnollisien syiden (RR 1.10; 95% CI: 1.04–1.17), sydän- ja verisuonisairauksien (RR 1.11; 95% CI: 1.03–1.19), ja hengityselimistön sairauksien (RR 1.21; 95% CI: 0.97–1.51) kuolleisuuden välillä. Viitteellistä näyttöä havaittiin muista terveyshaitoista. Tutkittaessa 51-vuoden koordinaattikohtaista säätä case-crossover-asetelmassa oikeuslääketieteellisesti vahvistettujen SÄK-tapausten kotiosoitteissa, ehdollisen logistisen regression mukaan SÄK:n riski oli yhteydessä kuolemaa edeltävään kylmäjaksoon (OR 1.33; 95% CI: 1.00–1.78). Lisääntyvä kylmien päivien lukumäärä ennen kuolemaa lisäsi riskiä keskimäärin 19% päivää kohden (OR 1.19; 95% CI: 1.07–1.32). Yhteys kausikohtaisten kylmäjaksojen ja SÄK:n välillä oli vahvin syksyllä ja talvella, ja heikoin keväällä ja kesällä. Yhteys oli vahvempi kylmäjaksojen ja iskeemisen SÄK:n (OR 1.55; 95% CI: 1.12–2.13) kuin kylmäjaksojen ja ei-iskeemisen SÄK:n (OR 0.68; 95% CI: 0.32–1.45) välillä (Q-statistic 3.85, p 0.05). Iskeemisen SÄK:n kokeneilla yhteys vaikutti vahvemmalta tapauksilla joilla ei ollut aiempaa iskeemisen sydänsairauden diagnoosia, kuin tapauksilla jotka oli diagnosoitu elinaikana. Yhteys vaikutti vahvemmalta vaikea-asteisesta sepelvaltimostenoosia sairastavilla (OR 1.60; 95% CI: 1.11–2.30), kuin lievempi-asteisessa stenoosissa (OR 0.97; 95% CI: 0.37–2.55). Aspiriini, β-salpaajat, ja nitraatit vaikuttivat vähentävän iskeemisen SÄK:n riskiä kylmäjakson aikana. Yhteenvetona, kylmäjaksot lisäsivät iskeemisen SÄK:n riskiä, ja potilaat vailla iskeemisen sydänsairauden diagnoosia ja lääkityksiä vaikuttivat olevan alttiimpia kylmäjaksojen haittavaikutuksille. Tulokset viittaavat sepelvaltimostenoosin keskeiseen rooliin kylmään liittyvän SÄK:n patogeneesissä. Varhainen iskeemisen sydänsairauden diagnoosi ja siihen liittyvä sydäntä suojaava lääkitys voisivat vähentää säähän liittyviä SÄK:a.

Bakgrund: Ett hjärtstopp är ett ytterst allvarligt tillstånd som påverkar inte bara patienten själv utan hela familjen, speciellt en nära anhörig. Patienten svävar mellan liv och död, och om patienten överlever är det ofta med mer eller mindre bestående men. Vid patientens sida finns de anhöriga som vill vara nära, hjälpa och stöda sin närstående samtidigt som det också kan vara en mycket svår situation för dem. Syfte: Syftet med den här kvalitativa litteraturstudien var att belysa anhörigas upplevelser av en närståendes hjärtstopp, för att i framtiden bättre kunna tillmötesgå dem inom vården. Metod: En kvalitativ sammanfattande litteraturstudie baserad på åtta vetenskapliga artiklar som hade studerat anhörigas upplevelser under själva hjärtstoppet, på intensiv-vårdsavdelningen eller efter hemkomst. Resultat: Hjärtstoppet var en kaotisk och traumatisk upplevelse för den anhöriga. Patienten var viktigast, all fokus var på patienten men det lämnade ofta den anhöriga ensam med den oro och rädsla situationen framkallat. Tillgång till kontinuerlig information och professionellt bemötande var ytterst viktigt för den anhöriga. Möjligheten att få vara nära närstående dygnet runt ingav säkerhet och trygghet. Brist på information och uppföljning efter utskrivning och en känsla av att vara ensam med allt ansvar var återkommande teman. Slutsats: Att som anhörig vara nära vid ett hjärtstopp var en stark existentiell upplevelse där alla aspekter av delaktighet fanns beskrivna; att veta, att göra och att vara. För bästa resultat, ett delaktigt vårdande i ljuset, krävs en samverkan mellan den vårdande personalen, patient och anhörig. Mer stöd och uppmärksamhet bör i framtiden riktas även mot den anhöriga. / Background: Sudden cardiac arrest is a life threatening condition, not only affecting the patient but the whole family. The patient’s life is on hold and if the patient survives, this is often with more or less physical and psychological complications. Close to the patient a family member or relative, tries to support and help the patient while at the same time the situation may be extremely stressful for the relative. Aim: The aim of this qualitative literature review was to get a better understanding of family members lived experiences during a loved one’s sudden cardiac arrest, in order to better also support the relatives in healthcare. Method: A summary of the literature based on eight qualitative studies on the perceptions of family members experiences of a sudden cardiac arrest by a loved one; during the cardiac arrest, at the intensive care unit and after discharge from hospital. Results: The cardiac arrest was experienced as a