Henning Bundgaard

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (109)473.18 Total impact

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    ABSTRACT: Several cardiac diseases are autosomal dominantly inherited. This includes cardiomyopathies, primary arrhythmias (channelopathies), dyslipidaemias, premature ischaemic heart diseases and diseases of the thoracic aorta. Sudden cardiac death in the young is also often due to one of the inherited cardiac diseases. Clinical and genetic cascade family screening of the relatives to patients with inherited cardiac diseases is now organized in a national network of centres of cardiology, sharing pedigrees, clinical and genetic information. This gives unique opportunities for offering focused prophylaxis in the group of high-risk relatives.
    Ugeskrift for laeger 11/2014; 176(46).
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    ABSTRACT: Sudden cardiac death (SCD) is responsible for a large proportion of non-traumatic, sudden and unexpected deaths in young individuals. Sudden cardiac death is a known manifestation of several inherited cardiac diseases. In post-mortem examinations, about two-thirds of the SCD cases show structural abnormalities at autopsy. The remaining cases stay unexplained after thorough investigations and are referred to as sudden unexplained deaths. A routine forensic investigation of the SCD victims in combination with genetic testing makes it possible to establish a likely diagnosis in some of the deaths previously characterized as unexplained. Additionally, a genetic diagnose in a SCD victim with a structural disease may not only add to the differential diagnosis, but also be of importance for pre-symptomatic family screening. In the case of SCD, the optimal establishment of the cause of death and management of the family call for standardized post-mortem procedures, genetic screening, and family screening. Studies of genetic testing in patients with primary arrhythmia disorders or cardiomyopathies and of victims of SCD presumed to be due to primary arrhythmia disorders or cardiomyopathies, were systematically identified and reviewed. The frequencies of disease-causing mutation were on average between 16 and 48% in the cardiac patient studies, compared with ∼10% in the post-mortem studies. The frequency of pathogenic mutations in heart genes in cardiac patients is up to four-fold higher than that in SCD victims in a forensic setting. Still, genetic investigation of SCD victims is important for the diagnosis and the possible investigation of relatives at risk.
    Europace 10/2014; · 2.77 Impact Factor
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    ABSTRACT: Background Myotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.Methods We selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.ResultsMyocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m2 (43¿83) vs. 46 g/m2 (36¿64), p = 0.02), increased left atrial volume (median (range) 52 ml/m2 (36¿87) vs. 46 ml/m2 (35¿69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38¿71) vs. 66% (60¿80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).Conclusion Patients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.
    Journal of Cardiovascular Magnetic Resonance 08/2014; 16(1):59. · 4.44 Impact Factor
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    ABSTRACT: This study evaluates the agreement between echocardiographic and cardiac magnetic resonance (CMR) imaging data, and the impact a discrepancy between the two may have on the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: From the Nordic ARVC Registry, 102 patients with definite ARVC who had undergone both echocardiography and CMR were included (median age 42 ± 16 years, 36% female, 78% probands). Patients were divided into two groups according to CMR-positive or -negative criteria, and the echocardiographic data were compared between the two. There were 72 CMR-positive patients. They had significantly larger RV dimensions and lower fractional area change on echocardiography compared with CMR-negative patients; parasternal long-axis right ventricular outflow tract (RVOT) 37 ± 7 vs. 32 ± 5 mm, parasternal short-axis RVOT 38 ± 7 vs. 32 ± 6 mm, fractional area shortening 31 ± 9 vs. 39 ± 9% (P < 0.003 for all). Only 36 (50%) of the CMR-positive patients fulfilled ARVC criteria by echocardiography, hence the diagnostic performance was low; sensitivity 50% and specificity 70%, positive predictive value 80% and negative predictive value 37%. Individuals with regional wall abnormalities on CMR were more likely to have ventricular arrhythmias (77 vs. 57%, P = 0.047). CONCLUSION: A significant proportion of patients with imaging-positive ARVC by CMR did not fulfil echocardiographic ARVC 2010 criteria. These findings confirm that echocardiographic evaluation of subtle structural changes in the right ventricle may be unreliable, and the diagnostic performance of CMR compared with echocardiography should be reflected in the guidelines.
