Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants-Reference-Cited by-同舟云学术

Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants

Published:2021-11-16 Issue:20 Volume:144 Page:1600-1611
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Gigli Marta¹,Stolfo Davide¹²^ORCID,Graw Sharon L.³,Merlo Marco¹,Gregorio Caterina⁴⁵,Nee Chen Suet³,Dal Ferro Matteo¹,PaldinoMD Alessia¹,De Angelis Giulia¹^ORCID,Brun Francesca¹,Jirikowic Jean³,Salcedo Ernesto E.³,Turja Sylvia³,Fatkin Diane⁶⁷^ORCID,Johnson Renee⁶,van Tintelen J. Peter⁸⁹,Te Riele Anneline S.J.M.⁸⁹,Wilde Arthur A.M.¹⁰,Lakdawala Neal K.¹¹,Picard Kermshlise¹¹,Miani Daniela¹²,Muser Daniele¹²,Maria Severini Giovanni¹³^ORCID,Calkins Hugh¹⁴^ORCID,James Cynthia A.¹⁴,Murray Brittney¹⁴,Tichnell Crystal¹⁴,Parikh Victoria N.¹⁵,Ashley Euan A.¹⁵^ORCID,Reuter Chloe¹⁵^ORCID,Song Jiangping¹⁶,Judge Daniel P.¹⁷,McKenna William J.¹⁸,Taylor Matthew R.G.³^ORCID,Sinagra Gianfranco¹,Mestroni Luisa³^ORCID

Affiliation:

1. Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy (M.G., D.S., M.M., M.D.F., A.P., G.D.A., F.B., G.S.).

2. Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden (D.S.).

3. Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora (S.G., S.N.C., J.J., E.E.S., S.T., M.R.G.T., L.M.).

4. Biostatistics Unit, Department of Medical Sciences, University of Trieste, Italy (C.G.).

5. MOX-Modeling and Scientific Computing Laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy (C.G.).

6. Molecular Cardiology Division, Victor Chang Cardiac Research Institute, and St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Australia (D.F., R.J.).

7. Cardiology Department, St Vincent’s Hospital, Sydney, Australia (D.F.).

8. Division of Medicine, Department of Genetics and Cardiology, University Medical Center, Utrecht, the Netherlands (J.P.v.T., A.S.J.M.T.R.).

9. Netherlands Heart Institute, Utrecht (J.P.v.T., A.S.J.M.T.R.).

10. Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, the Netherlands (A.W.).

11. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (N.K.L., K.P.).

12. University Hospital of Udine, Italy (D. Miani, D. Muser).

13. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy (G.M.S.).

14. Division of Cardiology, Department of Medicine, The Johns Hopkins University, Baltimore, MD (H.C., C.A.J., B.M., C.T.).

15. Stanford Center for Inherited Cardiovascular Disease, CA (V.N.P., E.A.A., C.R.).

16. National Center for Cardiovascular Diseases in Beijing, China (J.S.).

17. Medical University of South Carolina, Charleston (D.J.).

18. Institute of Cardiovascular Science, University College of London, United Kingdom (W.J.M.).

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 <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area – right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Link

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.053521

Reference30 articles.

1. Arrhythmogenic Cardiomyopathy

2. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy

3. Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life‐Threatening Arrhythmias

4. Arrhythmogenic cardiomyopathies (ACs): diagnosis, risk stratification and management

5. Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy

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