Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects.
OBJECTIVE
Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects.


RESULTS
We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001).


CONCLUSIONS
Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.
Dept of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Nina E
NE
Hasselberg
Thor
T
Edvardsen
Helle
H
Petri
Knut E
KE
Berge
Trond P
TP
Leren
Henning
H
Bundgaard
Kristina H
KH
Haugaa
D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D054537:Atrioventricular Block / Q000235:genetics / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D003718:Denmark; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009200:Myocardial Contraction / Q000235:genetics*; D009664:Norway; D010641:Phenotype; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000235:genetics*; D016277:Ventricular Function, Left / Q000235:genetics*; D054088:Ventricular Septum / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
C494847:LMNA protein, human; D034904:Lamin Type A
Atrioventricular block; Echocardiography; Genetic heart disease; Lamin A/C; Myocardial mechanics; Ventricular arrhythmias