1. Phenotypic Expression, Natural History and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants
- Author
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Giovanni Maria Severini, Daniel P. Judge, Alessia PaldinoMD, Diane Fatkin, Chloe M. Reuter, Francesca Brun, Neal K. Lakdawala, Daniele Muser, Euan A. Ashley, J. Peter van Tintelen, Matthew R.G. Taylor, Ernesto E. Salcedo, Cynthia A. James, Arthur A.M. Wilde, Sylvia Turja, Brittney Murray, Hugh Calkins, Giulia De Angelis, D. Miani, Sharon L. Graw, Kermshlise Picard, Gianfranco Sinagra, Jean Jirikowic, William J. McKenna, Crystal Tichnell, Marta Gigli, Caterina Gregorio, Davide Stolfo, Anneline S.J.M. te Riele, Marco Merlo, Jiangping Song, Matteo Dal Ferro, Suet Nee Chen, Renee Johnson, Luisa Mestroni, Victoria N. Parikh, Gigli, Marta, Stolfo, Davide, Graw, Sharon, Merlo, Marco, Gregorio, Caterina, Chen, Suet Nee, Dal Ferro, Matteo, Paldino, Alessia, De Angelis, Giulia, Brun, Francesca, Jirikowic, Jean, Salcedo, Ernesto E, Turja, Sylvia, Fatkin, Diane, Johnson, Renee, van Tintelen, J Peter, Te Riele, Anneline S J M, Wilde, Arthur, Lakdawala, Neal K, Picard, Kermshlise, Miani, Daniela, Muser, Daniele, Severini, Giovanni Maria, Calkins, Hugh, James, Cynthia A, Murray, Brittney, Tichnell, Crystal, Parikh, Victoria N, Ashley, Euan A, Reuter, Chloe, Song, Jiangping, Judge, Daniel, Mckenna, William J, Taylor, Matthew R G, Sinagra, Gianfranco, Mestroni, Luisa, Cardiology, and ACS - Heart failure & arrhythmias
- Subjects
Adult ,Male ,Outcome Assessment ,Genotype ,Filamins ,Cardiomyopathy ,Filamin ,Article ,Cardiomyopathies/diagnosis ,Filamins/genetics ,Physiology (medical) ,Outcome Assessment, Health Care ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Registries ,FLNCtv ,Death sudden cardiac ,Alleles ,Genetic Association Studies ,Genetics ,business.industry ,Disease Management ,Genetic Variation ,Middle Aged ,medicine.disease ,Prognosis ,Phenotype ,Combined Modality Therapy ,Arrhythmogenic right ventricular dysplasia ,Health Care ,Natural history ,Echocardiography ,Risk stratification ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies - Abstract
Background: Filamin C truncating variants ( FLNCtv ) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. Methods: FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP -related arrhythmogenic cardiomyopathies were used for prognostic comparison. Results: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. Conclusions: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.
- Published
- 2021
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