| 1. |
- Fernlund, Eva I., et al.
(författare)
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Serum biomarkers of early stages of hypertrophic cardiomyopathy in a young population
- 2015
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Ingår i: Journal of the American College of Cardiology. - 0735-1097. ; 65:10S, s. 787-787
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Konferensbidrag (refereegranskat)abstract
- Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder and the leading cause of sudden cardiac death in the young. Although in a majority of HCM cases there are gene mutations coding for sarcomere proteins, the onset for the clinical consequences of these mutations are difficult to predict, as these mutations do not show any clear relationship to the degree of myocardial hypertrophy. Hence identification of early markers for this disease is important. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis and coronary endotheliopathy in young presymtomatic HCM patients and in individuals at risk for developing HCM. Methods: Eighty-nine participants (18 HCM patients, 14 HCM-risk individuals, and 57 healthy controls) with median age of 15 (range 0-30) years underwent assessment with echocardiography and serum analysis for myostatin, cathepsin S, endostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP) 9, vascular (VCAM) and intercellular adhesion molecules (ICAM). In some individuals, myocardial perfusion was measured both at rest and after adenosine via magnetic resonance. Results: Both cathepsin S and endostatin were increased in the HCM group (p0.3) and diastolic function, expressed as E/e' (p0.3). In the HCM-risk group, myostatin was decreased (p0.1). Conclusion: To the best of our knowledge, this is the first study to suggest early onset changes in biomarkers of myoblast regulation, endothelial function and matrix remodeling in young presymptomatic HCM patients and in HCM-risk individuals.
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| 2. |
- I. Fernlund, Eva, et al.
(författare)
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Early repolarization in children with unexplained syncope
- 2011
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 44:2, s. 10-10
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Konferensbidrag (refereegranskat)abstract
- Introduction: It has traditionally been believed that early repolarization (ER) is benign. Significant association between ER and sudden cardiac arrest due to idiopathic ventricular fibrillation was recently found in a large cohort of adult survivors of sudden cardiac arrest. In some prior studies, unexplained syncope has been linked to risk of sudden death, but the mechanisms remain speculative.We assessed herein the prevalence of ER in children referred to our center for unexplained syncope. Methods: We evaluated retrospectively electrocardiograms from such children (n = 29; mean age, 12.1 years; range, 7-18 years) for presence of ER, which was defined as an elevation of the QRS-ST junction (J-point) in at least 2 leads of at least 1 mm (0.1 mV) above the baseline level. The anterior precordial leads (V1-V3) were excluded from the analysis to avoid inclusion of patients with right ventricular dysplasia or Brugada syndrome. Agematched children (n = 33; mean age, 12.3 years; range, 7-16 years) with noncardiac chest pain were included as controls. Results: Early repolarization was detected in 45% (13/29) of children with unexplained syncope vs 24% (8/33) in the chest pain group. Among children with syncope, ER was far more frequent in males than in females (8/12 vs 5/ 17, respectively). Echocardiography showed normal functional and structural findings in all children. Conclusion: In this relatively small-scale retrospective study of children with unexplained syncope with otherwise normal cardiac findings, we found particularly among those of male gender a greater prevalence of ER than in controls (noncardiac chest pain).With view to earlier findings of Haisaguerre et al (NEJM 2008), this intriguing association warrants further prospective studies addressing its precise clinical implication and underlying mechanisms.
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| 3. |
- I. FERNLUND, EVA, et al.
(författare)
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MYBPC3 hypertrophic cardiomyopathy can be detected by using advanced ECG in children and young adults
- 2016
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 49:3, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. Methods Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2 years, range 0-30 years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1 month-30 years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. Results Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p <0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p <0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p <0.001). Conclusions In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes.
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| 4. |
- I. Fernlund, Eva, et al.
(författare)
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Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death
- 2017
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Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 38:6, s. 1262-1268
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Tidskriftsartikel (refereegranskat)abstract
- Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.
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| 5. |
- I. Fernlund, Eva, et al.
(författare)
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Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young
- 2017
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Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 38:4, s. 853-863
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Tidskriftsartikel (refereegranskat)abstract
- Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p < 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e′ (p < 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p < 0.05) versus controls. Endostatin and mitral E/e′ correlated inversely to myocardial perfusion (p ≤ 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.
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| 7. |
- Starc, Vito, et al.
(författare)
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Can functional cardiac age be predicted from the ECG in a normal healthy population?
- 2012
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Ingår i: Computing in Cardiology 2012, CinC 2012. - 9781467320740 ; 39, s. 101-104
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Konferensbidrag (refereegranskat)abstract
- We hypothesized that in a normal healthy population changes in several ECG parameters together might reliably characterize the functional age of the heart. Data from 377 healthy subjects (209 men, 168 women, aged 4 to 75 years) were included in the study. In all subjects, ECG recordings (resting 5-minute 12-lead high fidelity ECG) were evaluated via custom software programs to calculate up to 120 different conventional and advanced ECG parameters. Using factor analysis, those 5 parameters that exhibited the highest linear correlations with age and that were mutually the least correlated were evaluated by multiple linear regression analysis to predict the functional electrical age of the heart. Ignoring small differences between males and females, functional electrical age was best predicted (R2 of 0.76, P < 0.001) by multiple linear regression analysis incorporating the RR-interval normalized high frequency variability of RRV; the RR-interval normalized value of a QT variability parameter called QTcor; the mean high frequency QRS (150-250 Hz) amplitude; the mean ST segment level at the J point; and the body mass index. In apparently healthy subjects, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG parameters.
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