To obtain sex-specific biomarkers, based on pathogenesis of microvascular disease, that improve the early diagnosis of diastolic dysfunction and HFPEF. These biomarkers come from innovative sources such as circulating endothelial cells,…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary aim is to improve the (early) diagnosis of diastolic dysfunction
and HFPEF with the discovery and validation of new biomarkers. Since HFPEF is
more prevalent in females, we will focus on discovery of sex-specific
biomarkers..
Endpoint: diagnosis of grade of diastolic dysfunction (LVDD) confirmed by E/e*
values or HFpEF
Additioneel ARGUS:
To describe the prevalence of CAD and coronary microvascular disease (CMD) in a
population of patients from the general population who are referred to the
Cardiology Center Netherlands, location Utrecht or the Diakonessenhuis by their
general practitioner and present with chest pain as the main symptom.
Secondary outcome
1. As a secondary objective, we aim to get a better understanding of the
aetiology of diastolic dysfunction and HFPEF. Discovery of causal biomarkers
may serve as lead targets for treatment of diastolic dysfunction and HFPEF.
2. To assess the prognostic ability of discovered biomarkers to predict
hospitalization for heart failure or death within 5 years.
3. To investigate the underlying genetics contribution to the development of
diastolic dysfunction and HFPEF.
Power will be limited to detect genetic associations with small effects and
HELPFUL will therefore join a genetic consortium that aims to perform a
genome-wide association study on diastolic dysfunction and HFPEF.
Addititional ARGUS:
To examine whether there are any blood (cell-based) biomarkers that predict
either a positive or a negative CAD and CMD imaging outcome.
To evaluate whether more extensive phenotyping of individuals who present with
chest pain complaints will improve long-term outcomes (time to) hospitalisation
for heart failure and all-cause mortality using linkage studies.
Background summary
Heart failure is a severe syndrome formed by two entities, systolic heart
failure and diastolic heart failure. Currently the term *heart failure with
reduced ejection fraction (HFREF)* is used for systolic heart failure and
*heart failure with preserved ejection fraction (HFPEF)* for diastolic heart
failure. Until recently it was thought that diastolic heart failure had a
better prognosis because the pump function of the heart was maintained. Most
research has therefore been in the area of systolic heart failure resulting in
good biomarkers, such as BNP, and better treatment options. Recent literature
has pointed out the severity of diastolic heart failure, for which current
biomarkers are not optimal and treatment options remain inadequate. New
medicine for diastolic heart failure is in phase II clinical trial setting,
which brings hope for better treatment options. To treat the correct type of
patient good diagnostic modalities are necessary. For diastolic heart failure
echocardiography is the golden standard, though there is much debate concerning
the cutoff value for the ejection fraction (a value for the pomp function of
the heart) and which combination of echocardiographic abnormalities should
classify diastolic dysfunction or heart failure. Wall motions of the left
ventricle, together with the volume of the left atrium, are viewed as the most
important parameters. The addition of a biomarker to this echo for improvement
of the diagnosis would be of great value. This is the goal of HELPFul, to
discover and validate a biomarker in the diagnosis of diastolic dysfunction and
HFPEF.
Recent data shows that the causes of HFPEF are different from HFREF. HFPEF
mostly affects women, with persistent high blood pressure and diabetes. These
risk factors appear to damage the endothelium (lining of the vascular wall) in
the small blood vessels of the heart (microvasculature). As a result these
small vessels will collaps, causing regional oxygen deficiency and thereby
thickening and stiffening of the heart. Another hypothese is that micro-embolia
(small clots) let go of artery sclerosis (erosion) and cause the small vessels
to get clogged. This could also result in thickening and stiffening of the
heart.
For the biomarker discovery we will aim for these two hypothese which centre
around the endothelium and the coagulation. We will study the transcriptoma
(information) of cells released from the smalls vessels of the heart for
information on the presence of diastolic dysfunction or HFPEF. Furthermore we
will study the blood for information suggestion the presence of micro-embolia.
Our biomarker discovery is mostly aimed at the endothelium and blood
coagulation. Promising biomarkers will be validated.
Additionally ARGUS:
Chest pain is a common symptom in the general practitioner*s office, affecting
between 20 and 40% of the general population during their lifetime. Chest pain
may be a symptom of underlying coronary artery disease (CAD), which is a
potentially life-threatening condition. Therefore, exclusion of CAD is the
first priority in patients with chest pain.
