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Mörner, Stellan
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Publications (10 of 51) Show all publications
Hellman, U., Mörner, S. & Henein, M. (2019). Genetic variants in cardiac calcification in Northern Sweden. Medicine (Baltimore, Md.), 98(15), Article ID e15065.
Open this publication in new window or tab >>Genetic variants in cardiac calcification in Northern Sweden
2019 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 98, no 15, article id e15065Article in journal (Refereed) Published
Abstract [en]

Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.

In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).

Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.

We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.

Place, publisher, year, edition, pages
Wolters Kluwer, 2019
Keywords
arterial calcification, coronary artery disease, gene
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-158611 (URN)10.1097/MD.0000000000015065 (DOI)000467331500017 ()30985656 (PubMedID)2-s2.0-85064852879 (Scopus ID)
Available from: 2019-05-02 Created: 2019-05-02 Last updated: 2019-06-18Bibliographically approved
Lorén, C., Dahl, C. P., Do, L., Almaas, V. M., Geiran, O. R., Mörner, S. & Hellman, U. (2019). Low Molecular Mass Myocardial Hyaluronan in Human Hypertrophic Cardiomyopathy. Cells, 8(2), Article ID 97.
Open this publication in new window or tab >>Low Molecular Mass Myocardial Hyaluronan in Human Hypertrophic Cardiomyopathy
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2019 (English)In: Cells, ISSN 2073-4409, Vol. 8, no 2, article id 97Article in journal (Refereed) Published
Abstract [en]

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
GEMMA, glucose, hyaluronan, hypertrophic cardiomyopathy, metabolomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-156750 (URN)10.3390/cells8020097 (DOI)000460896000019 ()30699940 (PubMedID)
Available from: 2019-02-26 Created: 2019-02-26 Last updated: 2019-04-04Bibliographically approved
Magnusson, P. & Mörner, S. (2017). EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM) – rationale and design: a prospective observational study on incidence of arrhythmias in Sweden. BMJ Open, 7(12), Article ID e019541.
Open this publication in new window or tab >>EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM) – rationale and design: a prospective observational study on incidence of arrhythmias in Sweden
2017 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 12, article id e019541Article in journal (Refereed) Published
Abstract [en]

Introduction: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with sudden cardiac death (SCD) mainly due to ventricular tachycardia (VT) or fibrillation even though life-threatening bradycardia occurs. Risk stratification takes several variables into consideration including non-sustained VT (NSVT). An implantable cardioverter defibrillator effectively prevents SCD. Atrial fibrillation (AF) is common among patients with HCM and warrants anticoagulation even without conventional risk factors according to European guidelines. Routinely, the evaluation of arrhythmias using a 48-hour ambulatory external monitor takes place every 6-24 months if patients do not report palpitations. The remaining time the potential burden arrhythmia is unknown. Therefore, the aim of the present study is to assess NSVT and AF incidence during 18 months by an insertable cardiac monitor (ICM).

Methods: Adult patients, aged 18-65 years, with a validated diagnosis of HCM are eligible for the study. The study sample is planned to include 30 patients. A Confirm Rx is implanted at the level of the fourth rib on the left side subcutaneously after local anaesthesia. The application for monitoring is installed in the patients' smartphone and symptoms registered by the patient activation and VT detection programmed as 160 bpm during >= 8 intervals. An AF episode is recorded based on >= 2 min duration. Bradycardia is recorded at <= 40 bpm or pause >= 3.0 s. The patients are followed during 18 months before explant.

Ethics and dissemination: The study was approved by The Regional Ethical Committee in Umea (protocol number 2017/13-31). The study protocol, including variables and prespecified research questions, the study was registered at Clinical Trial Registration NCT03259113. Each patient is informed about the study in both oral and written form by a physician and included after written consent.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-144973 (URN)10.1136/bmjopen-2017-019541 (DOI)000423826700214 ()29237655 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-05-21Bibliographically approved
Magnusson, P., Jonsson, J., Mörner, S. & Fredriksson, L. (2017). Living with hypertrophic cardiomyopathy and an implantable defibrillator. BMC Cardiovascular Disorders, 17, Article ID 121.
Open this publication in new window or tab >>Living with hypertrophic cardiomyopathy and an implantable defibrillator
2017 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 121Article in journal (Refereed) Published
Abstract [en]

Background: ICDs efficiently terminate life-threatening arrhythmias, but complications occur during long-term follow-up. Patients' own perspective is largely unknown. The aim of the study was to describe experiences of hypertrophic cardiomyopathy (HCM) patients with implantable defibrillators (ICDs).

