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

被引：72

作者：

Gigli, Marta ^{[1
]}

Stolfo, Davide ^{[1
,2
]}

Graw, Sharon L. ^{[3
,4
]}

Merlo, Marco ^{[1
]}

Gregorio, Caterina ^{[5
,6
]}

Chen, Suet Nee ^{[3
,4
]}

Dal Ferro, Matteo ^{[1
]}

PaldinoMD, Alessia ^{[1
]}

De Angelis, Giulia ^{[1
]}

Brun, Francesca ^{[1
]}

Jirikowic, Jean ^{[3
,4
]}

Salcedo, Ernesto E. ^{[3
,4
]}

Turja, Sylvia ^{[3
,4
]}

Fatkin, Diane ^{[7
,8
,9
]}

Johnson, Renee ^{[7
,8
]}

van Tintelen, J. Peter ^{[10
,11
]}

Te Riele, Anneline S. J. M. ^{[10
,11
]}

Wilde, Arthur A. M. ^{[12
]}

Lakdawala, Neal K. ^{[13
]}

Picard, Kermshlise ^{[13
]}

Miani, Daniela ^{[14
]}

Muser, Daniele ^{[14
]}

Severini, Giovanni Maria ^{[15
]}

Calkins, Hugh ^{[16
]}

James, Cynthia A. ^{[16
]}

Murray, Brittney ^{[16
]}

Tichnell, Crystal ^{[16
]}

Parikh, Victoria N. ^{[17
]}

Ashley, Euan A. ^{[17
]}

Reuter, Chloe ^{[17
]}

Song, Jiangping ^{[18
]}

Judge, Daniel P. ^{[19
]}

McKenna, William J. ^{[20
]}

Taylor, Matthew R. G. ^{[3
,4
]}

Sinagra, Gianfranco ^{[1
]}

Mestroni, Luisa ^{[3
,4
]}

机构：

[1] Univ Trieste, Azienda Sanitaria Univ Giuliano Isontina ASUGI, Cardiothoracovasc Dept, Trieste, Italy

[2] Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden

[3] Univ Colorado, Cardiovasc Inst, Anschutz Med Campus, Aurora, CO USA

[4] Univ Colorado, Adult Med Genet Program, Anschutz Med Campus, Aurora, CO USA

[5] Univ Trieste, Dept Med Sci, Biostat Unit, Trieste, Italy

[6] Politecn Milan, MOX Modeling & Sci Comp Lab, Dept Math, Milan, Italy

[7] UNSW Sydney, Victor Chang Cardiac Res Inst, Mol Cardiol Div, Sydney, NSW, Australia

[8] UNSW Sydney, St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia

[9] St Vincents Hosp, Cardiol Dept, Sydney, NSW, Australia

[10] Univ Med Ctr Utrecht, Dept Genet & Cardiol, Div Med, Utrecht, Netherlands

[11] Netherlands Heart Inst, Utrecht, Netherlands

[12] Univ Amsterdam, Heart Ctr, Dept Clin & Expt Cardiol, Amsterdam UMC, Amsterdam, Netherlands

[13] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[14] Univ Hosp Udine, Udine, Italy

[15] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy

[16] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA

[17] Stanford Ctr Inherited Cardiovasc Dis, Stanford, CA USA

[18] Natl Ctr Cardiovasc Dis Beijing, Beijing, Peoples R China

[19] Med Univ South Carolina, Charleston, SC 29425 USA

[20] UCL, Inst Cardiovasc Sci, London, England

来源：

CIRCULATION | 2021年 / 144卷 / 20期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

arrhythmogenic right ventricular dysplasia; death; sudden; cardiac; FLNC protein; human; heart failure; outcome studies; prognosis; EUROPEAN-SOCIETY; TASK-FORCE; ASSOCIATION; GUIDELINES; MUTATIONS;

D O I：

10.1161/CIRCULATIONAHA.121.053521

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (4215 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.

引用

页码：1600 / 1611

页数：12

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