An Arrhythmia Risk Stratification and Genetic Trial

Conditions

Arrhythmia, Calcium Metabolism Disorders, Cardiomyopathies, Primary, Sudden Cardiac Death

Keywords

sudden cardiac death, implantable cardioverter defibrillator, ventricular arrhythmias, genetic syndromes, calcium metabolism, ventricular repolarization, ECG, T wave, programmed electrical stimulation, alternans, late potentials, risk stratification

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.

Karl Heinrich Scholz, Thomas Meyer, Björn Lengenfelder, Christian Vahlhaus, Jörn Tongers et al. (17 authors)

Open Heart2021-05-0123 citations

10.1136/openhrt-2021-001650

Prognostic significance of emergency department bypass in stable and unstable patients with ST-segment elevation myocardial infarction

Karl Heinrich Scholz, Tim Friede, Thomas Meyer, Claudius Jacobshagen, Björn Lengenfelder et al. (17 authors)

European Heart Journal Acute Cardiovascular Care2018-11-2722 citations

10.1177/2048872618813907

Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial

Karl Heinrich Scholz, Sebastian K.G. Maier, Lars S. Maier, Björn Lengenfelder, Claudius Jacobshagen et al. (17 authors)

European Heart Journal2018-01-18353 citations

10.1093/eurheartj/ehy004

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype.

Seegers J, Vos MA, Flevari P, Willems R, Sohns C, Vollmann D, Lüthje L, Kremastinos DT, Floré V, Meine M, Tuinenburg A, Myles RC, Simon D, Brockmöller J, Friede T, Hasenfuß G, Lehnart SE, Zabel M, EUTrigTreat Clinical Study Investigators.

2011-11-2313 citations

10.1093/europace/eur352

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame
Total Mortality	2010-2014

Secondary

Measure	Time frame	Description
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.
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.
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.

Countries

Belgium, Germany, Greece, Netherlands

Outcome results