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Sudden Cardiac Death in Hypertrophic Cardiomyopathy

O'Mahony, C; (2013) Sudden Cardiac Death in Hypertrophic Cardiomyopathy. Doctoral thesis , UCL (University College London).

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Introduction: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease associated with sustained ventricular arrhythmias and sudden cardiac death (SCD). Patients at high risk of SCD are currently identified by specific clinical characteristics, as outlined in an algorithm proposed by the American College of Cardiology and European Society of Cardiology in 2003. Patients at high risk of SCD are treated with Implantable Cardioverter Defibrillators (ICD), but the accuracy of the risk stratification algorithm, the long term outcome of ICD recipients and the nature of ventricular arrhythmias are unclear. Objectives: The aims of the thesis were to: a) characterise the electrophysiological nature of ventricular arrhythmias; b) determine long term outcomes post ICD implantation; c) validate the current risk stratification strategy; d) develop a novel clinical risk prediction model for SCD. Methods: Retrospective, observational cohort studies. Results: Monomorphic ventricular tachycardia is the most common ICD-treated ventricular arrhythmia (86%), and premature ventricular complexes are the most common electrical triggers (72%). ICD recipients had an appropriate shock rate of 2.3%/year (none suffered SCD), but experienced inappropriate shocks (4.6%/year), implant complications (5.1%/year) and heart failure death/transplantation (1.7%/year). Cox proportional hazards analysis showed that the risk of SCD increases with the aggregation of risk factors, but the current risk stratification strategy has poor discrimination (time dependent receiver operating characteristic curve c=0.64 at 5 years). An alternative clinical risk prediction model providing more individualised SCD risk estimates is proposed. The risk prediction model was externally validated in an Italian cohort (Harrell’s c=0.78; calibration slope: 0.82). Conclusions: The mode of initiation and morphology of ventricular arrhythmias suggest that underlying mechanism is re-entry. The current risk stratification strategy has limited predictive capabilities, and as a consequence the majority of ICD recipients do not receive appropriate shocks and are exposed to ICD related complications. The novel SCD risk prediction model offers an alternative approach by providing validated SCD risk estimates.

Type: Thesis (Doctoral)
Title: Sudden Cardiac Death in Hypertrophic Cardiomyopathy
Language: English
Additional information: Permission for digitisation not received.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/1408332
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