Publications by authors named "Lars Dejgaard"

20 Publications

  • Page 1 of 1

Exercise training during childhood and adolescence is associated with favorable diastolic function in hypertrophic cardiomyopathy.

Int J Cardiol 2022 Oct 15;364:65-71. Epub 2022 Jun 15.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Experimental Medical Research, Oslo University Hospital Ullevål and University of Oslo, Oslo, Norway; K. G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway. Electronic address:

Background: Diastolic dysfunction is an important part of the clinical phenotype in hypertrophic cardiomyopathy (HCM). While exercise training is known to improve left ventricular (LV) diastolic function in normal hearts, the effects of exercise training during childhood and adolescence in carriers of HCM-associated genetic variants are unknown.

Methods: In a cross-sectional and retrospective study, we combined clinical and echocardiographic data with history of exercise training from childhood to time of examination in 187 participants with HCM or an HCM-causative genotype. Multiple linear regression was used to identify correlations between exercise training performed prior to 20 years of age and LV diastolic parameters from echocardiography.

Results: Exercise training during childhood and adolescence was correlated with a favorable e', E/e', E deceleration time, and end-diastolic volume (EDV), when adjusting for the effects of age at examination, and presence of left ventricular hypertrophy (LVH). This correlation was evident both in patients with a HCM phenotype (HCM LVH+), and in individuals with an HCM-causative genotype without LV hypertrophy (G+ LVH-). None of the diastolic parameters correlated unfavorably with increasing exercise exposure.

Conclusion: More exercise training during childhood and adolescence was associated with favorable LV diastolic function in both HCM LVH+ and G+ LVH- groups, regardless of presence of hypertrophy at the time of examination. These results indicate that exercise training initiated during childhood and adolescence has positive effects on cardiac function later in life for individuals with HCM or an HCM-causative genotype.
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http://dx.doi.org/10.1016/j.ijcard.2022.06.042DOI Listing
October 2022

Electrical markers and arrhythmic risk associated with myocardial fibrosis in mitral valve prolapse.

Europace 2022 Jul;24(7):1156-1163

Department of Cardiology, ProCardio Centre for Innovation, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway.

Aims: We aimed to characterize the substrate of T-wave inversion (TWI) using cardiac magnetic resonance (CMR) and the association between diffuse fibrosis and ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP).

Methods And Results: TWI was defined as negative T-wave ≥0.1 mV in ≥2 adjacent ECG leads. Diffuse myocardial fibrosis was assessed by T1 relaxation time and extracellular volume (ECV) fraction by T1-mapping CMR. We included 162 patients with MVP (58% females, age 50 ± 16 years), of which 16 (10%) patients had severe VA (aborted cardiac arrest or sustained ventricular tachycardia). TWI was found in 34 (21%) patients. Risk of severe VA increased with increasing number of ECG leads displaying TWI [OR 1.91, 95% CI (1.04-3.52), P = 0.04]. The number of ECG leads displaying TWI increased with increasing lateral ECV (26 ± 3% for TWI 0-1leads, 28 ± 4% for TWI 2leads, 29 ± 5% for TWI ≥3leads, P = 0.04). Patients with VA (sustained and non-sustained ventricular tachycardia) had increased lateral T1 (P = 0.004), also in the absence of late gadolinium enhancement (LGE) (P = 0.008).

Conclusions: Greater number of ECG leads with TWI reflected a higher arrhythmic risk and higher degree of lateral diffuse fibrosis by CMR. Lateral diffuse fibrosis was associated with VA, also in the absence of LGE. These results suggest that TWI may reflect diffuse myocardial fibrosis associated with VA in patients with MVP. T1-mapping CMR may help risk stratification for VA.
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http://dx.doi.org/10.1093/europace/euac017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301977PMC
July 2022

Cardiac Arrest in a Patient With Arrhythmic Mitral Valve Prolapse Syndrome: Multiple Possible Etiologies.

JACC Case Rep 2021 Nov 17;3(16):1769-1773. Epub 2021 Nov 17.

ProCardio Centre for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Arrhythmic mitral valve prolapse syndrome is associated with a high risk of death. A 60-year-old man with arrhythmic mitral valve prolapse syndrome was monitored with an implantable loop recorder. Nine months later dyspnea developed, followed by cardiac arrest. Echocardiography showed mitral valve chordal rupture. He underwent successful surgical mitral valve repair. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603045PMC
November 2021

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers.

