RT Journal Article
T1 Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.
A1 Crotti, Lia
A1 Spazzolini, Carla
A1 Tester, David J
A1 Ghidoni, Alice
A1 Baruteau, Alban-Elouen
A1 Beckmann, Britt-Maria
A1 Behr, Elijah R
A1 Bennett, Jeffrey S
A1 Bezzina, Connie R
A1 Bhuiyan, Zahurul A
A1 Celiker, Alpay
A1 Cerrone, Marina
A1 Dagradi, Federica
A1 De Ferrari, Gaetano M
A1 Etheridge, Susan P
A1 Fatah, Meena
A1 Garcia-Pavia, Pablo
A1 Al-Ghamdi, Saleh
A1 Hamilton, Robert M
A1 Al-Hassnan, Zuhair N
A1 Horie, Minoru
A1 Jimenez-Jaimez, Juan
A1 Kanter, Ronald J
A1 Kaski, Juan P
A1 Kotta, Maria-Christina
A1 Lahrouchi, Najim
A1 Makita, Naomasa
A1 Norrish, Gabrielle
A1 Odland, Hans H
A1 Ohno, Seiko
A1 Papagiannis, John
A1 Parati, Gianfranco
A1 Sekarski, Nicole
A1 Tveten, Kristian
A1 Vatta, Matteo
A1 Webster, Gregory
A1 Wilde, Arthur A M
A1 Wojciak, Julianne
A1 George, Alfred L
A1 Ackerman, Michael J
A1 Schwartz, Peter J
K1 Calmodulin
K1 Cathecolaminergic polymorphic ventricular tachycardia
K1 Idiopathic ventricular fibrillation
K1 Long QT syndrome
K1 Sudden death
AB 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.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/14081
UL http://hdl.handle.net/10668/14081
LA en
DS RISalud
RD Apr 11, 2025