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Mörner, Stellan
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Publications (10 of 63) Show all publications
Sörensen, J., Nordström, J., Baron, T., Mörner, S., Granstam, S.-O., Lubberink, M., . . . Harms, H. J. (2022). Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET. Journal of Nuclear Cardiology, 2361-2373
Open this publication in new window or tab >>Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET
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2022 (English)In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, p. 2361-2373Article in journal (Refereed) Published
Abstract [en]

Aim: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).

Methods: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.

Results: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).

Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
15O-water, Cardiac remodeling, Left ventricular hypertrophy, Positron emission tomography, Wall thickness
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-186445 (URN)10.1007/s12350-021-02734-3 (DOI)000675040900001 ()34286452 (PubMedID)2-s2.0-85110815639 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20190593
Available from: 2021-08-02 Created: 2021-08-02 Last updated: 2023-03-24Bibliographically approved
van der Crabben, S. N., Mörner, S., Lundström, A., Jonasson, J., Bikker, H., Amin, A. S., . . . Wilde, A. A. M. (2022). Should variants of unknown significance (VUS) be disclosed to patients in cardiogenetics or not; only in case of high suspicion of pathogenicity?. European Journal of Human Genetics, 30, 1208-1210
Open this publication in new window or tab >>Should variants of unknown significance (VUS) be disclosed to patients in cardiogenetics or not; only in case of high suspicion of pathogenicity?
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2022 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 30, p. 1208-1210Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-199393 (URN)10.1038/s41431-022-01173-z (DOI)000844578000001 ()36008533 (PubMedID)2-s2.0-85137082057 (Scopus ID)
Available from: 2022-09-29 Created: 2022-09-29 Last updated: 2023-05-25Bibliographically approved
Walsh, R., Lahrouchi, N., Tadros, R., Kyndt, F., Glinge, C., Postema, P. G., . . . Bezzina, C. R. (2021). Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls. Genetics in Medicine, 23(1), 47-58
Open this publication in new window or tab >>Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
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2021 (English)In: Genetics in Medicine, ISSN 1098-3600, E-ISSN 1530-0366, Vol. 23, no 1, p. 47-58Article in journal (Refereed) Published
Abstract [en]

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.

Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.

Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.

Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Place, publisher, year, edition, pages
Nature Publishing Group, 2021
Keywords
variant interpretation, LQTS, Brugada, ACMG/AMP guidelines
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-175470 (URN)10.1038/s41436-020-00946-5 (DOI)000566661000001 ()32893267 (PubMedID)2-s2.0-85090223596 (Scopus ID)
Available from: 2020-10-02 Created: 2020-10-02 Last updated: 2023-03-24Bibliographically approved
Magnusson, P. & Mörner, S. (2021). EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM): A prospective observational study on incidence of arrhythmias. Cardiovascular Electrophysiology, 32(1), 129-135
Open this publication in new window or tab >>EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM): A prospective observational study on incidence of arrhythmias
2021 (English)In: Cardiovascular Electrophysiology, ISSN 1045-3873, E-ISSN 1540-8167, Vol. 32, no 1, p. 129-135Article in journal (Refereed) Published
Abstract [en]

Background Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with arrhythmias. Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death and part of the current risk stratification. Furthermore, atrial fibrillation (AF), which increases the risk of stroke, is believed to be common in HCM patients. Routine ambulatory monitoring captures the rhythm only periodically over 24-48 h; thus, the true burden of arrhythmia is unknown. The insertable cardiac monitor (ICM) should help determine a more realistic arrhythmia assessment in HCM patients. Objective The purpose of this study was to ascertain the incidence of NSVT, AF, and bradycardia in unselected HCM patients by the use of an ICM. Methods Thirty adults, mean age 49.9 +/- 12.3 years, 25 (83.3%) males were implanted with a Confirm Rx ICM. The monitoring application was installed on the patient's smartphone, which allowed for patient activation in case of symptoms. The ICM was programmed as follows: ventricular tachycardia (VT) >= 160 beats per minute (bpm) for >= 8 intervals, AF >= 2 min of duration, and bradycardia <= 40 bpm or pause >= 3.0 s. Results The mean calculated 5-year risk was 2.3%, and 29/30 of the patients had a risk <4%. During follow-up, AF was found in nine patients (30.0%). At least one episode of NSVT was detected in seven patients (23.3%). In 13 patients (43.3%), sinoatrial block/sinus arrest/sinus bradycardia were seen. No arrhythmia was detected in nine patients (30.0%). Conclusion In this first prospective study using an ICM, the arrhythmia burden in HCM patients yielded 30.0% AF and 23.3% NSVT.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
arrhythmia, atrial fibrillation, hypertrophic cardiomyopathy, insertable cardiac monitor, non&#8208, sustained ventricular tachycardia
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-176894 (URN)10.1111/jce.14792 (DOI)000584551300001 ()33108031 (PubMedID)2-s2.0-85096724618 (Scopus ID)
Funder
Pfizer ABAstraZenecaNovo Nordisk
Available from: 2020-11-23 Created: 2020-11-23 Last updated: 2023-03-24Bibliographically approved
Bytyci, I., Nistri, S., Mörner, S. & Henein, M. Y. (2020). Alcohol Septal Ablation versus Septal Myectomy Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine, 9(10), Article ID 3062.
Open this publication in new window or tab >>Alcohol Septal Ablation versus Septal Myectomy Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis
2020 (English)In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, no 10, article id 3062Article, review/survey (Refereed) Published
Abstract [en]

