Gigli, Marta and Stolfo, Davide and Barbati, Giulia and Graw, Sharon and Chen, Suet Nee and Merlo, Marco and Medo, Kristen and Gregorio, Caterina and Dal Ferro, Matteo and Paldino, Alessia and Perotto, Maria and Peter van Tintelen, J. and Te Riele, Anneline S. J. M. and Baas, Annette F. and Wilde, Arthur M. and Amin, Ahmad S. and Houweling, Arjan C. and Elliott, Perry and Cannie, Douglas and Michels, Michelle and Schoonvelde, Stephan A. C. and Prasad, Sanjay and Tayal, Paz Upasana and Yazdani, Momina and Morris-Rosendahl, Deborah and Garcia-Pavia, Pablo and Cabrera-Romero, Eva and Bauce, Barbara and Pilichou, Kalliopi and Fatkin, Diane and Johnson, Renee and Judge, Daniel P. and Foil, Kimberly L. and Heymans, Stephane and Verdonschot, Job A. J. and Stroeks, Sophie L.V. M. and Lakdawala, Neal K. and Anisha, Purohit and O’Neill, Matthew and Shoemaker, M. Benjamin and Roden, Dan M. and Calkins, Hugh and James, Cynthia A. and Murray, Brittney and Parikh, Victoria N. and Ashley, Euan A. and Reuter, Chloe and Imazio, Massimo and Canepa, Marco and Ameri, Pietro and Song, Jiangping and Sinagra, Gianfranco and Taylor, Matthew R. G. and Mestroni, Luisa (2025) Arrhythmic Risk Stratification of Carriers of Filamin C Truncating Variants. JAMA Cardiology, 10 (4). p. 359. ISSN 2380-6583
Full text not available from this repository.Abstract
Importance
Filamin C truncating variants (FLNCtv) are a rare cause of cardiomyopathy with heterogeneous phenotypic presentations. Despite a high incidence of life-threatening ventricular arrhythmias and sudden cardiac death (SCD), reliable risk predictors to stratify carriers of FLNCtv are lacking.
Objective
To determine factors predictive of SCD/major ventricular arrhythmias (MVA) in carriers of FLNCtv.
Design, Setting, and Participants
This was an international, multicenter, retrospective cohort study conducted from February 2023 to June 2024. The Filamin C Registry Consortium included 19 referral centers for genetic cardiomyopathies worldwide. Participants included carriers of pathogenic or likely pathogenic FLNCtv. Phenotype negative was defined as the absence of any pathological findings detected by 12-lead electrocardiogram (ECG), Holter ECG monitoring, echocardiography, or cardiac magnetic resonance.
Exposures
Composite of SCD and MVA in carriers of FLNCtv.
Main Outcomes and Measures
The primary outcome was a composite of SCD and MVA, the last including aborted SCD, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) interventions.
Results
Among 308 individuals (median [IQR] age, 45 [33-56] years; 160 male [52%]) with FLNCtv, 112 (36%) were probands, and 72 (23%) were phenotype negative. Median (IQR) left ventricular ejection fraction (LVEF) was 51% (38%-59%); 89 participants (34%) had LVEF less than 45%, and 50 (20%) had right ventricular dysfunction. During a median (IQR) follow-up of 34 (8-63) months, 57 individuals (19%) experienced SCD/MVA, with an annual incidence rate of 4 cases per 100 person-years (95% CI, 3-6). Incidence rates were higher in probands vs nonprobands and in phenotype-positive vs phenotype-negative individuals. A predictive model estimating SCD/MVA risk was derived from multivariable analysis, which included older age, male sex, previous syncope, nonsustained ventricular tachycardia, and LVEF with a time-dependent area under the curve (AUC) ranging between 0.76 (95% CI, 0.67-0.86) at 12 months and 0.78 (95% CI, 0.70-0.86) at 72 months. Notably, the association of LVEF with the SCD/MVA risk was not linear, showing significant lower risk for values of LVEF greater than 58%, and no increase for values less than 58%. Internal validation with bootstrapping confirmed good accuracy and calibration of the model. Results were consistent in subgroups analysis (ie, phenotype-positive carriers and phenotype-positive carriers without MVA at onset).
Conclusions and Relevance
Results suggest that the risk of SCD/MVA in phenotype-positive carriers of FLNCtv was high. A 5-variable predictive model derived from this cohort allows risk estimation and could support clinicians in the shared decision for prophylactic ICD implantation. External cohort validation is warranted.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:33 |
| Last Modified: | 05 May 2025 06:33 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1684 |
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