Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy

Escobar-López, Luis; Ochoa, Juan Pablo; Mirelis, J. González; Espinosa, María Ángeles; Navarro, Marina; Gallego‐Delgado, María; Barriales‐Villa, Roberto; Robles‐Mezcua, Ainhoa; Basurte-Elorz, M. Teresa; García-Moreno, Laura Gutiérrez; Climent, Vicente; Jiménez‐Jáimez, Juan; Mogollón-Jiménez, María Victoria; López, Javier; Peña-Peña, María Luisa; García‐Álvarez, Ana; Brión, Marı́a; Ripoll‐Vera, Tomás; Palomino-Doza, Julián; Tirón, Coloma; Idiazabal, Uxua; Brogger, M N; García-Hernández, Soledad; Restrepo-Córdoba, María Alejandra; González-López, Esther; Méndez, Irene; Sabater, María; Villacorta, Eduardo; Larrañaga‐Moreira, José M.; Abecia, A; Fernández, Ana; García‐Pinilla, José Manuel; Palomares, José F. Rodríguez; Gimeno-Blanes, Juan Ramón; Bayés‐Genís, Antoni; Lara‐Pezzi, Enrique; Domínguez, Fernándo; García‐Pavía, Pablo

doi:10.1016/j.jacc.2021.08.039

Cited by 97 publications

(91 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The presence of myocardial scar determined by LGE on CMR and the presence of positive genotype are two new markers proposed to identify DCM patients with increased susceptibility to SCD. A recent study from our group analysing outcomes in 1005 genotyped DCM probands showed that those with P/LP variants had a worse clinical outcome than their G– peers 3 . The present study expands previous findings by combining genetic results with CMR findings.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy

Mirelis

Escobar-López

Ochoa

et al. 2022

European J of Heart Fail

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 83%

“…Recent studies suggest a genetic origin for DCM in ∼40% of patients, and several genotypes have been associated with increased arrhythmogenicity or progression to end‐stage heart failure (ESHF) 3–8 …”

Section: Introductionmentioning

confidence: 99%

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy

Mirelis

Escobar-López

Ochoa

et al. 2022

European J of Heart Fail

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, the presence of genetic DCM did not stratify between groups and did not seem to affect prognosis. Titin gene truncating variants, which are not known to confer additional prognostic risk, 11 , 19 , 20 were the most common genetic abnormality. There were few patients with variants in arrhythmogenic DCM genes that are known to affect outcome adversely.…”

Section: Discussionmentioning

confidence: 99%

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data

Tayal

Verdonschot²,

Hazebroek³

et al. 2022

Journal of the American College of Cardiology

View full text Add to dashboard Cite

“…Interestingly, our data are consistent with the findings from the study of 1005 patients diagnosed with nonischemic dilated cardiomyopathy which analysed prognostic impact of disease-causing variants classified based on the ACMG-AMP criteria. The rate of major adverse cardiovascular events, end stage heart failure and malignant ventricular arrhythmia in 10-year follow-up was significantly higher in the genotype-positive group compared to the genotype-negative but showed no trend towards higher rate of these conditions among patients carrying VUS [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Good performance of the criteria of American College of Medical Genetics and Genomics/Association for Molecular Pathology in prediction of pathogenicity of genetic variants causing thoracic aortic aneurysms and dissections

et al. 2022

View full text Add to dashboard Cite

Background The identification of pathogenic variant in patients with thoracic aortic aneurysms and dissections (TAAD) was previously found to be a significant indicator pointing to earlier need for surgical intervention. In order to evaluate available methods for classifying identified genetic variants we have compared the event-free survival in a cohort of TAAD patients classified as genotype-positive versus genotype-negative by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) criteria or by ClinVar database. Methods We analyzed previously unreported cohort of 132 patients tested in the routine clinical setting for genetic variants in a custom panel of 30 genes associated with TAAD or the TruSight Cardio commercial panel of 174 genes associated with cardiac disease. The identified variants were classified using VarSome platform. Kaplan–Meier survival curves were constructed to compare the event-free survival between probands defined as ‘genotype-positive’ and ‘genotype-negative’ using different classifications in order to compare their performance. Results Out of 107 rare variants found, 12 were classified as pathogenic/likely pathogenic by ClinVar, 38 were predicted to be pathogenic/likely pathogenic by ACMG. Variant pathogenicity as assessed by ACMG criteria was a strong predictor of event free survival (event free survival at 50 years 83% vs. 50%, for genotype positive patients vs. reference, respectively, p = 0.00096). The performance of ACMG criteria was similar to that of ClinVar (event free survival at 50 years 87% vs. 50%, for genotype positive patients vs. reference, respectively p = 0.023) but independent from it as shown by analysing variants with no ClinVar record (event free survival at 50 years 80% vs. 50%, p = 0.0039). Variants classified as VUS by ACMG criteria or ClinVar did not affect event-free survival. TAAD specific custom gene panel performed similar to the larger universal cardiac panel. Conclusions In our cohort of unrelated TAAD patients ACMG classification tool available at VarSome was useful in assessing pathogenicity of novel genetic variants. Gene panel containing the established genes associated with the highest risk of hereditary TAAD (ACTA1, COL3A1, FBN1, MYH11, SMAD3, TGFB2, TGFBR1, TGFBR2, MYLK) was sufficient to identify prevailing majority of variants most likely to be causative of the disease.

show abstract

Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy

Cited by 97 publications

References 33 publications

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data

Good performance of the criteria of American College of Medical Genetics and Genomics/Association for Molecular Pathology in prediction of pathogenicity of genetic variants causing thoracic aortic aneurysms and dissections

Contact Info

Product

Resources

About