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BACKGROUND Although sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union.OBJECTIVES The study objective was to determine the incidence of SCD and OHCA in the European Union.METHODS The study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)-attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark.RESULTS The average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women.CONCLUSIONS By combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Aim Depolarization-blocking drugs (DB-drugs) used for cardiac disease increase the risk of cardiac arrhythmia (ventricular tachycardia/ventricular fibrillation[VT/VF]) and out-of-hospital cardiac arrest (OHCA) in specific patient groups. However, it is unknown whether drugs for non-cardiac disease that block cardiac depolarization as off-target effect increase the risk of OHCA on a population level. Therefore, we aimed to investigate OHCA-risk of non-cardiac DB-drugs in the community. Methods We conducted a population-based case-control study. We included OHCA-cases from an Emergency Medical Services attended OHCA-registry in the Netherlands (ARREST:2009-2018), and age/sex/OHCA-date matched non-OHCA-controls. We calculated adjusted odds ratios (ORadj) of use of non-cardiac DB-drugs for OHCA, using conditional logistic regression. Stratified analyses were performed according to first-registered rhythm (VT/VF or non-VT/VF), sex and age (≤50, 50-70, or ≥70 years). Results We included 5,473 OHCA-cases of whom 427 (7.8%) used non-cardiac DB-drugs, and 21,866 non-OHCA-controls of whom 835 (3.8%) used non-cardiac DB-drugs, and found that non-cardiac DB-drug use was associated with increased OHCA-risk when compared to no-use (ORadj1.6[95%-CI:1.4-1.9]). Stratification by first-recorded rhythm revealed that this applied to OHCA with non-VT/VF (asystole) (ORadj2.5[95%-CI:2.1-3.0]), but not with VT/VF (ORadj1.0[95%-CI:0.8-1.2];P-value interaction

AimTo discuss ethical issues related to a complex study (PROFID) involving the development of a new, partly artificial intelligence-based, prediction model to enable personalised decision-making about the implantation of an implantable cardioverter defibrillator (ICD) in postmyocardial infarction patients, and a parallel non-inferiority and superiority trial to test decision-making informed by that model.MethodThe position expressed in this paper is based on an analysis of the PROFID trials using concepts from high-profile publications in the ethical literature.ResultsWe identify ethical issues related to the testing of the model in the treatment setting, and to both the superiority and the non-inferiority trial. We underline the need for ethical-empirical studies about these issues, also among patients, as a parallel to the actual trials. The number of ethics committees involved is an organisational, but also an ethical challenge.ConclusionThe PROFID trials, and probably other studies of similar scale and complexity, raise questions that deserve dedicated parallel ethics and social science research, but do not constitute a generic obstacle. A harmonisation procedure, comparable to the Voluntary Harmonization Procedure (VHP) for medication trials, could be needed for this type of trials.

Introduction: We evaluated the results of 15 years of cardiogenetic counseling in the Academic Medical Center (AMC). Methods: We retrospectively analyzed all families who were counseled between 1996 and 2011 with a suspected inherited arrhythmia syndrome including primary electrical diseases, cardiomyopathies, sudden (aborted) unexplained death (SUD). We analyzed the yield of molecular genetics over time and diagnosis at the moment they were included in our database. In case of counseling because of a SUD in the family, we analyzed the 'outcome' of the counseling and cardiological investigations. Results: Since 1996, 7036 counselees visited the AMC Cardiogenetics department, of whom 6959 are included in this study (n=2313different families (41±19years old, 49% male). In 726 families (31%) a possible disease causing mutation was detected. Most mutations were found in LQTS (50%), HCM (48%) and CPVT (40%) families. The mutation detection rate decreased over time, where the number of referrals importantly increased. Cascade-screening revealed n=1572 mutation carriers. The number of counseled families after SUD was 376. In 25% (n=95) of these families an inherited disease was established (molecular diagnosis in n=67/110(61%), including 15 families in whom the Dutch risk haplotype for 'idiopathic' VF was detected). Conclusions: Although the mutation-yield decreased over time, an important number of disease causing mutations in this large series of patients was detected. Systematic screening of these families identifies many (often asymptomatic) carriers, who can benefit from earlytreatment to prevent complications or SUD. Dedicated cardiogenetics clinics with multidisciplinaryteams are needed for proper interpretation of results of molecular genetics and cascade-screening.

Family screening in inherited cardiac arrhythmias has been performed in The Netherlands since 1996, when diagnostic DNA testing in long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) became technically possible. In multidisciplinary outpatient academic clinics, an adjusted protocol for genetic counselling, originally derived from predictive testing in Huntington's disease, is being used. 1110 individuals, including 842 relatives of index patients, were informed about their risks, and most were tested molecularly and/or clinically for carriership of the disease present in their family. Of 345 relatives who were referred for cardiologic follow-up, 189 are being treated, because of an increased risk of life-threatening arrhythmias. Evaluation of the psychological and social consequences of family screening for inherited arrhythmias can be performed by using the adapted criteria of Wilson and Jüngner, i.e., from a point of view of public health. Preliminary results of psychological research show that parents of children at risk for LQTS show high levels of distress. Many other aspects have to be evaluated yet, making final conclusions about the feasibility of family screening difficult, particularly in HCM. Clinical guidelines are urgently needed. Population screening by molecular testing, for instance in athletic preparticipation screening, will become possible in the future and has its own prerequisites for success.