Methods: We analyzed 26 Swedish patient interviews using hermeneutics and latent content analysis.

Results: Patients (aged 27-76 years) were limited by HCM especially if it deteriorates into heart failure. The ICD implies safety, gratitude, and is accepted as a part of the body even when inappropriate ICD shocks are encountered. Nobody regretted the implant. Both the disease and the ICD affected professional life and leisure time activities, especially at younger ages. Family support was usually strong, but sometimes resulted in overprotection, whereas health care focused on medical issues. Despite limitations, patients adapted, accepted, and managed challenges.

Conclusion: HCM patients with ICDs reported good spirit and hope even though they had to adapt and accept limitations over time.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Content analysis, Hermeneutics, Hypertrophic Cardiomyopathy, Implantable cardioverter defibrillator, Interview, Qualitative
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-135530 (URN)10.1186/s12872-017-0553-y (DOI)000401027600004 ()28490380 (PubMedID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2019-05-21Bibliographically approved
Magnusson, P., Palm, A., Branden, E. & Mörner, S. (2017). Misclassification of hypertrophic cardiomyopathy: validation of diagnostic codes. Clinical Epidemiology, 9, 403-410
Open this publication in new window or tab >>Misclassification of hypertrophic cardiomyopathy: validation of diagnostic codes
2017 (English)In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 403-410Article in journal (Refereed) Published
Abstract [en]

Purpose: To validate diagnostic codes for hypertrophic cardiomyopathy (HCM), analyze misclassfications, and estimate the prevalence of HCM in an unselected Swedish regional cohort.

Patients and methods: Using the hospitals’ electronic medical records (used for the Swedish National Patient Register), we identified 136 patients from 2006 to 2016 with the HCM-related codes 142.1 and 142.2 (International Classification of Diseases).

Results: Of a total of 129 residents in the catchment area, 88 patients were correctly classified as HCM (positive predictive value 68.2%) and 41 patients (31.8%) were misclassified as HCM. Among the 88 HCM patients (52.2% males), 74 were alive and 14 were dead (15.9%). This yields an HCM prevalence of 74/183,337, that is, 4.0 diagnosed cases per 10,000 in the adult population aged ≥18 years. The underlying diagnoses of misclassified cases were mainly hypertension (31.7%) and aortic stenosis (22.0%). Other types of cardiomyopathies accounted for several cases of misclassification: dilated (nonischemic or ischemic), left ventricular noncompaction, and Takotsubo. Miscellaneous diagnoses were amyloidosis, pulmonary stenosis combined with ventricular septal defect, aortic insufficiency, athelete’s heart, and atrioventricular conduction abnormality. The mean age was not significantly different between HCM and misclassified patients (65.8±15.8 vs 70.1±13.4 years; P=0.177). There were 47.8% females among HCM and 60.8% females among misclassified (P=0.118).

Conclusion: One-third of patients diagnosed as HCM are misclassified, so registry data should be interpreted with caution. A correct diagnosis is important for decision-making and implementation of optimal HCM care; efforts should be made to increase awareness of HCM and diagnostic competence throughout the health care system.

Keywords
diagnostic error, diagnosis, epidemiology, hypertrophic cardiomyopathy, International Classification Diseases, register
National Category
Cardiac and Cardiovascular Systems Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-139023 (URN)10.2147/CLEP.S139300 (DOI)000407833900001 ()
Available from: 2017-09-06 Created: 2017-09-06 Last updated: 2019-05-21Bibliographically approved
Magnusson, P., Gadler, F., Liv, P. & Mörner, S. (2016). Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden. Journal of Cardiovascular Medicine, 17(7), 478-484
Open this publication in new window or tab >>Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden
2016 (English)In: Journal of Cardiovascular Medicine, ISSN 1558-2027, E-ISSN 1558-2035, Vol. 17, no 7, p. 478-484Article in journal (Refereed) Published
Abstract [en]