chaotic and traumatic event by the relative. The patient was the most important person at the moment but at the same time it left the relative alone with her feelings of anxiety and fear that the situation induced. Receiving information continuously about their next of kin’s condition as well as a considerate and professional encounter with the intensive care unit staff was important for the relative. The possibility to stay with the patient at the intensive care unit felt comforting, reassuring and safe. Lack of information and follow up, as well as a feeling of being alone with the responsibility, was a common theme after discharge from the hospital. Conclusion: To be present during the next of kin’s cardiac arrest was a strong existential experience where all aspects of involvement and participation were described; to know, to do and to be. For best results, an involving care in the light, collaboration between the professional care, the patient and the family member is needed. More support and attention should be given to family members in the future.

Le ventricule droit (VD) possède une embryogénèse, une géométrie et despropriétés biomécaniques différentes du ventricule gauche (VG). L’infundibulum pulmonaire(RVOT) est une origine fréquente d’arythmies dans le VD sain ou pathologique. La tétralogiede Fallot (TOF) est la cardiopathie congénitale cyanogène la plus fréquente et est associée àune dysfonction du VD. Si la correction chirurgicale a augmenté l’espérance de vie despatients TOF, à l’âge adulte les séquelles chirurgicales du VD et RVOT conduisent souvent àune insuffisance cardiaque, des arythmies voire la mort subite cardiaque. Les objectifs decette thèse sont de : (i) définir les propriétés électrophysiologiques et structurelles du VDsain chez le cochon et (ii) caractériser le remodelage arythmogène des ventricules dans unmodèle porcin de réparation de TOF (rTOF). Nous avons démontré la présence d’unehétérogénéité de repolarisation et de conduction dans le VD sain en lien avec un profild’expression spécifique des canaux ioniques dans le RVOT sub-épicardique. Une approchehistologique a également permis de mettre en évidence une structure tissulaire spécifique auRVOT contribuant au ralentissement de l’activation de cette région. Les coeurs des cochonsrTOF témoignent d’un remodelage électrophysiologique et structurel pro-arythmique du VDcaractérisé par une dispersion de la repolarisation, et un ralentissement de la conductioncorrélé à un remodelage moléculaire et structurel. Nous décrivons également la présenced’un remodelage arythmogène distinct dans le VG rTOF sur le plan électrique et structurelsans modification des propriétés hémodynamiques. En conclusion, ces travaux révèlent laprésence de substrats arythmogènes du VD sain et un profond remodelage pro-arythmiquedans les ventricules rTOF. / The right ventricle (RV) has different embryologic history, geometry andbiomechanics properties compared to the left ventricle (LV). The right ventricular outflow tract(RVOT) is a common arrhythmia origin in the healthy or pathological RV. Tetralogy of Fallot(TOF) is the most frequent cyanotic congenital heart disease and is associated with RVdysfunction. Surgical correction has significantly increased patient’s life expectancy butsurgical lesions often lead to heart failure, arrhythmias even sudden cardiac death inadulthood. The aims of this work are to: (i) define RVOT electrophysiological and structuralproperties in the healthy pig and (ii) characterize a potential arrhythmogenic remodeling inboth ventricles in a porcine model mimicking repaired TOF (rTOF). We showed the presenceof repolarization and conduction heterogeneities in the healthy RV in relation to a specific ionchannel expression profile in the RVOT epicardium. Moreover, an histological approachhighlighted the presence of a specific tissue structure likely to contribute to the slowconduction observed in this region. A pro-arrhythmic electrophysiological and structuralremodeling was found in the RV of rTOF pigs. This remodeling was characterized by anincreased dispersion of repolarization and slower conduction properties which were linked toa molecular and structural remodeling. Interestingly, we also described a distinct electricaland structural arrhythmogenic remodeling in the rTOF LV in the absence of hemodynamicalteration. To conclude, this work revealed the presence of an arrhythmogenic substratewithin the healthy RV and a profound arrhythmogenic remodeling of both ventricles in rTOF.