The Brugada syndrome is associated with sodium channel dysfunction and the characteristic ST segment elevation is thought to arise from the right ventricle. We hypothesized that sodium channel blockade in Brugada syndrome patients cause more activation delay in leads overlying the right ventricle than in other leads. ECG data were recorded during infusion of a sodium channel blocker in 17 family members of Brugada syndrome patients. Signal averaged and filtered signals from a number of body surface leads were investigate for small potentials that are generated by myocardium close to the recording electrode. ST segment elevation in V1 during sodium channel blockade was accompanied by pronounced activation delay in V1 after the end of the QRS complex in lead II (32±18 ms), whereas activation in V6 was not later than end of QRS (12±13 ms). The latest activation in V1 was delayed to a greater extend than in control patients without ST elevation during sodium channel blockade (151±17 ms vs 128±10 ms, p

At present, cardiac rhythm disorders such as sick sinus syndrome (SSS) or AV nodal block (AVB) are usually treated by electronic pacemakers. These devices have significant shortcomings, including lack of autonomic modulation, and the need for repetitive procedures for battery replacement or lead repositioning. Biological pacemakers as replacement or complement to electronic pacemakers have been the subject of increasing research interest. This research has resulted in many encouraging preclinical studies. Various approaches in the field of gene and cell therapy have been developed by different groups and this combined effort makes it increasingly realistic that this therapy will eventually find its way to clinical applicability. (Neth Heart J 2007;15:318-22.)

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.

Background Common practice for asymptomatic Brugada syndrome (BrS) has included risk stratification with electrophysiologic studies (EPS) and defibrillator implantation when the latter are positive. However, several multicenter studies show that EPS has limited value for predicting spontaneous ventricular fibrillation. Therefore, in 2008 we started this Prospective International Registry. Methods Patients with a type 1 Brugada ECG, who have no arrhythmia-related symptoms and no heart disease, are included in the Registry. They receive quinidine therapy or no therapy depending on physician's/patient's preference. EPS are not recommended. Results In total, 132 patients from the Netherlands (51), Italy (41), Israel (20), Germany (13), and Japan (7) have been recruited; 93 (70%) are male. Age at presentation is 43 ± 12 (11–79) years. Symptoms include palpitations (20%), chest pain (10%) and vagal syncope (20%); 54 patients have a family history of BrS or sudden death before age 50. The reason for index ECG was medical screening in 41 (31%), cardiac symptoms in 34 (26%), noncardiac symptoms (eg, fever) in 18 (14%), and screening for familial history of sudden death or BrS in 39 (30%). The type 1 ECG pattern was spontaneous in 45 patients (including spontaneous on "high leads" in 7 and fever-induced in 8) and drug-induced in 87. Disease-causing mutations were found in 23% and genetic variants of unknown significance in 5%. Nineteen patients received empiric quinidine therapy. Of them, 4 had presented with syncope (believed to be vasovagal) and 4 were asymptomatic but had familial history of sudden death or BrS. Nine patients had a spontaneous type 1 ECG pattern. Five (26%) patients discontinued quinidine because of asymptomatic QT prolongation (2 patients), diarrhea, asymptomatic abnormal liver function tests, and patient's preference (1 patient each). Follow-up >4 months (1.8 ± 0.9 years) is available for 59 patients. The only serious adverse event was syncope (leading to defibrillator implantation) in 1 untreated patient. Conclusions In our Prospective Registry of asymptomatic patients with BrS, most physicians and patients opt for no therapy. Long-term quinidine therapy is well tolerated by 74%. The risk of an arrhythmic event proved to be low.

The ESCAPE-NET project has provided an important boost to the field of SCA research in two key ways: • it has created a marketplace to conduct SCA research in multiple dimensions • it has created a shared, harmonised database and DNA bank of SCA patients that is world-leading in regards to size and quality. The ESCAPE-NET consortium members have recognised the need to maintain this momentum. To achieve this, they actively reach out to other scientists to join this effort, e.g. by creating the PARQ project—Sudden cardiac arrest Prediction And Resuscitation network: improving the Quality of care, supported by COST (European Cooperation in Science and Technology, grant agreement No CA19137, https://parq-cost.eu). The PARQ project aims to extend the SCA research community beyond the ESCAPE-NET network by involving other regions within and outside of Europe and stimulating exchanges between junior and senior SCA investigators across Europe. It is the ambition that, through the PARQ project and the implementation of a business model, the SCA research marketplace and its shared harmonised database may be maintained and further expanded, thereby offering the opportunity to alleviate the societal problem of SCA.