Clinical trial NCT00478933: DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients.
Official title: Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Tachy-arrhythmia in ICD Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Death, Sudden, Cardiac
Ventricular Fibrillation
Tachycardia
Atrial Fibrillation
Sick Sinus Syndrome
Keywords: Arrhythmia
Ventricular
Atrial
Tachycardia
Fibrillation
Flutter
GNB3
GNAS
GNAQ
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2007-05-25
Enrollment: 1223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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 ).

Primary outcomes:
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype
timeFrame: 2 years
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype
timeFrame: 2 years
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype
timeFrame: 2 years
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype
timeFrame: 2 years
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype
timeFrame: 2 years
measure: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype
timeFrame: 2 years
measure: Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype
timeFrame: 2 years
Secondary outcomes:
measure: Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics
timeFrame: 2 years
measure: All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Padova, Italy
name: Domenico Corrado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Essen, Germany
name: Heiner Wieneke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.