Surgical myectomy (SM) and alcohol septal ablation (ASA) are two invasive therapies for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), despite medical therapy. This meta-analysis aims to compare the efficacy of the two procedures. We searched all electronic databases until February 2020 for clinical trials and cohorts comparing clinical outcomes of ASA and SM treatment of patients with HOCM. The primary endpoint was all-cause mortality, cardiovascular (CV) mortality, sudden cardiac death (SCD), re-intervention, and complications. Secondary endpoints included relief of clinical symptoms and drop of left ventricular outflow tract (LVOT) gradient. Twenty studies (4547 patients; 2 CTs and 18 cohorts) comparing ASA vs. SM with a mean follow-up of 47 ± 28.7 months were included. Long term (8.72 vs. 7.84%, p = 0.42) and short term (1.12 vs. 1.27%, p = 0.93) all-cause mortality, CV mortality (2.48 vs. 3.66%, p = 0.26), SCD (1.78 vs. 0.76%, p = 0.20) and stroke (0.36 vs. 1.01%, p = 0.64) were not different between procedures. ASA was associated with lower peri-procedural complications (5.57 vs. 10.5%, p = 0.04) but higher rate of re-interventions (10.1 vs. 0.27%; p < 0.001) and pacemaker dependency (12.4 vs. 4.31%, p = 0.0004) compared to SM. ASA resulted in less reduction in LVOT gradient (−47.8 vs. −58.4 mmHg, p = 0.01) and less improvement of clinical symptoms compared to SM (New York Heart Association (NYHA) class III/IV, 82.4 vs. 94.5%, p < 0.001, angina 53.2 vs. 84.2%, p = 0.02). Thus, ASA and SM treatment of HOCM carry a similar risk of mortality. Peri-procedural complications are less in alcohol ablation but re-intervention and pacemaker implantations are more common. These results might impact the procedure choice in individual patients, for the best clinical outcome.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
hypertrophic obstructive cardiomyopathy, alcohol septal ablation, septal myectomy
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-177064 (URN)10.3390/jcm9103062 (DOI)000586898300001 ()32977442 (PubMedID)2-s2.0-85105718265 (Scopus ID)
Available from: 2020-12-04 Created: 2020-12-04 Last updated: 2023-03-24Bibliographically approved
Magnusson, P. & Mörner, S. (2020). Current Knowledge of Hypertrophic Cardiomyopathy Among Health Care Providers in Sweden. Cureus, 12(12), Article ID e12220.
Open this publication in new window or tab >>Current Knowledge of Hypertrophic Cardiomyopathy Among Health Care Providers in Sweden
2020 (English)In: Cureus, E-ISSN 2168-8184, Vol. 12, no 12, article id e12220Article in journal (Refereed) Published
Abstract [en]

Introduction: Hypertrophic cardiomyopathy (HCM) is a common disorder with various manifestations, including sudden cardiac death. Patients with suspected or confirmed HCM may be encountered throughout the healthcare system, especially in internal medicine and cardiology. Thus, thorough knowledge of HCM is essential among healthcare providers.

Methods: A web-based questionnaire was developed to assess the cross-sectional evaluation of HCM knowledge. It covered aspects such as epidemiology and diagnosis, treatment, lifestyle, risk stratification of sudden cardiac death, and implantable cardioverter-defibrillator knowledge.

Results: In total, 123 subjects completed the survey. The mean age was 38.5 +/- 10.7 years and two-thirds (n=82) were females; 43.1% were physicians (non-specialist 24.4%, cardiologists 8.9%, specialist, other than cardiology 9.8%); and the remaining were nurses (nurses within cardiology 37.4%, nurses outside cardiology 19.5%). Almost all subjects had heard about the disease (95.9%) and the vast majority (77.2%) had taken part in the management of a patient with HCM. The total mean score was 15.9 +/- 3.9 credits and the 25th, 50th, and 75th percentiles were 14, 15, and 18 credits, respectively. The predefined arbitrary pass score of )60% was reached by 61.8%, and 20.3% were considered to pass with distinction. Physicians scored higher than nurses (70.7 +/- 17.0% vs 58.1 +/- 11.8; p<0.001). Within each professional category, there was a similar score with regard to gender.

