京都大学 / 新制・課程博士 / 博士(医学) / 甲第23809号 / 医博第4855号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 浅野 雅秀, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Voltage-gated sodium channels are composed of pore-forming α-subunits, and modulatory and multifunctional associated β subunits. While much of the field of cardiac electrophysiology and pathology has focused on treating and preventing cardiac arrhythmias by targeting the α subunit, there is also evidence that targeting the β subunits, particularly SCN1B, the gene that encodes β1 and an alternatively spliced variant β1B, has therapeutic potential. The first attempt at targeting the β1 subunit was with the generation of and treatment with an SCN1B Ig domain mimetic peptide βadp1. Here we describe further investigation into the function and mode-of-action of both βadp1 and novel peptides derived from the original βadp1 sequence. We find that in a heterologous expression system βadp1 initially disrupts β1-mediated trans-homophilic adhesion, but after approximately 30 hours eventually increases adhesion. Novel mimetic dimers increase β1 adhesion up to 48 hours post-treatment. Furthermore, it appears that βadp1 may increase β1 adhesion by upregulating the intramembrane proteolysis of β1, a process which has important downstream implications and effects on translation. Despite these exciting findings, we were unable to translate them into a primary culture of cardiac cells with endogenous expression of β1 because we found that both neonatal rat cardiomyocytes and isolated adult mouse cardiomyocytes do not express β1 at detectable levels, whereas they do appear to express β1B. In summary, we show exciting findings on the function and mode-of-action of SCN1B mimetic peptides and their therapeutic potential in targeting the β1 subunit, but further work is needed to determine the translatability of our findings to in vivo models and eventually to humans. / Doctor of Philosophy / Voltage-gated sodium channels have two main parts: the pore-forming α-subunits and the modulatory β subunits. Most research in heart function and issues has focused on fixing problems with the α subunit. However, there's evidence that working on the β subunits, specifically the SCN1B gene that makes β1 and another version called β1B, could be helpful. Previously, researchers used a peptide that is designed exactly like a part of β1, called βadp1, to target the β1 subunit. In our study, we explore more about how βadp1 works and test new peptides based on βadp1. We found that βadp1 initially disrupts trans-homophilic adhesion, where 2 β1 subunits interact with each other across the space between 2 cells, but after about 30 hours, it actually increases adhesion. New mimetic dimers also boost adhesion up to 48 hours later. It seems like βadp1 might enhance adhesion by triggering a process called intramembrane proteolysis of β1, which has important effects on translation. Despite these exciting findings, we couldn't confirm the presence of this protein in heart cells because we discovered that certain heart cells don't have enough β1, although they do have β1B. In conclusion, our study shows promising results about how SCN1B mimetic peptides work and their potential for treating arrhythmia. However, more research is needed to see if these findings apply to real-life situations and eventually to help people with cardiac conduction abnormalities.

No description available.

Aim: To describe and interpret patients’, family members’ and ambulance personnel’s experiences with regard to survival, attendance, and caring at cardiac arrests and deaths, and to analyze ethical conflicts that arise in relation to families and how the personnel’s ethical competence can affect caring and the ability to handle ethical problems. Method: The three interview studies were guided by a reflective lifeworld approach grounded in phenomenology and analyzed by searching for the essence of the phenomenon in two studies and by attaining a main interpretation in one study. In the fourth study, the general approach was supplemented by “reflective equilibrium” that guided the ethical analysis. Results: The survivors are striving towards a good life by means of efforts to reach meaning and coherence, facing existential fear and insecurity as well as gratitude and the joy of life. Family members lose everyday control through feelings of unreality, inadequacy and overwhelming responsibility. Ambulance personnel’s care mediates hope and despair until the announcement of survival or death. After the event, family members risk involuntary loneliness and anxiety about the future. For the ambulance personnel, caring for families involves a need for mobility in decision making, forcing the personnel to balance their own perceptions, feelings and reactions against interpretative reasoning. To base decision making on emotional reactions creates the risk of erroneous conclusions and a care relationship with elements of dishonesty, misdirected benevolence and false hopes. Identification with family members can promote recognition of and response to their existential needs, but also frustrate meeting family members emotions’ and handling one’s own vulnerability and inadequacy. It was found that futile cardiopulmonary resuscitation, administered to patients for the benefit of family members, is not an acceptable moral practice, due both to norms of not deliberately treating persons as mere means and to norms of taking care of families. Conclusions: Ethical conflicts exist when it comes to conveying realistic hope, relief from guilt, participation, responsibility for decision making, and fairness in the professional role. Ambulance personnel need support to enhance ethical caring competence and to deal with personal discomfort, as well as clear guidelines on family support.

