BibTex format
@article{Johnson:2025:eurheartj/ehaf380,
author = {Johnson, R and Fletcher, RA and Peters, S and Ohanian, M and Soka, M and Smolnikov, A and Abihider, KE and Ackerman, MJ and Ader, F and Akhtar, MM and Amin, AS and Ashley, EA and Atherton, JJ and Austin, R and Baas, AF and Bagnall, RD and Ross, SB and Blouin, J-L and Brown, EE and Bundgaard, H and Cannie, D and Chmielewski, P and Correnti, G and Crespo-Leiro, MG and Dal, Ferro M and Dellefave-Castillo, LM and Dominguez, F and Dooijes, D and Dybro, AM and Ed, Demri Y and El, Hachmi M and Escobar-Lopez, L and Foye, SJ and Franaszczyk, M and Gigli, M and Lopez, EG and Goudal, A and Graw, S and Guipponi, M and Haan, E and Haas, J and Hammersley, DJ and Hansen, FG and Hayward, CS and Hey, TM and Heymans, S and Ho, CY and Houweling, AC and Ingles, J and Ingrey, A and Jabbour, A and James, PA and Jansweijer, JA and Jongbloed, JDH and Keogh, AM and Larrañaga-Moreira, JM and Lekanne, Deprez RH and Macciocca, I and Macdonald, PS and Mansencal, N and Mansour, J and Martinez-Veira, C and McDonough},
doi = {eurheartj/ehaf380},
journal = {Eur Heart J},
pages = {5240--5257},
title = {Titin-related familial dilated cardiomyopathy: factors associated with disease onset.},
url = {http://dx.doi.org/10.1093/eurheartj/ehaf380},
volume = {46},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND AND AIMS: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. METHODS: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. RESULTS: A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80-30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06-5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27-3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35-9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08-.23). CONCLUSIONS: Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.
AU - Johnson,R
AU - Fletcher,RA
AU - Peters,S
AU - Ohanian,M
AU - Soka,M
AU - Smolnikov,A
AU - Abihider,KE
AU - Ackerman,MJ
AU - Ader,F
AU - Akhtar,MM
AU - Amin,AS
AU - Ashley,EA
AU - Atherton,JJ
AU - Austin,R
AU - Baas,AF
AU - Bagnall,RD
AU - Ross,SB
AU - Blouin,J-L
AU - Brown,EE
AU - Bundgaard,H
AU - Cannie,D
AU - Chmielewski,P
AU - Correnti,G
AU - Crespo-Leiro,MG
AU - Dal,Ferro M
AU - Dellefave-Castillo,LM
AU - Dominguez,F
AU - Dooijes,D
AU - Dybro,AM
AU - Ed,Demri Y
AU - El,Hachmi M
AU - Escobar-Lopez,L
AU - Foye,SJ
AU - Franaszczyk,M
AU - Gigli,M
AU - Lopez,EG
AU - Goudal,A
AU - Graw,S
AU - Guipponi,M
AU - Haan,E
AU - Haas,J
AU - Hammersley,DJ
AU - Hansen,FG
AU - Hayward,CS
AU - Hey,TM
AU - Heymans,S
AU - Ho,CY
AU - Houweling,AC
AU - Ingles,J
AU - Ingrey,A
AU - Jabbour,A
AU - James,PA
AU - Jansweijer,JA
AU - Jongbloed,JDH
AU - Keogh,AM
AU - Larrañaga-Moreira,JM
AU - Lekanne,Deprez RH
AU - Macciocca,I
AU - Macdonald,PS
AU - Mansencal,N
AU - Mansour,J
AU - Martinez-Veira,C
AU - McDonough,B
AU - McGaughran,J
AU - Medo,K
AU - Merlo,M
AU - Michalak,E
AU - Monserrat,L
AU - Mountain,H
AU - Muller,SA
AU - Murphy,AM
AU - Murray,B
AU - Oates,EC
AU - Ormondroyd,E
AU - Pachter,N
AU - Paldino,A
AU - Palmyre,A
AU - Pereira,NL
AU - Picard,KC
AU - Poplawski,N
AU - Prasad,S
AU - Proukhnitzky,J
AU - Pruny,J-F
AU - Reant,P
AU - Richard,P
AU - Ronan,A
AU - Sedaghat-Hamedani,F
AU - Semsarian,C
AU - Storm,G
AU - Stroeks,S
AU - Syrris,P
AU - Taylor,MRG
AU - Thomson,K
AU - Thompson,T
AU - van,Tintelen JP
AU - Vissing,CR
AU - Waddell-Smith,KE
AU - Wallis,M
AU - Zentner,D
AU - Australian,Genomics Cardiac Flagship
AU - Arnott,C
AU - Marian,AJ
AU - Oh,J
AU - Fokstuen,S
AU - James,CA
AU - Barriales-Villa,R
AU - Meder,B
AU - Wahbi,K
AU - Giudicessi,JR
AU - Parikh,VN
AU - Ware,JS
AU - Piriou,N
AU - Rooryck,C
AU - Lakdawala,NK
AU - Mestroni,L
AU - Sinagra,G
AU - Elliott,PM
AU - Watkins,H
AU - McNally,EM
AU - Charron,P
AU - van,Spaendonck-Zwarts KY
AU - Garcia-Pavia,P
AU - Peña-Peña,ML
AU - Mogensen,J
AU - Christensen,AH
AU - Biliska,ZT
AU - Rasmussen,TB
AU - Seidman,JG
AU - Seidman,CE
AU - Te,Riele ASJM
AU - Verdonschot,JAJ
AU - Pinto,YM
AU - Christiaans,I
AU - Fatkin,D
DO - eurheartj/ehaf380
EP - 5257
PY - 2025///
SP - 5240
TI - Titin-related familial dilated cardiomyopathy: factors associated with disease onset.
T2 - Eur Heart J
UR - http://dx.doi.org/10.1093/eurheartj/ehaf380
UR - https://www.ncbi.nlm.nih.gov/pubmed/40796136
VL - 46
ER -