| 1. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 2. |
- Liuba, Ioan, et al.
(författare)
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Scar progression in patients with nonischemic cardiomyopathy and ventricular arrhythmias
- 2014
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Ingår i: Heart Rhythm. - : Elsevier. - 1547-5271 .- 1556-3871. ; 11:5, s. 755-762
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Disease progression in patients with nonischemic cardiomyopathy (NICM) is poorly understood. OBJECTIVE To assess left ventricular(LV) scar progression and dilatation by using endocardial electroanatomic mapping. METHODS We studied 13 patients with NICM and recurrent ventricular tachycardia. Two detailed sinus rhythm endocardial voltage maps(265 +/- 122 points/map) were obtained after a mean of 32 months(range 9-77 months). The scar area, defined by low bipolar (BI; less than 1.5 mV) and unipolar(UNI; less than 8.3 mV) endocardial voltage, and the LV volume were measured and compared. A scar difference of greater than 6% of the LV surface and an increase in LV volume of greater than= 20 mL were considered beyond measurement error. RESULTS Six (46%) patients had an increase in scar area beyond boundaries of prior ablation. Five patients had an increase in UNI and 1 patient had an increase in both BI and UNI areas. The increase in BI area represented 16% and the increase in UNI area represented 6.5%-46.2% of the LV surface. A significant decrease in LV ejection fraction was found only in patients with scar progression (from 39% +/- 8%:p = .0003) (LV volume increase ranging between 9% and 23%) was noted in 3 patients, all of whom had scar progression. CONCLUSIONS Progressive scarring with an increase in the area of UNI and less commonly BI electrogram abnormality is seen in 46% of the patients with NICM and ventricular tachycardia and is associated with LV dilatation and decrease in LV ejection fraction. The prominent UNI abnormality suggests predominantly midmyo-cardial or epicardial scarring.
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| 3. |
- Muser, Daniele, et al.
(författare)
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Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias
- 2021
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 143:14, s. 1359-1373
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Tidskriftsartikel (refereegranskat)abstract
- Background: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. Methods: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. Results: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). Conclusions: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.
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| 4. |
- Muser, Daniele, et al.
(författare)
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Risk Stratification of Patients With Apparently Idiopathic Premature Ventricular Contractions A Multicenter International CMR Registry
- 2020
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Ingår i: JACC. - : ELSEVIER. - 2405-500X .- 2405-5018. ; 6:6, s. 722-735
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study investigated the prevalence and prognostic significance of concealed myocardial abnormalities identified by cardiac magnetic resonance (CMR) imaging in patients with apparently idiopathic premature ventricular contractions (PVCs). BACKGROUND The rote of CMR imaging in patients with frequent PVCs and otherwise negative diagnostic workup is uncertain. METHODS This was a multicenter, international study that included 518 patients (age 44 +/- 15 years; 57% men) with frequent (>1,000/24 h) PVCs and negative routine diagnostic workup. Patients underwent a comprehensive CMR protocol including late gadolinium enhancement imaging for detection of necrosis and/or fibrosis. The study endpoint was a composite of sudden cardiac death, resuscitated cardiac arrest, and nonfatal episodes of ventricular fibrillation or sustained ventricular tachycardia that required appropriate implantable cardioverter-defibrillator therapy. RESULTS Myocardial abnormalities were found in 85 (16%) patients. Mate gender (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.06 to 8.93; p = 0.01), family history of sudden cardiac death and/or cardiomyopathy (OR: 3.61; 95% CI: 1.33 to 9.82; p = 0.01), multifocat PVCs (OR: 11.12; 95% CI: 4.35 to 28.46; p < 0.01), and non-left bundle branch block inferior axis morphology (OR: 14.11; 95% CI: 7.35 to 27.07; p < 0.01) were alt significantly related to the presence of myocardial abnormalities. After a median follow-up of 67 months, the composite endpoint occurred in 26 (5%) patients. Subjects with myocardial abnormalities on CMR had a higher incidence of the composite outcome (n = 25; 29%) compared with those without abnormalities (n = 1; 0.2%; p < 0.01). CONCLUSIONS CMR can identify concealed myocardial abnormalities in 16% of patients with apparently idiopathic frequent PVCs. Presence of myocardial abnormalities on CMR predict worse clinical outcomes. (C) 2019 by the American College of Cardiology Foundation.
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