Atrial Fibrillation, Death, Sudden, Cardiac, Sick Sinus Syndrome, Tachycardia, Ventricular Fibrillation
Conditions
Keywords
Arrhythmia, Ventricular, Atrial, Tachycardia, Fibrillation, Flutter, GNB3, GNAS, GNAQ
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.
Interventions
DEVICEDefibrillator, 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.
PROCEDUREBlood sampling
Blood sampling
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
patients and investigators were blinded to the genetic markers during the study. Therefore, no arm is specified as this is not applicable.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 ).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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.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 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.-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. |
Secondary
| Measure | Time frame |
|---|---|
| All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter | 2 years |
| Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics | 2 years |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ICD Therapy, Blood Sampling 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.
Blood sampling: Blood sampling for genetic analysis on pre-specified SNPs | 1,198 |
| Total | 1,198 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inadequate data available | 53 |
| Overall Study | Informed consent not verified | 3 |
| Overall Study | Protocol Violation | 22 |
Baseline characteristics
| Characteristic | ICD Therapy, Blood Sampling |
|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment Austria | 40 participants |
| Region of Enrollment Denmark | 57 participants |
| Region of Enrollment Finland | 25 participants |
| Region of Enrollment France | 84 participants |
| Region of Enrollment Germany | 491 participants |
| Region of Enrollment Greece | 26 participants |
| Region of Enrollment Hungary | 59 participants |
| Region of Enrollment Italy | 54 participants |
| Region of Enrollment Norway | 26 participants |
| Region of Enrollment Poland | 134 participants |
| Region of Enrollment Spain | 189 participants |
| Region of Enrollment United Kingdom | 13 participants |
| Sex: Female, Male Female | 194 Participants |
| Sex: Female, Male Male | 1004 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 1,145 |
| serious Total, serious adverse events | 265 / 1,145 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype | 253 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype | 42 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype | 2 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype | 268 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype | 29 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype | 0 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype | 85 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype | 143 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype | 69 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype | 103 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype | 136 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype | 59 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype | 145 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype | 123 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype | 29 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype | 63 participants with VT < 400 msec |
| c.393C>T CT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype | 136 participants with VT < 400 msec |
| c.393C>T TT Genotype | Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype | 98 participants with VT < 400 msec |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| c.393C>T CC Genotype | Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype | 135 participants with VT < 400 msec |
| c.393C>T CT Genotype | Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype | 136 participants with VT < 400 msec |
| c.393C>T TT Genotype | Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype | 26 participants with VT < 400 msec |
Secondary
All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter
Time frame: 2 years
Secondary
Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics
Time frame: 2 years