title: Prediction of thrombo-embolic risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA).
abstract: OBJECTIVE
  Atrial fibrillation (AF) and thrombo-embolism (TE) are associated with reduced survival in hypertrophic cardiomyopathy (HCM), but the absolute risk of TE in patients with and without AF is unclear. The primary aim of this study was to derive and validate a model for estimating the risk of TE in HCM. Exploratory analyses were performed to determine predictors of TE, the performance of the CHA2 DS2 -VASc score, and outcome with vitamin K antagonists (VKAs).
  
  
  RESULTS
  A retrospective, longitudinal cohort of seven institutions was used to develop multivariable Cox regression models fitted with pre-selected predictors. Bootstrapping was used for validation. Of 4821 HCM patients recruited between 1986 and 2008, 172 (3.6%) reached the primary endpoint of cerebrovascular accident (CVA), transient ischaemic attack (TIA), or systemic peripheral embolus within 10 years. A total of 27.5% of patients had a CHA2 DS2 -VASc score of 0, of whom 9.8% developed TE during follow-up. Cox regression revealed an association between TE and age, AF, the interaction between age and AF, TE prior to first evaluation, NYHA class, left atrial (LA) diameter, vascular disease, and maximal LV wall thickness. There was a curvilinear relationship between LA size and TE risk. The model predicted TE with a C-index of 0.75 [95% confidence interval (CI) 0.70-0.80] and the D-statistic was 1.30 (95% CI 1.05-1.56). VKA treatment was associated with a 54.8% (95% CI 31-97%, P = 0.037) relative risk reduction in HCM patients with AF.
  
  
  CONCLUSIONS
  The study shows that the risk of TE in HCM patients can be identified using a small number of simple clinical features. LA size, in particular, should be monitored closely, and the assessment and treatment of conventional vascular risk factors should be routine practice in older patients. Exploratory analyses show for the first time evidence for a reduction of TE with VKA treatment. The CHA2 DS2 -VASc score does not appear to correlate well with the clinical outcome in patients with HCM and should not be used to assess TE risk in this population.
authors.affiliation: The Inherited Cardiac Diseases Unit, The Heart Hospital/University College London, London, UK.
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Guttmann
authors.affiliation: Department of Statistical Science, University College London, London, UK.
authors.forename: Menelaos
authors.initials: M
authors.lastname: Pavlou
authors.affiliation: The Inherited Cardiac Diseases Unit, The Heart Hospital/University College London, London, UK.
authors.forename: Constantinos
authors.initials: C
authors.lastname: O'Mahony
authors.affiliation: Cardiology Department and Research Unit, A Coruña University Hospital, Galician Health Service, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.affiliation: Unit of Inherited Cardiovascular Diseases, 1st Department of Cardiology, University of Athens, Athens, Greece.
authors.forename: Aristides
authors.initials: A
authors.lastname: Anastasakis
authors.affiliation: Institute of Cardiology, Department of Specialised, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.affiliation: Institute of Cardiology, Department of Specialised, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Biagini
authors.affiliation: Cardiac Department, University Hospital Virgen Arrixaca, Murcia-Cartagena s/n, El Palmar, Murcia, Spain.
authors.forename: Juan Ramon
authors.initials: JR
authors.lastname: Gimeno
authors.affiliation: Monaldi Hospital, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Limongelli
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Pavia
authors.affiliation: The Inherited Cardiac Diseases Unit, The Heart Hospital/University College London, London, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.affiliation: Department of Statistical Science, University College London, London, UK.|Biostatistics Group, University College London Hospitals/University College London Clinical Research Centre, University College London, London, UK.
authors.forename: Rumana Z
authors.initials: RZ
authors.lastname: Omar
authors.affiliation: The Inherited Cardiac Diseases Unit, The Heart Hospital/University College London, London, UK.
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
mesh_terms: D000367:Age Factors; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications*; D015331:Cohort Studies; D005260:Female; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008962:Models, Theoretical; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013923:Thromboembolism / Q000209:etiology* / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: Atrial fibrillation; Hypertrophic cardiomyopathy; Thrombo-embolism