دورية أكاديمية
Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy
| العنوان: | Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy |
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| المؤلفون: | Skriver, Sofie Vinther, Krett, Bjørg, Poulsen, Nanna Scharf, Krag, Thomas, Walas, Helle Rudkjær, Christensen, Alex Hørby, Bundgaard, Henning, Vissing, John, Vissing, Christoffer Rasmus |
| المصدر: | Skriver , S V , Krett , B , Poulsen , N S , Krag , T , Walas , H R , Christensen , A H , Bundgaard , H , Vissing , J & Vissing , C R 2024 , ' Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy ' , JACC: Heart Failure , vol. 12 , no. 4 , pp. 740-753 . https://doi.org/10.1016/j.jchf.2023.10.010Test |
| سنة النشر: | 2024 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | genotype, inherited cardiomyopathies, phenotype, truncating titin variants |
| الوصف: | Background Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal muscle phenotype in individuals carrying heterozygous truncating TTN variants (TTNtv), the leading cause of DCM, is understudied. Objectives This study aimed to assess the skeletal muscle phenotype associated with TTNtv. Methods Participants with TTNtv were included in a cross-sectional study. Skeletal muscle fat fraction was evaluated by magnetic resonance imaging (compared with healthy controls and controls with non-TTNtv DCM). Muscle strength was evaluated by dynamometry and muscle biopsy specimens were analyzed. Results Twenty-five TTNtv participants (11 women, mean age 51 ± 15 years, left ventricular ejection fraction 45% ± 10%) were included (19 had DCM). Compared to healthy controls (n = 25), fat fraction was higher in calf (12.5% vs 9.9%, P = 0.013), thigh (12.2% vs 9.3%, P = 0.004), and paraspinal muscles (18.8% vs 13.9%, P = 0.008) of TTNtv participants. Linear mixed effects modelling found higher fat fractions in TTNtv participants compared to healthy controls (2.5%; 95% CI: 1.4-3.7; P < 0.001) and controls with non-TTNtv genetic DCM (n = 7) (1.5%; 95% CI: 0.2-2.8; P = 0.025). Muscle strength was within 1 SD of normal values. Biopsy specimens from 21 participants found myopathic features in 13 (62%), including central nuclei. Electron microscopy showed well-ordered Z-lines and T-tubuli but uneven and discontinuous M-lines and excessive glycogen depositions flanked by autophagosomes, lysosomes, and abnormal mitochondria with mitophagy. Conclusions Mild skeletal muscle involvement was prevalent in patients with TTNtv. The phenotype was characterized by an increased muscle fat fraction and excessive accumulation of glycogen, possibly due to reduced autophagic flux. These findings indicate an impact of TTNtv beyond the heart. ; Background: Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1016/j.jchf.2023.10.010 |
| الإتاحة: | https://doi.org/10.1016/j.jchf.2023.10.010Test https://curis.ku.dk/portal/da/publications/skeletal-muscle-involvement-in-patients-with-truncations-of-titin-and-familial-dilated-cardiomyopathyTest(d52c181f-a8c9-44cc-a376-ee5f3cc91a67).html |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.A415CA82 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jchf.2023.10.010 |
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