Long-term prognosis and genetic background of cardiomyopathy in 223 pediatric mitochondrial disease patients.

Cardiomyopathies / diagnosis Child Genetic Background Humans Hypertrophy, Left Ventricular Infant, Newborn Mitochondrial Diseases / diagnosis Prognosis Risk Factors
Genetic risk factors Mitochondrial cardiomyopathy Mitochondrial disease Mitochondrial respiratory chain complex deficiencies Pediatric cardiomyopathy

Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
15 Oct 2021
Historique:
received: 03 02 2021
revised: 18 06 2021
accepted: 23 06 2021
pubmed: 24 7 2021
medline: 21 10 2021
entrez: 23 7 2021
Statut: ppublish

Résumé

Cardiomyopathy is a risk factor for poor prognosis in pediatric patients with mitochondrial disease. However, other risk factors including genetic factors related to poor prognosis in mitochondrial disease has yet to be fully elucidated. Between January 2004 and September 2019, we enrolled 223 consecutive pediatric mitochondrial disease patients aged <18 years with a confirmed genetic diagnosis, including 114 with nuclear gene mutations, 89 patients with mitochondrial DNA (mtDNA) point mutations, 11 with mtDNA single large-scale deletions and 9 with chromosomal aberrations. Cardiomyopathy at baseline was observed in 46 patients (21%). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all-cause mortality. Over a median follow-up of 36 months (12-77), there were 85 deaths (38%). The overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p < 0.001, log-rank test). By multivariable analysis, left ventricular (LV) hypertrophy (HR = 4.6; 95% CI: 2.8-7.3), neonatal onset (HR = 2.9; 95% CI: 1.8-4.5) and chromosomal aberrations (HR = 2.9; 95% CI: 1.3-6.5) were independent predictors of all-cause mortality. Patients with LV hypertrophy with neonatal onset and/or chromosomal aberrations had higher mortality (100% in 21 patients) than those with LV hypertrophy alone (71% in 14 patients). In pediatric patients with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increased mortality. LV hypertrophy, neonatal onset and chromosomal aberrations were independent predictors of all-cause mortality. Prognosis is particularly unfavorable if LV hypertrophy is combined with neonatal onset and/or chromosomal aberrations.

Sections du résumé

BACKGROUND BACKGROUND
Cardiomyopathy is a risk factor for poor prognosis in pediatric patients with mitochondrial disease. However, other risk factors including genetic factors related to poor prognosis in mitochondrial disease has yet to be fully elucidated.
METHODS AND RESULTS RESULTS
Between January 2004 and September 2019, we enrolled 223 consecutive pediatric mitochondrial disease patients aged <18 years with a confirmed genetic diagnosis, including 114 with nuclear gene mutations, 89 patients with mitochondrial DNA (mtDNA) point mutations, 11 with mtDNA single large-scale deletions and 9 with chromosomal aberrations. Cardiomyopathy at baseline was observed in 46 patients (21%). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all-cause mortality. Over a median follow-up of 36 months (12-77), there were 85 deaths (38%). The overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p < 0.001, log-rank test). By multivariable analysis, left ventricular (LV) hypertrophy (HR = 4.6; 95% CI: 2.8-7.3), neonatal onset (HR = 2.9; 95% CI: 1.8-4.5) and chromosomal aberrations (HR = 2.9; 95% CI: 1.3-6.5) were independent predictors of all-cause mortality. Patients with LV hypertrophy with neonatal onset and/or chromosomal aberrations had higher mortality (100% in 21 patients) than those with LV hypertrophy alone (71% in 14 patients).
CONCLUSION CONCLUSIONS
In pediatric patients with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increased mortality. LV hypertrophy, neonatal onset and chromosomal aberrations were independent predictors of all-cause mortality. Prognosis is particularly unfavorable if LV hypertrophy is combined with neonatal onset and/or chromosomal aberrations.

Identifiants

DOI: 10.1016/j.ijcard.2021.06.042 PMID: 34298071
pubmed: 34298071
pii: S0167-5273(21)01080-9
doi: 10.1016/j.ijcard.2021.06.042
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

48-55

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Atsuko Imai-Okazaki (A)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Ayako Matsunaga (A)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Yukiko Yatsuka (Y)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Kazuhiro R Nitta (KR)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Yoshihito Kishita (Y)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Ayumu Sugiura (A)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Yohei Sugiyama (Y)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Takuya Fushimi (T)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Masaru Shimura (M)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Keiko Ichimoto (K)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Makiko Tajika (M)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Minako Ogawa-Tominaga (M)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Tomohiro Ebihara (T)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Tetsuro Matsuhashi (T)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Tomoko Tsuruoka (T)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Masakazu Kohda (M)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Tomoko Hirata (T)

Laboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Hiroko Harashima (H)

Department of Pediatrics & Clinical Genomics, Saitama Medical University, Saitama, Japan; Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.

Shuko Nojiri (S)

Clinical Research and Trial Center, Juntendo University, Japan.

Atsuhito Takeda (A)

Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Akihiro Nakaya (A)

Department of Genome Data Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.

Shigetoyo Kogaki (S)

Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.

Yasushi Sakata (Y)

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Akira Ohtake (A)

Department of Pediatrics & Clinical Genomics, Saitama Medical University, Saitama, Japan; Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.

Kei Murayama (K)

Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Yasushi Okazaki (Y)

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Laboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan. Electronic address: ya-okazaki@juntendo.ac.jp.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Cardiomyopathies › Long-term prognosis and genetic background of...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Long-term prognosis and genetic background of...
questionsmedicales.fr › Phénomènes génétiques › Contexte génétique › Long-term prognosis and genetic background of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Long-term prognosis and genetic background of...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Hypertrophie › Cardiomégalie › Hypertrophie ventriculaire gauche › Long-term prognosis and genetic background of...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Long-term prognosis and genetic background of...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Maladies mitochondriales › Long-term prognosis and genetic background of...
questionsmedicales.fr › Diagnostic › Pronostic › Long-term prognosis and genetic background of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Long-term prognosis and genetic background of...