Publication:
Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene.

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2020-09-23

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Akhtar, Mohammed Majid
Lorenzini, Massimiliano
Cicerchia, Marcos
Ochoa, Juan Pablo
Hey, Thomas Morris
Sabater Molina, Maria
Restrepo-Cordoba, Maria Alejandra
Dal Ferro, Matteo
Stolfo, Davide
Johnson, Renee

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Abstract

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 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.

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Adult
Aged
Aged, 80 and over
Arrhythmias, Cardiac
Cardiomyopathy, Dilated
Connectin
Europe
Female
Genetic Predisposition to Disease
Genetic Variation
Heart Failure
Humans
Longitudinal Studies
Male
Middle Aged
New South Wales
Phenotype
Prognosis
Risk Assessment
Risk Factors
Sex Factors
Stroke Volume
Time Factors
Ventricular Dysfunction, Left
Ventricular Function, Left
Ventricular Remodeling

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Keywords

cardiomyopathy, dilated, connectin, heart failure, phenotype, sex

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