Omega 3 poly unsaturated fatty acids (n-3 PUFA) have been shown to protect against sudden cardiac death following myocardial infarction and reduce the risk of ventricular arrhythmias in patients with heart failure. At the inception of this study, there was one clinical study that reported n-3 PUFA supplementation reduced the risk of atrial fibrillation (AF) following CABG. As AF is a very common arrhythmia and as there are no safe and effective means of preventing AF, we designed this study to further validate the findings of the previous study in a more robust study design. In addition, this study also aimed to evaluate the cellular changes that underpin the beneficial anti-arrhythmic effect of n-3 PUFA.The outcome of this study shows that n-3 PUFA does not reduce the risk of AF following CABG. However, short term supplementation with n-3 PUFA reliably increases the membrane incorporation in phospholipids and results in alteration in the expression levels of cardiac calcium handling proteins phospholamban and ryanodine receptors. In addition, such incorporation in animal (rat) ventricular myocytes leads to changes in the rate of decay of the systolic calcium transient and an increase in the amplitude of the caffeine induced calcium transient thereby indicating a greater activity of SERCA. These findings needs further evaluation but is clearly interesting as the clinical situations where n-3 PUFA have been shown to be anti-arrhythmic are situations where cellular calcium overload is the main mechanism of arrhythmogenesis.

Introduction : De nombreuses différences liées au sexe ont été décrites en pathologie cardiovasculaire. Cependant, les données concernant les spécificités liées au sexe, dans le domaine de la mort subite, sont rares. Objectifs : Dans ce travail, nous avons souhaité décrire les caractéristiques des morts subites survenant pendant une activité sportive, en fonction du sexe. Ensuite, nous avons décidé d’étudier le pronostic de la mort subite en fonction du sexe en population générale. L’étape suivante a pour objectif de décrire et analyser les interventions coronaires réalisées en fonction du sexe. Enfin, le dernier travail a eu pour objectif d’étudier les caractéristiques selon le sexe des patients ayant présenté une mort subite en population générale. Matériels et méthodes : Pour la première partie du travail, nous avons inclus les patients de l’observatoire des morts subites du sportif (cas de morts subites pendant le sport dans 60 départements français de 2005 à 2010). Nous avons comparé les caractéristiques et l’incidence de ces morts subites, par tranche d’âge et par sexe. Dans la deuxième partie, nous avons réalisé une revue systématique de la littérature avec une méta-analyse des études rapportant le pronostic après une mort subite en fonction du sexe. La méta-analyse a suivi un modèle à effets aléatoires, et nous avons rapporté l’hétérogénéité statistique entre les études suivant la statistique I2. La troisième partie a inclus les patients de la base de données PROCAT (patients admis en réanimation à l’hôpital Cochin après une mort subite réanimée). Parmi ces patients, nous avons étudié la fréquence de réalisation d’une coronarographie et d’une angioplastie en fonction du sexe, et l’association entre intervention coronaire précoce et pronostic en fonction du sexe. Les analyses ont été réalisées suivant une régression logistique uni- puis multivariée ; le critère de jugement était la survie avec un bon résultat neurologique en sortie d’hôpital. Enfin, dans la dernière partie, la population d’étude était composée des patients inclus dans le registre régional du Centre d’Expertise Mort Subite CEMS (morts subites survenues dans Paris et les 4 départements de la petite couronne), de 2011 à 2016. Nous avons étudié les caractéristiques, le pronostic et les étiologies des morts subites en fonction du sexe. Résultats : Pour la première partie du travail, 820 morts subites du sportif ont été colligées (dont 5% de femmes). L’incidence était de 0.51 cas par million de pratiquants chez les femmes contre 10.1 chez les hommes (P<0.001), avec une répartition différente en fonction de l’âge. Les caractéristiques Utstein des patients étaient homogènes entre hommes et femmes dans la mort subite du sportif, et les femmes avaient une survie significativement meilleure à l’arrivée à l’hôpital (47% vs 30%, P=0.02). Dans la 2e partie, concernant la mort subite en population générale, la revue systématique a inclus 13 études sur le sujet, et la méta-analyse a retrouvé une survie meilleure chez les femmes (OR ajusté=1.1, IC95% 1.03-1.20, P=0.006). Dans la troisième partie, nous avons mis en évidence que les femmes ont moins souvent une coronarographie que les hommes à l’admission (OR ajusté de coronarographie=0.57, IC95% 0.41-0.79, P=0.001) mais que les taux d’angioplastie après une coronarographie étaient similaires, et l’association au pronostic ne différait pas en fonction du sexe. Enfin, dans la 4e partie, nous avons démontré que le meilleur pronostic retrouvé chez les femmes était essentiellement lié à un meilleur taux de survie préhospitalier (OR=1.3, IC95% 1.2-1.5, P<0.001). De plus, les hommes avaient plus souvent une cause ischémique que les femmes (51% vs 28%), et les femmes davantage de causes hypoxiques ou d’embolies pulmonaires. (...) / Introduction: Several gender-specificities have been described in cardiovascular diseases. By contrast, data regarding gender-specificities in the field of sudden cardiac death remain sparse. Objectives: Our first aim was to describe the characteristics of sports-related sudden death, according to gender. Secondly, we assessed the prognosis after sudden death according to gender. The third step aimed at describing and analyzing gender differences in early invasive strategy after cardiac arrest. In the last part, we wanted to assess the respective characteristics of sudden death in men and women in general population. Material and Methods: In the first part, we included cases of sports-related sudden death observatory (sudden deaths that occurred during sport activity in 60 french districts between 2005 and 2010). We compared characteristics and incidence of sudden death, according to age and sex. In the second part, we performed a systematic review and meta-analysis to assess the association between gender and survival after sudden cardiac death. We used a random-effects model, and reported statistical heterogeneity across the studies using I2 statistic. The third part included patients from PROCAT database (cohort of patients admitted alive in intensive care unit in Cochin hospital after a resuscitated sudden death). Among these patients, we studied gender differences regarding early coronary angiogram and percutaneous intervention after sudden death. We also reported the association between coronary intervention and prognosis, according to gender. Analyses were performed with uni and multivariate logistic regression; primary outcome was favorable neurologic outcome at hospital discharge). In the last part, population was drawn from Sudden Death Expertise Center registry (including sudden death in Paris and 4 districts around), from 2011 to 2016. We described characteristics, prognosis and etiologies of sudden death according to gender. Results: In the first part, 820 sport-related sudden deaths were included (including 5% women). Incidence was 0.51 cases per million among women, compared with 10.1 in men (P<0.001), with different distribution among age categories. Utstein characteristics of patients were homogeneous between men and women in sport-related sudden deaths, and women had significantly higher survival at hospital admission (47% vs 30%, P=0.02). In the second part, systematic review included 13 studies, and meta-analysis found a significant association between female gender and survival after sudden death (adjusted OR=1.1, 95% CI 1.03-1.20, P=0.006). In the third part, we found that women had less coronary angiography than men (adjusted OR for coronary angiography=0.57, 95% CI 0.41-0.79, P=0.001) but the rates of percutaneous interventions after coronary angiography were similar. Association between coronary intervention and prognosis did not differ according to sex. Finally, in the fourth part, we reported that the better prognosis reported among women was mainly related to a better survival rate before hospital admission (OR=1.3, 95% CI 1.2-1.5, P <0.001). In addition, men had more often ischemic cause than women (51% vs 28%), who presented more hypoxic causes or pulmonary embolism. Conclusion: In this work, we used several sources (a national observatory, a systematic review of the literature, an hospital database and a regional registry) to clarify the specificities of sudden death in women. We highlighted several specificities associated with female gender in sudden death, regarding characteristics, management and prognosis. Assessing the medical history prior to the event, and examining the long-term prognosis according to gender are the next steps to explore.

