Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.

Details

Serval ID
serval:BIB_59356BCA7069
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.
Journal
European heart journal
Author(s)
Crotti L., Spazzolini C., Tester D.J., Ghidoni A., Baruteau A.E., Beckmann B.M., Behr E.R., Bennett J.S., Bezzina C.R., Bhuiyan Z.A., Celiker A., Cerrone M., Dagradi F., De Ferrari G.M., Etheridge S.P., Fatah M., Garcia-Pavia P., Al-Ghamdi S., Hamilton R.M., Al-Hassnan Z.N., Horie M., Jimenez-Jaimez J., Kanter R.J., Kaski J.P., Kotta M.C., Lahrouchi N., Makita N., Norrish G., Odland H.H., Ohno S., Papagiannis J., Parati G., Sekarski N., Tveten K., Vatta M., Webster G., Wilde AAM, Wojciak J., George A.L., Ackerman M.J., Schwartz P.J.
ISSN
1522-9645 (Electronic)
ISSN-L
0195-668X
Publication state
Published
Issued date
14/09/2019
Peer-reviewed
Oui
Volume
40
Number
35
Pages
2964-2975
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1-3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome.
A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1-5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0-8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively.
Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.
Keywords
Calmodulin, Cathecolaminergic polymorphic ventricular tachycardia, Idiopathic ventricular fibrillation, Long QT syndrome, Sudden death, Calmodulin , Cathecolaminergic polymorphic ventricular tachycardia , Idiopathic ventricular fibrillation , Long QT syndrome
Pubmed
Web of science
Create date
24/06/2019 9:14
Last modification date
08/10/2019 6:10
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