Cardiology 2021;146(6):763-771. Epub 2021 Sep 1.

Department of Clinical Genetics, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Introduction: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2).

Methods: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed.

Results: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731).

Conclusion: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.
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http://dx.doi.org/10.1159/000519231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743907PMC
December 2021

Tricuspid Annulus Disjunction: Novel Findings by Cardiac Magnetic Resonance in Patients With Mitral Annulus Disjunction.

JACC Cardiovasc Imaging 2021 08 17;14(8):1535-1543. Epub 2021 Mar 17.

ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address:

Objectives: This study aimed to assess whether patients with MAD also have disjunction of the tricuspid annulus.

Background: Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus. Whether the disjunction extends to the right side of the heart is not known.

Methods: In a cohort of patients with MAD, we assessed the presence of tricuspid annulus disjunction (TAD) with the use of cardiac magnetic resonance. We explored the associations between TAD and MAD characteristics and the relationship to ventricular arrhythmias (nonsustained/sustained ventricular tachycardias and aborted cardiac arrest).

Results: We included 84 patients (mean age: 48 ± 16 years; 63% female). We observed TAD in 42 (50%). Patients with TAD were older (age 52 ± 16 years vs. 43 ± 15 years; p = 0.02), had greater circumferential extent of MAD (164 ± 57° vs. 115 ± 58°; p = 0.002), greater maximum longitudinal MAD distance (9.4 ± 2.9 mm vs. 6.2 ± 2.8 mm; p < 0.001), and more frequent mitral valve prolapse (n = 39 [92%] vs. n = 24 [57%]; p < 0.001). Ventricular arrhythmias had occurred in 34 patients (41%), who were younger (age 39 ± 14 years vs. 54 ± 14 years; p < 0.001) and had lower prevalence of TAD (n = 22 [29%] vs. n = 12 [52%]; p = 0.03). TAD was not associated with ventricular arrhythmias when adjusted for age (odds ratio adjusted for age: 0.54; 95% confidence interval: 0.20 to 1.45; p = 0.22).

Conclusions: We report for the first time the existence of right-sided annulus disjunction as a common finding in patients with MAD. TAD was associated with more severe left-sided annulus disjunction and mitral valve prolapse, but not with ventricular arrhythmias.
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http://dx.doi.org/10.1016/j.jcmg.2021.01.028DOI Listing
August 2021

Mitral annulus disjunction is associated with adverse outcome in Marfan and Loeys-Dietz syndromes.

Eur Heart J Cardiovasc Imaging 2021 08;22(9):1035-1044

Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway.

Aims: We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS).

Methods And Results: We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys-Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7-10) mm vs. 7 (6-8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001).

Conclusion: MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.
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http://dx.doi.org/10.1093/ehjci/jeaa324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370565PMC
August 2021

Cardiac Phenotypes and Markers of Adverse Outcome in Elite Athletes With Ventricular Arrhythmias.

JACC Cardiovasc Imaging 2021 01 28;14(1):148-158. Epub 2020 Oct 28.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address:

Objectives: This study describes the cardiac phenotypes and markers of adverse outcome in athletes with ventricular arrhythmias with no other discernable etiology than high exercise doses.

Background: Little is known about phenotypes and risk markers of life-threatening arrhythmic events in athletes with ventricular arrhythmia.

Methods: We compared high-performance athletes who have ventricular arrhythmia with healthy controls using clinical data and cardiac imaging. None of the patients had family history of arrhythmogenic cardiomyopathy or any other discernable etiology of ventricular arrhythmia. Right (RV) and left ventricular (LV) function was assessed by echocardiographic longitudinal strain (right ventricular free wall strain longitudinal [RVFWSL] and left ventricular global longitudinal strain [LVGLS]). Mechanical dispersion was defined as the standard deviation of time to peak strain in 16 LV segments. RV ejection fraction and presence of late gadolinium enhancement was assessed by cardiac magnetic resonance.

