Finn Lund Henriksen

Low disease prevalence and inappropriate implantable cardioverter defibrillator shock rate in Brugada syndrome: a nationwide study

AIMS Brugada syndrome (BrS) is an inherited channelopathy that predisposes to malignant ventricular arrhythmias and thereby syncope and sudden cardiac death. Prior studies characterizing BrS patients have used highly selected referral populations from tertiary centres and prevalence estimates have been carried out using electrocardiogram (ECG) surveys only. We aimed to identify and characterize all diagnosed BrS patients in Denmark (population 5.4 million). METHODS AND RESULTS Brugada syndrome patients were identified using several modalities including identification in all Danish tertiary referral centres, search in public health registries, contact to all cardiology departments in Denmark, and searching in a pedigree database for inherited heart disease used nationwide in Denmark. We identified 43 definite diagnosed BrS patients and 25 possible BrS patients, corresponding to a prevalence of 1.1 definite BrS cases per 100 000 inhabitants. Most definite BrS patients were men (86%) and the median age at diagnosis was 48 years. A total of 35 definite BrS patients (81%) had an implantable cardioverter defibrillator (ICD) implanted and of these 9 (26%) experienced appropriate shocks and 3 (8%) experienced inappropriate shocks during a median follow-up of 47 months. No patient died or experienced aborted sudden cardiac death during follow-up. CONCLUSIONS We report the first nationwide study of BrS patients. We found a low incidence of diagnosed definite BrS compared with estimates from ECG surveys. Follow-up data show a lower rate of inappropriate therapies in ICD carriers than that reported in previous studies.

Cascade screening in families with inherited cardiac diseases driven by cardiologists: feasibility and nationwide outcome in long QT syndrome

Objectives: We assessed the outcome of cascade screening of families with congenital long QT syndrome (LQTS) in Danish heart centers. Methods: Affected family members were identified through systematic family screening. Results: In total, 228 affected relatives were identified from 90 families. A disease-causing mutation useful for presymptomatic genetic testing was found in 82% of probands. Two-thirds of affected relatives fulfilled electrocardiographic criteria for the diagnosis, whereas diagnosis was based on genetic findings in only one-third. The majority of affected relatives were asymptomatic. Symptomatic relatives and probands most often presented with syncope, followed by aborted cardiac arrest and sudden cardiac death. A serious cardiac event (SCE, such as syncope, aborted cardiac arrest or cardiac arrest) was reported by 32% of affected relatives and 87% of probands (p < 0.0001). Fifty-two percent of affected relatives were on β-blockers and 11% had an implantable cardioverter defibrillator (ICD), as compared to 88 and 49% of probands (p < 0.0001). Appropriate ICD therapy was given to 13% of affected relatives and to 27% of probands (p = 0.1). Conclusions: Clinically driven cascade screening of Danish LQTS families identified 2-3 affected relatives per proband. Affected relatives had milder disease courses, but SCEs in a subset strongly support screening. Danish cardiologists have adopted cascade screening of LQTS families according to specific Danish guidelines.

Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations

Objective The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. Methods The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. Results We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope). As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10–33) vs 43 years (IQR, 25–54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43–175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32–139)). Multifocal atrial tachycardia was the predominant symptom in five patients. Conclusions In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.

Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2

BackgroundLong QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A.MethodsWe describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2.ResultsTwenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 “unrelated” families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000.ConclusionThe genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.

Newly detected abnormal glucose regulation and long-term prognosis after acute myocardial infarction: Comparison of an oral glucose tolerance test and glycosylated haemoglobin A1c

BACKGROUND An oral glucose tolerance test (OGTT) and/or glycosylated haemoglobin A1c (HbA1c) in patients with acute myocardial infarction (AMI) identify patients with increased mortality risk, but no comparison of the long-term prognostic values has yet been investigated. METHODS This study was a prospective cohort enrolling patients with AMI between 2002 until 2008 and follow-up until 1st October, 2012. Patients without known diabetes mellitus (DM) underwent an OGTT. Seventy-nine patients with known DM did not have an OGTT performed. Primary endpoint was all-cause mortality. We included 548 patients with AMI, of whom 469 underwent a standardized OGTT and were stratified according to OGTT and HbA1c. RESULTS During 9.8years of follow-up, 179 (33%) patients died. In patients having increased HbA1c ≥6.5%, a significantly increased mortality was observed (Hazard Ratio (HR) 1.60 [1.09-2.34]). However, when adjusting for known DM, no significance was detected. An OGTT did not show a significantly increased mortality, if used separately. A combined estimate showed a significantly increased mortality in patients categorized as newly diagnosed DM by OGTT and HbA1c<6.5% (HR 1.56 [95% CI 1.07-2.30]) compared to patients categorized as normal/impaired fasting glycaemia/impaired glucose tolerance by OGTT and HbA1c <6.5%. Approximately 50% of the patients with newly diagnosed DM by OGTT were only detected due to 2-hour post-load glucose values. CONCLUSION An OGTT is recommended in AMI patients without known DM and HbA1c<6.5%. Patients categorized as newly diagnosed DM by OGTT although HbA1c <6.5% share the same high risk of mortality as patients with HbA1c≥6.5%.

