CARdiomyopathy in Type 2 DIAbetes Mellitus (CARDIATEAM)

Institut National de la Santé Et de la Recherche Médicale, France

Status: Enrolling

Conditions: Cardiomyopathy, Diabetic

Study type: Observational

Funder types: Other

Identifiers

NCT04303364

C19-10

Details and patient eligibility

About

The objective of the CARDIATEAM clinical study is 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.

Full description

CARDIATEAM study will address the uniqueness of DCM, and its progression towards heart failure (HF) with preserved ejection fraction (HFpEF) by recruiting a prospective CARDIATEAM cohort (n=1600 individuals) from existing cohorts using a defined set of selection criteria and will include type2-Diabetes mellitus (T2DM)and non-diabetic patients with a large spectrum of demographic, metabolic and cardiac clinical data. This will yield a wide range of T2DM - related phenotypes including common confounders such as BMI, smoking, age and blood pressure.

To clarify the phenotype of DCM and to differentiate it from the other forms of HF such as HFpEF or HCM, CARDIATEAM will perform unbiased clustering analysis from an in-depth phenotyping of these patients' populations

Enrollment: 1,600 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Female or male, aged between ≥ 40 and ≤80 years

• Normal LVEF AND absence of akinetic segment assessed by echocardiography (i.e. LVEF≥50%)

• Patients diagnosed according to the specific diagnostic criteria of each disease (Cf. table below (definition criteria)). For each group, the diagnosis will be based on current accepted criteria:

  • 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
  • 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
  • T2DM: HbA1c ≥ 6.5% (≥ 48 mmol/L) AND Fasting Plasma Glucose ≥7.0 mmol/L (≥126 mg/dL) or anti-diabetic treatment
  • Non T2DM: HbA1c < 6.5% AND Fasting Plasma Glucose <7.0 mmol/L without any anti-diabetic treatment including normoglycemic subjects
  • 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:

  • 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 48 months before inclusion

• Patient covered by a health insurance

Non-inclusion criteria:

• 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 chemotherapy 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
• 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 gadolinium based product (including gadoteric acid and meglumine)
• Known COVID-19 symptomatic infection requiring hospitalization

Trial design

1,600 participants in 6 patient groups

Subjects without T2DM and without HF

Patients without T2DM and with HFpEF

Patients with T2DM and without HFpEF

Patients with T2DM and HFpEF

Patients without T2DM and with hypertrophic cardiomyopathy

Patients with T2DM and with hypertrophic cardiomyopathy