    European Heart Journal – Cardiovascular Imaging 06/2014; · 3.67 Impact Factor
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    ABSTRACT: Injection drug users (IDUs) account for a considerable number of the hospitalizations for infective endocarditis (IE), but the prevalence of diagnosed and unrecognized IE in IDUs is unknown. The aim of the present study was to assess the prevalence of valvular abnormalities suggestive of IE in IDUs attending a supervised injection facility. We performed transthoracic echocardiographic examinations on-site in the injection facilities. A total of 206 IDUs (mean age 43 ± 9 years, 23% women) with a median injection drug abuse of 18 years (interquartile range 10 to 26) were included. Fourteen IDUs (14 of 206, 7%, 95% confidence interval [CI] 4% to 11%) had a previous history of IE. IDUs with a history of IE were significantly older than IDUs without a history of IE (48 ± 8 vs 42 ± 9 years, respectively, p = 0.03) and had a longer duration of injection drug use (27 [18 to 36] vs 17 years [10 to 25], p = 0.008). In the subgroup of IDUs with a history of IE, 4 subjects (4 of 14, 29%, 95% CI 11% to 55%) had persistent or relapse vegetations. Of the remaining 10 IDUs with a history of IE, 5 (5 of 10, 50%, 95% CI 24% to 76%) had moderate-to-severe regurgitation. In the subgroup of IDUs without a history of IE, vegetations were seen in 9 subjects (9 of 192, 5%, 95% CI 2% to 9%). This group of IDUs with possibly unrecognized IE was older than IDUs without vegetations (48 ± 12 vs 42 ± 9, respectively, p = 0.04). Among the IDUs without a history of IE who did not have vegetations, 30 IDUs (30 of 183, 16%, 95% CI 11% to 22%) had moderate-to-severe regurgitation with or without concomitant thickening of leaflets. Thus, in IDUs without a history of IE, some extent of valvular abnormalities was seen in 20% (39 of 192, 95% CI 15% to 27%) of subjects. None of the IDUs with valvular vegetations had current symptoms consistent with active IE. In conclusion, valvular abnormalities assessed by echocardiography were prevalent in asymptomatic IDUs without a medical history of IE, and vegetations were seen in 5% of subjects.
    The American journal of cardiology 04/2014; · 3.58 Impact Factor
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    ABSTRACT: To quantify the association between myotonic dystrophy (DM) and cardiac disease in a nationwide cohort. We identified a nationwide cohort of 1146 DM patients (period 1977-2011) using the National Patient Registry (NPR) and a subcohort of 485 patients who had undergone genetic testing for DM1. Information on incident cardiac diseases was obtained from the NPR. We estimated standardized incidence ratios (SIRs) of cardiac disease compared with the background population, overall and according to selected diagnostic subgroups (cardiomyopathy, heart failure, conduction disorders, arrhythmias, and device implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95% confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59 (95% CI: 2.03-3.25). For a cardiac disease belonging to the selected subgroups, the risk was particularly high in the first year after DM diagnosis [SIR 15.4 (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR 6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20-39 years: SIR 18.1 (95% CI: 12.3-25.8)] compared with older [e.g. 60-79 years: SIR 3.99 (95% CI: 2.98-5.23)] but remained significantly increased in all age categories. Results were similar in separate analyses of the genetically confirmed DM1 patients. Myotonic dystrophy is strongly associated with cardiac disease. The risk is pronounced in the young and remains elevated throughout life, stressing the importance of lifelong cardiac follow-up from time of DM diagnosis.