Abstract “Early repolarization” (ER), consisting of J waves and ST-segment elevation in the standard 12-lead electrocardiogram (ECG), has been considered a benign finding for over 60 years until 2008 an over-presentation of ER ECG pattern in infero-lateral leads was described in patients with idiopathic ventricular fibrillation. The purpose of this thesis was to assess the prevalence and prognostic significance, and to characterize the clinical features of this ECG pattern primarily in the general population. This thesis investigated the electrocardiographic features of a total of 20,308 general population individuals, 565 athletes, 432 victims of sudden cardiac death and 532 survivors of an acute coronary event. The overall prevalence of infero-lateral ER ECG pattern in the general population samples was in range between 3.3 and 6.1 percent. ER seemed to have a heritable basis as siblings of individuals displaying the ER pattern had significantly increased odds for presenting this ECG pattern. Several strong associations between ER pattern and clinical factors were observed in all populations. The ER patterns with horizontal or descending ST-segments were associated with significantly increased arrhythmic mortality during a follow-up of 30±11 years, and high amplitude (>0.2mV) J waves in the inferior leads were associated with a high risk of arrhythmic death (multivariate adjusted hazard ratio 3.13 (95% confidence interval 1.55 to 6.32). The ER ECG pattern was also independently associated with sudden cardiac death during an acute coronary event, with an odds ratio of 2.02 (95% CI 1.04 to 3.61) for suffering sudden death. The ER patterns with rapidly ascending ST-segments, the dominant type of ER ECG in young, healthy individuals, were not associated with any adverse outcomes. A multicentre meta-analysis of genome wide association study of ER ECG pattern performed in a total of 14,633 individuals pointed to an associated locus in KCND3 (Kv4.3) gene, which encodes a subunit of the Ito channel, but the association did not reach genome-wide significance and could not be replicated in all study populations. In conclusion, the results of these studies demonstrated that the ER ECG pattern with horizontal or descending ST-segments, especially in the inferior leads, is associated with an increased risk of sudden arrhythmic death in the general population, and that individuals carrying this ECG pattern are at increased risk of suffering fatal arrhythmia during an acute coronary event. The ER pattern with rapidly ascending ST-segments is common in young healthy athletes and is not associated with any increased risk of fatal events. Although the ER ECG pattern increases the relative risk of arrhythmic events, the absolute risk in an individual is low and therefore this ECG pattern should not be interpreted as a high-risk marker of mortality. The genetic background of this ECG pattern remains to be clarified. / Tiivistelmä Normaalissa 12-kytkentäisessä sydänfilmissä (EKG) J-aallosta ja ST-segmentin noususta koostuvaa varhaista repolarisaatiota (ER) pidettiin yli 60 vuotta hyvänlaatuisena muutoksena, kunnes vuonna 2008 ER:n esiintyminen alaseinä-lateraalikytkennöissä liitettiin idiopaattiseen kammiovärinään. Tämän väitöstutkimuksen tarkoitus oli selvittää EKG muutoksen esiintyvyys ja ennustearvo normaaliväestössä, sekä selvittää sen kliinisiä erityispiirteitä. Väitöstutkimusta varten tutkittiin 20,308 normaaliväestön henkilöä, 565 urheilijaa, 432 äkillisesti (sydänperäisesti) menehtynyttä henkilöä ja 532 akuutista sepelvaltimotautikohtauksesta selviytynyttä potilasta. ER-EKG:n kokonaisesiintyvyys alaseinä-lateraalikytkennöissä normaaliväestön otoksissa vaihteli 3.3 % ja 6.1 % välillä. ER-EKG:n esiintyessä merkittävästi muita useammin sisaruksilla ER-EKG vaikutti periytyvältä muutokselta, ja lisäksi kaikissa otoksissa ER-EKG liittyi useisiin muihin tunnettuihin kliinisiin muuttujiin. ER-EKG, ts. J-aallot, joita seurasivat horisontaalinen tai laskeva ST-segmentti, liittyivät merkittävästi lisääntyneeseen rytmihäiriökuolleisuuteen pitkän seuranta-ajan (30±11 vuotta) aikana, ja korkea-amplitudiset (>0.2mV) J-aallot alaseinäkytkennöissä liittyivät korkeaan riskiin kuolla äkillisesti rytmihäiriöön (monimuuttuja-vakioitu riskisuhde 3.13, 95 % luottamusväli 1.55–6.32). ER-EKG lisäsi lisäksi itsenäisesti sydänperäisen äkkikuoleman riskiä akuutin sepelvaltimotautikohtauksen aikana (vetosuhde 2.02, 95 % luottamusväli 1.04–3.61). Etenkin nuorilla ja terveillä urheilijoilla esiintynyt