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  • 1.
    Backman, Christer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Burned out myocardium in biventricular hypertrophic cardiomyopathy presenting with congestive heart failure: importance of ECG changes2014Ingår i: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, nr 3, s. 159-160Artikel i tidskrift (Refereegranskat)
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  • 2. Begue, Celine
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Brito, Dulce
    Hengstenberg, Christian
    Cleland, John G. F.
    Arbustini, Eloisa
    Galve, Enrique
    Wichter, Thomas
    Richter, Anette
    Golmard, Jean-Louis
    Bernard, Maguy
    Dubourg, Olivier
    Komajda, Michel
    Charron, Philippe
    Isnard, Richard
    Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy2020Ingår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 106, nr 3, s. 196-202Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Bytyci, Ibadete
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Universi College, Bardhosh, Prishtina, Kosovo; Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo.
    Nistri, Stefano
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Molecular and Clinic Research Institute, St George University, Brunel University, London, UK; Institute of Fluid Dynamics, Brunel University, London, UK.
    Alcohol Septal Ablation versus Septal Myectomy Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis2020Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 10, artikel-id 3062Artikel, forskningsöversikt (Refereegranskat)
    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.

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  • 4.
    Do, Lan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Dahl, Christen P
    Kerje, Susanne
    Hansell, Peter
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Ulla
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.2015Ingår i: International Journal of Cell Biology, ISSN 1687-8876, E-ISSN 1687-8884, artikel-id 938013Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hyaluronan is a negatively charged polydisperse polysaccharide where both its size and tissue concentration play an important role in many physiological and pathological processes. The various functions of hyaluronan depend on its molecular size. Up to now, it has been difficult to study the role of hyaluronan in diseases with pathological changes in the extracellular matrix where availability is low or tissue samples are small. Difficulty to obtain large enough biopsies from human diseased tissue or tissue from animal models has also restricted the study of hyaluronan. In this paper, we demonstrate that gas-phase electrophoretic molecular mobility analyzer (GEMMA) can be used to estimate the distribution of hyaluronan molecular sizes in biological samples with a limited amount of hyaluronan. The low detection level of the GEMMA method allows for estimation of hyaluronan molecular sizes from different parts of small organs. Hence, the GEMMA method opens opportunity to attain a profile over the distribution of hyaluronan molecular sizes and estimate changes caused by disease or experimental conditions that has not been possible to obtain before.

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  • 5.
    Engvall, Christer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Can myocardial strain differentiate hypertrophic from infiltrative etiology of a thickened septum?2011Ingår i: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 28, nr 4, s. 408-415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Septal systolic strain measurements showed reduced longitudinal function but its localized nature failed to demonstrate radial disturbances in patients with pathologically thickened septum. No difference was found in systolic strain between patients according to the etiology of septal thickness. This limitation might be either technical or is explained by the maintained radial function in all patient groups.

  • 6. Friedrich, Felix W.
    et al.
    Wilding, Brendan R.
    Reischmann, Silke
    Crocini, Claudia
    Lang, Patrick
    Charron, Philippe
    Mueller, Oliver J.
    McGrath, Meagan J.
    Vollert, Ingra
    Hansen, Arne
    Linke, Wolfgang A.
    Hengstenberg, Christian
    Bonne, Gisele
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wichter, Thomas
    Madeira, Hugo
    Arbustini, Eloisa
    Eschenhagen, Thomas
    Mitchell, Christina A.
    Isnard, Richard
    Carrier, Lucie
    Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy2012Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 21, nr 14, s. 3237-3254Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM is caused by mutations in sarcomeric genes, but in 40 of patients, the mutation is not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. We evaluated 121 HCM patients, devoid of a mutation in known disease genes. We identified three novel variants in FHL1 (c.134delA/K45Sfs, c.459CA/C153X and c.827GC/C276S). Whereas the c.459CA variant was associated with muscle weakness in some patients, the c.134delA and c.827GC variants were associated with isolated HCM. Gene transfer of the latter variants in C2C12 myoblasts and cardiac myocytes revealed reduced levels of FHL1 mutant proteins, which could be rescued by proteasome inhibition. Contractility measurements after adeno-associated virus transduction in rat-engineered heart tissue (EHT) showed: (i) higher and lower forces of contraction with K45Sfs and C276S, respectively, and (ii) prolonged contraction and relaxation with both mutants. All mutants except one activated the fetal hypertrophic gene program in EHT. In conclusion, this study provides evidence for FHL1 to be a novel gene for isolated HCM. These data, together with previous findings of proteasome impairment in HCM, suggest that FHL1 mutant proteins may act as poison peptides, leading to hypertrophy, diastolic dysfunction and/or altered contractility, all features of HCM.

  • 7.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Cardiology, Heart Centre, Umeå University, Umeå, Sweden.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruks universitet.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Rongquist, Gunnar
    Institutionen för medicinska vetenskaper, Klinisk kemi.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Cardiology, Heart Centre, Umeå University, Umeå, Sweden.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes2013Ingår i: Journal of Extracellular Vesicles, E-ISSN 2001-3078, artikel-id 20167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes.

    Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression.

    The exosomes were rounded in shape and had an average size of 50–90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups.

