title: Impact of Genotype on the Occurrence of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.
abstract: 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.
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.
authors: Carolina
authors: C
authors: Bongini
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: cecilia.ferrantini@unifi.it.
authors: Cecilia
authors: C
authors: Ferrantini
authors: Genetic Diagnostics Unit, Laboratory Department, Careggi University Hospital, Florence, Italy.
authors: Francesca
authors: F
authors: Girolami
authors: Department of NeuroFarBa, University of Florence, Florence, Italy.
authors: Raffaele
authors: R
authors: Coppini
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.
authors: Anna
authors: A
authors: Arretini
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.
authors: Mattia
authors: M
authors: Targetti
authors: Genetic Diagnostics Unit, Laboratory Department, Careggi University Hospital, Florence, Italy.
authors: Sara
authors: S
authors: Bardi
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.
authors: Gabriele
authors: G
authors: Castelli
authors: Genetic Diagnostics Unit, Laboratory Department, Careggi University Hospital, Florence, Italy.
authors: Francesca
authors: F
authors: Torricelli
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Franco
authors: F
authors: Cecchi
authors: Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors: Michael J
authors: MJ
authors: Ackerman
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Luigi
authors: L
authors: Padeletti
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Corrado
authors: C
authors: Poggesi
authors: Referral Center for Cardiomyopathies, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.
authors: Iacopo
authors: I
authors: Olivotto
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000235:genetics*; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D000066491:Clinical Decision-Making; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000235:genetics*; D011237:Predictive Value of Tests; D015995:Prevalence; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human