Author + information
- Received November 22, 2017
- Accepted December 8, 2017
- Published online February 12, 2018.
- Jaap I. van Waning, MDa,
- Kadir Caliskan, MD, PhDb,
- Yvonne M. Hoedemaekers, MD, PhDc,
- Karin Y. van Spaendonck-Zwarts, MD, PhDd,
- Annette F. Baas, MD, PhDe,
- S. Matthijs Boekholdt, MD, PhDf,
- Joost P. van Melle, MDg,
- Arco J. Teske, MD, PhDh,
- Folkert W. Asselbergs, MD, PhDh,
- Ad P.C.M. Backx, MDi,
- Gideon J. du Marchie Sarvaas, MDj,
- Michiel Dalinghaus, MD, PhDk,
- Johannes M.P.J. Breur, MD, PhDl,
- Marijke P.M. Linschoten, MsCh,
- Laura A. Verlooij, MDc,
- Isabella Kardys, MD, PhDb,
- Dennis Dooijes, PhDe,
- Ronald H. Lekanne Deprez, PhDd,
- Arne S. IJpma, PhDa,
- Maarten P. van den Berg, MD, PhDg,
- Robert M.W. Hofstra, PhDa,
- Marjon A. van Slegtenhorst, PhDa,
- Jan D.H. Jongbloed, PhDc and
- Danielle Majoor-Krakauer, MD, PhDa,∗ ()
- aDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands
- bDepartment of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
- cDepartment of Clinical Genetics, University Medical Center Groningen, Groningen, the Netherlands
- dDepartment of Clinical Genetics, Amsterdam Medical Center, Amsterdam, the Netherlands
- eDepartment of Clinical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
- fDepartment of Cardiology, Amsterdam Medical Center, Amsterdam, the Netherlands
- gDepartment of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
- hDepartment of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
- iDepartment of Pediatrics, Amsterdam Medical Center, Amsterdam, the Netherlands
- jDepartment of Pediatrics, University Medical Center Groningen, Groningen, the Netherlands
- kDepartment of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands
- lDepartment of Pediatrics, University Medical Center, Utrecht, the Netherlands
- ↵∗Address for correspondence:
Dr. Danielle Majoor-Krakauer, Department of Clinical Genetics, EE 2036, Erasmus Medical Center, PO Box 2040, 3000CA Rotterdam, the Netherlands.
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.
Dr. van Waning was supported by a grant from the Jaap Schouten Foundation.
All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 22, 2017.
- Accepted December 8, 2017.
- 2018 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.