    We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

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  • 8.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ronquist, Gunnar
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes2013Ingår i: Journal of Extracellular Vesicles, E-ISSN 2001-3078, Vol. 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes. Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression. The exosomes were rounded in shape and had an average size of 50-90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups. We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

  • 9.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruks universitet.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    OPLS-DA of myocardial gene expression in the progression of cardiac hypertrophy in aorta ligated ratManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Malm, Linus
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Using OPLS-DA to find new hypotheses in vast amounts of gene expression data - Studying the progression of cardiac hypertrophy in the heart of aorta ligated rat2013Ingår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 522, nr 1, s. 27-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the great problems facing science today lies in data mining of the vast amount of data. In this study we explore a new way of using orthogonal partial least squares-discrimination analysis (OPLS-DA) to analyze multidimensional data. Myocardial tissues from aorta ligated and control rats (sacrificed at the acute, the adaptive and the stable phases of hypertrophy) were analyzed with whole genome microarray and OPLS-DA. Five functional gene transcript groups were found to show interesting clusters associated with the aorta ligated or the control animals. Clustering of "ECM and adhesion molecules" confirmed previous results found with traditional statistics. The clustering of "Fatty acid metabolism", "Glucose metabolism", "Mitochondria" and "Atherosclerosis" which are new results is hard to interpret, thereby being possible subject to new hypothesis formation. We propose that OPLS-DA is very useful in finding new results not found with traditional statistics, thereby presenting an easy way of creating new hypotheses.

  • 11.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wikström, Gerhard
    Institutionen för Medicinska Vetenskaper, Kardiologi, Uppsala univerisitet.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Samuel, Jane-Lise
    INSERM U 942, Hôpital Lariboisière, Paris, France.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellam
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Transcriptional regulation of cardiac genes balance pro and anti hypertrophic mechanisms in hypertrophic cardiomyopathy2012Ingår i: Cardiogenetics, ISSN 2035-8148, Vol. 2, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy. HCM is often hereditary, but the knowledge about the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocardium of HCM patients may contribute to the understanding of the mechanisms that drive and stabilize the hypertrophy.

    Design and Methods: Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA).

    Results: When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the MYH6, EGR1, APOB and FOS genes, and significant transcriptional up-regulation of the ACE2, JAK2, NPPA (ANP), APOA1 and HDAC5genes. 

    Conclusion: The transcriptional regulation revealed both pro and anti hypertrophic mechanisms. The pro hypertrophic response was explained by the transcriptional down-regulation of MYH6, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of JAK2 in JAK-STAT pathway. The anti hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), FOS and EGR1, and a transcriptional up-regulation of ACE2 and HDAC5. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.

  • 12.
    Gustafsson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå Heart Centre.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå Heart Centre.
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå Heart Centre.
    Can echocardiography differentiate hereditary transthyretin amyloidosis from hypertrophic cardiomyopathy?2013Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, nr Supplement: 1, s. 213-213Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: Hereditary transthyretin amyloidosis (ATTR) andhypertrophic cardiomyopathy (HCM) have many phenotypic similarities when examined by echocardiography. As the two conditions have different treatment strategies it is of importance to accurately diagnose these patients early in the disease. This study aimed to identify the most accurate echocardiographic method in differentiating these two conditions by using traditional and speckle tracking echocardiographyas well as myocardial texture analysis.

    Methods: We investigated 40 healthy controls, 33 patients with biopsy proven ATTR and 20 with HCM. All patients had septal thickness >12 mm. We measured left ventricular (LV) global strain as intrinsic systolic function and LV E/e' to estimate filling pressures. We also tested septal cyclic integrated backscatter (cIBS) and septal entropy as both being measures for myocardial highly reflection pattern whereas cIBS showing motion of highly reflective echoes and entropy the distribution of highly reflective echoes.

    Results: LV global strain, cIBS and E/e' were not useful in differentiating ATTR from HCM. However, septal entropy was found to be significantly different and showed an area under the curve from ROC analysis of 0.66 separating ATTR from HCM.

    Conclusion: After using detailed analysis of different aspects of LV morphology and function we found that myocardial texture behavior from entropy analysis was the only method useful in differentiating patients with ATTR fromHCM.

  • 13.
    Gustafsson, Ulf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Assessment of regional rotation patterns improves the understanding of the systolic and diastolic left ventricular function: an echocardiographic speckle-tracking study in healthy individuals2009Ingår i: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, nr 10, s. 56-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM To elucidate the complexity of left ventricular motion throughout the cardiac cycle, we studied regional rotation in detail. METHODS AND RESULTS: Regional rotation in six subdivisions of the circumference at three levels was studied by using speckle-tracking echocardiography in 40 healthy subjects. At the basal level the inferoseptal segments rotated significantly more clockwise during systole than the opposing anterolateral segments. At the papillary level the inferoseptal segments differed significantly from the anterolateral segments, where the inferoseptal segments rotated clockwise and the anterolateral segments rotated counter-clockwise. The apical level showed significant difference in regional rotation only at aortic valve opening. In early systole, untwist before the main systolic twist was seen at the basal and apical levels; however, the duration of the basal untwist was much longer than that of the apical. The diastolic phases of rotation at the basal and apical levels matched the different filling phases. CONCLUSION: Large regional differences in rotation are present at the basal and papillary levels in healthy subjects. The diastolic untwist matches the phases of both the E-wave and A-wave and seems to be related with intraventricular pressure differences, indicating that untwist plays an important role in the filling of the ventricle.

