In:
European Journal of Heart Failure, Wiley, Vol. 19, No. 4 ( 2017-04), p. 512-521
Abstract:
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 . Methods and results 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 ). Conclusions 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 .
Type of Medium:
Online Resource
ISSN:
1388-9842
,
1879-0844
DOI:
10.1002/ejhf.2017.19.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1500332-2
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