Natural History, Phenotype Spectrum and Clinical Outcomes of Desmin ( DES )-Associated Cardiomyopathy.

Autor:	Asatryan B; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Rieder M; Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Murray B; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Muller SA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Division of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands., Tichnell C; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Gasperetti A; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Carrick RT; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Joseph E; Welch Medical Library, Johns Hopkins School of Medicine, Baltimore, MD, USA., Leung DG; Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Te Riele ASJM; Division of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Netherlands Heart Institute, Utrecht, the Netherlands., Zimmerman SL; The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Calkins H; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., James CA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Barth AS; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Aug 26. Date of Electronic Publication: 2024 Aug 26.
DOI:	10.1101/2024.08.24.24311904
Abstrakt:	Background: Pathogenic/likely pathogenic (P/LP) desmin ( DES ) variants cause heterogeneous cardiomyopathy and/or skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACE), including cardiac conduction disease (CCD), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, LVAD/cardiac transplant, HF-related death), in patients with P/LP DES variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. Objectives: We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with P/LP DES variants through a systematic review and individual patient data meta-analysis using published reports. Methods: We searched Medline (PubMed) and Embase for studies that evaluated cardiac phenotypes in patients with P/LP DES variants. Cardiomyopathy diagnosis or occurrence of MACE were considered evidence of cardiac involvement/penetrance. Lifetime event-free survival from CCD, sustained VA, HF events, and composite MACE was assessed. Results: Out of 4,212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% male, 52.2% probands, median age: 31 years [22.0; 42.8] at first evaluation, median follow-up: 3 years [0; 11.0]). Overall, 124 (53.9%) patients were diagnosed with cardiomyopathy, predominantly dilated cardiomyopathy (14.8%), followed by restrictive cardiomyopathy (13.5%), whereas other forms were less common: arrhythmogenic cardiomyopathy (7.0%), hypertrophic cardiomyopathy (6.1%), arrhythmogenic right ventricular cardiomyopathy (5.2%), and other forms (7.4%). Overall, 132 (57.4%) patients developed MACE, with 96 [41.7%] having CCD, 36 [15.7%] sustained VA, and 43 [18.7%] HF events. Familial penetrance of cardiac disease was 63.6% among relatives with P/LP DES variants. Male sex was associated with increased risk of sustained VA (HR 2.28, p=0.02) and HF events (HR 2.45, p=0.008). Conclusions: DES cardiomyopathy exhibits heterogeneous phenotypes and distinct natural history, characterized by high familial penetrance and substantial MACE burden. Male patients face higher risk of sustained VA events.
Databáze:	MEDLINE
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