AimsImplantable defibrillators (ICDs) successfully terminate ventricular arrhythmias in hypertrophic cardiomyopathy (HCM), protect against bradycardia, and monitor atrial arrhythmias. This may alter the natural history and causes of death.MethodsThis nationwide observational longitudinal retrospective study of all HCM patients implanted during 1995-2012 obtained data from the Swedish ICD Registry, the National Patient Register, the Cause of Death Register, and were validated by review of medical records.ResultsOf 342 patients (mean age 51.8 years, 70.8% males), 45 died during a total follow-up of 1847 years (mean 5.4 years). Mean age at death was 68.2 years (range 21-83 years; 12 were 75 years). Mean follow-up time among the deceased was 4.9 years (quartiles 1.4-7.4 years). All-cause mortality was higher in HCM patients compared with the age and sex-matched Swedish general population (standardized mortality ratio 3.4; 95% confidence interval 2.4-4.5; P<0.001). Main cause of death was heart failure (n=27), stroke (n=5), cancer (n=3), myocardial infarction (n=2), sepsis (n=2), and others (n=4). Two patients died suddenly, one after the ICD was turned off because of inappropriate shocks, and one patient whose device system was removed after infection. HCM was the main cause of death in 76% of the cases, mainly because of progressive heart failure.ConclusionFor HCM patients, ICDs almost eliminate premature arrhythmic death and result in a shift to heart failure as the cause of death in the majority of cases. Still, mortality in HCM patients remains elevated and management of heart failure and comorbidities must be improved to increase survival.

Keywords
epidemiology, heart failure, hypertrophic cardiomyopathy, implantable defibrillator, mortality
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-123969 (URN)10.2459/JCM.0000000000000359 (DOI)000377826800004 ()26808417 (PubMedID)
Available from: 2016-12-01 Created: 2016-07-07 Last updated: 2019-05-21Bibliographically approved
Stattin, E.-L., Westin, I. M., Cederquist, K., Jonasson, J., Jonsson, B.-A., Mörner, S., . . . Wisten, A. (2016). Genetic screening in sudden cardiac death in the young can save future lives. International journal of legal medicine (Print), 130(1), 59-66
Open this publication in new window or tab >>Genetic screening in sudden cardiac death in the young can save future lives
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2016 (English)In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 130, no 1, p. 59-66Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds.

METHODS AND RESULTS: From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40%). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT).

CONCLUSION: Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.

Keywords
Sudden unexplained death, Sudden cardiac death, Molecular autopsy, Long QT syndrome, Catecholaminergic polymorphic ventricular tachycardia
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-128555 (URN)10.1007/s00414-015-1237-8 (DOI)000368685400006 ()26228265 (PubMedID)
Available from: 2016-12-07 Created: 2016-12-07 Last updated: 2019-05-10Bibliographically approved
Magnusson, P., Mörner, S., Gadler, F. & Karlsson, J. (2016). Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators. Health and Quality of Life Outcomes, 14, Article ID 62.
Open this publication in new window or tab >>Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators
2016 (English)In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 14, article id 62Article in journal (Refereed) Published
Abstract [en]

Background: Health-related quality of life (HRQL) in hypertrophic cardiomyopathy (HCM) patients with implantable cardioverter-defibrillators (ICDs) is largely unknown. The aim was to assess HRQL, including comparisons between groups, using the questionnaire SF-36, and compare it to a Swedish age-and sex-matched population. Methods and Results: Validated data on adult HCM patients with ICDs were used. The SF-36 response rate was 82.5 % and 245 patients (mean age 55.9 years, 70.2 % men) were analyzed using the Mann-Whitney U-test, t-test, Spearman correlation and effect size calculations. In all SF-36 domains the patients' score was lower (p-value of <0.0001) than norms except for bodily pain. The general health domain showed the highest effect size (0.77) and the impact was more pronounced in the SF-36 physical component summary score (0.62) than the mental component summary score (0.46). Older age was correlated with lower scores on the physical component and higher scores on the mental component. Atrial fibrillation and/or systolic heart failure were associated with worse physical health. HRQL was similar in primary vs secondary prevention cases. Inappropriate ICD shock was associated with worse mental health while appropriate therapy trended toward better mental health. Conclusion: HCM patients with ICDs suffer from poor HRQL regardless of age, sex, or primary vs secondary prevention indication. Atrial fibrillation and systolic heart failure are determinants of poor physical health. Inappropriate shocks, but not appropriate therapies, are associated with poorer mental health.

