Aims: 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. Methods and results: 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. Conclusion: 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.
Crotti, L., Spazzolini, C., Tester, D., Ghidoni, A., Baruteau, A., Beckmann, B., et al. (2019). Calmodulin mutations and life-threatening cardiac arrhythmias: Insights from the International Calmodulinopathy Registry. EUROPEAN HEART JOURNAL, 40(35), 2964-2975.
|Citazione:||Crotti, L., Spazzolini, C., Tester, D., Ghidoni, A., Baruteau, A., Beckmann, B., et al. (2019). Calmodulin mutations and life-threatening cardiac arrhythmias: Insights from the International Calmodulinopathy Registry. EUROPEAN HEART JOURNAL, 40(35), 2964-2975.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Calmodulin mutations and life-threatening cardiac arrhythmias: Insights from the International Calmodulinopathy Registry|
|Autori:||Crotti, L; Spazzolini, C; Tester, D; Ghidoni, A; Baruteau, A; Beckmann, B; Behr, E; Bennett, J; Bezzina, C; Bhuiyan, Z; Celiker, A; Cerrone, M; Dagradi, F; De Ferrari, G; Etheridge, S; Fatah, M; Garcia-Pavia, P; Al-Ghamdi, S; Hamilton, R; Al-Hassnan, Z; Horie, M; Jimenez-Jaimez, J; Kanter, R; Kaski, J; Kotta, M; Lahrouchi, N; Makita, N; Norrish, G; Odland, H; Ohno, S; Papagiannis, J; Parati, G; Sekarski, N; Tveten, K; Vatta, M; Webster, G; Wilde, A; Wojciak, J; George, A; Ackerman, M; Schwartz, P|
CROTTI, LIA (Corresponding)
|Data di pubblicazione:||2019|
|Rivista:||EUROPEAN HEART JOURNAL|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/eurheartj/ehz311|
|Appare nelle tipologie:||01 - Articolo su rivista|