    European Heart Journal 04/2014; · 14.72 Impact Factor
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    ABSTRACT: Patients with myotonic dystrophy type 1 (DM1) have a three-fold higher risk of sudden cardiac death (SCD) than age-matched healthy controls. Despite numerous attempts to define the cardiac phenotype and natural history, existing literature suffers from low power, selection-bias and lack of controls. Thus, the optimal strategy for assessing cardiac involvement in DM1 is unclear. In this large single-centre study, we evaluated 129 unselected DM1 patients (49.6% men), mean (SD) age 44 (14.7) years with family history, physical examination, electrocardiogram (ECG), echocardiography, Holter-monitoring and muscle strength testing. Cardiac involvement was found in 71 patients (55%) and included: 1) Conduction abnormalities: atrio-ventricular block grade I (AVB grade I) (23.6%), AVB grade II (5.6%), right/left bundle branch block (5.5/3.2%) and prolonged QTc (7.2%); 2) arrhythmias: atrial fibrillation/flutter (4.1%), other supraventricular tachyarrhythmia (7.3%) and non-sustained ventricular tachycardia (4.1%); and 3) structural abnormalities: left ventricular systolic dysfunction (20.6%) and reduced global longitudinal strain (21.7%). A normal ECG was not significantly associated with normal findings on Holter-monitoring or echocardiography. Patients with abnormal cardiac findings had weaker muscle strength than those with normal cardiac findings: ankle dorsal flexion (median (range) 4.5 (0-5) vs. 5.0 (2.5-5), p=0.004) and handgrip (median 4.0 (0-5) vs. 4.50 (2-5), p=0.02). The cardiac phenotype of DM1 includes a high prevalence of conduction disorders, arrhythmias and risk factors of SCD. Systematic cardiac screening with ECG, Holter-monitoring and echocardiography is needed in order to make a proper characterization of cardiac involvement in DM1.
    International journal of cardiology 03/2014; · 6.18 Impact Factor
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    ABSTRACT: Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics. In subgroups of pre-disposed patients, e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs, the absolute risk of drug-induced arrhythmia may be considerable. On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications were weighted and categorized into three risk categories. Additionally, we suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a prudent follow-up for patients with an increased risk. We believe this clinically manageable guideline might improve safety in the many and rapidly increasing number of patients on psychotropic drugs.
    European Heart Journal 03/2014; · 14.72 Impact Factor
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    ABSTRACT: Long 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. We 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. Twenty-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. The 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.
    BMC Medical Genetics 03/2014; 15(1):31. · 2.54 Impact Factor
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    ABSTRACT: -Knowledge of the burden and causes of sudden cardiac death (SCD) is sparse in persons below the age of 50 years; better understanding is needed to lower the risk of SCD. The aim of this study was to report SCD incidence rates and autopsy findings in persons aged 1-49 years. -All deaths in persons aged 1-49 years were included in 2007-2009. Death certificates were reviewed by two physicians. History of previous admissions to hospital was assessed, and discharge summaries were read. Sudden unexpected death cases were identified and autopsy reports were collected. In the 3-year study-period there were 7849 deaths of which we identified 893 (11%) SCD cases. The annual incidence rate per 100,000 persons increased from 2.3 (95% CI: 2.0 to 2.7) to 21.7 (95% CI: 20.2 to 23.4) in persons aged 1-35 and 36-49 years, respectively. Coronary artery disease (CAD) was the most common cause of death and was found in 158 (36%) autopsied cases, followed by 135 (31%) cases of sudden unexplained death (SUD). -In a nationwide cohort of persons aged below 50 years the annual incidence rate of SCD was nearly 10 times higher in persons aged 36-49 years than in persons aged 1-35 years, respectively. Notably, CAD was the most common cause of SCD, followed by unexplained deaths. These findings may help developing strategies to prevent SCD in the future.