  • 14.
    Gustavsson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?2015Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 22, nr 3, s. 163-170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. Methods: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. Results: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). Conclusion: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

  • 15. Haas, Jan
    et al.
    Frese, Karen S
    Peil, Barbara
    Kloos, Wanda
    Keller, Andreas
    Nietsch, Rouven
    Feng, Zhu
    Müller, Sabine
    Kayvanpour, Elham
    Vogel, Britta
    Sedaghat-Hamedani, Farbod
    Lim, Wei-Keat
    Zhao, Xiaohong
    Fradkin, Dmitriy
    Köhler, Doreen
    Fischer, Simon
    Franke, Jennifer
    Marquart, Sabine
    Barb, Ioana
    Li, Daniel Tian
    Amr, Ali
    Ehlermann, Philipp
    Mereles, Derliz
    Weis, Tanja
    Hassel, Sarah
    Kremer, Andreas
    King, Vanessa
    Wirsz, Emil
    Isnard, Richard
    Komajda, Michel
    Serio, Alessandra
    Grasso, Maurizia
    Syrris, Petros
    Wicks, Eleanor
    Plagnol, Vincent
    Lopes, Luis
    Gadgaard, Tenna
    Eiskjær, Hans
    Jørgensen, Mads
    Garcia-Giustiniani, Diego
    Ortiz-Genga, Martin
    Crespo-Leiro, Maria G
    Deprez, Rondal H Lekanne Dit
    Christiaans, Imke
    van Rijsingen, Ingrid A
    Wilde, Arthur A.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bolognesi, Martino
    Bellazzi, Riccardo
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bermejo, Justo Lorenzo
    Monserrat, Lorenzo
    Villard, Eric
    Mogensen, Jens
    Pinto, Yigal M
    Charron, Philippe
    Elliott, Perry
    Arbustini, Eloisa
    Katus, Hugo A
    Meder, Benjamin
    Atlas of the clinical genetics of human dilated cardiomyopathy2015Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, nr 18, s. 1123-U43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

  • 16.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Hellström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Aberg, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Oliviero, Patricia
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat2008Ingår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 332, nr 1, s. 49-56Artikel i tidskrift (Refereegranskat)
  • 17.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ma, Li-Ping
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan2010Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 5, nr 12, s. e14393-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Co-cultivation of cardiomyocytes and fibroblasts (80%/20%) increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.

  • 18.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ma, Li-Ping
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyaluronan is both a product and stimulator of cardiomyocytes: a study in cell cultures of cardiomyocytes and fibroblastsManuskript (preprint) (Övrigt vetenskapligt)
  • 19.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy2010Ingår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 96, nr 2, s. 73-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy. To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study this correlation over time. A subset of differentially expressed genes was identified with a transcriptional regulation correlating to the increased synthesis of hyaluronan, suggesting a common regulatory pathway. Four transcription factors, Myc, Fos, Junb and Egr1, were also up-regulated. Furthermore, the Ace gene was up-regulated, representing increase of angiotensin II, an inducer of these transcription factors and fetal genes in cardiac hypertrophy. This demonstrates a coordinated synthesis of hyaluronan and pro-hypertrophic gene expression, regulated by immediate early genes, with angiotensin II as a possible mediator.

  • 20.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Molecular & Clinical Sciences Research Institute, St. George University, London; Brunel University, Middlesex, UK.
    Genetic variants in cardiac calcification in Northern Sweden2019Ingår i: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 98, nr 15, artikel-id e15065Artikel i tidskrift (Refereegranskat)
    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.

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  • 21.
    Hellström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyaluronan and collagen in human hypertrophic cardiomyopathy: a morphological analysis2012Ingår i: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, Vol. 2012, s. 545219-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hypertrophic cardiomyopathy (HCM) disease process is not only limited to cardiomyocyte abnormalities but also engages the extracellular matrix. Hyaluronan (HA) and its receptor CD44 are involved in cellular growth and tissue proliferation but have so far been less studied in myocardial hypertrophy. In HCM, collagens are abundant but their histological distribution and relation to hyaluronan have not been described. Material and Methods. Myocardial specimens from 5 patients with symptomatic left ventricular tract obstruction undergoing myectomy due to HCM were processed for histochemistry and immunohistochemistry. Results. HA staining was more intense in HCM patients. The histological distribution of HA was the same in patients and controls, that is, interstitial staining including the space between cardiomyocytes, in fibrous septa, and in the adventitia of intramyocardial blood vessels. CD44 was not detected in the myocardium of patients or controls. Collagen I showed the same general localisation as HA but detailed distribution differed. Conclusions. This is the first study that describes the distribution of hyaluronan in human HCM. HA staining is more intense in HCM patients but without coexpression of its receptor CD44, at least not in the chronic phase of HCM. HA and collagen I have the same localisation.