Results: We included 43 athletes (45 ± 14 years of age, 16% female) with ventricular arrhythmias and 30 healthy athletes (41 ± 9 years of age, 7% female). Athletes with ventricular arrhythmias had worse RV function than healthy athletes by echocardiography (RVFWSL: -22.9 ± 4.8% vs. -26.6 ± 3.3%; p < 0.001) and by cardiac magnetic resonance (RV ejection fraction 48 ± 7% vs. 52 ± 6%; p = 0.04), and had more late gadolinium enhancement (24% vs. 3%; p = 0.03). Life-threatening arrhythmic events (aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy) had occurred in 23 (53%) athletes with ventricular arrhythmias. These had impaired LV function compared to those with less severe ventricular arrhythmias (LVGLS: -17.1 ± 3.0% vs. -18.8 ± 2.0%; p = 0.04). LV mechanical dispersion was an independent marker of life-threatening events (adjusted odds ratio: 2.2 [1.1 to 4.8] by 10 ms increments; p = 0.03).

Conclusions: Athletes with ventricular arrhythmias had impaired RV function and more myocardial fibrosis compared to healthy athletes. Athletes with life-threatening arrhythmic events had additional LV contraction abnormalities. These phenotypes mimic arrhythmogenic cardiomyopathy and may potentially be induced by high doses of exercise in susceptible individuals.
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http://dx.doi.org/10.1016/j.jcmg.2020.07.039DOI Listing
January 2021

Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A/C Genotype.

J Am Heart Assoc 2020 01 20;9(2):e012937. Epub 2020 Jan 20.

Department of Cardiology Oslo University Hospital Rikshospitalet Oslo Norway.

Background Lamin A/C cardiomyopathy is a malignant and highly penetrant inheritable cardiomyopathy. Competitive sports have been associated with adverse events in these patients, but data on recreational exercise are lacking. We aimed to explore associations between exercise exposure and disease severity in patients with lamin A/C genotype. Methods and Results Lamin A/C genotype positive patients answered a questionnaire on exercise habits from age 7 years until genetic diagnosis. We recorded exercise hours >3 metabolic equivalents and calculated cumulative lifetime exercise. Patients were grouped in active or sedate based on lifetime exercise hours above or below median. We performed echocardiography, 12-lead ECG, Holter monitoring, and biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide). We defined left ventricular ejection fraction <45% as a clinically significant impairment of left ventricular function. We included 69 patients (age 42±14 years, 41% probands, 46% women) with median lifetime exercise 4160 (interquartile range 1041-6924) hours. Active patients were more frequently probands (53% versus 29%, =0.04), had lower left ventricular ejection fraction (43±13% versus 51±11%, =0.006), and higher NT-proBNP (78 [interquartile range 32-219] pmol/L versus 30 [interquartile range 13-64] pmol/L, =0.03) compared with sedate, while age did not differ (45±13 years versus 40±16 years, =0.16). The decrease in left ventricular ejection fraction per tertile increment in lifetime exercise was 4% (95% CI -7% to -0.4%, =0.03), adjusted for age and sex and accounting for dependence within families. Left ventricular ejection fraction <45% was observed at a younger age in active patients (log rank =0.007). Conclusions Active lamin A/C patients had worse systolic function compared with sedate which occurred at younger age. Our findings may improve exercise recommendations in patients with lamin A/C.
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http://dx.doi.org/10.1161/JAHA.119.012937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033829PMC
January 2020

Increased levels of sST2 in patients with mitral annulus disjunction and ventricular arrhythmias.

Open Heart 2019;6(1):e001016. Epub 2019 Apr 28.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Objective: Displacement of the mitral valve, mitral annulus disjunction (MAD), is described as a possible aetiology of sudden cardiac death. Stress-induced fibrosis in the mitral valve apparatus has been suggested as the underlying mechanism. We aimed to explore the association between stretch-related and fibrosis-related biomarkers and ventricular arrhythmias in MAD. We hypothesised that soluble suppression of tumourigenicity-2 (sST2) and transforming growth factor-β1 (TGFβ1) are markers of ventricular arrhythmias in patients with MAD.

Methods: We included patients with ≥1 mm MAD on cardiac MRI. We assessed left ventricular ejection fraction (LVEF) and fibrosis by late gadolinium enhancement (LGE). The occurrence of ventricular arrhythmia, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was retrospectively assessed. We assessed circulating sST2 and TGFβ1 levels.

