An Arrhythmia Risk Stratification and Genetic Trial
- Conditions
- Sudden Cardiac DeathCalcium Metabolism DisordersCardiomyopathies, PrimaryArrhythmia
- Registration Number
- NCT01209494
- Lead Sponsor
- University Medical Center Goettingen
- Brief Summary
The prospective EUTrigTreat multi-center study is an observational, advanced diagnostics and genetic risk stratification trial in patients with standard indications for ICD treatment, with and without myocardial infarction in their history.
Its aims are fourfold: 1) To accurately risk stratify a large cohort of implantable cardioverter-defibrillator (ICD) patients for ICD shock risk and mortality using traditional risk markers as well as genetic markers 2) To find a link between repolarization biomarkers and genetic markers of calcium metabolism. 3) To compare invasive and noninvasive electrophysiologic (EP) testing systematically 4) To assess temporal changes of typical noninvasive risk stratifiers and their prognostic implication.
In five European academic clinical centers, 700 ICD patients are prospectively enrolled (optionally the number of enrolled patients may be expanded to 1000 patients). Comprehensive non-invasive risk stratifying ECG diagnostics including beat-to-beat variability of repolarization (BVR) are applied, and candidate genes associated with malignant arrhythmias are analyzed. Programmed electrical stimulation is performed to test for inducibility of malignant ventricular arrhythmias and BVR. In a subset of patients, electrophysiologic studies include recording of monophasic action potentials (MAP) from the right ventricle for assessment of restitution properties. Non-invasive risk stratifying ECG methods are repeated annually. Outcome (mortality, ICD shocks) will be assessed until September 2014.
- Detailed Description
An increasing number of patients receive implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. Within this group, it is difficult to differentiate between patients at high risk with need for additional treatment and, on the other hand, patients at low risk without benefit from implantable cardioverter-defibrillator therapy. Risk stratification techniques have been studied extensively over the last decades, but no conclusive recommendations can be found in the current guidelines for prevention of SCD. Furthermore, new genetic markers associated with sudden cardiac death were discovered recently, however, have not been implemented in concurrent risk analysis. Last, time dependent changes of risk stratification assessment are unknown.
The prospective EUTrigTreat multi-center study is an observational, advanced diagnostics and genetic risk stratification trial in patients with standard indications for ICD treatment and without myocardial infarction in their history.
Its aims are fourfold: 1) To accurately risk stratify a large cohort of implantable cardioverter-defibrillator (ICD) patients for ICD shock risk and mortality using traditional risk markers as well as genetic markers 2) To find a link between repolarization biomarkers and genetic markers of calcium metabolism. 3) To compare invasive and noninvasive electrophysiologic (EP) testing systematically 4) To assess temporal changes of typical noninvasive risk stratifiers and their prognostic implication.
In four European academic clinical centers, 700 ICD patients are prospectively enrolled. Optionally, the number of patients may be expanded to 1000. Comprehensive non-invasive risk stratifying ECG diagnostics including beat-to-beat variability of repolarization (BVR) are applied, and candidate genes associated with malignant arrhythmias are analyzed. Programmed electrical stimulation is performed to test for inducibility of malignant ventricular arrhythmias and BVR. In a subset of patients, electrophysiologic studies include recording of monophasic action potentials (MAP) from the right ventricle for assessment of restitution properties. Non-invasive risk stratifying ECG methods are repeated annually. Outcome (mortality, ICD shocks) will be assessed until September 2014.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 672
- Standard indication for ICD treatment according to ACC/AHA/ESC guidelines for primary or secondary prevention of SCD
- Age ≥ 18 years
- Nonischemic cardiomyopathies: DCM, HCM/HOCM, ARVC or
- Channelopathies: Brugada, LQT, CPVT or
- Idiopathic VT/VF or
- Diffuse coronary artery disease, without transmural myocardial infarction in history (ACS and NSTEMI with CK maximum of 400 U/l allowed)
- Unstable cardiac disease
- PCI or CABG < 3 months ago
- Implantation of a CRT device < 6 months ago
- ICD unable to deliver programmed ventricular stimulation via programmer (only in the noninvasive EP study group)
- Women of childbearing potential in case of positive pregnancy test at the time of enrollment
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Total Mortality 2010-2014
- Secondary Outcome Measures
Name Time Method Sudden Cardiac, Cardiac and Non-Cardiac Mortality 2010-2014 The standard definition of SCD applied. A cardiac death is defined as any death presumed to have occurred from a cardiac cause other than SCD. Non-cardiac deaths are all other deaths.
Secondary Composite Endpoints 2010-2014 A secondary composite endpoint of total mortality and appropriate ICD shocks is defined. Another secondary composite endpoint is defined as the sum of appropriate and inappropriate ICD shocks, i.e. all ICD shocks.
Appropriate and Inappropriate Shocks 2010-2014 Appropriate shock is a secondary endpoint. ICD shock is classified as appropriate if delivered for a true ventricular tachyarrhythmia in the VT or VF zone. Appropriate ICD shock is classified as 1 primarily delivered in the VF zone, 2 secondarily delivered as a backup to failed ATP in the VT zone or 3 secondarily delivered after acceleration of failed ATP to VF zone.
Inappropriate shock is a secondary endpoint. Inappropriate shock is an ICD shock caused by oversensing of cardiac or non-cardiac electrical signals as VT or VF, or by inappropriate interpretation of SVT as VT/VF by the device.
Trial Locations
- Locations (4)
Universitair Medisch Centrum Utrecht, Depts. of Cardiology and Physiology
🇳🇱Utrecht, Netherlands
Attikon Hospital University of Athens, BRFAA, Dept. of Cardiology
🇬🇷Athens, Greece
Katholieke Universiteit Leuven, Dept. of Cardiology
🇧🇪Leuven, Belgium
University Medical Center Goettingen, Dept. of Cardiology and Pneumology
🇩🇪Goettingen, Germany