Long-term follow-up of R403W MYH7 and R92W TNNT2 HCM families : mutations determine left ventricular dimensions but not wall thickness during disease progression
Date
2007-06
Journal Title
Journal ISSN
Volume Title
Publisher
Clinics Cardiv Publishing
Abstract
The clinical profile and prognosis of patients
with hypertrophic cardiomyopathy, a primary cardiac
muscle disease caused mostly by mutations in sarcomeric
protein-encoding genes, have been linked to particular
disease-causing mutations in the past. However, such associations
are often based on cross-sectional observations,
as longitudinal studies of the progression of the disease in
genotypically defined patients are sparse. Most importantly,
the relative contribution of age, gender and genetic cause to
disease profile and progression has not yet been reported,
and the question remains whether one or more of these
factors could mask the effect of the other(s).
Methods: We previously described cross-sectional family
studies of two hypertrophic cardiomyopathy (HCM)-causing
mutations, R92WTNNT2 and R403WMYH7, both associated
with minimal hypertrophy, but with widely different life
expectancies. We re-investigated 22 and 26 R92WTNNT2 and
R403WMYH7 mutation carriers in these and additional South
African R92WTNNT2 families after a mean 11.08 ± 2.79 years,
and compared the influence of the two mutations, in the context of age and gender, on disease progression.
Results: We demonstrated a positive correlation between age
and interventricular septal thickness for both mutations,
with more than a third of all mutation carriers developing
clinically recognised hypertrophy only after the age of
35 years. This period of hypertrophically silent HCM also
coincided with the years in which most sudden cardiac
deaths occurred, particularly in male R92WTNNT2 carriers.
Statistical analyses indicated that the particular mutation
was the strongest determinant of left ventricular remodelling;
particularly, LVESD increased and EF reduction was
noted in the majority of R403WMYH7 carriers, which may
require clinical follow-up over the longer term.
Conclusions: Statistical modelling of follow-up data suggests
that an interplay between unidentified, possibly genderassociated
factors, and the causal mutation are the determinants
of eventual cardiac function and survival, but not
of the extent of hypertrophy, and emphasises the need for
long-term follow-up even in individuals with apparently
mild disease.
Description
The original publication is available at http://www.cvja.co.za/
CVJA holds the copyright
CVJA holds the copyright
Keywords
Hypertrophic cardiomyopathy, Heart muscles -- Diseases, Cardiac arrest, Heart attack
Citation
Revera, M. et al. 2007. Long-term follow-up of R403WMYH7 and R92WTNNT2 HCM families: mutations determine left ventricular dimensions but not wall thickness during disease progression. Cardiovascular Journal of Africa, 18(3), 146-153.