RT Journal Article
T1 Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene.
A1 Akhtar, Mohammed Majid
A1 Lorenzini, Massimiliano
A1 Cicerchia, Marcos
A1 Ochoa, Juan Pablo
A1 Hey, Thomas Morris
A1 Sabater-Molina, Maria
A1 Restrepo-Cordoba, Maria Alejandra
A1 Dal-Ferro, Matteo
A1 Stolfo, Davide
A1 Johnson, Renee
A1 Larrañaga-Moreira, Jose M
A1 Robles-Mezcua, Ainhoa
A1 Rodriguez-Palomares, Jose F
A1 Casas, Guillem
A1 Peña-Peña, Maria Luisa
A1 Lopes, Luis Rocha
A1 Gallego-Delgado, Maria
A1 Franaszczyk, Maria
A1 Laucey, Gemma
A1 Rangel-Sousa, Diego
A1 Basurte, Mayte
A1 Palomino-Doza, Julian
A1 Villacorta, Eduardo
A1 Bilinska, Zofia
A1 Limeres-Freire, Javier
A1 Garcia-Pinilla, Jose M
A1 Barriales-Villa, Roberto
A1 Fatkin, Diane
A1 Sinagra, Gianfranco
A1 Garcia-Pavia, Pablo
A1 Gimeno, Juan R
A1 Mogensen, Jens
A1 Monserrat, Lorenzo
A1 Elliott, Perry M
K1 cardiomyopathy, dilated
K1 connectin
K1 heart failure
K1 phenotype
K1 sex
AB Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P=0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P=0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P<0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (P=0.07). TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.
PB Lippincott Williams & Wilkins
YR 2020
FD 2020-10
LK http://hdl.handle.net/10668/16299
UL http://hdl.handle.net/10668/16299
LA en
NO Akhtar MM, Lorenzini M, Cicerchia M, Ochoa JP, Hey TM, Sabater Molina M, et al. Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene. Circ Heart Fail. 2020 Oct;13(10):e006832.
DS RISalud
RD Sep 16, 2025