Natural History of MYH7-Related Dilated Cardiomyopathy

Frutos, Fernando de; Ochoa, Juan Pablo; Navarro-Peñalver, Marina; Baas, Annette F.; Bjerre, Jesper Vandborg; Zorio, Esther; Méndez, Irene; Lorca, Rebeca; Verdonschot, Job A.J.; García‐Granja, Pablo Elpidio; Bilińska, Zofia T.; Fatkin, Diane; Fuentes‐Cañamero, María Eugenia; García‐Pinilla, José Manuel; García-Álvarez, María I.; Girolami, Francesca; Barriales‐Villa, Roberto; Díez‐López, Carles; Lopes, Luís Rocha; Wahbi, Karim; García‐Álvarez, Ana; Rodríguez-Sánchez, Ibon; Rekondo-Olaetxea, Javier; Palomares, José F. Rodríguez; Gallego‐Delgado, María; Meder, Benjamin; Kubánek, Miloš; Hansen, Frederikke G; Restrepo-Córdoba, María Alejandra; Palomino-Doza, Julián; Ruiz-Guerrero, Luis; Sarquella‐Brugada, Georgia; Perez-Perez, Alberto José; Bermúdez-Jiménez, Francisco; Ripoll‐Vera, Tomás; Rasmussen, Torsten Bloch; Jansen, Manon A. A.; Sabater-Molina, María; Elliot, Perry; García‐Pavía, Pablo

doi:10.1016/j.jacc.2022.07.023

Cited by 34 publications

(15 citation statements)

References 32 publications

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“…27,28 MYH7 -related DCM features include an early onset which corroborates with the characteristics observed in our cases. 29…”

Section: Discussionmentioning

confidence: 99%

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Hirono,

Hata,

Ichimata

et al. 2024

Preprint

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Background: Dilated cardiomyopathy (DCM) is a progressive myocardial disorder characterized by impaired cardiac contraction and ventricular dilation. Some patients with DCM could manifest improvement in these abnormalities called left ventricular reverse remodeling (LVRR). However, the detailed association between genotypes and clinical outcomes, including LVRR, particularly among pediatric patients, remains uncertain. Methods: We prospectively enrolled pediatric patients with DCM from Japanese multi-institutional centers between 2014 and 2023. We identified DCM-related genes and explored the association between gene variants and clinical outcomes, including LVRR, which was defined as any increase in left ventricular ejection fraction during the observation period. Results: A total of 123 pediatric patients (62 males; mean age of 8 months [range, 1?51 months]) were retrospectively enrolled. There were 50 pathogenic variants in 45 patients (35.0%). The most identified gene was MYH7 (14.0%), followed by RYR2 (12.0%), and TPM1 (8.0%). A novel variant in the CASZ1 gene (NM_001079843.2 c.3356G>A, p. Trp1119Ter) was identified. LVRR was achieved in 47.5% of patients. In patients with sarcomere gene variants, the left ventricular ejection fraction remained unchanged (31.4% to 39.8%, P = 0.1913), whereas it significantly increased in patients with non-sarcomere gene variants (33.4% to 47.8%, P = 0.0466) and in patients without gene variants (33.6% to 54.1%, P = 0.003). Conclusions: Pediatric patients with DCM exhibited a marked genetic heterogeneity with a different landscape from adults with DCM. LVRR was not uniform across functional gene groups, opening the door to tailor-made gene-guided prediction in pediatric patients with DCM.

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“…27,28 MYH7 -related DCM features include an early onset which corroborates with the characteristics observed in our cases. 29…”

Section: Discussionmentioning

confidence: 99%

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Hirono,

Hata,

Ichimata

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…32 The majority of patients with DCM-causing MYH7 (myosin heavy chain 7) variants, may present with excessive trabeculation on CMR imaging, whereas midwall fibrosis distribution is the most frequently detected patern. 33 Additionally, MYH7 variants have been associated with increased risk of end-stage heart failure, 33 while patients carrying P/LP variants in both TNNT2 and MYH7 genes may develop severe cardiomyopathy early in life. 34…”

Section: Dcm Genes and Imaging Phenotypesmentioning

confidence: 99%

Imagenetics for Precision Medicine in Dilated Cardiomyopathy

Antonopoulos,

Xintarakou,

Protonotarios

et al. 2024

Circ: Genomic and Precision Medicine

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Dilated cardiomyopathy (DCM) is a common heart muscle disorder of nonischemic etiology associated with heart failure development and the risk of malignant ventricular arrhythmias and sudden cardiac death. A tailored approach to risk stratification and prevention of sudden cardiac death is required in genetic DCM given its variable presentation and phenotypic severity. Currently, advances in cardiogenetics have shed light on disease mechanisms, the complex genetic architecture of DCM, polygenic contributors to disease susceptibility and the role of environmental triggers. Parallel advances in imaging have also enhanced disease recognition and the identification of the wide spectrum of phenotypes falling under the DCM umbrella. Genotype-phenotype associations have been also established for specific subtypes of DCM, such as DSP (desmoplakin) or FLNC (filamin-C) cardiomyopathy but overall, they remain elusive and not readily identifiable. Also, despite the accumulated knowledge on disease mechanisms, certain aspects remain still unclear, such as which patients with DCM are at risk for disease progression or remission after treatment. Imagenetics, that is, the combination of imaging and genetics, is expected to further advance research in the field and contribute to precision medicine in DCM management and treatment. In the present article, we review the existing literature in the field, summarize the established knowledge and emerging data on the value of genetics and imaging in establishing genotype-phenotype associations in DCM and in clinical decision making for DCM patients.

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“…Genetic variants in MYH7 are reported to be the third most common cause of DCM ( 7 ), about 10% of all cases. The clinical characteristics for these were recently comprehensively evaluated ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Affimers targeting proteins in the cardiomyocyte Z-disc: Novel tools that improve imaging of heart tissue

Parker

Tang²,

Rogers³

et al. 2023

Front. Cardiovasc. Med.

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Dilated Cardiomyopathy is a common form of heart failure. Determining how this disease affects the structure and organization of cardiomyocytes in the human heart is important in understanding how the heart becomes less effective at contraction. Here we isolated and characterised Affimers (small non-antibody binding proteins) to Z-disc proteins ACTN2 (α-actinin-2), ZASP (also known as LIM domain binding protein 3 or LDB3) and the N-terminal region of the giant protein titin (TTN Z1-Z2). These proteins are known to localise in both the sarcomere Z-discs and the transitional junctions, found close to the intercalated discs that connect adjacent cardiomyocytes. We use cryosections of left ventricles from two patients diagnosed with end-stage Dilated Cardiomyopathy who underwent Orthotopic Heart Transplantation and were whole genome sequenced. We describe how Affimers substantially improve the resolution achieved by confocal and STED microscopy compared to conventional antibodies. We quantified the expression of ACTN2, ZASP and TTN proteins in two patients with dilated cardiomyopathy and compared them with a sex- and age-matched healthy donor. The small size of the Affimer reagents, combined with a small linkage error (the distance from the epitope to the dye label covalently bound to the Affimer) revealed new structural details in Z-discs and intercalated discs in the failing samples. Affimers are thus useful for analysis of changes to cardiomyocyte structure and organisation in diseased hearts.

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Natural History of MYH7-Related Dilated Cardiomyopathy

Cited by 34 publications

References 32 publications

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Imagenetics for Precision Medicine in Dilated Cardiomyopathy

Affimers targeting proteins in the cardiomyocyte Z-disc: Novel tools that improve imaging of heart tissue

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