Clinical evaluation of unselected cardiac arrest survivors in a tertiary center over a 1-year period (the LAZARUZ study) ☆ ☆☆

OBJECTIVES When the cause of an aborted cardiac arrest is unclear the initiation of therapy, counseling and family screening is challenging. METHODS We included 43 unselected, prospectively identified cardiac arrest survivors with or without a diagnosis. Family history for cardiac disease and supplemental electrocardiograms were evaluated for additional diagnostic information. RESULTS 43 cardiac arrest survivors were included, 34 (79%) were male and the average age was 48years (range 23-64, SD 13.0). The most common etiologies identified in cardiac arrest survivors were ischemic heart disease (33%), cardiomyopathies (14%), miscellaneous (e.g. drug induced arrhythmias, coronary spasms) (12%) and channelopathies (5%). Family history of cardiac disease - even inheritable conditions - was not indicative of etiology in cardiac arrest survivors. Supplemental ECGs were abnormal in 10 of 43 patients; in the majority of these patients (7) no conclusive diagnosis was reached. CONCLUSIONS In this study 16/43 (37%) of unselected, prospectively included cardiac arrest survivors remained without a diagnosis despite exhaustive investigations. We may extract additional diagnostic information from simple maneuvers during the recording of the electrocardiogram. We suggest that these ECG derived clues be investigated in future studies including genetic test results and data from relatives.

FirstAED Emergency Dispatch, Global Positioning of First Responders with Distinct Roles - A Solution to Reduce the Response Times and Ensuring Early Defibrillation in the Rural Area Langeland

FirstAED is a supplement to the existing emergency response systems. The aim is to shorten the first responder response times at emergency calls to below 5 minutes. FirstAED defines a way to dispatch the nearby three first responders and organize their roles in the hope of reducing response times, ensuring citizens safety and equal possibility to early defibrillation.

Calibration, specificity and trueness of a postheparin plasma lipoprotein lipase assay

Abstract Measurement of lipoprotein lipase activity in postheparin plasma is generally accompanied by moderate within-run variation Cvw-R (﹤10％) and higher between-run variation Cvb-R (5–25％). A calibration system was introduced in order to improve the reproducibility of measurements and to compare lipoprotein lipase activities from different days. Every day a calibration curve for lipoprotein lipase activity was constructed. Fifteen calibration curves designed over 2 years, show linearity over the whole biological spectrum and a considerable reduction of between-run variation in lipoprotein lipase activity, from 42％ to 5.3％ as estimated from two control postheparin plasma samples. The lipoprotein lipase calibration system is an easy and very cheap arrangement, which makes it possible to compare lipoprotein lipase activities achieved over years. When the lipoprotein lipase control values are compared with reference lipoprotein lipase samples determined in other lipase laboratories, the calibration-control system becomes an important tool for reducing analytical bias. The article reviews the original analytical criteria of catalytic measurement of lipoprotein lipase activity and describes the implementation of the calibrationcontrol system. We describe a model for reduction of the analytical variability in the measurement of lipoprotein lipase activity. Other standardization efforts need to be made in the future, especially to define the reference material for calibration.

Emergency dispatch, global positioning of first responders with distinct roles and automatic external defibrillators: a logistic solution to secure basic life support and defibrillation

Published on behalf of the European Society of Cardiology. All rights reserved.

Emergency dispatch, FirstAED global positioning of first responders with distinct roles - a solution to reduce the response times and ensuring early defibrillation in the rural area Langeland

Methods First aid and cardiopulmonary resuscitation is provided by 215 first responders who use their smartphone (iPhone 4S/5). The population purchased 95 AEDs which are available around the clock and placed less than two kilometres apart. FirstAED is an auxiliary to the public services and it enables the emergency dispatcher to send an organized team of first responders with distinct roles to the scene. FirstAED global positioning system GPStrack the 9 nearby first responders. FirstAED chooses the 3 most optimally located first responders who have accepted the alarm. FirstAED organizes the three first responders in a team: no. 1 reaches the patient to give cardiopulmonary resuscitation; no. 2 brings the AED; and no. 3 is the onsite coordinator.