Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy.
BACKGROUND
The clinical outcomes of noncompaction cardiomyopathy (NCCM) range from asymptomatic to heart failure, arrhythmias, and sudden cardiac death. Genetics play an important role in NCCM.


OBJECTIVES
This study investigated the correlations among genetics, clinical features, and outcomes in adults and children diagnosed with NCCM.


METHODS
A retrospective multicenter study from 4 cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16% (45 adults; 8 children) of patients; or 3) sporadic, no family history, without mutation in 52% (149 adults; 21 children) of patients. Clinical features and major adverse cardiac events (MACE) during follow-up were compared across the children and adults.


RESULTS
MYH7, MYBPC3, and TTN mutations were the most common mutations (71%) found in genetic NCCM. The risk of having reduced left ventricular (LV) systolic dysfunction was higher for genetic patients compared with the probably genetic and sporadic cases (p = 0.024), with the highest risk in patients with multiple mutations and TTN mutations. Mutations were more frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults were more likely to have sporadic NCCM. High risk for cardiac events in children and adults was related to LV systolic dysfunction in mutation carriers, but not in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03).


CONCLUSIONS
NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status.
['van Waning|Jaap I|JI|', 'Caliskan|Kadir|K|', 'Hoedemaekers|Yvonne M|YM|', 'van Spaendonck-Zwarts|Karin Y|KY|', 'Baas|Annette F|AF|', 'Boekholdt|S Matthijs|SM|', 'van Melle|Joost P|JP|', 'Teske|Arco J|AJ|', 'Asselbergs|Folkert W|FW|', 'Backx|Ad P C M|APCM|', 'du Marchie Sarvaas|Gideon J|GJ|', 'Dalinghaus|Michiel|M|', 'Breur|Johannes M P J|JMPJ|', 'Linschoten|Marijke P M|MPM|', 'Verlooij|Laura A|LA|', 'Kardys|Isabella|I|', 'Dooijes|Dennis|D|', 'Lekanne Deprez|Ronald H|RH|', 'IJpma|Arne S|AS|', 'van den Berg|Maarten P|MP|', 'Hofstra|Robert M W|RMW|', 'van Slegtenhorst|Marjon A|MA|', 'Jongbloed|Jan D H|JDH|', 'Majoor-Krakauer|Danielle|D|']
D000293:Adolescent D000328:Adult D002648:Child D002675:Child, Preschool D016757:Death, Sudden, Cardiac D005260:Female D005500:Follow-Up Studies D006801:Humans D007223:Infant D007231:Infant, Newborn D056830:Isolated Noncompaction of the Ventricular Myocardium D008297:Male D008875:Middle Aged D009154:Mutation D009426:Netherlands D012189:Retrospective Studies D013997:Time Factors D016896:Treatment Outcome D055815:Young Adult
genetics outcome noncompaction cardiomyopathy LVNC prognosis