Bermudez-Jimenez, Francisco J;
Protonotarios, Alexandros;
García-Hernández, Soledad;
Pérez Asensio, Ana;
Rampazzo, Alessandra;
Zorio, Esther;
Brodehl, Andreas;
... Jimenez-Jaimez, Juan; + view all
(2024)
Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.
JACC: Clinical Electrophysiology
10.1016/j.jacep.2024.02.031.
(In press).
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Syrris_Jimenez-Jaimez-JEP103123-1246-TRR.pdf - Accepted Version Access restricted to UCL open access staff until 9 May 2025. Download (1MB) |
Abstract
Background: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. // Objectives: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. // Methods: We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. // Results: Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. // Conclusions: DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
| Type: | Article |
|---|---|
| Title: | Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy |
| Location: | United States |
| DOI: | 10.1016/j.jacep.2024.02.031 |
| Publisher version: | http://dx.doi.org/10.1016/j.jacep.2024.02.031 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Arrhythmogenic cardiomyopathy; desmin; desminopathy; genetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10193346 |
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