Abstract 14840: International Calmodulinopathy Registry (ICaMR)
Introduction: The recently discovered association between Calmodulin (CaM) mutations and diverse conditions associated with life-threatening arrhythmias, ranging from long QT syndrome (LQTS), to catecholaminergic polymorphic ventricular tachycardia (CPVT), to idiopathic ventricular fibrillation (IVF), has led to the definition of a new clinical entity called calmodulinopathy. Only a few reports based on small numbers are available so far. To define the natural history and response to therapy we have established an international calmodulinopathy registry (ICaMR).
Methods: ICaMR is an observational multi-center study enrolling patients (pts) with a mutation in one of the 3 CaM genes, which will be followed prospectively for 10 years. Genetic and clinical data are collected through a dedicated form sent to centers in Europe, North America and Japan.
Results: At this time the ICaMR includes 49 [55% females, median age 10 years] heterozygous CALM1(n=32), CALM2 (n=12) or CALM3 (n=5) mutation-positive subjects. Cardiac events occurred in 41 pts (84%) at a median age of 4 years (IQR 1.5-9). Cardiac arrests (CA) or sudden deaths (SD), occurred in 30 (61%). In 29% of patients there was a fetal/perinatal presentation of LQTS, with a mean QTc of 650 ms, bradycardia, 2:1 AV block and/or T wave alternans. There are 2 main phenotypes: 1) CaM-LQTS (18 individuals in 18 families); 2) CaM-CPVT (19 subjects in 5 families). The remaining cases include 2 families with IVF, 4 with SD and 2 with overlapping LQTS/CPVT. In 80% of the probands the mutation was de novo. A mutation in the EF-hand IV was found in 13/18 (72%) CaM-LQTS, and in none of the 19 CaM-CPVT (p<0.0001), suggesting a correlation between mutation location and phenotype. Seven pts had SD without therapy; among 34 pts known to be treated with beta-blockers, mexiletine, left sympathectomy and/or implantable devices, 18 (53%) had recurrences, including 4 SD and 5 appropriate ICD shocks.
Conclusions: Data from the ICaMR confirm the malignant course of calmodulinopathy, unveil a large spectrum of phenotypic features and provide preliminary insights into mutation-site specific clinical manifestation. The Registry will provide data for understanding the natural history and for guiding a rational approach to therapy.
Author Disclosures: L. Crotti: None. C. Spazzolini: None. N. Boczek: None. J. Jimenez Jaimez: None. N. Makita: None. D. Tester: None. S. Etheridge: None. B. Beckmann: None. J. Papagiannis: None. G. Webster: None. N. Lahrouchi: None. C. Bezzina: None. M. Horie: None. M. Nyegaard: None. R. Bennhagen: None. R. Hamilton: None. A. Wilde: None. A. George: None. M. Ackerman: None. P. Schwartz: None.
- © 2016 by American Heart Association, Inc.