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  • 22.
    Henein, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Backman, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Long mitral valve leaflets determine left ventricular outflow tract obstruction during exercise in hypertrophic cardiomyopathy2016Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 212, s. 47-53Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    Henein, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Holmner, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Long anterior mitral leaflet causing outflow tract obstruction in a symptomatic patient with hypertrophic cardiomyopathy: the role of mitral valve surgical correction2016Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 204, s. 86-87Artikel i tidskrift (Refereegranskat)
  • 24.
    Henein, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Impaired left ventricular systolic function reserve limits cardiac output and exercise capacity in HFpEF patients due to systemic hypertension2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, nr 2, s. 1088-1093Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Heart failure (HF) patients with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) due to systemic hypertension (SHT) are known to have limited exercise tolerance. Despite having normal EF at rest, we hypothesize that these patients have abnormal systolic function reserve limiting their exercise capacity. METHODS: Seventeen patients with SHT (mean age 68±9years) but no valve disease and 14 healthy individuals (mean age of 65±10years) underwent resting and peak exercise echocardiography using conventional, tissue Doppler and speckle tracking techniques. The differences between resting and peak exercise values were also analyzed (Δ). Exercise capacity was determined as the workload divided by body surface area. RESULTS: Resting values for left atrial (LA) volume/BSA (r=-0.66, p<0.001) and global longitudinal strain rate (GLSR) in early (e) and late (a) diastole (r=0.47 and 0.46, p<0.05 for both) correlated with exercise capacity. LVEF increased during exercise in normals (mean Δ EF=10±8%) but failed to do so in patients (mean Δ EF=0.6±9%, p<0.001 between groups). LV GLSR during systole (s) also failed to increase with exercise in patients, to the same extent as it did in normals (0.2±0.2 vs. 0.6±0.3 1/s, p<0.001). The difference between rest and exercise (Δ) in LV lateral wall systolic velocity from tissue Doppler (s') (0.71, p<0.001), Δ in cardiac output (r=0.60, p<0.001) and Δ GLSRs (r=0.48, p<0.05) all correlated with exercise capacity independent of changes in heart rate. CONCLUSION: HFpEF patients with hypertensive LV disease have significantly limited exercise capacity which is related to left atrial enlargement as well as compromised LV systolic function at the time of the symptoms. The limited myocardial systolic function reserve seems to be underlying important explanation for their limited exercise capacity.

  • 25.
    Henein, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå Heart Center.
    The normal impact of age and gender on right heart structure and function2014Ingår i: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 31, nr 1, s. 5-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: As the proportion of elderly population increases rapidly, it might be difficult to differentiate physiological changes in cardiac function due to age from the pathophysiological ones. In addition, cardiac function variations with gender are well established. The right ventricular (RV) plays an important role in the overall cardiac function, but reference values varying with age and gender are lacking.

    MATERIAL AND METHODS: We studied 255 healthy individuals from a general population register, mean age of 58 ± 19 (range 22-89) years, 125 were females. We used 2D and M-mode echocardiography to measure RV inflow tract (RVIT) and RV outflow tract (RVOT) dimensions and fractional shortening (fs). Spectral Doppler echocardiography was also used.

    RESULTS: We found a modest decrease in RVIT dimensions (P < 0.05), but increase in RVOT dimensions with advancing age (P < 0.05). A small decrease in RVOT fs with age was also found (P < 0.05). Estimated pulmonary pressures and pulmonary vascular resistance increased (P < 0.001) as did RVOT wall thickness (P < 0.001), but RV diastolic function was not altered (P < 0.001) with age. Despite correction for the BSA, males showed larger RVIT dimensions (P < 0.001 for both), but RVOT end-diastolic dimension was larger in females (P < 0.05). RVIT and RVOT fractional shortening were increased in females (P < 0.01 for both).

    CONCLUSION: In a cohort of normal individuals, age has significant impact on RV structure and function, inlet area falls and outflow tract dimensions increase and fractional shortening also increase in females. In addition, RVOT wall thickness significantly increases and Doppler markers of pulmonary vascular resistance show a consistent rise. The age-related changes should carefully be considered when commenting on normality and when using absolute values.

  • 26.
    Johansson, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a morphological analysis2008Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 126, nr 2, s. 252-257Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To clarify the morphological basis of the limited coronary reserve in hypertrophic cardiomyopathy (HCM). BACKGROUND: Some of the symptoms in Hypertrophic cardiomyopathy (HCM), such as chest pain, dyspnea and arrhythmia, may be explained by myocardial ischemia. Many patients with HCM are known to exhibit these symptoms in the absence of atherosclerosis in the major coronary vessels. Decreased myocardial perfusion has been demonstrated in HCM, however, little is known about the myocardial capillary morphology in this disease. METHODS: Using immunohistochemistry and morphometry, we analysed capillaries and cardiomyocytes in myectomy specimens from 5 patients with HCM with moderate hypertrophy and left ventricular outflow tract obstruction and in 5 control hearts. RESULTS: The number of capillaries per cardiomyocyte (p<0.009) and number of capillaries per cardiomyocyte area unit, reflecting cardiomyocyte mass (p=0.009), were lower in individuals with HCM, i.e. indicating loss of capillaries. In HCM, the capillary density was 33% lower (p<0.05). CONCLUSIONS: Our morphologic findings show that the capillary supply, and thus the coronary reserve, is impaired in HCM with moderate hypertrophy and left ventricular outflow tract obstruction. These data may partly explain the limitation of myocardial perfusion in HCM, which is associated with worse prognosis. Furthermore, we present evidence of actual loss of myocardial capillaries in HCM and a defective capillary growth.

