TY - JOUR
T1 - Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy
AU - Jansweijer, Joeri A.
AU - Nieuwhof, Karin
AU - Russo, Francesco
AU - Hoorntje, Edgar T.
AU - Jongbloed, Jan D.H.
AU - Lekanne Deprez, Ronald H.
AU - Postma, Alex V.
AU - Bronk, Marieke
AU - van Rijsingen, Ingrid A.W.
AU - de Haij, Simone
AU - Biagini, Elena
AU - van Haelst, Paul L.
AU - van Wijngaarden, Jan
AU - van den Berg, Maarten P.
AU - Wilde, Arthur A.M.
AU - Mannens, Marcel M.A.M.
AU - de Boer, Rudolf A.
AU - van Spaendonck-Zwarts, Karin Y.
AU - van Tintelen, J. Peter
AU - Pinto, Yigal M.
N1 - Publisher Copyright:
© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology
PY - 2017/4
Y1 - 2017/4
N2 - Aims: 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.
AB - Aims: 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.
UR - http://www.scopus.com/inward/record.url?scp=84996837298&partnerID=8YFLogxK
U2 - 10.1002/ejhf.673
DO - 10.1002/ejhf.673
M3 - Article
C2 - 27813223
AN - SCOPUS:84996837298
SN - 1388-9842
VL - 19
SP - 512
EP - 521
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 4
ER -