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Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy.
- Source :
- European Journal of Heart Failure; Apr2017, Vol. 19 Issue 4, p512-521, 10p, 1 Diagram, 2 Charts, 3 Graphs
- Publication Year :
- 2017
-
Abstract
- <bold>Aims: </bold>Truncating titin mutations (tTTN) occur in 25% of dilated cardiomyopathy (DCM) cases, but the phenotype and severity of disease they cause have not yet been systematically studied. We studied whether tTTN variants are associated with a clinically distinguishable form of DCM.<bold>Methods and Results: </bold>We compared clinical data on DCM probands and relatives with a tTTN mutation (n = 45, n = 73), LMNA mutation (n = 28, n = 29), and probands who tested negative for both genes [idiopathic DCM (iDCM); n = 60]. Median follow-up was at least 2.5 years in each group. TTN subjects presented with DCM at higher age than LMNA subjects (probands 47.9 vs. 40.4 years, P = 0.004; relatives 59.8 vs. 47.0 years, P = 0.01), less often developed LVEF <35% [probands hazard ratio (HR) 0.38, P = 0.002], had higher age of death (probands 70.4 vs. 59.4 years, P < 0.001; relatives 74.1 vs. 58.4 years, P = 0.008), and had better composite outcome (malignant ventricular arrhythmia, heart transplantation, or death; probands HR 0.09, P < 0.001; relatives HR 0.21, P = 0.02) than LMNA subjects and iDCM subjects (HR 0.36, P = 0.07). An LVEF increase of at least 10% occurred in 46.9% of TTN subjects after initiation of standard heart failure treatment, while this only occurred in 6.5% of LMNA subjects (P < 0.001) and 18.5% of iDCM subjects (P = 0.02). This was confirmed in families with co-segregation, in which the 10% point LVEF increase occurred in 55.6% of subjects (P = 0.003 vs. LMNA, P = 0.079 vs. iDCM).<bold>Conclusions: </bold>This study shows that tTTN-associated DCM is less severe at presentation and more amenable to standard therapy than LMNA mutation-induced DCM or iDCM. [ABSTRACT FROM AUTHOR]
- Subjects :
- DILATED cardiomyopathy
GENETIC mutation
CONNECTIN
PHENOTYPES
FOLLOW-up studies (Medicine)
HEART failure treatment
ARRHYTHMIA
HEART transplantation
HEART failure
LONGITUDINAL method
MORTALITY
PROGNOSIS
PROTEINS
PROPORTIONAL hazards models
RETROSPECTIVE studies
SEVERITY of illness index
CASE-control method
HEART assist devices
STROKE volume (Cardiac output)
GENOTYPES
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 13889842
- Volume :
- 19
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- European Journal of Heart Failure
- Publication Type :
- Academic Journal
- Accession number :
- 122251419
- Full Text :
- https://doi.org/10.1002/ejhf.673