Cardiac Function and Microcirculation: Type 2 DIABetes and ECHOcardiographic Changes Over Time

The most frequent heart disease in patients with Type 2 Diabetes Mellitus (T2DM) is the premature development of coronary atherosclerosis, which often leads to overt ischemic heart disease (IHD). T2DM can lead to both cardiac dysfunction due to IHD or to diabetic cardiomyopathy. Diabetic cardiomyopathy is defined as an impairment of left ventricular (LV) function without overt obstructive coronary vessel disease. Diabetic cardiomyopathy has been associated with microvascular dysfunction, which leads to the inability of the heart to circulate blood effectively. The microvascular atherosclerotic changes are well known in patients with diabetes, such as impaired vision, kidney function and sensibility. The macrovascular atherosclerotic changes such as plaques in the coronary arteries are strongly associated with reduced left ventricular function.

However, the relationship between micro- and macrovascular atherosclerotic changes and the impact on cardiac function is less certain.

Estimation of cardiac function includes: Left Atrial (LA) Strain, LA Strain Rate (SR), LA Emptying Function (LAEF), LV Ejection Fraction (EF), Fractional Shortening (FS), Global Longitudinal Strain (GLS), Circumferential Strain (CS) and Radial Strain (RS), Strain Rate (SR), Peak Systolic Strain, Post Systolic Strain, Early mitral filling velocity (E), late mitral filling velocity (A), E/A ratio, Deceleration Time (DCT) of early mitral filling velocity, medial and lateral mitral velocities using tissue doppler (e' , a' and s'), E/e' ratio, Isovolumetric Relaxation Time (IVRT), Isovolumetric Closing Time (IVCT), Ejection Time (ET), Myocardial Performance Index (MPI) and Myocardial Work Index (MWI).

In this study, participants will be consisting of non-diabetic subjects and patients with diabetes type 1 + 2. All of the participants have no history of myocardial infarction, heart failure and current symptoms of cardiac disease.

The study population will undergo following examinations:

• 12-lead electrocardiogram (ECG)
• Urine- and blood samples.
• Measurements of anthropometric data and vital parameters
• Recording of medical history
• 2D transthoracic echocardiography
• Coronary flow velocity reserve (CFVR) with adenosine infusion.
• Coronary computed tomography angiography (CCTA).
• Free fractional reserve computed tomography (FFR-CT)

The examinations will be repeated at follow-up (however non-diabetic subjects will only have 1 CCTA performed at baseline).

The non-invasive FFR-CT will only be performed once in a subgroup of diabetic patients and non-diabetic subjects from November 2016 until May 2017.

Inclusion criteria

• Ability to give informed consent
• Estimated glomerular filtration rate (eGFR) > 45 ml/min
• NYHA I + II

Exclusion criteria

• 2° or 3° AV-block at baseline
• Long QT-syndrome at baseline
• Sinus node dysfunction with long sinus arrest at baseline
• Angina pectoris at baseline
• Ejection fraction (EF) < 40% at baseline
• Atrial fibrillation at baseline
• Usage of dipyridamol at baseline
• Aortic stenosis and left ventricle hypertrophia at baseline
• Aortic insufficiency and left ventricle dilatation at baseline
• Medication for asthma within the last 4 years prior to baseline
• Medication for chronic obstructive pulmonary disease (COPD) at baseline
• Allergy to contrast agent at baseline
• Significant stenosis in left main (LM) / left anterior descending (LAD) artery at baseline
• Not feasible to measure or perform coronary flow velocity reserve (CFVR)
• Poor quality of echocardiographic images
• History of pacemaker
• History of myocardial infarction (MI)
• History of heart failure (HF)
• History of coronary artery bypass grafting (CABG)
• History of aortic valve replacement
• History of atrial fibrillation