EKG tyyppi, J-aallot ST-segmentin nousujen yhteydessä, ei liittynyt huonoon ennusteeseen. Monikeskusmeta-analyysi perimänlaajuisista assosiaatiotutkimuksista (GWAS) 14,633 henkilöllä antoi viitteitä geenimuutoksesta KCND3, joka koodittaa osaa Ito kanavasta, mutta löydöstä ei kyetty toistamaan kaikissa tutkituissa aineistoissa. Väitöstutkimuksen osatöiden perusteella ER-EKG muutos ilman ST-segmentin nousua, erityisesti alaseinäkytkennöissä esiintyessään, liittyy normaaliväestössä lisääntyneeseen riskiin sydänperäiselle rytmihäiriökuolemalle, ja että henkilöillä, joilla muutos esiintyy, on lisääntynyt riski menehtyä äkillisesti sepelvaltimotautikohtauksen aikana. ER-EKG ST-segmentin nousuihin liittyen on yleinen löydös nuorilla terveillä urheilijoilla ja se ei näytä liittyvän lisääntyneeseen riskiin rytmihöiriöille. Vaikka ER-EKG lisääkin suhteellista riskiä rytmihäiriöille ja ennenaikaiselle kuolemalle väestötasolla, absoluuttinen riski on pieni, eikä muutosta tulisi luokitella suureksi riskitekijäksi. Löydöksen geneettinen tausta on vielä avoin kysymys.

Rates of survival of victims of sudden cardiac arrest (SCA) using cardio pulmonary resuscitation (CPR) have shown little improvement over the past three decades. Since registered nurses (RNs) comprise the largest group of healthcare providers in U.S. hospitals, it is essential that they are competent in performing the four primary measures (compression, ventilation, medication administration, and defibrillation) of CPR in order to improve survival rates of SCA patients. The purpose of this experimental study was to test a color-coded SMOCK system on:1) time to implement emergency patient care measures 2) technical skills performance 3) number of medical errors, and 4) team performance during simulated CPR exercises. The study sample was 260 RNs (M 40 years, SD=11.6) with work experience as an RN (M 7.25 years, SD=9.42).Nurses were allocated to a control or intervention arm consisting of 20 groups of 5-8 RNs per arm for a total of 130 RNs in each arm. Nurses in each study arm were given clinical scenarios requiring emergency CPR. Nurses in the intervention group wore different color labeled aprons (smocks) indicating their role assignment (medications, ventilation, compression, defibrillation, etc) on the code team during CPR. Findings indicated that the intervention using color-labeled smocks for pre-assigned roles had a significant effect on the time nurses started compressions (t=3.03, p=0.005), ventilations (t=2.86, p=0.004) and defibrillations (t=2.00, p=.05) when compared to the controls using the standard of care. In performing technical skills, nurses in the intervention groups performed compressions and ventilations significantly better than those in the control groups. The control groups made significantly (t=-2.61, p=0.013) more total errors (7.55 SD 1.54) than the intervention group (5.60, SD 1.90). There were no significant differences in team performance measures between the groups. Study findings indicate use of colored labeled smocks during CPR emergencies resulted in: shorter times to start emergency CPR; reduced errors; more technical skills completed successfully; and no differences in team performance.

The Cardiovascular diseases may evocated the high percentual risk of sudden cardiac death in whole world. In several western countries is the number of death higher then number of cancer death. In this time is used a lot of methods for prediction of sudden cardiac death with focus on ECG T-wave alternance. The aim of the theses was to do stronger relation and cooperation with Internal Cardiac Clinic of Faculty Hospital Brno Bohunice on the risk analysis of sudden cardiac death. Secondly, we met the methods used for detection and quantification of simulated TWA. Last but not least was necessary to find TWA detection methods improvement and process the data on real signals obtained from Faculty Hospital Brno Bohunice. First part of the Thesis is focused on summary of pathologic artifacts in ECG signal, which are important for sudden cardiac risk stratification. There are described further known detection and quantification methods for TWA analysis. An interesting part for clinical practice is analysis of TWA trend in time and looking for the best method, which is able to catch and track the short TWA trend changes. Second part describes the new methods improvements, which were tested with interesting outputs. Further, there was developed method for TWA presence statement probability evaluation.