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Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss Muscular Dystrophy in a long-term follow-up

Michał Marchel1, Agnieszka Madej-Pilarczyk2, Roman Steckiewicz1, Przemysław Stolarz1, Michał Peller1, Agata Tymińska1, Ewa Ostrowska1, Krzysztof Ozierański1, Paweł Balsam1, Marcin Grabowski1, Grzegorz Opolski1
DOI: 10.33963/KP.a2021.0159
·
Pubmed: 34783354
Affiliations
  1. 1st Chair and Department of Cardiology, Medical University of Warsaw, Warszawa, Poland
  2. Department of Medical Genetics, The Children's Memorial Health Institute, Warszawa, Poland

open access

Online first
Original article
Published online: 2021-11-16

Abstract

BACKGROUND: Emery-Dreifuss Muscular Dystrophy (EDMD) is an extremely rare muscular dystrophy due to either emerinopathy (EMD) or laminopathy (LMNA). The main risk for patients is that of cardiovascular complications.

AIMS: The aim of this study was to identify predictors of adverse clinical events in patients with EDMD in long-term follow-up observation.

METHODS: A total of 45 patients with confirmed EMD or LMNA mutation were included in the study. The relationships between clinical parameters, the overall survival rate, and risk factors for disease progression were assessed. The primary endpoint was defined as death, while the secondary endpoint comprised death, resuscitated cardiac arrest (RCA), heart transplant (HTX), stroke, end-stage heart failure (ESHF), and hospitalization due to heart failure (HF).

RESULTS: During a median length of follow-up observation of ten years (interquartile range, 5–15), ten patients (22%) died, one suffered RCA, two had HTX, and six suffered ischemic strokes (13%). Seven patients developed ESHF and eight were hospitalized due to HF. The secondary endpoint occurred in 16 patients (36%). LMNA mutation (hazard ratio [HR], 6.01; 95% confidence interval [CI], 1.61–22.4; P = 0.008) and higher serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP) concentration (HR, 1.29; 95% CI, 1.06–1.56 per 100 pg/ml; P = 0.01) increased the risk of death. Higher tricuspid annular plane systolic excursion (TAPSE) decreased the risk for the secondary endpoint (HR, 0.78; 95% CI, 0.68–0.90 mm; P <0.001). NT-proBNP >257 pg/ml and TAPSE <21 mm may be assumed as the best cut-off values for the primary and secondary endpoints, respectively.

CONCLUSIONS: LMNA mutation and higher NT-proBNP concentration were associated with increased mortality in EDMD. Lower TAPSE was a predictor of a composite secondary endpoint in EDMD.

Abstract

BACKGROUND: Emery-Dreifuss Muscular Dystrophy (EDMD) is an extremely rare muscular dystrophy due to either emerinopathy (EMD) or laminopathy (LMNA). The main risk for patients is that of cardiovascular complications.

AIMS: The aim of this study was to identify predictors of adverse clinical events in patients with EDMD in long-term follow-up observation.

METHODS: A total of 45 patients with confirmed EMD or LMNA mutation were included in the study. The relationships between clinical parameters, the overall survival rate, and risk factors for disease progression were assessed. The primary endpoint was defined as death, while the secondary endpoint comprised death, resuscitated cardiac arrest (RCA), heart transplant (HTX), stroke, end-stage heart failure (ESHF), and hospitalization due to heart failure (HF).

RESULTS: During a median length of follow-up observation of ten years (interquartile range, 5–15), ten patients (22%) died, one suffered RCA, two had HTX, and six suffered ischemic strokes (13%). Seven patients developed ESHF and eight were hospitalized due to HF. The secondary endpoint occurred in 16 patients (36%). LMNA mutation (hazard ratio [HR], 6.01; 95% confidence interval [CI], 1.61–22.4; P = 0.008) and higher serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP) concentration (HR, 1.29; 95% CI, 1.06–1.56 per 100 pg/ml; P = 0.01) increased the risk of death. Higher tricuspid annular plane systolic excursion (TAPSE) decreased the risk for the secondary endpoint (HR, 0.78; 95% CI, 0.68–0.90 mm; P <0.001). NT-proBNP >257 pg/ml and TAPSE <21 mm may be assumed as the best cut-off values for the primary and secondary endpoints, respectively.

CONCLUSIONS: LMNA mutation and higher NT-proBNP concentration were associated with increased mortality in EDMD. Lower TAPSE was a predictor of a composite secondary endpoint in EDMD.

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Keywords

EMD, cardiomyopathy, heart failure, laminopathy, LMNA

About this article
Title

Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss Muscular Dystrophy in a long-term follow-up

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Online first

Article type

Original article

Published online

2021-11-16

DOI

10.33963/KP.a2021.0159

Pubmed

34783354

Keywords

EMD
cardiomyopathy
heart failure
laminopathy
LMNA

Authors

Michał Marchel
Agnieszka Madej-Pilarczyk
Roman Steckiewicz
Przemysław Stolarz
Michał Peller
Agata Tymińska
Ewa Ostrowska
Krzysztof Ozierański
Paweł Balsam
Marcin Grabowski
Grzegorz Opolski

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