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Observational Study
. 2018 Mar 7;39(10):853-860.
doi: 10.1093/eurheartj/ehx596.

Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation

Nina Eide Hasselberg  1   2   3 , Trine Fink Haland  1   2   3 , Jørg Saberniak  1   2   3 , Pål Haugar Brekke  1 , Knut Erik Berge  4 , Trond Paul Leren  4 , Thor Edvardsen  1   2   3 , Kristina Hermann Haugaa  1   2   3
Affiliations
Observational Study

Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation

Nina Eide Hasselberg et al. Eur Heart J. .

Abstract

Aims: Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients.

Methods and results: During 2003-15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up.

Conclusion: LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation.

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Figures

Figure 1
Figure 1
(A) Comparison of ages of documented penetrant cardiac phenotype between 48 lamin A/C genotype-positive probands and in 31 asymptomatic lamin A/C genotype-positive family members. Censored individuals still lacked the phenotype at last follow-up. (B) Kaplan–Meier plot showing time from genotype diagnosis to a documented penetrant cardiac phenotype in 31 asymptomatic lamin A/C genotype-positive family members. Censored individuals still lacked the phenotype at last follow-up.
Figure 2
Figure 2
(A) Kaplan–Meier plot showing better freedom from sustained ventricular arrhythmia (VA) in patients without atrioventricular (AV) block. (B) Kaplan–Meier plot showing better survival free from heart transplantation and death in patients with left ventricular ejection fraction (LVEF) ≥45% at presentation.
Take home figure
Take home figure
Illustration showing cardiac penetrance and outcome in 79 genotype-postitive patients with lamin A/C cardiomyopathy. AV, atrioventricular; EF, ejection fraction; VA, ventricular arrhythmia.
None
See this image and copyright information in PMC

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