Genes associated with hypertrophic cardiomyopathy (HC) are not uniformly expressed
in the atrial myocardium. Whether this may impact susceptibility to atrial fibrillation
(AF) is unresolved. To analyze the prevalence and clinical correlates of AF in relation
to genotype in a large HC cohort, prevalence and clinical profile of AF were assessed
in 237 patients with HC, followed for 14 ± 10 years. Patients were divided into 3
genetic subgroups: (1) MYBPC3 (58%), (2) MYH7 (28%), and (3) “other genotypes” (14%; comprising TNNT2, TNNI3, TPM1, MYL2, complex genotypes, Z-line, and E-C coupling genes). Left atrial size was similar
in the 3 subsets. AF occurred in 74 patients with HC (31%), with no difference among
groups (31% in MYBPC3, 37% in MYH7 and 18% in other genotypes, p = 0.15), paroxysmal/persistent AF (12%, 18%, and 12%,
respectively; p = 0.53), paroxysmal/persistent evolved to permanent (12%, 12%, and
3%, p = 0.36) or permanent AF (7%, 7%, and 3%, p = 0.82). Age at AF onset was younger
in the group with other genotypes (37 ± 10 years) compared to the first 2 groups (53
± 14 and 51 ± 17, respectively; p = 0.05) because of early onset associated with complex
genotypes and a specific JPH2 mutation associated with abnormal intracellular calcium handling. At multivariate
analysis, independent predictors of AF were atrial diameter (p ≤0.05) and age at diagnosis
(p = 0.09), but not genetic subtype (p = 0.35). In conclusion, in patients with HC,
genetic testing cannot be used in clinical decision making with regard to management
strategies for AF. Genotype is not predictive of onset or severity of AF, which appears
rather driven by hemodynamic determinants of atrial dilatation. Exceptions are represented
by rare genes suggesting specific molecular pathways for AF in genetic cardiomyopathies.
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Article Info
Publication History
Published online: January 13, 2016
Accepted:
December 26,
2015
Received in revised form:
December 26,
2015
Received:
September 22,
2015
Footnotes
This work was supported by the Italian Ministry of Health : RF 2010 – 2313451 “Hypertrophic cardiomyopathy: new insights from deep sequencing and psychosocial evaluation”, WFR GR-2011-02350583 “Atrial Dilatation as a substrate for Atrial Fibrillation in Hypertrophic cardiomyopathy: cellular mechanisms and novel therapeutic approaches” and NET-2011-02347173 “Mechanisms and treatment of coronary microvascular dysfunction in patients with genetic or secondary left ventricular hypertrophy”.
See page 1157 for disclosure information.
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© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