    Circulation Arrhythmia and Electrophysiology 03/2014; · 5.95 Impact Factor
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    ABSTRACT: Lesion of the atrioventricular conduction system is a well known adverse effect of alcohol septal ablation (ASA) in patients with obstructive hypertrophic cardiomyopathy (HCM). We assessed the atrioventricular conduction at long-term follow-up after ASA. In patients with a pacemaker implanted for high-grade atrioventricular block after ASA, the atrioventricular conduction was assessed prospectively by ECGs and 48-h Holter recordings. In the remaining patients, the atrioventricular conduction was analysed retrospectively for comparison. A total of 24 (28%) of 87 patients with obstructive HCM without a pacemaker at baseline had a pacemaker implanted due to high-grade atrioventricular block after ASA. Ten of these patients were not available for follow-up. Holter recordings in the remaining 14 patients revealed normalized atrioventricular conduction in 6 patients 6.2 years (range 2.1-9.4) after ASA. Patients with high-grade atrioventricular block at follow-up had longer PR intervals at baseline [205 ms (200-230)] than the rest of the cohort [180 ms (140-200), P = 0.004] and a higher incidence of acute complete heart block (63 vs. 15%; P = 0.007) during ASA. A PR interval of at least 200 ms at baseline was associated with higher prevalence of high-grade atrioventricular block at follow-up (30 vs. 2%; P = 0.0013). The incidence of late-onset complete heart block was 1.5% per year after ASA. We found normalized atrioventricular conduction at long-term follow-up, suggesting recovery in 6 of 14 patients with a pacemaker implanted in relation to ASA. Permanent atrioventricular conduction abnormalities were associated with baseline PR intervals of at least 200 ms and acute persistent complete heart block during ASA.
    Journal of Cardiovascular Medicine 03/2014; 15(3):214-21. · 2.66 Impact Factor
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    ABSTRACT: Objectives To assess skeletal muscle weakness and progression as well as the cardiopulmonary involvement in oculopharyngeal muscular dystrophy (OPMD). Materials and methodsCross-sectional study including symptomatic patients with genetically confirmed OPMD. Patients were assessed by medical history, ptosis, ophthalmoplegia, facial and limb strength, and swallowing capability. Cardiopulmonary function was evaluated using forced expiratory capacity in 1 s (FEV1), electrocardiogram (ECG), Holter monitoring, and echocardiography. ResultsWe included 13 symptomatic patients (six males, mean age; 64 years (41–80) from 8 families. Ptosis was the first symptom in 8/13 patients followed by limb weakness in the remaining 5 patients Dysphagia was never the presenting symptom. At the time of examination, all affected patients had ptosis or had previously been operated for ptosis, while ophthalmoplegia was found in 9 patients. Dysphagia, tested by cold-water swallowing test, was abnormal in 9 patients (17-116 s, ref <8 s). Six patients could not climb stairs of whom two were wheelchair bound and one used a rollator. Six patients had reduced FEV1 (range 23%–59%). No cardiac involvement was identified. Conclusions Limiting limb weakness is common in OPMD and can even be the presenting symptom of the disease. In contrast, dysphagia was not the initial symptom in any of our patients, although it was obligatory for diagnosing OPMD before genetic testing became available. Mild respiratory dysfunction, but no cardiac involvement, was detected.
    Acta Neurologica Scandinavica 03/2014; · 2.47 Impact Factor
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    ABSTRACT: Sudden cardiac death (SCD) is rare, yet well-known in children and adolescents. We present two cases of aborted SCD which reminds us of the importance of comprehensive family history as it proved difficult to ask the right questions revealing the number of family members with cardiac symptoms. Earlier recognition of sudden deaths in the family might have led to more extensive multidisciplinary examinations, and earlier diagnosis.
    Ugeskrift for laeger 02/2014; 176(7A).