Results: We included 72 patients with MAD, of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60 % (±6) vs 63% (±6), p = 0.04), more frequently papillary muscle fibrosis (14 (64%) vs 10 (20%), p < 0.001) and higher sST2 levels (31.6 ± 10.1 ng/mL vs 25.3 ± 9.2 ng/mL, p = 0.01) compared with those without, while TGFβ1 levels did not differ (p = 0.29). Combining sST2 level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmia (area under the curve 0.82, 95% CI 0.73 to 0.92) and improved the risk model (p < 0.05) compared with single parameters.

Conclusion: Circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared with arrhythmia-free patients. Combining sST2, LVEF and LGE assessment improved risk stratification in patients with MAD.
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http://dx.doi.org/10.1136/openhrt-2019-001016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519435PMC
April 2019

Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center.

Int J Cardiol 2019 Mar 27;279:79-83. Epub 2018 Dec 27.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway. Electronic address:

Background: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time.

Methods: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing.

Results: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ± 17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1-6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ± 1.3 vs. 6.8 ± 4.3, p = 0.01) and family members (0.7 ± 1.1 vs. 7.7 ± 5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7-16.4, p = 0.004).

Conclusion: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease.
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http://dx.doi.org/10.1016/j.ijcard.2018.12.066DOI Listing
March 2019

The Mitral Annulus Disjunction Arrhythmic Syndrome.

J Am Coll Cardiol 2018 10;72(14):1600-1609

Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address:

Background: Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral valve leaflet hinge point. MAD has been associated with mitral valve prolapse (MVP) and sudden cardiac death.

Objectives: The purpose of this study was to describe the clinical presentation, MAD morphology, association with MVP, and ventricular arrhythmias in patients with MAD.

Methods: The authors clinically examined patients with MAD. By echocardiography, the authors assessed the presence of MVP and measured MAD distance in parasternal long axis. Using cardiac magnetic resonance (CMR), the authors assessed circumferential MAD in the annular plane, longitudinal MAD distance, and myocardial fibrosis. Aborted cardiac arrest and sustained ventricular tachycardia were defined as severe arrhythmic events.

Results: The authors included 116 patients with MAD (age 49 ± 15 years; 60% female). Palpitations were the most common symptom (71%). Severe arrhythmic events occurred in 14 (12%) patients. Longitudinal MAD distance measured by CMR was 3.0 mm (interquartile range [IQR]: 0 to 7.0 mm) and circumferential MAD was 150° (IQR: 90° to 210°). Patients with severe arrhythmic events were younger (age 37 ± 13 years vs. 51 ± 14 years; p = 0.001), had lower ejection fraction (51 ± 5% vs. 57 ± 7%; p = 0.002) and had more frequently papillary muscle fibrosis (4 [36%] vs. 6 [9%]; p = 0.03). MVP was evident in 90 (78%) patients and was not associated with ventricular arrhythmia.

Conclusions: Ventricular arrhythmias were frequent in patients with MAD. A total of 26 (22%) patients with MAD did not have MVP, and MVP was not associated with arrhythmic events, indicating MAD itself as an arrhythmogenic entity. MAD was detected around a large part of the mitral annulus circumference and was interspersed with normal tissue.
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http://dx.doi.org/10.1016/j.jacc.2018.07.070DOI Listing
October 2018

Prediction of Life-Threatening Ventricular Arrhythmia in Patients With Arrhythmogenic Cardiomyopathy: A Primary Prevention Cohort Study.

JACC Cardiovasc Imaging 2018 10 18;11(10):1377-1386. Epub 2018 Jul 18.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Institute for Surgical Research, University of Oslo, Oslo, Norway. Electronic address:

Objectives: This study aimed to identify clinical, electrocardiographic (ECG) and cardiac imaging predictors of first-time life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy (AC).

Background: The role of clinical, electrocardiographic, and cardiac imaging parameters in risk stratification of patients without ventricular arrhythmia is unclear.

Methods: We followed consecutive AC probands and mutation-positive family members with no documented ventricular arrhythmia from time of diagnosis to first event. We assessed clinical, electrocardiographic, and cardiac imaging parameters according to Task Force Criteria of 2010 in addition to left ventricular (LV) and strain parameters. High-intensity exercise was defined as >6 metabolic equivalents.