Keywords
Adult, Hypertrophic cardiomyopathy, Implantable cardioverter-defibrillator, Quality of life, SF-36
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-121475 (URN)10.1186/s12955-016-0467-x (DOI)000374526800001 ()27079917 (PubMedID)
Available from: 2016-06-20 Created: 2016-06-02 Last updated: 2018-06-07Bibliographically approved
Henein, M., Holmgren, A., Holmner, F., Mörner, S. & Lindqvist, P. (2016). Long anterior mitral leaflet causing outflow tract obstruction in a symptomatic patient with hypertrophic cardiomyopathy: the role of mitral valve surgical correction [Letter to the editor]. International Journal of Cardiology, 204, 86-87
Open this publication in new window or tab >>Long anterior mitral leaflet causing outflow tract obstruction in a symptomatic patient with hypertrophic cardiomyopathy: the role of mitral valve surgical correction
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2016 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 204, p. 86-87Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Hypertrophic cardiomyopathy, Anterior mitral leaflet, Obstruction, Exercise echocardiography
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-114604 (URN)10.1016/j.ijcard.2015.11.153 (DOI)000367008200027 ()26655547 (PubMedID)
Available from: 2016-02-11 Created: 2016-01-25 Last updated: 2018-06-07Bibliographically approved
Henein, M., Arvidsson, S., Pilebro, B., Backman, C., Mörner, S. & Lindqvist, P. (2016). Long mitral valve leaflets determine left ventricular outflow tract obstruction during exercise in hypertrophic cardiomyopathy. International Journal of Cardiology, 212, 47-53
Open this publication in new window or tab >>Long mitral valve leaflets determine left ventricular outflow tract obstruction during exercise in hypertrophic cardiomyopathy
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2016 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 212, p. 47-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Development of left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM) is important for explaining symptoms and designing management. LVOTO is mostly caused by a combination of septal hypertrophy and systolic anterior movement of the mitral valve (SAM). The aim of the present study was to determine predictors of exercise induced LVOTO in a group of HCM patients.

METHODS: We performed supine exercise Doppler echocardiography, including measurements of LV morphology and function and anterior mitral leaflet length, in 51 mildly symptomatic HCM (septal thickness≥15mm) and compared them with 50 healthy controls. Measurements were made at 1) rest, 2) Valsalva maneuver, 3) peak exercise and 4) post exercise. LVOTO was diagnosed as a LVOT gradient of >30mmHg at rest, after Valsalva and after exercise or ≥50mmHg at peak exercise.

RESULTS: All patients stopped exercise because of exhaustion. 35% of the patients had resting LVOTO and 48% during Valsalva. At peak exercise, only 37% had LVOTO, who increased to 64% post exercise. Patients who developed LVOTO at peak exercise were more prone to continue having it post exercise (p<0.001), to have attenuated systolic blood pressure rise (p=0.011) and to have long anterior mitral valve leaflets (p<0.001). Backward multiple regression analysis showed the anterior mitral leaflet length as the strongest single independent predictor (β=0.36, p=0.010) for increased LVOT velocities, followed by basal septal thickness.

CONCLUSION: In patients with HCM, LV outflow tract obstruction seems to be relatively uncommon during exercise but rather occurring minutes after stopping exercise. Exercise LVOTO seems to be determined by long anterior mitral leaflets in addition to the well established septal hypertrophy.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
transthyretin, Amyloidosis hereditary, echocardiography, scintigraphy, amyloid cardiomyopathy, VEREUX RB, 1986, AMERICAN JOURNAL OF CARDIOLOGY, V57, P450 bue G, 2003, AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS5th Int Symp on Familial yloidotic Polyneuropathy and Other Transthyretin Related Disorders/4th Int Workshop on Liver ansplantation in Familial Amyloid Polyneuropathy, SEP 24-27, 2002, MATSUMOTO, JAPAN, V10, P32 gueh Sherif F., 2009, EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY, V10, P165 ille M, 2002, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, V29, P376
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-119478 (URN)10.1016/j.ijcard.2016.03.041 (DOI)000374474600012 ()27031819 (PubMedID)
Available from: 2016-04-20 Created: 2016-04-20 Last updated: 2018-06-07Bibliographically approved
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