Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Long-term outcome and risk stratification in dilated cardiolaminopathies.

Authors: Pasotti, M  Klersy, C  Pilotto, A  Marziliano, N  Rapezzi, C  Serio, A  Mannarino, S  Gambarin, F  Favalli, V  Grasso, M  Agozzino, M  Campana, C  Gavazzi, A  Febo, O  Marini, M  Landolina, M  Mortara, A  Piccolo, G  Vigano, M  Tavazzi, L  Arbustini, E 
Citation: Pasotti M, etal., J Am Coll Cardiol. 2008 Oct 7;52(15):1250-60.
Pubmed: (View Article at PubMed) PMID:18926329
DOI: Full-text: DOI:10.1016/j.jacc.2008.06.044

OBJECTIVES: The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. BACKGROUND: Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. METHODS: Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. RESULTS: Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. CONCLUSIONS: Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 2306091
Created: 2009-03-19
Species: All species
Last Modified: 2009-03-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.