Results: We included 117 patients (29% probands, 50% female, age 40 ± 17 years). During 4.2 (interquartile range [IQR]: 2.4 to 7.4) years of follow-up, 18 (15%) patients experienced life-threatening ventricular arrhythmias. The 1-, 2-, and 5-year incidence was 6%, 9%, and 22%, respectively. History of high-intensity exercise, T-wave inversions ≥V, and greater LV mechanical dispersion were the strongest risk markers (adjusted hazard ratio [HR]: 4.7 [95% confidence interval (CI): 1.2 to 17.5]; p = 0.02, 4.7 [95% CI: 1.6 to 13.9]; p = 0.005), and 1.4 [95% CI: 1.2 to 1.6] by 10-ms increments; p < 0.001, respectively). Median arrhythmia-free survival in patients with all risk factors was 1.2 (95% CI: 0.4 to 1.9) years, compared with an estimated 12.0 (95% CI: 11.5 to 12.5) years in patients without any risk factors.

Conclusions: History of high-intensity exercise, electrocardiographic T-wave inversions ≥V, and greater LV mechanical dispersion were strong predictors of life-threatening ventricular arrhythmia. Patients without any of these risk factors had minimal risk, whereas ≥2 risk factors increased the risk dramatically. This may help to make decisions on primary preventive implantable cardioverter defibrillator (ICD) therapy.
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http://dx.doi.org/10.1016/j.jcmg.2018.05.017DOI Listing
October 2018

Harmful Effects of Exercise Intensity and Exercise Duration in Patients With Arrhythmogenic Cardiomyopathy.

JACC Clin Electrophysiol 2018 06 28;4(6):744-753. Epub 2018 Mar 28.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Institute for Surgical Research, University of Oslo, Oslo, Norway. Electronic address:

Objectives: The goal of this study was to explore the association between exercise duration versus exercise intensity and adverse outcome in patients with arrhythmogenic cardiomyopathy (AC).

Background: Vigorous exercise aggravates and accelerates AC, but there are no data assessing the harmful effects of exercise intensity and duration in these patients.

Methods: Exercise habits at time of diagnosis were recorded by standardized interviews in consecutive AC patients. Exercise >6 metabolic equivalents was defined as high intensity, and exercise duration was categorized as long if above median. Life-threatening ventricular arrhythmia (VA) was defined as aborted cardiac arrest, documented sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy.

Results: We included 173 AC patients (53% probands; 44% female; 41 ± 16 years of age). Median weekly exercise duration was 2.5 h (interquartile range: 2.0 to 5.5 h), and 91 patients (52%) reported high-intensity exercise. VA had occurred in 83 patients (48%) and was more prevalent in patients with high-intensity exercise than low-intensity exercise (74% vs. 20%, p < 0.001), and more prevalent in long-duration than short-duration exercise (65% vs. 31%, p < 0.001). High-intensity exercise was a strong and independent marker of VA, even when adjusted for the interaction with long-duration exercise (odds ratio: 3.8; 95% confidence interval: 1.3 to 11.0, p < 0.001), whereas long-duration exercise was not.

Conclusions: High-intensity exercise was a strong and independent marker of life-threatening VA in AC patients, independent of exercise duration. AC patients could be advised to restrict their exercise intensity.
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http://dx.doi.org/10.1016/j.jacep.2018.01.010DOI Listing
June 2018

Global Longitudinal Strain: Ready for Clinical Use and Guideline Implementation.

J Am Coll Cardiol 2018 05;71(18):1958-1959

Center for Cardiological Innovation and Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

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http://dx.doi.org/10.1016/j.jacc.2018.03.015DOI Listing
May 2018

Vigorous exercise in patients with hypertrophic cardiomyopathy.

Int J Cardiol 2018 Jan;250:157-163

Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address:

Background: We aimed to investigate if history of vigorous exercise was associated with changes in left ventricular morphology, left ventricular function and ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy genotype positive, phenotype negative (Genotype+ LVH-) and in phenotype positive (HCM LVH+).