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    ABSTRACT: Hitherto, sudden cardiac death in children (SCDc)-defined as sudden cardiac death (SCD) in the 1-18 years old-has been incompletely described in the general population. Knowledge on incidence rates, causes of death and symptoms prior to death is sparse and has been affected by reporting and referral bias. In a nationwide setting all deaths in children aged 1-18 years in Denmark in 2000-06 were included. To chart causes of death and incidence rates, death certificates and autopsy reports were collected and read. By additional use of the extensive healthcare registries in Denmark, we were also able to investigate prior disease and symptoms. During the 7-year study period there was an average of 1.11 million persons aged 1-18 years. There were a total of 1504 deaths (214 deaths per year) from 7.78 million person-years. A total of 114 (7.5%) were sudden and unexpected. A cardiac disease was known prior to death in 18% of all sudden unexpected death cases. In two-thirds of all sudden unexpected death cases no previous medical history was registered. Causes of death in autopsied cases were cardiac or unknown in 70%. Unexplained deaths, presumed to be a primary cardiac arrhythmia, accounted for 28% of autopsied sudden unexpected death cases. Autopsy rate was 77%. There were a total of 87 cases of SCDc (5.8% of all deaths). Prodromal symptoms were noted in 26% and antecedent symptoms in 45% of SCDc cases. The most frequent antecedent symptoms were seizures, dyspnoea, and syncope. In total, 61% of SCDc were not known with any prior disease; 23% were known with congenital or other heart disease prior to death. In total, 43 (49%) of all sudden unexpected deaths died of a potential inherited cardiac disease. The incidence rate of sudden unexpected death was 1.5 per 100 000 person-years. The highest possible incidence rate of SCDc was 1.1 per 100 000 person-years. From a nationwide study of all deaths in a 7-year period more than half of all victims of SCDc experienced antecedent and/or prodromal symptoms prior to death. The incidence rate of sudden death and SCDc was 1.5 and 1.1 per 100 000 person-years, respectively. Cardiac symptoms in young persons should warrant clinical work-up and an autopsy should be performed in all cases of sudden unexpected death in which the deceased was not known with congenital heart disease prior to death. This is pivotal, in the subsequent familial cascade screening, to diagnose and treat potential inherited cardiac diseases in family members.
    European Heart Journal 12/2013; · 14.72 Impact Factor
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    ABSTRACT: Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult. This study is a retrospective review of all patients with Melody valve implantation in a tertiary centre. Between November 2006 and November 2012, 43 procedures were performed in 42 patients (mean age 25years, 6-67years). At a median follow-up of 27months (2-66months), six patients were suspected for IE. However, repeated transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) showed no evidence of IE and the patients were diagnosed as possible cases according to the modified Duke's criteria. Two patients did not respond to antibiotic treatment and underwent intra-cardiac echocardiography (ICE), which clearly demonstrated vegetations. These two cases required surgical explantation, while the other four patients were treated medically without complications. IE after Melody valve implantation is uncommon, but difficult to verify since TTE and TEE often cannot demonstrate vegetations inside the stent. ICE should be considered in suspected cases of IE following PPVR with negative TTE and TEE examinations in order to early tailor the best treatment for the individual patient suspected for IE.
    International journal of cardiology 10/2013; · 6.18 Impact Factor
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    ABSTRACT: Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects.METHODS AND RESULTS: We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001).CONCLUSION: Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.
    Europace 09/2013; · 2.77 Impact Factor
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    ABSTRACT: [This corrects the article on p. 54 in vol. 1.].
    Molecular genetics & genomic medicine. 09/2013; 1(3):187.
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    ABSTRACT: 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. © 2013 S. Karger AG, Basel.
