To phenotype and genotype the population of patients with IVF in our cohort, and to find alternative diagnoses as a cause of the event of VF.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Cardiac and vascular disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Alternative diagnoses discovered during follow-up in patients with IVF.
Secondary outcome
• Description of the population of our cohort (Prognosis, recurrence of
arrhythmias, therapy, (in)appropriate shocks, presence of cardiac anomalies not
sufficient for an alternative diagnosis)
• The detection of prognostic factors for IVF (family history, use of
medication, gender, ECG features etc).
• Discovering new susceptibility genes for idiopathic VF
In patients who have no structural or electrical heart disease nor a known gene
mutation responsible for ventricular fibrillation, we will pursue a *hypothesis-
driven* approach and search for mutations in genes that are predicted to be of
importance in IVF, based on existing gene networks and existing literature.
When no susceptibility genes are discovered, sequencing will be extended to
whole exome sequencing.
• Quality of life measurements of IVF patients, compared to the healthy
population.
Background summary
Our cohort contains 95 patients diagnosed with idiopathic ventricular
fibrillation, who experienced an OHCA because of VF between 1985 and present
day and who were admitted to the University Medical Centre Utrecht. In order to
confirm which patients have developed a structural heart disease and have had
ventricular fibrillation as first symptom of an underlying heart disease, the
missing investigations must be performed. This is all regular diagnostic
work-up which is indicated by the consensus on the standardisation of clinical
evaluation of IVF.
Our hypothesis is that idiopathic ventricular fibrillation is a non-existing
diagnosis and that in every patient there is an underlying etiology either
substrate that may give rise to VF. In order to detect this etiology, the first
step is to define and phenotype the population in further detail, as documented
in current consensus statements.
In a further stage of the study, all patients with idiopathic ventricular
fibrillation will undergo further genetic testing, either targeted gene
sequencing or whole exome sequencing in order to find novel genes that can
give rise to arrhythmias such as VF. This may be of great clinical importance,
as it has been for example in the case of finding the autosomal dominant DPP6
risk haplotype (which confers a greatly increased risk of sudden cardiac death
between the ages of 20 and 60 years), that justifies life-saving primary
prevention with an ICD.10 This finding has been of utmost importance, as
genetic testing has proven to be the only way to identify the individuals at
risk for sudden cardiac death in these families, as no way of functional
cardiac testing can identify the individuals with the allele predisposing to
sudden cardiac death at a young age.
Our cohort is the largest in the world and presently, no study with such a
large group of IVF-patients has been published.
Study objective
To phenotype and genotype the population of patients with IVF in our cohort,
and to find alternative diagnoses as a cause of the event of VF.
Study design
A retrospective cross-sectional study.
Study burden and risks
All patients have had diagnostic work-up after the event of VF and almost all
patients received an ICD. These patients attend yearly or half yearly routine
control, however a number of patients have missing data in their follow-up. To
complete the work- and follow-up, extra procedures must be performed, such as
echocardiography, or genetic testing. These procedures are all part of the
current regular diagnostic work-up, except for advanced genetic testing in the
form of whole exome sequencing (WES) in a selected group of patients. In some
patients not all procedures of the regular work-up have been performed and the
event of IVF occurred many years ago. Nowadays, the insights on diagnostic
work-up after an OHCA based on VF have been renewed and the protocol has been
adjusted, therefore alternative diagnoses can be missed. In order to detect
these alternative diagnoses, the missing procedures must be performed. Per
patient, an analysis is made of which procedures are missing and which
procedures are necessary. Procedures that could be additionally performed are:
echocardiography, MRI/CT, ajmaline test, ergonovine test, adrenalin test,
holter, coronary angiography, exercise-ECG and genetic testing. The risks and
burden associated with participation are low, since all procedures are part of
the regular work-up. The risks depend on what procedures need to be performed.
The possible benefits are: Detection of a cause for the VF, improvement of
treatment and, in a case of a pathogenic genetic mutation either a familial
disease, the possibility of prophylactic treatment of affected family members.
Per patient, the results will be carefully evaluated and per missing procedure
will be determined if it is necessary and useful to perform the procedure.
In patients without any detectable cause for the VF, WES will be performed as
an extension of the regular genetic testing, to take the first step in
discovering new -genetic- etiologies and mechanisms of IVF.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
All documented patients who had an OHCA, who were successfully resuscitated and had ventricular fibrillation as initial rhythm and were finally diagnosed as idiopathic VF.
Exclusion criteria
N/A
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47917.041.14 |