Methods
Study Design and Patient Population
The study population consisted of 152 consecutive HCM patients who received an ICD between April 1994 and December 31, 2011, at the Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands, or the University Hospitals Leuven, Leuven, Belgium. All patients gave written informed consent for ICD implantation and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. The study was approved by the institutional review board. Each patient had an established diagnosis of HCM, based on unexplained left ventricular hypertrophy of ≥15 mm. Patients with HCM linked to Noonan's syndrome, Fabry's disease, mitochondrial disease, or congenital heart defects were excluded.
ICDs were implanted for primary prevention of SCD, based on the presence of established major risk factors for SCD (non-sustained ventricular tachycardia [VT] on Holter-monitoring, unexplained syncope, abnormal blood pressure response during exercise testing, left ventricular wall thickness ≥30 mm or a family history of ≥1 HCM-related SCD in close relatives), or for secondary prevention of SCD in patients with a history of ventricular fibrillation (VF) or sustained VT. ICDs were also implanted in HCM patients who developed complete atrioventricular (AV) block after alcohol septal ablation (ASA).
The following clinical characteristics and other less well-established risk factors for SCD were examined: gender, age at implantation, New York Heart Association (NYHA) functional class, indication for cardiac resynchronization therapy (CRT), atrial fibrillation (AF), left ventricular outflow tract (LVOT) obstruction, history of myectomy or ASA, the presence of delayed gadolinium enhancement on magnetic resonance imaging (MRI), genotype, coronary artery disease, inducible VF during electrophysiological testing, and anti-arrhythmic medication used by patients. If genetic testing was applied, the following genes were screened for mutations: cardiac myosin binding protein C (MYBPC3), β-cardiac myosin heavy chain (MYH7), myosin regulatory light chain (MYL2), cardiac troponin T, cardiac troponin I, α-actin, and α-tropomyosin.
Devices
Patients received single or dual-chamber ICDs, or biventricular ICDs if CRT was indicated, with transvenous lead systems. All devices were capable of antitachycardia and antibradycardia pacing and can deliver shock therapy. The rate cutoff for detection of VF or VT and activation of antitachycardia pacing was set at the discretion of the treating electrophysiologist.
End Points
End points were total and cardiac mortality, appropriate ICD intervention, appropriate ICD shocks, inappropriate ICD shocks, and ICD related complications. Cardiac mortality was defined as SCD, death from stroke, death from end-stage heart failure, and heart transplantation. Patients undergoing heart-transplantation were censored at the time of the procedure. Mortality, ICD interventions, and complications were retrieved from hospital patient records, from civil service population registers, and from information provided by general practitioners or other centers where follow-up had occurred. All ICD interventions were evaluated by an experienced electrophysiologist. Appropriate ICD intervention was defined as an intervention (either shock or antitachycardia pacing) triggered by an arrhythmia that was ventricular in origin. Appropriate ICD shock was defined as an ICD shock triggered by a sustained ventricular arrhythmia. Inappropriate ICD shock was defined as ICD shocks triggered by non-sustained ventricular arrhythmias, supraventricular arrhythmias, sinus tachycardia, oversensing, or device malfunction (eg, lead fracture leading to inappropriate shocks). If revision or hospital readmission related to the device was required, it was identified as a major complication. Follow-up started at the time of ICD implantation. The administrative censoring date was set at July 1, 2012.
Statistical Analysis
SPSS version 20 (IBM, Armonk, NY) and Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA) were used for all statistical analyses. Categorical variables were summarized as percentages. Normally distributed continuous data are expressed as mean ± SD and non-normally distributed data were expressed as median ± interquartile range. For comparing variables either χ-test or Mann-Whitney U test were used, for categorical and continuous data respectively. Estimated survival and actuarial event-free rates from ICD intervention were calculated according to the Kaplan-Meier method and were compared using the log-rank test. Patients who underwent heart transplantation were censored alive on the day of transplantation. Cox regression analysis was used to determine predictors of outcome. Variables were selected for multivariable analysis if univariable P value was <.10 and were expressed as hazard ratio (HR) with 95% confidence interval. The final number of variables was restricted according to the number of end point events to avoid overfitting the multivariable model. P < .05 was considered statistically significant.
No extramural funding was used to support this work, and the authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the manuscript.