Methods: In this cross sectional study we included 187 subjects (age 49±16years, 89(48%) female, 121(65%) HCM LVH+ and 66 (35%) Genotype+ LVH-) who answered a questionnaire on physical activity history. Exercise ≥6 metabolic equivalents was defined as vigorous. Subjects with a history of vigorous exercise ≥4h/week during ≥6years were defined as athletes. All underwent echocardiography and Holter monitoring. VAs were defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia.

Results: In both Genotype+ LVH- and HCM LVH+, lifetime vigorous exercise correlated with larger left ventricular end-diastolic volume (rho 0.44 and 0.38 respectively, both p<0.001). Lifetime vigorous exercise correlated with increased left ventricular mass in Genotype+ LVH- (rho 0.28, p=0.03), but not in HCM LVH+ (p=0.53). Left ventricular systolic function was similar between athletes and non-athletes in Genotype+ LVH- and HCM LVH+. HCM LVH+ athletes had lower E/e' (p=0.03) and higher e' (p=0.02) compared to non-athletes, while this difference was not observed in Genotype+ LVH-. Lifetime vigorous exercise was similar among HCM LVH+ with and without VAs (p=0.89).

Conclusions: Increased lifetime vigorous exercise was associated with larger left ventricular volumes in hypertrophic cardiomyopathy, but correlated to left ventricular mass only in Genotype+ LVH-. Vigorous exercise was associated with favorable diastolic function in HCM LVH+, and was not associated with VAs.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.015DOI Listing
January 2018

Lower than expected burden of premature ventricular contractions impairs myocardial function.

ESC Heart Fail 2017 11 10;4(4):585-594. Epub 2017 Jul 10.

Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Aims: We aimed to explore the burden of frequent premature ventricular contractions (PVCs) associated with myocardial dysfunction in patients with outflow tract arrhythmia (OTA). We hypothesized that this threshold is lower than the previously suggested threshold of 24 000 PVCs/24 h (24%PVC) when systolic function is assessed by strain echocardiography. Furthermore, we aimed to characterize OTA patients with malignant arrhythmic events.

Methods And Results: We included 52 patients referred for OTA ablation (46 ± 12 years, 58% female). Left ventricular global longitudinal strain (GLS) and mechanical dispersion were assessed by speckle tracking echocardiography. A subset underwent cardiac magnetic resonance imaging. PVC burden (%PVC) was assessed by Holter recording. Sinus rhythm QRS duration and PVC QRS duration were recorded from electrocardiogram, and the ratio was calculated (PVC QRS duration / sinus rhythm QRS duration). Median %PVC was 7.2 (0.2-60.0%). %PVC correlated with GLS (R = 0.44, P = 0.002) and with mechanical dispersion (R = 0.48, P < 0.001), but not with ejection fraction (R = 0.22, P = 0.12). %PVC was higher in patients with impaired systolic function by GLS (worse than -18%) compared with patients with normal function (22% vs. 5%, P = 0.001). Greater than 8%PVC optimally identified patients with abnormal GLS (area under the curve 0.79). Serious arrhythmic events occurred in 11/52 (21%) patients characterized by high QRS ratios (1.56 vs. 1.91, P < 0.001).

Conclusions: More than 8%PVC was associated with impaired systolic function by GLS, which is a lower threshold than previously reported. Patients with serious arrhythmic events had higher QRS ratios, which may represent a more malignant phenotype of OTA.
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http://dx.doi.org/10.1002/ehf2.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695171PMC
November 2017

Data on exercise and cardiac imaging in a patient cohort with hypertrophic cardiomyopathy.

Data Brief 2017 Dec 12;15:30-39. Epub 2017 Sep 12.

Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Data presented in this paper are supplementary material to our study "Vigorous exercise in patients with hypertrophic cardiomyopathy" [1]. The current article presents supplementary data on collection and analyses of exercise parameters and genetic data in the original research article.
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http://dx.doi.org/10.1016/j.dib.2017.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609871PMC
December 2017

An integrative appraisal of mechano-electric feedback mechanisms in the heart.

Prog Biophys Mol Biol 2017 11 26;130(Pt B):404-417. Epub 2017 Aug 26.