    Cardiology 08/2013; 126(2):131-137. · 1.52 Impact Factor
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    ABSTRACT: Disturbances in plasma potassium concentration (pK) are well-known risk factors for the development of cardiac arrhythmia. The aims of the present study were to evaluate the effect of haemodialysis on exercise pK dynamics and QT hysteresis, and whether QT hysteresis is associated with the pK decrease following exercise. Twenty-two end-stage renal disease patients exercised on a cycle ergometer with incremental work load before and following haemodialysis. ECG was recorded and pK was measured during exercise and recovery. During exercise, pK increased from 5.1 ± 0.2 to 6.1 ± 0.2 mmol/l (Mean ± SEM, p < 0.0001) before haemodialysis and from 3.8 ± 0.1 to 5.1 ± 0.1 mmol/l (p < 0.0001) following haemodialysis. After 2 minutes of recovery, pK had decreased to 5.0 ± 0.2 mmol/l and 4.1 ± 0.1 mmol/l (p < 0.0001) before and following haemodialysis, respectively. pK increase during exercise was accentuated after haemodialysis. The pK increase was negatively, linearly correlated with pK before exercise (β = -0.21, R(2) = 0.23, p = 0.001). QT hysteresis was negatively, linearly correlated with the decrease in pK during recovery (β = -28 msec/(mmol/l), R(2) = 0.36, p = 0.006). Thus, during recovery, low pK was associated with relatively longer QT interval. In conclusion, new major findings are an accentuated increase in pK during exercise after haemodialysis, an attenuated increase in pK in hyperkalemia, and an association between pK and QT interval adaptation during recovery. The acute pK shift following exercise may modulate QT interval adaptation and trigger cardiac arrhythmias.
    Journal of Applied Physiology 05/2013; · 3.48 Impact Factor
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    ABSTRACT: Since the initial description in 2010 of anoctamin 5 deficiency as a cause of muscular dystrophy, a handful of papers have described this disease in cases of mixed populations. We report the first large regional study and present data on new aspects of prevalence, muscular and cardiac phenotypic characteristics, and muscle protein expression. All patients in our neuromuscular unit with genetically unclassified, recessive limb girdle muscular dystrophy (LGMD2), Miyoshi-type distal myopathy (MMD) or persistent asymptomatic hyperCK-emia (PACK) were assessed for mutations in the ANO5 gene. Genetically confirmed patients were evaluated with muscular and cardiopulmonary examination. Among 40 unclassified patients (28 LGMD2, 5 MMD, 7 PACK), 20 were homozygous or compound heterozygous for ANO5 mutations, (13 LGMD2, 5 MMD, 2 PACK). Prevalence of ANO5 deficiency in Denmark was estimated at 1:100.000 and ANO5 mutations caused 11 % of our total cohort of LGMD2 cases making it the second most common LGMD2 etiology in Denmark. Eight patients complained of dysphagia and 3 dated symptoms of onset in childhood. Cardiac examinations revealed increased frequency of premature ventricular contractions. Four novel putative pathogenic mutations were discovered. Total prevalence and distribution of phenotypes of ANO5 disease in a representative regional cohort are described for the first time. A high prevalence of ANO5 deficiency was found among patients with unclassified LGMD2 (46 %) and MMD (100 %). The high incidence of reported dysphagia is a new phenotypic feature not previously reported, and cardiac investigations revealed that ANO5-patients may have an increased risk of ventricular arrhythmia.
    Journal of Neurology 05/2013; · 3.58 Impact Factor

Publication Stats

893 Citations
473.18 Total Impact Points

Institutions

  • 1999–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1997–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1996–2014
    • Heart Research Centre
      Melbourne, Victoria, Australia
  • 2000–2012
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 2009–2011
    • Rigshospitalet
      • Department of Cardiology
      Copenhagen, Capital Region, Denmark
  • 1998–2011
    • Statens Serum Institut
      • Department of Clinical Biochemistry and Immunology
      København, Capital Region, Denmark
  • 2010
    • Kolling Institute of Medical Research
      Sydney, New South Wales, Australia
  • 2003–2010
    • University of Copenhagen
      • • Department of Cardiology
      • • Heart Centre
      • • Department of Oral Medicine
      København, Capital Region, Denmark
    • University of Cologne
      • Department of Internal Medicine
      Köln, North Rhine-Westphalia, Germany
    • Slovak Academy of Sciences
      • Institute for Heart Research
      Presburg, Bratislavský, Slovakia
  • 2008
    • University of Sydney
      • School of Chemistry
      Sydney, New South Wales, Australia