An Arrhythmia Risk Stratification and Genetic Trial (EUTrigTreat)

University Medical Center Goettingen

Status: Completed

Conditions: Cardiomyopathies, Primary; Arrhythmia; Calcium Metabolism Disorders; Sudden Cardiac Death

Study type: Observational

Funder types: Other

Identifiers

NCT01209494

HEALTH-F2-2009-241526

Details and patient eligibility

About

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.

Full 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.

Enrollment: 672 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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

Trial design

672 participants in 2 patient groups

Invasive EP Study Group

Description:

200 patients are studied before clinically indicated (according to AHA/ACC/ESC guidelines) first ICD implantation or ICD exchange. Invasive EP study is performed to test inducibility of malignant arrhythmia. In addition MAP recordings are performed for measurements of restitution properties. Pacing is done for 12-lead ECG and MAP recordings for analysis of BVR and TWA, if applicable.

Noninvasive EP Study Group

Description:

The assignment of patients to the invasive and noninvasive EP groups does not occur by randomization or for intervention. In the noninvasive EP study group, 500 patients with chronically implanted ICD (\>3 month after implantation) are investigated using non-invasive EP study via ICD programmer. Programmed electrical stimulation is performed to test for inducibility of malignant arrhythmia. In addition pacing is done for measurements of BVR from the 12-lead ECG.