  • 27. Kostareva, Anna
    et al.
    Gudkova, Alexandra
    Sjöberg, Gunnar
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Semernin, Eugene
    Krutikov, Alexander
    Shlyakhto, Eugene
    Sejersen, Thomas
    Deletion in TNNI3 gene is associated with restrictive cardiomyopathy2009Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 131, nr 3, s. 410-412Artikel i tidskrift (Refereegranskat)
  • 28.
    Lindqvist, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Borgström, E
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Gustafsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asynchronous normal regional left ventricular function assessed by speckle tracking echocardiography: appearances can be deceptive2009Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 134, nr 2, s. 195-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Speckle tracking echocardiography (STE) is an angle independent method with high temporal resolution, which offers quantification of regional left ventricular (LV) wall motion. We studied radial and longitudinal LV wall motion by STE in healthy subjects with normal wall motion analysis (WMA) by eye-balling. MATERIALS AND METHODS: Eighteen healthy subjects were studied. We acquired parasternal short and apical long axis projections to determine the basal, mid and apical radial and longitudinal functions. At each level we measured; (I) radial and longitudinal peak displacement and displacement at aortic valve closure (AVC) and (II) the time interval from the Q-wave to the AVC and peak displacement. RESULTS: WMA indicated normal wall motion in all subjects. The mean peak radial displacement varied in different segments (range 3.9-9.8 mm) with highest values in the mid-level (6.9+/-1.5 mm), compared to basal level (5.9+/-1.0 mm, p<0.01) and apical level (5.4+/-1.0 mm, p<0.001). The time from Q-wave to AVC was 393 ms and in 89% of the analysed segments peak radial displacement occurred after AVC, thus mean peak radial displacement occurred 60 ms after AVC. The peak longitudinal amplitude was more synchronous with respect to AVC and with the highest amplitudes found in the two basal segments. CONCLUSIONS: In normal LV function, significant differences in peak displacement exist between segments at various LV levels using STE. In addition, in early diastole, significant discrepancy occurs between radial and longitudinal time of peak displacement, suggesting a shape change. Finally, while radial displacement was highest at mid-cavity level longitudinal displacement was highest at basal level.

  • 29.
    Lindqvist, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Cardiac mechanisms underlying normal exercise tolerance: gender impact2012Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 112, nr 2, s. 451-459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study is to test our hypothesis that normal exercise tolerance differs according to gender and to identify potential functional cardiac relationships, which could explain those differences. A total of 44 healthy individuals with mean age of 49 ± 12 years (28-74 years, 22 males) constituted the study cohort. All individuals underwent resting and exercise Doppler echocardiogram simultaneously with peak oxygen uptake analysis (pVO(2)). At equal pVO(2), males achieved higher peak exercise workload (p < 0.001) and females higher heart rate (p < 0.001) but the two groups maintained similar indexed left ventricular (LV) stroke volume (SV) and cardiac output. Indexed LV end-diastolic (LVDVI) and end-systolic volumes (LVSVI) were smaller in females (p < 0.001 and p < 0.01, respectively), but filling time (FT) was shorter (p < 0.001) and they had higher early diastolic (E) velocity (p = 0.004), E/E (m) (myocardial E velocity) (p < 0.001) and global longitudinal strain rate atrial velocity (GLSRa') (p = 0.02), compared to males. In males, workload (p < 0.01), LVDVI (p < 0.01), LVSVI (p < 0.05), SVI (p < 0.001) directly but LV myocardial isovolumic relaxation time (IVRTm) (p < 0.01) inversely correlated with pVO(2). In females, mitral E velocity (p < 0.01), GLSRs' (p < 0.05) positively and LVFT negatively (p < 0.05) correlated with pVO(2). In a multivariable analysis SVI in males (p < 0.01) and GLSRs' in females (p < 0.01) were the strongest predictors for pVO(2). Thus, normal exercise capacity as determined by pVO(2) is related to the indexed stroke volume in males and left atrial pressure in females. These native normal differences between genders may explain the known vulnerability of women to endurance exercise compared to men.

  • 30.
    Lindqvist, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Olofsson, Bert-Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Backman, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lundblad, Dan
    Sunderbyn Research Unit Luleå, Sweden.
    Forsberg, H
    Department of Medicine, Sunderbyn Research Unit,Luleå, Sweden.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ventricular dysfunction in type 1 myotonic dystrophy: Electrical, mechanical, or both?2010Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 143, nr 3, s. 378-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. METHODS: Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. RESULTS: Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR>/=200 ms, 11 had QRS duration >120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. CONCLUSIONS: In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials.

  • 31.
    Lorén, Christina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Dahl, Christen P.
    Do, Lan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Almaas, Vibeke M.
    Geiran, Odd R.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Low Molecular Mass Myocardial Hyaluronan in Human Hypertrophic Cardiomyopathy2019Ingår i: Cells, E-ISSN 2073-4409, Vol. 8, nr 2, artikel-id 97Artikel i tidskrift (Refereegranskat)
    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.

