To assess the uniqueness of diabetic cardiomyopathy (DCM) relative to other forms of cardiomyopathy using unsupervised clustering approaches based on deep phenotyping (clinical, imaging and biological) information. With the results of this study we…
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is quality of the phenotypic clustering analysis, as
assessed by the measurement of between-clusters overlap (<10% target),
connectivity, stability and within-clusters compactness. The 3 year follow-up
data of cardiovascular events will provide crucial information to assess the
clinical relevance and prognostic value of identified clusters.
Secondary outcome
- To enrich the phenomapping with complementary multi-OMICs information to
evaluate their added value for discriminating between clusters.
- To identify the best clinical, biological, imaging and multi-OMICs predictors
of belonging to the DCM cluster (diagnostic perspective).
- To explore the pathophysiological and causal pathways characterizing DCM, in
order to better understand the underlying mechanisms responsible for
establishment and progression of disease.
- To assess the predictive value of the DCM cluster identified for overall
survival and cardiovascular events (prognostic perspective)
Background summary
In recent decades it has become clear that there is a relationship between type
2 diabetes mellitus (T2DM) and heart failure (HF). Although not all patients
with T2DM develop a cardiomyopathy or progress to HF, they are more than 2.5
times more likely than non-diabetic patients to present with myocardial
dysfunction and progression to HF. The simultaneous presence of confounders
such as hypertension, obesity, systemic inflammation and certain genetic
disorders makes it difficult to objectify the specific contribution of the
glucometabolic state to myocardial dysfunction. The hypothesis is that diabetic
cardiomyopathy (DCM) is the result of deregulation of a specific, to be
identified, signalling pathway that leads to a particular cardiac dysfunction
which is different from other forms of HF.
Study objective
To assess the uniqueness of diabetic cardiomyopathy (DCM) relative to other
forms of cardiomyopathy using unsupervised clustering approaches based on deep
phenotyping (clinical, imaging and biological) information. With the results of
this study we aim to improve the clinical care of T2DM patients by discovering
new opportunities for personalized preventive and therapeutic strategies.
Study design
CARDIATEAM is a prospective, multicenter and multinational cohort study.
Study burden and risks
There is minimum risk associated with this study. For more details please see
study protocol *10.5 Benefits and risks assessment, group relatedness*
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
* Female or male, aged between >= 40 and <=80 years
* Normal LVEF AND absence of akinetic segment assessed by echocardiography
(i.e. LVEF>=50%)
* For each group, the diagnosis will be based on current accepted criteria [7,
8] :
o HFpEF: left ventricular ejection fraction (LVEF) LVEF>=50% AND presence/or
history of symptoms (e.g. breathlessness, ankle swelling and fatigue) or signs
(e.g. elevated jugular venous pressure, pulmonary crackles and peripheral
oedema) of heart failure AND significant diastolic dysfunction (left atrial
volume index >34 mL/m2 or a LVMI >=115 g/m2 for males and >=95 g/m2 for female,
E/e* >=13 and e* <9 cm/s) OR NT-proBNP >125 pg/mL
o No HFpEF: LVEF>=50% AND absence of symptoms (e.g. breathlessness, ankle
swelling and fatigue) or signs (e.g. elevated jugular venous pressure,
pulmonary crackles and peripheral oedema) of heart failure
o T2DM: HbA1c >=6.5% (>=48 mmol/L) AND Fasting Plasma Glucose >=7.0 mmol/L (>=126
mg/dL) or anti-diabetic treatment
o Non T2DM: HbA1c < 6.5% AND Fasting Plasma Glucose <7.0 mmol/L without any
anti-diabetic treatment including normoglycemic subjects
o HCM: patients with non-obstructive HCM of sarcomeric cause (proven with
common genetic cause) and with LV wall thickness >= 15 mm in one or more
myocardial segments in the absence of abnormal afterload conditions.
* Suitable echocardiographic window
* Absence of history of coronary artery disease including history of myocardial
ischaemia, myocardial infarction or percutaneous coronary intervention
* Absence of significant coronary artery disease (CAD) defined as
o the absence of coronary artery stenosis >=50% on a cardiac computed tomography
(CT) OR a coronary angiography OR normal Fractional Flow Reserve (FFR >0.80) OR
Coronary Artery Calcium score (CAC) < 100 performed within the 24 months before
inclusion. Coronary CT and/or stress tests will not be performed as part of the
study in the Dutch centers. Only patient in which the absence of CAD has
previously been confirmed by this definition (due to clinical indication) will
be included.
* Patient covered by a health insurance
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
* Diabetes mellitus other than type 2 (type 1, LADA, MODY, NODAT, etc.)
* Suboptimal echocardiographic window
* Significant valvular heart disease defined as severe aortic regurgitation or
severe primary mitral regurgitation or aortic stenosis with a peak
transvalvular velocity >=3m/s or mitral stenosis with a mitral valve area <
1.5cm²
* Chronic atrial fibrillation or any significant arrhythmia at inclusion
* Renal insufficiency defined as eGFR<30 mL/min/1.73m²
* History of and candidate to bariatric surgery
* Obstructive hypertrophic cardiomyopathy (definition: maximal gradient at rest
<30 mmHg)
* Hypertrophic cardiomyopathy due to a non-sarcomeric etiology, i.e. known
infiltrative or storage disorder mimicking HCM such as Fabry disease or
amyloidosis
* Life threatening comorbidities (i.e. history of or active cancer treated with
chemo-therapy or radiotherapy, end-stage heart failure, severe lung disease,
cirrhosis)
* Pregnancy
* Lactating mother.
* Any condition which in the Investigator*s opinion makes it undesirable for
the subject to participate in the study or which would jeopardize compliance
with the protocol (e.g. known contrast allergy)
* Inability to understand the local language
* Individuals deprived of liberty
* Protected persons (under guardianship or curatorship)
* Contra-indication to CMR (please see CMR_SOP)
* Known hypersensitivity to gandolinium based product (including gadoteric acid
and meglumine)
* Known symptomatic COVID-19 infection requiring hospitalization.
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 |
|---|---|
| ClinicalTrials.gov | NCT04303364 |
| CCMO | NL71063.068.19 |