However, not only obstructive CAD, which affects the coronary arteries, but
also non-obstructive CAD with microvascular obstruction is associated with a
poor prognosis. Despite angiographical lack of macrovascular obstruction,
ischemia induced by coronary microvascular disease (CMD) can give rise to
symptoms as well.
Approximately two-thirds of all patients with chest pain and non-obstructive
CAD have some form of coronary microvascular dysfunction.
Current algorithms and scores have been developed and validated for the
exclusion of obstructive CAD only, but not for CMD. This may lead to
unintentional false reassurance and discharge of CMD patients with a poor
prognosis and potentially fatal result.
The aim of this proposal therefore is to develop an algorithm that can be used
by the general
practitioner that identifies individuals who do not have any coronary ischemia
either from obstructive CAD or CMD, and whose referral to a screening center or
a cardiologist is unnecessary, based on information derived from a drop of
blood.
To this end, we perform extensive cardiac and coronary imaging in individuals
referred to screening centers for chest pain. In addition we draw blood.
Advances in CCTA together with CMR imaging allows for quantified measures of
the macro- and microvascular disease of the heart. Based on imaging outcome, we
can identify two groups: 1) CAD and/or CMD and 2) no ischemia at all,
not requiring further additional testing.
ARGUS will result in an algorithm based on clinical information and extensive
blood-based information for the exclusion diagnosis of myocardial ischemia.
This algorithm will be validated in hospitalized and outpatient clinics
individuals in a cross-sectional manner, also using follow-up information on
hospitalizations and mortality. In the new era of predictive modeling and
machine learning, ARGUS will uncover nuances and patterns that yet remained
hidden within the wealth of medical data to improve clinical care and outcome.
Study objective
To obtain sex-specific biomarkers, based on pathogenesis of microvascular
disease, that improve the early diagnosis of diastolic dysfunction and HFPEF.
These biomarkers come from innovative sources such as circulating endothelial
cells, extracellular vesicles and endothelial micropartcicles
Endpoint: diagnosis of grade of diastolic dysfunction (LVDD) confirmed by E/e*
values or HFpEF.
Additioneel ARGUS:
To develop an algorithm based on clinical information and blood-based
information that
accurately excludes coronary vascular disease.
Study design
Case cohort study.
Study burden and risks
There is a small risk to the patient of getting bruises after venapuncture. But
this is the same risk as venapuncture within healthcare.
Additioneel ARGUS:
As part of the ARGUS study, participants will be invited for a cardiac CT scan
(using x-rays and intravenous (IV) infusion of an iodine contrast agent) and a
cardiac MRI scan (using IV adenosine and gadolinium contrast). Nine tubes of
venous blood (each 5-10cc) will be drawn from the patient at the day of
consultation for the CT scan. For these investigations the risk is the same
risk as during a regular care CT or MR-scan.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Patients in the cardiology outpatient clinic of Cardiology Centre
Netherlands, Diakonessenhuis Utrecht or HeartLife Klinieken Utrecht who
receive cardial screening, including an echocardiography, because of general
practitioner*s request
- Age 45 year and older
- Patient is willing and able to provide written informed consent for
participation in this study
- The inclusion criteria match the criteria for diagnosis of diastolic
dysfunction or HFpEF., Additional ARGUS, Inclusion criteria ARGUS
In order to be eligible to participate in the ARGUS study, a subject must meet
the additional following criterium:
• Chest pain as main symptom
Exclusion criteria
• Patients from whom no informed consent is obtained
• Incapacitated adults: language barriers or other obstacles for full
understanding of the study objectives
• Patients with former cardiac procedures.
• Patients with congenital heart disease,
Additional ARGUS:
A potential subject who meets any of the mentioned criteria or any of the
following will be excluded from participation in the ARGUS study:
• Patients for whom (a part of) the cardiac CT study protocol is contra
indicated prior to inclusion (if CT is contra indicated after completion of
MRI-scan patient will not be excluded but collected data will be used in study)
• Patients for whom (a part of) the cardiac MRI study protocol is contra
indicated prior to inclusion (if MRI is contra indicated after completion of
CT-scan patient will not be excluded but collected data will be used in study)
• Participants who are referred for an intervention immediately after
completing the cardiac CT scan
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL57077.041.16 |