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  • 32.
    Lysell-Bergström, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Widman, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johnson, Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Progressive conduction disease late after adriamycin treatment of lymphoma, despite normalised ejection fraction2014Ingår i: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, nr 3, s. 160-161Artikel i tidskrift (Refereegranskat)
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  • 33. Magnusson, P.
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Evaluation of arrhythmias using an insertable cardiac monitor in patients with hypertrophic cardiomyopathy2019Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, s. 4169-4169Artikel i tidskrift (Övrigt vetenskapligt)
  • 34. Magnusson, Peter
    et al.
    Gadler, Fredrik
    Liv, Per
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden2016Ingår i: Journal of Cardiovascular Medicine, ISSN 1558-2027, E-ISSN 1558-2035, Vol. 17, nr 7, s. 478-484Artikel i tidskrift (Refereegranskat)
    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.

  • 35.
    Magnusson, Peter
    et al.
    Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gadler, Fredrik
    Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Liv, Per
    Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hypertrophic Cardiomyopathy and Implantable Defibrillators in Sweden: Inappropriate Shocks and Complications Requiring Surgery2015Ingår i: Cardiovascular Electrophysiology, ISSN 1045-3873, E-ISSN 1540-8167, Vol. 26, nr 10, s. 1088-1094Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inappropriate ICD Shocks and Complications in HCM IntroductionThe expanded use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) based on risk stratification in individuals without known previous ventricular arrhythmia is justified by an acceptable risk of device-related adverse events. Such complications, leading to surgical procedures or inappropriate electrical shocks, may impact mortality, morbidity, quality of life, and cost-effectiveness. Methods and ResultsFrom the Swedish ICD Registry, implants due to HCM since 1995 until November 2012 in patients aged 18 years were identified and medical records reviewed. Inappropriate ICD shock occurred in 14.3% (46 of 321 patients; mean follow-up 5.4 years) with a recurrent episode in 28.2% of them. In multivariable analysis, hazard ratio (HR) for atrial fibrillation was 3.5 (95% confidence interval 1.8-6.8; P < 0.001) but showed no significant association to male sex (HR = 0.77), age (HR = 0.99), secondary indication (HR = 1.02) or device, ICD-DR/CRTD vs. ICD-VR (HR 1.07). Inappropriate shocks were triggered by atrial fibrillation/flutter or ectopic tachycardia (56.5%), sinus tachycardia (14.5%), lead dysfunction (14.5%), and T-wave oversensing (13.0%). A reintervention, besides elective device replacement, occurred in 92 patients (totally 150 procedures). The majority were lead-related (70.0%) procedures, especially of the ICD lead. Reintervention was associated with female sex (HR = 1.6 P = 0.04). ConclusionInappropriate ICD shock triggered by atrial arrhythmias, lead dysfunction, or complications requiring surgical interventions, is a concern in HCM patients who will be eligible for long-term prevention of sudden death. Efforts to avoid adverse events and provide balanced risk-benefit information are important, especially in primary prevention.

  • 36. Magnusson, Peter
    et al.
    Gadler, Fredrik
    Liv, Per
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy2016Ingår i: Pacing and Clinical Electrophysiology, ISSN 0147-8389, E-ISSN 1540-8159, Vol. 39, nr 3, s. 291-301Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluations from patients at highly specialized centers.

    Aim To evaluate risk markers for appropriate implantable cardioverter defibrillator (ICD) therapy in an unselected, nationwide cohort of HCM. MethodsPatients with an ICD due to HCM were identified from the Swedish ICD Registry since its start in 1995, merged with Patient Register data, and medical records were retrieved. Risk markers for ventricular arrhythmias leading to appropriate ICD therapy were analyzed using Cox proportional hazard ratio (HR).

    Results Of 321 patients (70.1% males), at least one appropriate therapy occurred in 77 (24.0%) during a mean follow-up of 5.4 years (5.3% per year; primary prevention 4.5%, secondary prevention 7.0%). Cumulative incidences at 1 year, 3 years, and 5 years were 8.1%, 15.3%, and 21.3%, respectively. Cardioversion effectively restored rhythm in 52% of the first episode and antitachycardia pacing was sufficient in the remaining. For the whole cohort, ejection fraction (EF) <50% (HR 2.63; P < 0.001) was associated with appropriate ICD therapy. In primary prevention, patients with established risk markers experienced appropriate therapy; atrial fibrillation (AF; HR 2.54; P = 0.010), EF < 50% (HR 2.78; P = 0.004), and nonsustained ventricular tachycardia (HR 1.80; P = 0.109) had the highest HR, and wall thickness 30 mm, syncope, exercise blood pressure response, or family history of SCD had weaker associations.

    Conclusion ICD therapy successfully terminates ventricular arrhythmias in HCM. In addition to conventional risk markers, a history of AF or EF < 50% may be considered in risk stratification.

