Abstract
Objectives
Little is known about cardiac involvement in m.3243A>G variant carriers. Thus, this study aimed to assess type and frequency of cardiac disease in symptomatic and asymptomatic m.3243A>G carriers.
Methods
Systematic literature review.
Results
The m.3243A>G variant may manifest phenotypically as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), myoclonic epilepsy with ragged red fiber (MERRF), Leigh syndrome, or MELAS/KSS (Kearns-Sayre syndrome) overlap. Only few systematic studies which prospectively investigated m.3243A>G carriers for cardiac involvement were found. Cardiac abnormalities reported in m.3243A>G carriers include myocardial abnormalities, arrhythmias, or conduction defects. Myocardial abnormalities include myocardial thickening, hypertrophic cardiomyopathy, dilated cardiomyopathy, noncompaction, myocardial fibrosis, systolic dysfunction, heart failure, or arterial hypertension. Arrhythmias reported in m.3243A>G carriers include paroxysmal supraventricular or ventricular arrhythmias, including sinus tachycardia, atrial fibrillation and nonsustained ventricular tachycardia, and sudden cardiac death. Conduction defects in this group of patients include Wolff–Parkinson–White syndrome and left/right bundle branch block. Asymptomatic m.3243A>G carriers usually do not develop clinical or subclinical cardiac disease.
Conclusions
Cardiac involvement in m.3243A>G carriers has been only rarely systematically studied, which is perhaps why the incidence of cardiac diseases in MELAS is lower than would be expected. Myocardial abnormalities are much more frequent than arrhythmias or conduction defects. All symptomatic and asymptomatic m.3243A>G carriers should be systematically investigated for cardiac disease.
Zusammenfassung
Zielsetzung
Über die kardiale Beteiligung bei Trägern der m.3243A>G-Variante ist wenig bekannt. Daher sollten in der vorliegenden Studie die Formen und Häufigkeiten von Herzerkrankungen bei symptomatischen und asymptomatischen m.3243A>G-Trägern ermittelt werden.
Methoden
Systematische Literaturübersicht.
Ergebnisse
Die m.3243A>G-Variante kann sich phänotypisch als mitochondriale Enzephalopathie, Laktatazidose und schlaganfallähnliche Episoden (MELAS), Diabetes und Taubheit mit maternaler Vererbung (MIDD), myoklonische Epilepsie mit „ragged red fibers“ (MERRF), Leigh-Syndrom oder Kombination von MELAS und Kearns-Sayre-Syndrom (KSS) manifestieren. Es wurden nur wenige systematische Studien gefunden, in denen m.3243A>G-Träger prospektiv auf eine kardiale Beteiligung untersucht wurden. Zu den bei m.3243A>G-Trägern dokumentierten Herzfehlern zählen Myokardanomalien, Herzrhythmusstörungen oder Leitungsstörungen. Myokardiale Anomalien sind unter anderem myokardiale Wandverdickung, hypertrophe Kardiomyopathie, dilatative Kardiomyopathie, „non-compaction“, Myokardfibrose, systolische Dysfunktion, Herzinsuffizienz oder arterielle Hypertonie. Zu den bei m.3243A>G-Trägern beschriebenen Herzrhythmusstörungen zählen paroxysmale supraventrikuläre oder ventrikuläre Arrhythmien, einschließlich Sinustachykardie, Vorhofflimmern und nichtanhaltende ventrikuläre Tachykardie, sowie der plötzliche Herztod. Leitungsstörungen sind in dieser Patientengruppe unter anderem das Wolff-Parkinson-White-Syndrom und der Links- bzw. Rechtsschenkelblock. Bei asymptomatischen m.3243A>G-Trägern entwickelt sich gewöhnlich keine klinische oder subklinische Herzerkrankung.
Schlussfolgerungen
Die kardiale Beteiligung bei m.3243A>G-Trägern wurde bislang kaum systematisch untersucht. Vielleicht werden Herzerkrankungen deshalb bei MELAS seltener diagnostiziert, als zu erwarten wäre. Myokardiale Anomalien sind weitaus häufiger als Herzrhythmusstörungen oder Leitungsstörungen. Alle symptomatischen und asymptomatischen m.3243A>G-Träger sollten systematisch auf Herzerkrankungen untersucht werden.
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Both authors contributed equally, J. Finsterer: design, literature search, discussion, first draft, S. Zarrouk-Mahjoub: literature search, discussion, critical comments.
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J. Finsterer and S. Zarrouk-Mahjoub declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
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Finsterer, J., Zarrouk-Mahjoub, S. The heart in m.3243A>G carriers. Herz 45, 356–361 (2020). https://doi.org/10.1007/s00059-018-4739-6
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DOI: https://doi.org/10.1007/s00059-018-4739-6