%0 Journal Article
%A Crotti, Lia
%A Spazzolini, Carla
%A Tester, David J
%A Ghidoni, Alice
%A Baruteau, Alban-Elouen
%A Beckmann, Britt-Maria
%A Behr, Elijah R
%A Bennett, Jeffrey S
%A Bezzina, Connie R
%A Bhuiyan, Zahurul A
%A Celiker, Alpay
%A Cerrone, Marina
%A Dagradi, Federica
%A De Ferrari, Gaetano M
%A Etheridge, Susan P
%A Fatah, Meena
%A Garcia-Pavia, Pablo
%A Al-Ghamdi, Saleh
%A Hamilton, Robert M
%A Al-Hassnan, Zuhair N
%A Horie, Minoru
%A Jimenez-Jaimez, Juan
%A Kanter, Ronald J
%A Kaski, Juan P
%A Kotta, Maria-Christina
%A Lahrouchi, Najim
%A Makita, Naomasa
%A Norrish, Gabrielle
%A Odland, Hans H
%A Ohno, Seiko
%A Papagiannis, John
%A Parati, Gianfranco
%A Sekarski, Nicole
%A Tveten, Kristian
%A Vatta, Matteo
%A Webster, Gregory
%A Wilde, Arthur A M
%A Wojciak, Julianne
%A George, Alfred L
%A Ackerman, Michael J
%A Schwartz, Peter J
%T Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.
%D 2019
%U http://hdl.handle.net/10668/14081
%X 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.
%K Calmodulin
%K Cathecolaminergic polymorphic ventricular tachycardia
%K Idiopathic ventricular fibrillation
%K Long QT syndrome
%K Sudden death
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