  • 37.
    Magnusson, Peter
    et al.
    VO kardiologi, Gävle sjukhus, Centrum för forskning och utveckling/Region Gävleborg, Uppsala universitet, Sweden.
    Gadler, Fredrik
    Hjärtkliniken, Karolinska universitetssjukhuset; båda institutionen för medicin, Karolinska institutet, Stockholm, Sweden.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hypertrofisk kardiomyopati vanligaste ärftliga hjärtsjukdomen: Sjukdomsförloppet är ofta godartat - Men risken för plötslig död i arytmi är välkänd: [Management of hypertrophic cardiomyopathy - The most common inherited heart disease]2018Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, nr 24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertrophic cardiomyopathy is the most common cardiogenetic disease affecting 1/500–1/1 000 individuals. Dyspnea is common but chest pain, dizziness or fainting may also cause considerable limitation for the patient. The diagnosis can be suspected from ECG. Echocardiography confirms hypertrophy of at least 15 mm, usually in the septum. If the obstruction of the outflow tract is severe, myectomy or alcohol ablation can relieve symptoms. Genetic evaluation of family members is advisable. To reduce symptoms, betablockers are used; verapamil or disopyramide are alternatives. Atrial fibrillation is often prevalent and requires special attention concerning anticoagulation and rhythm or rate control. An end-stage heart failure warrants advanced treatment options such as cardiac resynchronization therapy, ventricular assist devices or heart transplant. Sudden cardiac death is unpredictable and evaluation of risk markers is important to identify potential candidates for an implantable defibrillator.

  • 38. Magnusson, Peter
    et al.
    Jonsson, Jessica
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Fredriksson, Lennart
    Living with hypertrophic cardiomyopathy and an implantable defibrillator2017Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, artikel-id 121Artikel i tidskrift (Refereegranskat)
    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.

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  • 39. Magnusson, Peter
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Current Knowledge of Hypertrophic Cardiomyopathy Among Health Care Providers in Sweden2020Ingår i: Cureus, E-ISSN 2168-8184, Vol. 12, nr 12, artikel-id e12220Artikel i tidskrift (Refereegranskat)
    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.

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  • 40. Magnusson, Peter
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM) – rationale and design: a prospective observational study on incidence of arrhythmias in Sweden2017Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 7, nr 12, artikel-id e019541Artikel i tidskrift (Refereegranskat)
    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.

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  • 41. Magnusson, Peter
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM): A prospective observational study on incidence of arrhythmias2021Ingår i: Cardiovascular Electrophysiology, ISSN 1045-3873, E-ISSN 1540-8167, Vol. 32, nr 1, s. 129-135Artikel i tidskrift (Refereegranskat)
    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.

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  • 42. Magnusson, Peter
    et al.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Gadler, Fredrik
    Karlsson, Jan
    Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators2016Ingår i: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 14, artikel-id 62Artikel i tidskrift (Refereegranskat)
    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.

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  • 43. Magnusson, Peter
    et al.
    Nordström, Jonny
    Harms, Hendrik J.
    Lubberink, Mark
    Gadler, Fredrik
    Sörensen, Jens
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy2020Ingår i: IJC Heart & Vasculature, E-ISSN 2352-9067, Vol. 26, artikel-id 100452Artikel i tidskrift (Refereegranskat)
    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.

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  • 44.
    Magnusson, Peter
    et al.
    Uppsala Universitet - Centrum för forskning och utveckling, Region Gävleborg, Gävle Sweden Uppsala Universitet - Centrum för forskning och utveckling, Sweden Region Gävleborg, Uppsala, Sweden.
    Nordström, Jonny
    Uppsala Universitet - Center of Research and Development Region Gävleborg Gävle, Sweden Uppsala Universitet - Center of Research and Development Region Gävleborg Gävle, Sweden.
    Lubberink, Mark
    Uppsala Universitet - Institutionen för kirurgiska vetenskaper, Radiologi Uppsala, Sweden Uppsala Universitet - Institutionen för kirurgiska vetenskaper, Radiologi Uppsala, Sweden, Sweden.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sörensen, Jens
    Uppsala Universitet - Institutionen för kirurgiska vetenskaper, Radiologi Uppsala, Sweden Uppsala Universitet - Institutionen för kirurgiska vetenskaper, Radiologi Uppsala, Sweden, Sweden.
    PET med O-15-vatten påvisade myokard­ischemi där övrig utredning gick bet2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Elevation of troponin reflects myocardial infarction. The underlying causes should be assessed, as treatment and prognosis may differ widely. Myocardial damage with non-obstructive coronary arteries requires further evaluation including magnetic resonance tomography. We report a case of significant myocardial ischemia which was unnoticed by myocardial scintigraphy but detected by positron emission tomography (PET). The 15O-water tracer allows for quantitative assessment of myocardial perfusion including regional abnormalities and may thus diagnose microvascular dysfunction.

  • 45. Magnusson, Peter
    et al.
    Palm, Andreas
    Branden, Eva
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart Center.
    Misclassification of hypertrophic cardiomyopathy: validation of diagnostic codes2017Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, s. 403-410Artikel i tidskrift (Refereegranskat)
    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.

