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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Patterns of disease progression in hypertrophic cardiomyopathy: an individualized approach to clinical staging.Circ Heart Fail. 2012; 5: 535-546
- Hypertrophic cardiomyopathy.Lancet. 2013; 381: 242-255
- Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine.J Am Coll Cardiol. 2014; 64: 83-99
- Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy.Circulation. 2001; 104: 2517-2524
- Clinical significance of atrial fibrillation in hypertrophic cardiomyopathy.Curr Cardiol Rep. 2001; 3: 141-146
- Left atrial remodeling in hypertrophic cardiomyopathy and susceptibility markers for atrial fibrillation identified by cardiovascular magnetic resonance.Am J Cardiol. 2014; 113: 1394-1400
- Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy.J Am Coll Cardiol. 2002; 39: 301-307
- Clinical profile and prognostic significance of atrial fibrillation in hypertrophic cardiomyopathy.Cardiology. 2013; 126: 258-264
- Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation.Am J Cardiol. 1999; 83: 13H-18H
- Alterations in contractile protein composition and function in human atrial dilatation and atrial fibrillation.J Mol Cell Cardiol. 2006; 41: 467-477
- Outcomes of nonpharmacologic treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy.Heart Rhythm. 2015; 12: 1438-1447
- Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy.Mayo Clin Proc. 2008; 83: 630-638
- Significance of sarcomere gene mutations analysis in the end-stage phase of hypertrophic cardiomyopathy.Am J Cardiol. 2014; 114: 769-776
- Effects of chronic atrial fibrillation on active and passive force generation in human atrial myofibrils.Circ Res. 2010; 107: 144-152
- Tension generation and relaxation in single myofibrils from human atrial and ventricular myocardium.Pflugers Arch. 2007; 454: 63-73
- Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2013; 127: 1916-1926
- Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.Genet Med. 2015; 17: 880-888
- Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives.J Am Coll Cardiol. 2012; 60: 705-715
- Genetic advances in sarcomeric cardiomyopathies: state of the art.Cardiovasc Res. 2015; 105: 397-408
- Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression.Europace. 2010; 12: 347-355
- Atrial fibrillation ablation in patients with hypertrophic cardiomyopathy: long-term outcomes and clinical predictors.J Am Coll Cardiol. 2015; 65: 1485-1487
- Sex differences in myosin heavy chain isoforms of human failing and nonfailing atria.Am J Physiol Heart Circ Physiol. 2014; 307: H265-H272
- Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.J Am Coll Cardiol. 2014; 64: 2589-2600
- Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization.J Am Coll Cardiol. 2013; 62: 2010-2019
- Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice.Am J Physiol Heart Circ Physiol. 2014; 307: H1317-H1326
- Ca(2+) leak in atrial fibrillation: junctophilin-2 stabilizes ryanodine receptor.J Am Coll Cardiol. 2013; 62: 2020-2022
- Genetic basis of atrial fibrillation.Curr Opin Cardiol. 2014; 29: 220-226
- Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy.Circulation. 2013; 127: 575-584
- Ranolazine in the treatment of atrial fibrillation: results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following an ELectricaL CardiOversion) study.Heart Rhythm. 2015; 12: 872-878
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.
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