Depuis le début des années 2000, le défibrillateur automatique implantable (DAI) est prescrit de manière prophylactique aux populations à risque de mort subite. Nombre de ces implantations semblent prématurées, ce qui pose problème en raison des complications post-opératoires encourues. Il apparaît donc important de mieux définir la population à risque de mort subite, afin d'optimiser la sélection des patients.Le pouvoir prédictif de mort subite des différents descripteurs du Holter a fait l'objet de nombreuses études univariées, sans permettre d'amélioration des critères de sélection. Dans ce mémoire, nous présentons l'analyse multivariée des descripteurs du Holter que nous avons menée. Nous avons extrait l'ensemble des descripteurs calculables sur la base étiquetée d'enregistrements de patients, victimes ou non d'arythmies traitées par le DAI, dont nous disposons. À l'aide de connaissances physiologiques sur l'arythmogenèse, nous avons réalisé une sélection des descripteurs les plus pertinents. Puis, par une méthode originale de conception et d'évaluation de classifieur, nous avons construit un classifieur ad hoc, basé, sur les connaissances physiologiques de l'arythmogenèse ; ce classifieur discrimine les patients à risque, des patients pour lesquels l'implantation ne paraît pas opportune.Au vu des performances atteintes, il semble possible d'améliorer la fiabilité des indications d'implantation prophylactique, à l'aide de méthodes d'apprentissage statistique. Pour valider cette conclusion, il paraît néanmoins nécessaire d'appliquer la méthode exposée dans la présente étude à une base de données de plus grande dimension, et de contenu mieux adapté à nos objectifs. / Implantable cardioverter defibrillators (ICD) have been prescribed for prophylaxis since the early 2000?s, for patients at high risk of SCD. Unfortunately, most implantations to date appear unnecessary. This result raises an important issue because of the perioperative and postoperative risks. Thus, it is important to improve the selection of the candidates to ICD implantation in primary prevention. Risk stratification for SCD based on Holter recordings has been extensively performed in the past, without resulting in a significant improvement of the selection of candidates to ICD implantation. The present report describes a nonlinear multivariate analysis of Holter recording indices. We computed all the descriptors available in the Holter recordings present in our database. The latter consisted of labelled Holter recordings of patients equipped with an ICD in primary prevention, a fraction of these patients received at least one appropriate therapy from their ICD during a 6-month follow-up. Based on physiological knowledge on arrhythmogenesis, feature selection was performed, and an innovative procedure of classifier design and evaluation was proposed. The classifier is intended to discriminate patients who are really at risk of sudden death from patients for whom ICD implantation does not seem necessary. In addition, we designed an ad hoc classifier that capitalizes on prior knowledge on arrhythmogenesis. We conclude that improving prophylactic ICD-implantation candidate selection by automatic classification from Holter recording features may be possible. Nevertheless, that statement should be supported by the study of a more extensive and appropriate database.

No description available.

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.

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.