Simula Research Laboratory, Martin Linges vei 25, Fornebu, 1364, Norway; Center for Cardiological Innovation, Songsvannsveien 9, Oslo, 0372, Norway. Electronic address:

Mechanically-induced alterations in cardiac electrophysiology are referred to as mechano-electric feedback (MEF), and play an important role in electrical regulation of cardiac performance. The influence of mechanical stress and strain on electrophysiology has been investigated at all levels, however the role of MEF in arrhythmia remains poorly understood. During the normal contraction of the heart, mechano-sensitive processes are an implicit component of cardiac activity. Under abnormal mechanical events, stretch-activated mechanisms may contribute to local or global changes in electrophysiology (EP). While such mechanisms have been hypothesised to be involved in mechanically-initiated arrhythmias, the details of these mechanisms and their importance remain elusive. We assess the theoretical role of stretch mechanisms using coupled models of cellular electrophysiology and sarcomere contraction dynamics. Using models of single ventricular myocytes, we first investigated the potential MEF contributions of stretch-activated currents (SAC), and stretch-induced myofilament calcium release, to test how strain and fibrosis may alter cellular electrophysiology. For all models investigated, SACs were alone not sufficient to create a pro-arrhythmic perturbation of the action potential with stretch. However, when combined with stretch-induced myofilament calcium release, the action potential could be shortened depending on the timing of the strain. This effect was highly model dependent, with a canine epicardial EP model being the most sensitive. These model results suggest that known mechanisms of mechano-electric coupling in cardiac myocyte may be sufficient to be pro-arrhythmic, but only in combination and under specific strain patterns.
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http://dx.doi.org/10.1016/j.pbiomolbio.2017.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716869PMC
November 2017

The systolic paradox in hypertrophic cardiomyopathy.

Open Heart 2017;4(1):e000571. Epub 2017 May 16.

Department of Cardiology, Institute for Surgical Research and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Objective: We explored cardiac volumes and the effects on systolic function in hypertrophic cardiomyopathy (HCM) patients with left ventricular hypertrophy (HCM LVH+) and genotype-positive patients without left ventricular hypertrophy (HCM LVH-).

Methods: We included 180 HCM LVH+, 100 HCM LVH- patients and 80 healthy individuals. End-Diastolic Volume Index (EDVI), End-Systolic Volume Index (ESVI) and ejection fraction (EF) were assessed by echocardiography. Left ventricular (LV) global longitudinal strain (GLS) was measured by speckle tracking echocardiography.

Results: EDVI and ESVI were significantly smaller in HCM LVH+ compared with HCM LVH- patients (41±14 mL/m vs 49±13 mL/m and 16±7 mL/m vs 19±6 mL/m, respectively, both p<0.001) and in healthy individuals (41±14 mL/m vs 57±14 mL/m and 16±7 mL/m vs 23±9 mL/m, respectively, both p<0.001). HCM LVH- patients had significantly lower EDVI and ESVI compared with healthy individuals (49±13 mL/m vs 57±14 mL/m and 19±6 mL/m vs 23±9 mL/m, both p<0.001). EF was similar (61%±7% vs 60%±8% vs 61%±6%, p=0.43) in the HCM LVH+, HCM LVH- and healthy individuals, despite significantly worse GLS in the HCM LVH+ (-16.4%±3.7% vs -21.3%±2.4% vs -22.3%±3.7%, p<0.001). GLS was worse in the HCM LVH- compared with healthy individuals in pairwise comparison (p=0.001). Decrease in ESVI was closely related to EF in HCM LVH+ and HCM LVH- (R=0.45, p<0.001 and R=0.43, p<0.001) as expected, but there was no relationship with GLS (R=0.02, p=0.77 and R=0.11, p=0.31). Increased maximal wall thickness (MWT) correlated significantly with worse GLS (R=0.58, p<0.001), but not with EF (R=0.018, p=0.30) in the HCM LVH+ patients.

Conclusion: HCM LVH+ had smaller cardiac volumes that could explain the preserved EF, despite worse GLS that was closely related to MWT. HCM LVH- had reduced cardiac volumes and subtle changes in GLS compared with healthy individuals, indicating a continuum of both volumetric and systolic changes present before increased MWT.
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http://dx.doi.org/10.1136/openhrt-2016-000571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471858PMC
May 2017
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