DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients. (DISCOVERY)

Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Tachy-arrhythmia in ICD Patients.

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Ventricular Fibrillation; Tachycardia; Death, Sudden, Cardiac; Sick Sinus Syndrome
• Intervention / Treatment: Procedure: Blood sampling; Device: Defibrillator, Dual Chamber ; Implantable

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 Type: Interventional
• Enrollment (Actual): 1223
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ICD Therapy, blood sampling; Blood sampling Defibrillator, Dual Chamber ; Implantable	Procedure: Blood sampling; Blood sampling; Device: Defibrillator, Dual Chamber ; Implantable; Patient must wear a dual chamber ICD to remain in study. Can be enrolled 10 days prior to implant. Is excluded if device type changes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype	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.	2 years
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype	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.	2 years
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype	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.	2 years
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype	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.	2 years
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype	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.	2 years
Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype	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.	2 years
Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype	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.	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Medtronic Bakken Research Center
• Investigators: Principal Investigator: Domenico Corrado, MD, University of Padova, Italy; Principal Investigator: Heiner Wieneke, MD, Universitätsklinikum Essen, Germany

Publications and helpful links

General Publications

• Wieneke H, Svendsen JH, Lande J, Spencker S, Martinez JG, Strohmer B, Toivonen L, Le Marec H, Garcia-Fernandez FJ, Corrado D, Huertas-Vazquez A, Uy-Evanado A, Rusinaru C, Reinier K, Foldesi C, Hulak W, Chugh SS, Siffert W. Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. J Am Heart Assoc. 2016 Nov 28;5(12):e003905. doi: 10.1161/JAHA.116.003905.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 24, 2007
• First Posted (Estimate): May 25, 2007

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: July 4, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Arrhythmia; Ventricular; Tachycardia; Fibrillation; Atrial; GNAS; Flutter; GNB3; GNAQ
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Death; Heart Arrest; Arrhythmia, Sinus; Heart Block; Atrial Fibrillation; Ventricular Fibrillation; Tachycardia; Death, Sudden, Cardiac; Sick Sinus Syndrome; Death, Sudden
• Other Study ID Numbers: DISCOVERY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: study is closed several years ago; this is not applicable for this study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No