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  • 46. Maras, Dejan
    et al.
    Chung, Robin
    Duncan, Alison
    Li, Wei
    Thorp, Christine
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Patterns of cardiac dysfunction coinciding with exertional breathlessness in hypertrophic cardiomyopathy2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 170, nr 2, s. 233-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The commonest cause of breathlessness in hypertrophic cardiomyopathy (HCM) is left ventricular outflow tract (LVOT) obstruction which improves with its removal. However, in the absence of outflow tract obstruction, as in dilated cardiomyopathy, patients may be limited by similar symptoms, thus suggesting a potential common mechanism for the two conditions. We aimed to assess cardiac function at the time of symptoms in a group of unselected patients with HCM to identify other patterns of cardiac dysfunction which coincide with their breathlessness.

    METHODS: We studied 37 HCM patients (aged 55±15years, 13 female) with septal thickness >15mm and 17 controls (aged 58±12years, 12 female) using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms, >20mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine dosage of 40μg/kg/min.

    RESULTS: At rest: LV systolic function was maintained (EF 68±7 v 76±12%, respectively), LVOT velocity raised (p<0.005), lateral and septal long axis amplitude reduced (p<0.05 and p<0.005, respectively) and dyssynchronous and QRS duration was also broader (p<0.005) in patients compared to controls. At peak stress: Overall LVOT velocities were higher in patients than controls (4.3±1.7 v 1.7±1.0m/s, p<0.005, respectively) due to systolic anterior movement of the mitral valve and mitral regurgitation developing. In the 15 patients who did not develop significant LVOT obstruction (velocity <4m/s), LV ejection time increased and peak systolic amplitude did not increase. In the 10 patients with neither LVOT obstruction nor restrictive filling, QRS duration prolonged by 12ms (p <0.05), post-ejection shortening worsened and peak systolic amplitude fell (p<0.005). Also, LV ejection time prolonged by 5s/min (p<0.05), filling time failed to increase as it did in controls (p<0.005) and Tei index was higher than controls (p<0.01).

    CONCLUSION: Exertional breathlessness in HCM is associated with LV outflow tract obstruction and functional mitral regurgitation in almost two thirds of patients. The remaining one third have either resistant restrictive physiology or dyssynchronous cavity at fast heart rate. Despite similar exercise limiting breathlessness in the three groups, means of management should be quite different.

  • 47.
    Mörner, Stellan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kazzam, Elsadig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Amyloid heart disease mimicking hypertrophic cardiomyopathy.2005Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, nr 3, s. 225-230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the importance of transthyretin (TTR) gene mutations in explaining the phenotypic expression in patients diagnosed with hypertrophic cardiomyopathy (HCM) in northern Sweden. BACKGROUND: Hypertrophic cardiomyopathy is relatively common and often caused by mutations in sarcomeric protein genes. Mutations in the TTR gene are also common, one of which causes familial amyloid polyneuropathy (FAP), with peripheral polyneuropathy and frequently, cardiac hypertrophy. These circumstances were highlighted by the finding of an index case with amyloidosis, presenting itself as HCM. Initial rectal and fat biopsies did not show amyloid deposits. Later on, the patient was shown to carry a TTR gene mutation, and cardiac amyloidosis was confirmed by myocardial biopsy. Only then was a repeated fat biopsy positive for amyloid deposits. DESIGN: Cross-sectional study. SETTING: Cardiology tertiary referral centre. SUBJECTS: Forty-six unrelated individuals with HCM and the index case were included. Common diagnostic criteria for HCM were used. The 46 patients with HCM were previously analysed for mutations in eight sarcomeric protein genes and the TTR gene was now analysed by denaturing high-performance liquid chromatography and direct sequencing. RESULTS: One mutation in the TTR gene (Val30Met) was found in three individuals and the index case. CONCLUSIONS: Three of the 46 cases with HCM carried the Val30Met mutation, and were considered likely to have cardiac amyloidosis, like the index case. As a correct diagnosis of cardiac amyloidosis is mandatory for a potentially life-saving treatment, TTR mutation analysis should be considered in cases of HCM not explained by mutations in sarcomeric protein genes.

  • 48.
    Mörner, Stellan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart centre, Umeå.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart centre, Umeå.
    Cardiovascular genetics: the ultimate investigation for optimum management?2013Ingår i: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, nr 2, s. 57-58Artikel i tidskrift (Övrigt vetenskapligt)
  • 49.
    Mörner, Stellan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Arrhythmogenic left ventricular apical aneurysm in hypertrophic cardiomyopathy2010Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 151, nr 1, s. e8-e9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A 70-year old lady with prior myectomy for hypertrophic obstructive cardiomyopathy presented with sustained ventricular tachycardia. She was found to have a large left ventricular (LV) apical aneurysm. Surgical intervention was not advised, due to the risk of creating a small LV cavity after surgery and ICD was not advised based on the risk of injuring a very thin walled aneurysm. The patient's arrhythmia settled on medical therapy, but unfortunately she suffered an unwitnessed death three months later.

    This case represents a rare complication to a rare disease with limited management options. In such patients evidence based medicine is of little help, if any.

  • 50.
    Mörner, Stellan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Letter to editor: Tako-tsubo cardiomyopathy in the setting of pre-existing myocardial disease2010Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 145, nr 3, s. 605-Artikel, forskningsöversikt (Övrigt vetenskapligt)
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