Conclusions: There is a considerable lack of knowledge of HCM among healthcare professionals working within the field of internal medicine/cardiology. This insufficient knowledge may contribute to less implementation of evidence-based medicine and current guidelines, although further studies are needed to confirm this.

Place, publisher, year, edition, pages
Cureus Inc., 2020
Keywords
arrhythmia, hypertrophic cardiomyopathy, sudden cardiac death
National Category
Cardiac and Cardiovascular Systems Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-179072 (URN)10.7759/cureus.12220 (DOI)000602925300010 ()
Available from: 2021-01-26 Created: 2021-01-26 Last updated: 2023-01-25Bibliographically approved
Begue, C., Mörner, S., Brito, D., Hengstenberg, C., Cleland, J. G. F., Arbustini, E., . . . Isnard, R. (2020). Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy. Heart, 106(3), 196-202
Open this publication in new window or tab >>Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy
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2020 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 106, no 3, p. 196-202Article in journal (Refereed) Published
Abstract [en]

Objectives N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. Methods We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. Results Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10(-4)) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). Conclusions MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2020
Keywords
natriuretic peptide, MR-proANP, NT-proBNP, hypertrophic cardiomyopathy
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-168136 (URN)10.1136/heartjnl-2019-314826 (DOI)000507910100009 ()31350276 (PubMedID)2-s2.0-85077728839 (Scopus ID)
Available from: 2020-02-21 Created: 2020-02-21 Last updated: 2023-03-23Bibliographically approved
Magnusson, P., Nordström, J., Harms, H. J., Lubberink, M., Gadler, F., Sörensen, J. & Mörner, S. (2020). Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. IJC Heart & Vasculature, 26, Article ID 100452.
Open this publication in new window or tab >>Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy
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2020 (English)In: IJC Heart & Vasculature, E-ISSN 2352-9067, Vol. 26, article id 100452Article in journal (Refereed) Published
Abstract [en]

Background: The objectives of the study were to describe positron emission tomography (PET) parameters, using the tracers 15O-water at rest/stress, 11C-acetate, and 11C-HED, with regard to nonsustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy (HCM). PET offers quantitative assessment of pathophysiology throughout the left ventricular segments, including the endocardium/epicardium. The potential use PET in risk stratification remains to be elucidated. NSVT provides a marker for sudden cardiac death.

Methods: Patients with a validated diagnosis of HCM who had an implantable cardioverter-defibrillator were interrogated at 12 months and independently of PET-examinations.

Results: In total, 25 patients (mean age 56.8 ± 12.9 years, 76% males) were included and 10 reported NSVT. Mean myocardial blood flow (MBF) at rest was 0.91 ml/g/min and decreased at stress, 1.59 ml/g/min. The mean gradient (endocardium/epicardium quotient) at rest was 1.14 ± 0.09, while inverse at stress (mean 0.92 ± 0.16). Notably, MBF gradient at stress was significantly lower in patients with NSVT (p = 0.022) and borderline at rest (p = 0.059) while global MBF at rest and stress were not. Mean myocardial oxygen consumption (MVO2) was 0.088 ml/g/min (higher in NSVT, p = 0.023) and myocardial external efficiency 18.5%. Using 11C-HED, the mean retention index was 0.11 min−1 and a higher volume of distribution (p = 0.089) or transmural gradient of clearance rate (p = 0.061) or lower clearance rate (p = 0.052) showed a tendency of association of NSVT.

Conclusions: The endocardium/epicardium MBF gradient at stress is significantly lower in HCM patients with NSVT. This provides a novel approach to further refine risk stratification of sudden cardiac death.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Arrhythmia, Hypertrophic cardiomyopathy, Positron emission tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-170548 (URN)10.1016/j.ijcha.2019.100452 (DOI)000524981900032 ()32140548 (PubMedID)2-s2.0-85077002642 (Scopus ID)
Available from: 2020-06-01 Created: 2020-06-01 Last updated: 2023-03-24Bibliographically approved
Magnusson, P. & Mörner, S. (2019). Evaluation of arrhythmias using an insertable cardiac monitor in patients with hypertrophic cardiomyopathy. Paper presented at Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Paris, FRANCE, AUG 31-SEP 04, 2019.. European Heart Journal, 40, 4169-4169
Open this publication in new window or tab >>Evaluation of arrhythmias using an insertable cardiac monitor in patients with hypertrophic cardiomyopathy
2019 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, p. 4169-4169Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-168187 (URN)10.1093/eurheartj/ehz746.1163 (DOI)000507313003843 ()
Conference
Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Paris, FRANCE, AUG 31-SEP 04, 2019.
Note

Supplement: 1. Meeting Abstract: P6575.

Available from: 2020-03-12 Created: 2020-03-12 Last updated: 2020-03-12Bibliographically approved
Hellman, U., Mörner, S. & Henein, M. (2019). Genetic variants in cardiac calcification in Northern Sweden. Medicine, 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, 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: 2022-02-10Bibliographically approved
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