DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients.

Not Applicable

Completed

• Conditions: Death, Sudden, Cardiac; Ventricular Fibrillation; Atrial Fibrillation; Sick Sinus Syndrome; Tachycardia
• Interventions: Device: Defibrillator, Dual Chamber ; Implantable; Procedure: Blood sampling

• Registration Number: NCT00478933
• Lead Sponsor: Medtronic Bakken Research Center

Brief Summary

To prospectively evaluate if the analysis of genetic polymorphisms can be used to identify patients at risk of ventricular tachycardia.

To evaluate the influence of ICD-based diagnostic information on the long term treatment and management of primary prevention ICD-patients.

Detailed Description

Evaluate the positive predictive value of single nucleotide polymorphisms (SNPs) in the genes GNB3, GNAS and GNAQ as predictors of ventricular arrhythmia \<400 msec.

1. Evaluate the positive predictive value of Single Nucleotide Polymorphisms as predictor for death, cardiac death and atrial fibrillation/flutter in the genes GNB3, GNAS, GNAQ and other SNPs involving signal transduction components which impact on the activity of cardiac ion channels.

2. Evaluate the best combination of genetic parameters, baseline data and follow-up data as predictor of primary endpoint, All cause Mortality, cardiac death and atrial arrhythmia.

3. Evaluate the usage of ICD-system diagnostics (battery status, impedance, pacing threshold, sensing) resulting in medical consequences\*.

4. Evaluate the usage of ICD-based patient diagnostics (arrhythmia, IEGM, heart frequency, %pacing, Cardiac Compass) resulting in medical consequences\*.

5. Evaluate the frequency of programming changes involving AF-prevention and AF-therapy algorithms.

6. Evaluate the frequency of pacing-parameter programming changes and the resulting medical consequences\*.

* Medical consequences include: Hospitalization, medical interventions, medication, surgery, additional diagnostics and ICD-programming changes.

Study Timeline

• Study Start: 2007-02
• Study First Submitted: 2007-05-23
• Study First Submitted QC: 2007-05-24
• Study First Posted: 2007-05-25
• Primary Completion: 2012-07
• Study Completion: 2012-12
• Status Verified: 2017-07
• Results First Submitted: 2017-07-04
• Results First Submitted QC: 2017-07-04
• Last Update Submitted: 2017-07-04
• Results First Posted: 2017-11-22
• Last Update Posted: 2017-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1223

Inclusion Criteria

• Implantation of a market approved Medtronic Dual-chamber ICD with long term clinical trends Cardiac Compass,
• Subjects requiring the implantation of an ICD for primary prevention according to the current AHA/ACC/ESC guidelines,
• Subject able to comply with the Clinical InvestigationPlan,
• Subject is expected to remain available for follow-up visits,
• Subject has signed the informed consent form within 10 days of implant,
• The system implanted for this study is the first ICD implant for patient.

Exclusion Criteria

• Women who are pregnant, or women of childbearing potential not on a reliable form of birth control,

• Subject is enrolled in a concurrent study that may confound the results of this study,

• Subject has a life expectancy less than two years,

• Subject is post heart transplant or awaiting heart transplantation,

• Subject is anticipated to demonstrate poor compliance,

• Subjects with syndromes known to be associated with ion channel pathologies such as:

  • Long- or short-QT Syndrome
  • Brugada Syndrome
  • Catecholaminergic Polymorphic Ventricular Tachycardia (CPTV ).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ICD Therapy, blood sampling	Blood sampling	Blood sampling Defibrillator, Dual Chamber ; Implantable
ICD Therapy, blood sampling	Defibrillator, Dual Chamber ; Implantable	Blood sampling Defibrillator, Dual Chamber ; Implantable

Primary Outcome Measures

Name	Time	Method
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype	2 years	The GNAS c.2273C\>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype	2 years	The GNAQ c.-909/-908GC\>TT single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype	2 years	The GNB3 c.825C\>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype	2 years	The GNAS c.393C\>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype	2 years	The GNAS c.2291C\>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype	2 years	The GNAQ c.-382G\>A single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype	2 years	The GNAQ c.-387G\>A single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia \<400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias \<400 msec were tracked by genotype.

Secondary Outcome Measures

Name	Time	Method
Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics	2 years
All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter	2 years