Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations.
OBJECTIVE
To test the hypothesis that carriers of Dutch founder mutations in cardiac myosin-binding protein C (MYBPC3), without left ventricular hypertrophy (LVH) or electrocardiographic abnormalities, have diastolic dysfunction on tissue Doppler imaging (TDI), which can be used for the screening of family members in the hypertrophic cardiomyopathy (HCM) population.


BACKGROUND
TDI is a more sensitive technique for the assessment of left ventricular contraction and relaxation abnormalities than is conventional echocardiography.


METHODS
Echocardiographic studies including TDI were performed in genotyped hypertrophic cardiomyopathy patients (genotype-positive, G+/LVH+; n = 27), mutation carriers without LVH (G+/LVH-; n = 27), and healthy controls (n = 55). The identified mutations in MYBPC3 in the G+/LVH+ subjects were c.2864_2865delCT (12 subjects), c.2373dupG (n = 8), and p. Arg943X (n = 7). In the G+/LVH- subjects, the following mutations were identified: c.2864_2865delCT (n = 11), c.2373dupG (n = 8), and p. Arg943X (n = 8).


RESULTS
Mean TDI-derived systolic and early and late diastolic mitral annular velocities were significantly lower in the G+/LVH+ subjects compared with the other groups. However, there was no difference between controls and G+/LVH- subjects. Mean TDI-derived late mitral annular diastolic velocities were significantly higher in the G+/LVH- subjects compared with controls and G+/LVH+ subjects. Using a cut-off value of mean +/- 2 SD, an abnormal late mitral annular diastolic velocity was found in 14 (51%) of G+/LVH- patients. There was no difference among the 3 different mutations.


CONCLUSIONS
In contrast to earlier reports, mean mitral annular systolic velocity and early mitral annular diastolic velocity velocities were not reduced in G+/LVH- subjects, and TDI velocities were not sufficiently sensitive for determination of the affected status of an individual subject. Our findings, however, support the theory that diastolic dysfunction is a primary component of pre-clinical HCM.
Michels
Michelle
M
Department of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, the Netherlands.
Soliman
Osama I I
OI
Kofflard
Marcel J
MJ
Hoedemaekers
Yvonne M
YM
Dooijes
Dennis
D
Majoor-Krakauer
Danielle
D
ten Cate
Folkert J
FJ
D000328:Adult; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000235:genetics*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C